Reviews

The introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs) in 2001 for treatment of chronic myelogenous leukemia (CML) marked a paradigm shift in management of the disease. With that advance, CML has been largely managed as a chronic condition, with daily medication and frequent monitoring. Optimizing monitoring methods and identifying factors associated with response and long-term outcomes has thus been a major clinical research focus. Given the improved understanding of surveillance techniques in CML and the advent of several recently approved second- and third-generation TKIs, there have been recent updates to clinical practice guidelines.

Click on the PDF icon at the top of this introduction to read the full article.
 

The introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs) in 2001 for treatment of chronic myelogenous leukemia (CML) marked a paradigm shift in management of the disease. With that advance, CML has been largely managed as a chronic condition, with daily medication and frequent monitoring. Optimizing monitoring methods and identifying factors associated with response and long-term outcomes has thus been a major clinical research focus. Given the improved understanding of surveillance techniques in CML and the advent of several recently approved second- and third-generation TKIs, there have been recent updates to clinical practice guidelines.

Click on the PDF icon at the top of this introduction to read the full article.
 

The introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs) in 2001 for treatment of chronic myelogenous leukemia (CML) marked a paradigm shift in management of the disease. With that advance, CML has been largely managed as a chronic condition, with daily medication and frequent monitoring. Optimizing monitoring methods and identifying factors associated with response and long-term outcomes has thus been a major clinical research focus. Given the improved understanding of surveillance techniques in CML and the advent of several recently approved second- and third-generation TKIs, there have been recent updates to clinical practice guidelines.

Click on the PDF icon at the top of this introduction to read the full article.
 

BABY SEVERELY HANDICAPPED AFTER PREMATURE LABOR: $42.9M VERDICT
A 27-year-old mother had a normal prenatal ultrasonography (US) result in March 2007. In July, she went to the emergency department (ED) with pelvic pressure. A maternal-fetal medicine (MFM) specialist noted that the patient’s cervix had shortened to 1.3 cm. US showed that excessive amniotic fluid was causing uterine distention. The patient was monitored by an on-call ObGyn for 3.5 hours before being discharged home on pelvic and modified bed rest.

Two days later, the mother reported frequent contractions to her ObGyn. The baby was born the next day by emergency cesarean delivery at 25 weeks’ gestation. The newborn had seizures and a brain hemorrhage. The child has mental disabilities, blindness, spastic quadriparesis, cerebral palsy, gastroesophageal reflux, and complex feeding disorder.

PARENTS’ CLAIM The on-call ObGyn did not give the patient specific instructions for pelvic and bed rest upon discharge. The MFM specialist and on-call ObGyn failed to admit the patient to the hospital, and failed to administer intravenous steroids (betamethasone) to protect the fetal brain and induce respiratory development.

DEFENDANTS’ DEFENSE There was no indication during the MFM specialist’s examination that delivery was imminent. The use of betamethasone would not have prevented or inhibited premature labor. The infant’s problems were due to prematurity and low birth weight.

VERDICT A $42.9 million Pennsylvania verdict was returned against the MFM specialist; the on-call ObGyn and hospital were vindicated.

PELVIC LYMPH NODES NOT SAMPLED
When a 68-year-old woman reported vaginal spotting to her gynecologist (Dr. A) in March 2006, the results of an endometrial biopsy were negative. She saw another gynecologist (Dr. B) for a second opinion when bleeding continued. After dilation and curettage, grade 1B endometrial cancer was identified. The patient underwent a hysterectomy and bilateral salpingo-oophorectomy. She received a diagnosis of metastatic cancer of the pelvis and pelvic and para-aortic lymph nodes 18 months later. After additional surgery, the patient died in March 2008.

ESTATE’S CLAIM Dr. A was negligent in failing to diagnose the cancer in March 2006. Dr. B should have performed pelvic lymphadenectomy at hysterectomy; a lymphadenectomy would have accurately staged metastatic cancer.

DEFENDANTS’ DEFENSE Care and treatment were appropriate. Performing a lymphadenectomy would have exposed the patient to a significant risk of morbidity.

VERDICT A $750,000 California verdict was reduced to $250,000 under the state cap.

LARGE BABY: ERB’S PALSY
Shoulder dystocia was encountered when a 38-year-old woman gave birth. The child later received a diagnosis of Erb’s palsy, and has had several operations. At trial, the child had loss of function of the affected arm and wore a brace.

PARENTS’ CLAIM A vaginal delivery should not have been performed because the mother had gestational diabetes and the baby weighed 8 lb 8 oz at birth. Cesarean delivery was never offered.

DEFENDANTS’ DEFENSE Labor appeared normal. Proper delivery techniques were used when shoulder dystocia was encountered.

VERDICT A $12.9 million Michigan verdict was reduced to $4 million under the state cap.

Related articles:
You are the second responder to a shoulder dystocia emergency. What do you do first? Robert L. Barbieri, MD (Editorial; May 2013)
STOP all activities that may lead to further shoulder impaction when you suspect possible shoulder dystocia  Ronald T. Burkman, MD (Stop/Start; March 2013)
The natural history of obstetric brachial plexus injury Robert L. Barbieri, MD (Editorial, February 2013)

SPINAL CORD INJURY
During anesthesia administration before cesarean delivery, a mother’s spinal cord was injured, resulting in irritation of multiple nerve roots. She has chronic nerve pain syndrome.

PATIENT’S CLAIM The anesthesiologist was negligent in how he administered the spinal block.

PHYSICIAN’S DEFENSE There was no negligence. The injury is a known complication of the procedure.

VERDICT An Indiana defense verdict was returned.

AORTA PUNCTURED: $4M VERDICT
A 35-year-old woman underwent laparoscopic cystectomy on her left ovary performed by her gynecologist. During the procedure, the patient’s aorta was punctured, and she lost more than half her blood volume. After immediate surgery to repair the aorta, she was hospitalized for 5 days.

PATIENT’S CLAIM The injury was due to improper insertion of the laparoscopic instruments; the trocars were improperly angled and too forcefully inserted. The injury was a known risk of the procedure for obese patients, but she is not obese. She has a residual scar and is at increased risk of developing adhesions.

PHYSICIAN’S DEFENSE The instruments were properly inserted. The injury is a known risk of the procedure.

VERDICT A $4 million New York verdict was returned.

RESUSCITATION TOOK 22 MINUTES
At 40 6/7 weeks’ gestation, a mother went to the ED after her membranes spontaneously ruptured. The child was delivered by vacuum extraction 30 hours later.

At birth, the baby was blue and limp with Apgar scores of 2, 3, and 7, at 1, 5, and 10 minutes, respectively. The infant required 22 minutes of resuscitation. The neonatal record included metabolic acidosis, respiratory distress, possible sepsis, shoulder dystocia, and seizure activity. The child suffered hypoxic ischemic encephalopathy and permanent neurologic injury.

PARENTS’ CLAIM Cesarean delivery should have been performed due to repetitive decelerations, fetal tachycardia, and increasingly long uterine contractions. Continued use of oxytocin contributed to the infant’s injuries.

DEFENDANTS’ DEFENSE Fetal heart-rate tracings were reassuring during labor. Decreased variability, rising fetal heart rate, and late decelerations are normal during labor and delivery. The infant’s blood gas did not fall below 7.0 pH. The use of oxytocin was proper. There was no way to determine cephalopelvic disproportion or the baby’s size at 6 days postterm. The mother was opposed to a cesarean delivery and requested vaginal delivery (although no such request was included in the medical records).

VERDICT A $55 million Pennsylvania verdict was returned.

INJURY DURING OVARIAN REMNANT RESECTION
A woman in her 40s reported lower left quadrant pain. A previous oophorectomy report indicated that ovarian tissue attached to the bowel had not been removed. Thinking the pain might be related to residual ovarian tissue, her gynecologist recommended resection. During surgery, the patient’s bowel was injured. Four additional operations were required, including bowel resection with colostomy, and then colostomy reversal 5 months later.

PATIENT’S CLAIM The gynecologist was negligent in failing to properly perform surgery. The surgeon’s report from the oophorectomy indicated that there were extensive adhesions, which increased the risk of complications from surgery to remove the remnant. Ovarian remnant syndrome could have been treated with medication to induce menopause.

PHYSICIAN’S DEFENSE The patient might have suffered injury from medication-induced menopause. Surgery was appropriate; the injury is a known risk of the procedure.

VERDICT A $200,000 New York verdict was returned.

SEVERE INFECTION AFTER BIRTH
A 32-year-old woman left the hospital within hours of giving birth because her mother was ill. Before discharge, she reported severe abdominal pain and was examined by a first-year resident. The patient returned to the hospital 6 hours later with a severe uterine infection. She was hospitalized for a month.

PATIENT’S CLAIM The resident failed to properly assess her symptom reports, failed to order testing, and was negligent in allowing her to leave the hospital.

DEFENDANTS’ DEFENSE The patient left the hospital against medical recommendations. She might have acquired the infection after leaving the hospital.

VERDICT A $285,000 Michigan verdict was returned. The patient was found to be 40% at fault.

TERMINAL BRADYCARDIA: $12M VERDICT WITH MIXED FAULT
Four days after her due date, a mother’s blood pressure was elevated, and labor was induced. Two days after oxytocin was started, decelerations occurred. The ObGyn was called after the second deceleration, and witnessed the fourth deceleration about an hour later. After six decelerations, the fetal heart rate dropped to 70 bpm and did not return to baseline. A cesarean delivery was performed 26 minutes later. The child was born with a severe brain injury.

PARENTS’ CLAIM The nurses and ObGyn failed to recognize, report, and address nonreassuring fetal heart signs, and did not discontinue oxytocin after the second deceleration. Hospital protocols were ignored. An earlier cesarean delivery would have avoided injury; the fetus was without oxygen from the sixth deceleration until delivery.

DEFENDANTS’ DEFENSE There was no causation between the alleged violation of hospital protocols and the outcome. The ObGyn was appropriately notified. The injury was caused by terminal bradycardia during a prolonged deceleration that resulted from cord compression; it was unpredictable.

The ObGyn claimed earlier delivery was not indicated. Decelerations did not predict a bradycardic event from which the fetus would not recover nor indicate a need to stop oxytocin. The fetal heart rate had always recovered until the final deceleration. Bradycardia is unpredictable.

VERDICT A $12.165 million Hawaii verdict was returned, with the ObGyn 35% at fault, and the hospital 65% at fault. 

Related article: Stop staring at that Category-II fetal heart-rate tracing… Robert L. Barbieri, MD (Editorial, April 2011)

BREAST BIOPSY MIXUP; SHE DIDN’T HAVE CANCER
A 53-year-old woman reported right breast pain. Mammography revealed scattered fibroglandular elements. Targeted US showed a solid nodule that could be an intramammary lymph node or small fibroadenoma. After an office-based biopsy, the breast surgeon (Dr. A) told the patient that she had breast cancer. 

Because Dr. A was not in her health insurance plan, the patient took her imaging studies and biopsy results to Dr. B, another surgeon. Dr. B performed a mastectomy with lymphadenectomy. There was no evidence of malignancy in the pathologic review of breast and lymph tissue.

PATIENT’S CLAIM Dr. A performed biopsies on several women that same day; all were sent to the same laboratory for analysis. Dr. A and the laboratory failed to properly label and handle the biopsy specimens. Incorrect diagnosis caused her to undergo unnecessary mastectomy, lymph node biopsy, and a long, complicated breast reconstruction.

DEFENDANTS’ DEFENSE The case was settled at trial.

VERDICT A $1,780,000 Virginia settlement was reached.

Related article: Does screening mammography save lives? Janelle Yates (April 2014)

CLUES MISSED; BABY HAS CP, OTHER INJURIES
A 19-year-old mother had regular prenatal care. In early June, she weighed 221 lb and had a fundal height of 36 cm. The certified nurse midwife (CNM) noted little fetal movement, was uncertain of the fetal position, and made a note to check the amniotic fluid at the next visit. A week later, US did not indicate a decrease in amniotic fluid. Records do not indicate that the amniotic fluid index was checked at the next visit (38 weeks’ gestation).

Two days later, the patient reported decreased fetal movement. At the ED, nonreassuring fetal heart tracings were recorded. Fifteen minutes later, the fetal heart rate fell to 50 bpm and did not recover. The on-call ObGyn artificially ruptured the membranes and placed a direct fetal lead. An emergency cesarean delivery was performed in 15 minutes through thick meconium.

Apgar scores were 0, 2, and 4 at 1, 5, and 10 minutes, respectively. The baby weighed 4 lb 4 oz, and was transferred to a children’s hospital, where she stayed for 6 weeks. She suffered seizures and was tube fed. The child has cerebral palsy and profound neurologic impairment. At age 7, she is unable to speak.

PATIENT’S CLAIM The CNM was negligent for not being more proactive when she questioned the amniotic fluid index and noted reduced fetal movement in early June and at subsequent visits. The presence of meconium at birth attested that the fetus had been in distress.

DEFENDANTS’ DEFENSE The case was settled at trial.

VERDICT A $2 million Massachusetts settlement was reached.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

TELL US WHAT YOU THINK!
Drop us a line and let us know what you think about this or other current articles, which topics you'd like to see covered in future issues, and what challenges you face in daily practice. Tell us what you think by emailing us at: [email protected] Please include your name, city and state.
Stay in touch! Your feedback is important to us!

BABY SEVERELY HANDICAPPED AFTER PREMATURE LABOR: $42.9M VERDICT
A 27-year-old mother had a normal prenatal ultrasonography (US) result in March 2007. In July, she went to the emergency department (ED) with pelvic pressure. A maternal-fetal medicine (MFM) specialist noted that the patient’s cervix had shortened to 1.3 cm. US showed that excessive amniotic fluid was causing uterine distention. The patient was monitored by an on-call ObGyn for 3.5 hours before being discharged home on pelvic and modified bed rest.

Two days later, the mother reported frequent contractions to her ObGyn. The baby was born the next day by emergency cesarean delivery at 25 weeks’ gestation. The newborn had seizures and a brain hemorrhage. The child has mental disabilities, blindness, spastic quadriparesis, cerebral palsy, gastroesophageal reflux, and complex feeding disorder.

PARENTS’ CLAIM The on-call ObGyn did not give the patient specific instructions for pelvic and bed rest upon discharge. The MFM specialist and on-call ObGyn failed to admit the patient to the hospital, and failed to administer intravenous steroids (betamethasone) to protect the fetal brain and induce respiratory development.

DEFENDANTS’ DEFENSE There was no indication during the MFM specialist’s examination that delivery was imminent. The use of betamethasone would not have prevented or inhibited premature labor. The infant’s problems were due to prematurity and low birth weight.

VERDICT A $42.9 million Pennsylvania verdict was returned against the MFM specialist; the on-call ObGyn and hospital were vindicated.

PELVIC LYMPH NODES NOT SAMPLED
When a 68-year-old woman reported vaginal spotting to her gynecologist (Dr. A) in March 2006, the results of an endometrial biopsy were negative. She saw another gynecologist (Dr. B) for a second opinion when bleeding continued. After dilation and curettage, grade 1B endometrial cancer was identified. The patient underwent a hysterectomy and bilateral salpingo-oophorectomy. She received a diagnosis of metastatic cancer of the pelvis and pelvic and para-aortic lymph nodes 18 months later. After additional surgery, the patient died in March 2008.

ESTATE’S CLAIM Dr. A was negligent in failing to diagnose the cancer in March 2006. Dr. B should have performed pelvic lymphadenectomy at hysterectomy; a lymphadenectomy would have accurately staged metastatic cancer.

DEFENDANTS’ DEFENSE Care and treatment were appropriate. Performing a lymphadenectomy would have exposed the patient to a significant risk of morbidity.

VERDICT A $750,000 California verdict was reduced to $250,000 under the state cap.

LARGE BABY: ERB’S PALSY
Shoulder dystocia was encountered when a 38-year-old woman gave birth. The child later received a diagnosis of Erb’s palsy, and has had several operations. At trial, the child had loss of function of the affected arm and wore a brace.

PARENTS’ CLAIM A vaginal delivery should not have been performed because the mother had gestational diabetes and the baby weighed 8 lb 8 oz at birth. Cesarean delivery was never offered.

DEFENDANTS’ DEFENSE Labor appeared normal. Proper delivery techniques were used when shoulder dystocia was encountered.

VERDICT A $12.9 million Michigan verdict was reduced to $4 million under the state cap.

Related articles:
You are the second responder to a shoulder dystocia emergency. What do you do first? Robert L. Barbieri, MD (Editorial; May 2013)
STOP all activities that may lead to further shoulder impaction when you suspect possible shoulder dystocia  Ronald T. Burkman, MD (Stop/Start; March 2013)
The natural history of obstetric brachial plexus injury Robert L. Barbieri, MD (Editorial, February 2013)

SPINAL CORD INJURY
During anesthesia administration before cesarean delivery, a mother’s spinal cord was injured, resulting in irritation of multiple nerve roots. She has chronic nerve pain syndrome.

PATIENT’S CLAIM The anesthesiologist was negligent in how he administered the spinal block.

PHYSICIAN’S DEFENSE There was no negligence. The injury is a known complication of the procedure.

VERDICT An Indiana defense verdict was returned.

AORTA PUNCTURED: $4M VERDICT
A 35-year-old woman underwent laparoscopic cystectomy on her left ovary performed by her gynecologist. During the procedure, the patient’s aorta was punctured, and she lost more than half her blood volume. After immediate surgery to repair the aorta, she was hospitalized for 5 days.

PATIENT’S CLAIM The injury was due to improper insertion of the laparoscopic instruments; the trocars were improperly angled and too forcefully inserted. The injury was a known risk of the procedure for obese patients, but she is not obese. She has a residual scar and is at increased risk of developing adhesions.

PHYSICIAN’S DEFENSE The instruments were properly inserted. The injury is a known risk of the procedure.

VERDICT A $4 million New York verdict was returned.

RESUSCITATION TOOK 22 MINUTES
At 40 6/7 weeks’ gestation, a mother went to the ED after her membranes spontaneously ruptured. The child was delivered by vacuum extraction 30 hours later.

At birth, the baby was blue and limp with Apgar scores of 2, 3, and 7, at 1, 5, and 10 minutes, respectively. The infant required 22 minutes of resuscitation. The neonatal record included metabolic acidosis, respiratory distress, possible sepsis, shoulder dystocia, and seizure activity. The child suffered hypoxic ischemic encephalopathy and permanent neurologic injury.

PARENTS’ CLAIM Cesarean delivery should have been performed due to repetitive decelerations, fetal tachycardia, and increasingly long uterine contractions. Continued use of oxytocin contributed to the infant’s injuries.

DEFENDANTS’ DEFENSE Fetal heart-rate tracings were reassuring during labor. Decreased variability, rising fetal heart rate, and late decelerations are normal during labor and delivery. The infant’s blood gas did not fall below 7.0 pH. The use of oxytocin was proper. There was no way to determine cephalopelvic disproportion or the baby’s size at 6 days postterm. The mother was opposed to a cesarean delivery and requested vaginal delivery (although no such request was included in the medical records).

VERDICT A $55 million Pennsylvania verdict was returned.

INJURY DURING OVARIAN REMNANT RESECTION
A woman in her 40s reported lower left quadrant pain. A previous oophorectomy report indicated that ovarian tissue attached to the bowel had not been removed. Thinking the pain might be related to residual ovarian tissue, her gynecologist recommended resection. During surgery, the patient’s bowel was injured. Four additional operations were required, including bowel resection with colostomy, and then colostomy reversal 5 months later.

PATIENT’S CLAIM The gynecologist was negligent in failing to properly perform surgery. The surgeon’s report from the oophorectomy indicated that there were extensive adhesions, which increased the risk of complications from surgery to remove the remnant. Ovarian remnant syndrome could have been treated with medication to induce menopause.

PHYSICIAN’S DEFENSE The patient might have suffered injury from medication-induced menopause. Surgery was appropriate; the injury is a known risk of the procedure.

VERDICT A $200,000 New York verdict was returned.

SEVERE INFECTION AFTER BIRTH
A 32-year-old woman left the hospital within hours of giving birth because her mother was ill. Before discharge, she reported severe abdominal pain and was examined by a first-year resident. The patient returned to the hospital 6 hours later with a severe uterine infection. She was hospitalized for a month.

PATIENT’S CLAIM The resident failed to properly assess her symptom reports, failed to order testing, and was negligent in allowing her to leave the hospital.

DEFENDANTS’ DEFENSE The patient left the hospital against medical recommendations. She might have acquired the infection after leaving the hospital.

VERDICT A $285,000 Michigan verdict was returned. The patient was found to be 40% at fault.

TERMINAL BRADYCARDIA: $12M VERDICT WITH MIXED FAULT
Four days after her due date, a mother’s blood pressure was elevated, and labor was induced. Two days after oxytocin was started, decelerations occurred. The ObGyn was called after the second deceleration, and witnessed the fourth deceleration about an hour later. After six decelerations, the fetal heart rate dropped to 70 bpm and did not return to baseline. A cesarean delivery was performed 26 minutes later. The child was born with a severe brain injury.

PARENTS’ CLAIM The nurses and ObGyn failed to recognize, report, and address nonreassuring fetal heart signs, and did not discontinue oxytocin after the second deceleration. Hospital protocols were ignored. An earlier cesarean delivery would have avoided injury; the fetus was without oxygen from the sixth deceleration until delivery.

DEFENDANTS’ DEFENSE There was no causation between the alleged violation of hospital protocols and the outcome. The ObGyn was appropriately notified. The injury was caused by terminal bradycardia during a prolonged deceleration that resulted from cord compression; it was unpredictable.

The ObGyn claimed earlier delivery was not indicated. Decelerations did not predict a bradycardic event from which the fetus would not recover nor indicate a need to stop oxytocin. The fetal heart rate had always recovered until the final deceleration. Bradycardia is unpredictable.

VERDICT A $12.165 million Hawaii verdict was returned, with the ObGyn 35% at fault, and the hospital 65% at fault. 

Related article: Stop staring at that Category-II fetal heart-rate tracing… Robert L. Barbieri, MD (Editorial, April 2011)

BREAST BIOPSY MIXUP; SHE DIDN’T HAVE CANCER
A 53-year-old woman reported right breast pain. Mammography revealed scattered fibroglandular elements. Targeted US showed a solid nodule that could be an intramammary lymph node or small fibroadenoma. After an office-based biopsy, the breast surgeon (Dr. A) told the patient that she had breast cancer. 

Because Dr. A was not in her health insurance plan, the patient took her imaging studies and biopsy results to Dr. B, another surgeon. Dr. B performed a mastectomy with lymphadenectomy. There was no evidence of malignancy in the pathologic review of breast and lymph tissue.

PATIENT’S CLAIM Dr. A performed biopsies on several women that same day; all were sent to the same laboratory for analysis. Dr. A and the laboratory failed to properly label and handle the biopsy specimens. Incorrect diagnosis caused her to undergo unnecessary mastectomy, lymph node biopsy, and a long, complicated breast reconstruction.

DEFENDANTS’ DEFENSE The case was settled at trial.

VERDICT A $1,780,000 Virginia settlement was reached.

Related article: Does screening mammography save lives? Janelle Yates (April 2014)

CLUES MISSED; BABY HAS CP, OTHER INJURIES
A 19-year-old mother had regular prenatal care. In early June, she weighed 221 lb and had a fundal height of 36 cm. The certified nurse midwife (CNM) noted little fetal movement, was uncertain of the fetal position, and made a note to check the amniotic fluid at the next visit. A week later, US did not indicate a decrease in amniotic fluid. Records do not indicate that the amniotic fluid index was checked at the next visit (38 weeks’ gestation).

Two days later, the patient reported decreased fetal movement. At the ED, nonreassuring fetal heart tracings were recorded. Fifteen minutes later, the fetal heart rate fell to 50 bpm and did not recover. The on-call ObGyn artificially ruptured the membranes and placed a direct fetal lead. An emergency cesarean delivery was performed in 15 minutes through thick meconium.

Apgar scores were 0, 2, and 4 at 1, 5, and 10 minutes, respectively. The baby weighed 4 lb 4 oz, and was transferred to a children’s hospital, where she stayed for 6 weeks. She suffered seizures and was tube fed. The child has cerebral palsy and profound neurologic impairment. At age 7, she is unable to speak.

PATIENT’S CLAIM The CNM was negligent for not being more proactive when she questioned the amniotic fluid index and noted reduced fetal movement in early June and at subsequent visits. The presence of meconium at birth attested that the fetus had been in distress.

DEFENDANTS’ DEFENSE The case was settled at trial.

VERDICT A $2 million Massachusetts settlement was reached.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

TELL US WHAT YOU THINK!
Drop us a line and let us know what you think about this or other current articles, which topics you'd like to see covered in future issues, and what challenges you face in daily practice. Tell us what you think by emailing us at: [email protected] Please include your name, city and state.
Stay in touch! Your feedback is important to us!

BABY SEVERELY HANDICAPPED AFTER PREMATURE LABOR: $42.9M VERDICT
A 27-year-old mother had a normal prenatal ultrasonography (US) result in March 2007. In July, she went to the emergency department (ED) with pelvic pressure. A maternal-fetal medicine (MFM) specialist noted that the patient’s cervix had shortened to 1.3 cm. US showed that excessive amniotic fluid was causing uterine distention. The patient was monitored by an on-call ObGyn for 3.5 hours before being discharged home on pelvic and modified bed rest.

Two days later, the mother reported frequent contractions to her ObGyn. The baby was born the next day by emergency cesarean delivery at 25 weeks’ gestation. The newborn had seizures and a brain hemorrhage. The child has mental disabilities, blindness, spastic quadriparesis, cerebral palsy, gastroesophageal reflux, and complex feeding disorder.

PARENTS’ CLAIM The on-call ObGyn did not give the patient specific instructions for pelvic and bed rest upon discharge. The MFM specialist and on-call ObGyn failed to admit the patient to the hospital, and failed to administer intravenous steroids (betamethasone) to protect the fetal brain and induce respiratory development.

DEFENDANTS’ DEFENSE There was no indication during the MFM specialist’s examination that delivery was imminent. The use of betamethasone would not have prevented or inhibited premature labor. The infant’s problems were due to prematurity and low birth weight.

VERDICT A $42.9 million Pennsylvania verdict was returned against the MFM specialist; the on-call ObGyn and hospital were vindicated.

PELVIC LYMPH NODES NOT SAMPLED
When a 68-year-old woman reported vaginal spotting to her gynecologist (Dr. A) in March 2006, the results of an endometrial biopsy were negative. She saw another gynecologist (Dr. B) for a second opinion when bleeding continued. After dilation and curettage, grade 1B endometrial cancer was identified. The patient underwent a hysterectomy and bilateral salpingo-oophorectomy. She received a diagnosis of metastatic cancer of the pelvis and pelvic and para-aortic lymph nodes 18 months later. After additional surgery, the patient died in March 2008.

ESTATE’S CLAIM Dr. A was negligent in failing to diagnose the cancer in March 2006. Dr. B should have performed pelvic lymphadenectomy at hysterectomy; a lymphadenectomy would have accurately staged metastatic cancer.

DEFENDANTS’ DEFENSE Care and treatment were appropriate. Performing a lymphadenectomy would have exposed the patient to a significant risk of morbidity.

VERDICT A $750,000 California verdict was reduced to $250,000 under the state cap.

LARGE BABY: ERB’S PALSY
Shoulder dystocia was encountered when a 38-year-old woman gave birth. The child later received a diagnosis of Erb’s palsy, and has had several operations. At trial, the child had loss of function of the affected arm and wore a brace.

PARENTS’ CLAIM A vaginal delivery should not have been performed because the mother had gestational diabetes and the baby weighed 8 lb 8 oz at birth. Cesarean delivery was never offered.

DEFENDANTS’ DEFENSE Labor appeared normal. Proper delivery techniques were used when shoulder dystocia was encountered.

VERDICT A $12.9 million Michigan verdict was reduced to $4 million under the state cap.

Related articles:
You are the second responder to a shoulder dystocia emergency. What do you do first? Robert L. Barbieri, MD (Editorial; May 2013)
STOP all activities that may lead to further shoulder impaction when you suspect possible shoulder dystocia  Ronald T. Burkman, MD (Stop/Start; March 2013)
The natural history of obstetric brachial plexus injury Robert L. Barbieri, MD (Editorial, February 2013)

SPINAL CORD INJURY
During anesthesia administration before cesarean delivery, a mother’s spinal cord was injured, resulting in irritation of multiple nerve roots. She has chronic nerve pain syndrome.

PATIENT’S CLAIM The anesthesiologist was negligent in how he administered the spinal block.

PHYSICIAN’S DEFENSE There was no negligence. The injury is a known complication of the procedure.

VERDICT An Indiana defense verdict was returned.

AORTA PUNCTURED: $4M VERDICT
A 35-year-old woman underwent laparoscopic cystectomy on her left ovary performed by her gynecologist. During the procedure, the patient’s aorta was punctured, and she lost more than half her blood volume. After immediate surgery to repair the aorta, she was hospitalized for 5 days.

PATIENT’S CLAIM The injury was due to improper insertion of the laparoscopic instruments; the trocars were improperly angled and too forcefully inserted. The injury was a known risk of the procedure for obese patients, but she is not obese. She has a residual scar and is at increased risk of developing adhesions.

PHYSICIAN’S DEFENSE The instruments were properly inserted. The injury is a known risk of the procedure.

VERDICT A $4 million New York verdict was returned.

RESUSCITATION TOOK 22 MINUTES
At 40 6/7 weeks’ gestation, a mother went to the ED after her membranes spontaneously ruptured. The child was delivered by vacuum extraction 30 hours later.

At birth, the baby was blue and limp with Apgar scores of 2, 3, and 7, at 1, 5, and 10 minutes, respectively. The infant required 22 minutes of resuscitation. The neonatal record included metabolic acidosis, respiratory distress, possible sepsis, shoulder dystocia, and seizure activity. The child suffered hypoxic ischemic encephalopathy and permanent neurologic injury.

PARENTS’ CLAIM Cesarean delivery should have been performed due to repetitive decelerations, fetal tachycardia, and increasingly long uterine contractions. Continued use of oxytocin contributed to the infant’s injuries.

DEFENDANTS’ DEFENSE Fetal heart-rate tracings were reassuring during labor. Decreased variability, rising fetal heart rate, and late decelerations are normal during labor and delivery. The infant’s blood gas did not fall below 7.0 pH. The use of oxytocin was proper. There was no way to determine cephalopelvic disproportion or the baby’s size at 6 days postterm. The mother was opposed to a cesarean delivery and requested vaginal delivery (although no such request was included in the medical records).

VERDICT A $55 million Pennsylvania verdict was returned.

INJURY DURING OVARIAN REMNANT RESECTION
A woman in her 40s reported lower left quadrant pain. A previous oophorectomy report indicated that ovarian tissue attached to the bowel had not been removed. Thinking the pain might be related to residual ovarian tissue, her gynecologist recommended resection. During surgery, the patient’s bowel was injured. Four additional operations were required, including bowel resection with colostomy, and then colostomy reversal 5 months later.

PATIENT’S CLAIM The gynecologist was negligent in failing to properly perform surgery. The surgeon’s report from the oophorectomy indicated that there were extensive adhesions, which increased the risk of complications from surgery to remove the remnant. Ovarian remnant syndrome could have been treated with medication to induce menopause.

PHYSICIAN’S DEFENSE The patient might have suffered injury from medication-induced menopause. Surgery was appropriate; the injury is a known risk of the procedure.

VERDICT A $200,000 New York verdict was returned.

SEVERE INFECTION AFTER BIRTH
A 32-year-old woman left the hospital within hours of giving birth because her mother was ill. Before discharge, she reported severe abdominal pain and was examined by a first-year resident. The patient returned to the hospital 6 hours later with a severe uterine infection. She was hospitalized for a month.

PATIENT’S CLAIM The resident failed to properly assess her symptom reports, failed to order testing, and was negligent in allowing her to leave the hospital.

DEFENDANTS’ DEFENSE The patient left the hospital against medical recommendations. She might have acquired the infection after leaving the hospital.

VERDICT A $285,000 Michigan verdict was returned. The patient was found to be 40% at fault.

TERMINAL BRADYCARDIA: $12M VERDICT WITH MIXED FAULT
Four days after her due date, a mother’s blood pressure was elevated, and labor was induced. Two days after oxytocin was started, decelerations occurred. The ObGyn was called after the second deceleration, and witnessed the fourth deceleration about an hour later. After six decelerations, the fetal heart rate dropped to 70 bpm and did not return to baseline. A cesarean delivery was performed 26 minutes later. The child was born with a severe brain injury.

PARENTS’ CLAIM The nurses and ObGyn failed to recognize, report, and address nonreassuring fetal heart signs, and did not discontinue oxytocin after the second deceleration. Hospital protocols were ignored. An earlier cesarean delivery would have avoided injury; the fetus was without oxygen from the sixth deceleration until delivery.

DEFENDANTS’ DEFENSE There was no causation between the alleged violation of hospital protocols and the outcome. The ObGyn was appropriately notified. The injury was caused by terminal bradycardia during a prolonged deceleration that resulted from cord compression; it was unpredictable.

The ObGyn claimed earlier delivery was not indicated. Decelerations did not predict a bradycardic event from which the fetus would not recover nor indicate a need to stop oxytocin. The fetal heart rate had always recovered until the final deceleration. Bradycardia is unpredictable.

VERDICT A $12.165 million Hawaii verdict was returned, with the ObGyn 35% at fault, and the hospital 65% at fault. 

Related article: Stop staring at that Category-II fetal heart-rate tracing… Robert L. Barbieri, MD (Editorial, April 2011)

BREAST BIOPSY MIXUP; SHE DIDN’T HAVE CANCER
A 53-year-old woman reported right breast pain. Mammography revealed scattered fibroglandular elements. Targeted US showed a solid nodule that could be an intramammary lymph node or small fibroadenoma. After an office-based biopsy, the breast surgeon (Dr. A) told the patient that she had breast cancer. 

Because Dr. A was not in her health insurance plan, the patient took her imaging studies and biopsy results to Dr. B, another surgeon. Dr. B performed a mastectomy with lymphadenectomy. There was no evidence of malignancy in the pathologic review of breast and lymph tissue.

PATIENT’S CLAIM Dr. A performed biopsies on several women that same day; all were sent to the same laboratory for analysis. Dr. A and the laboratory failed to properly label and handle the biopsy specimens. Incorrect diagnosis caused her to undergo unnecessary mastectomy, lymph node biopsy, and a long, complicated breast reconstruction.

DEFENDANTS’ DEFENSE The case was settled at trial.

VERDICT A $1,780,000 Virginia settlement was reached.

Related article: Does screening mammography save lives? Janelle Yates (April 2014)

CLUES MISSED; BABY HAS CP, OTHER INJURIES
A 19-year-old mother had regular prenatal care. In early June, she weighed 221 lb and had a fundal height of 36 cm. The certified nurse midwife (CNM) noted little fetal movement, was uncertain of the fetal position, and made a note to check the amniotic fluid at the next visit. A week later, US did not indicate a decrease in amniotic fluid. Records do not indicate that the amniotic fluid index was checked at the next visit (38 weeks’ gestation).

Two days later, the patient reported decreased fetal movement. At the ED, nonreassuring fetal heart tracings were recorded. Fifteen minutes later, the fetal heart rate fell to 50 bpm and did not recover. The on-call ObGyn artificially ruptured the membranes and placed a direct fetal lead. An emergency cesarean delivery was performed in 15 minutes through thick meconium.

Apgar scores were 0, 2, and 4 at 1, 5, and 10 minutes, respectively. The baby weighed 4 lb 4 oz, and was transferred to a children’s hospital, where she stayed for 6 weeks. She suffered seizures and was tube fed. The child has cerebral palsy and profound neurologic impairment. At age 7, she is unable to speak.

PATIENT’S CLAIM The CNM was negligent for not being more proactive when she questioned the amniotic fluid index and noted reduced fetal movement in early June and at subsequent visits. The presence of meconium at birth attested that the fetus had been in distress.

DEFENDANTS’ DEFENSE The case was settled at trial.

VERDICT A $2 million Massachusetts settlement was reached.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

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Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment option for several hematologic malignancies and other congenital diseases including immunodeficiencies or hemoglobinopathies. When the first allografts were performed, most patients given bone marrow (BM) from donors other than homozygotic twins developed skin, gut, and/or liver injury. This disease was defined by Billingham in 1966 as graft-versushost disease (GVHD). He also described 3 standard tenets for GVHD pathophysiology, which remain valid today even with rapid advances in this area: (1) donor graft must have immune-competent cells, (2) recipient must be incapable of rejecting the graft, and (3) recipient must have tissue antigens not present in the donor.

To read the full article in PDF:

Click here

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment option for several hematologic malignancies and other congenital diseases including immunodeficiencies or hemoglobinopathies. When the first allografts were performed, most patients given bone marrow (BM) from donors other than homozygotic twins developed skin, gut, and/or liver injury. This disease was defined by Billingham in 1966 as graft-versushost disease (GVHD). He also described 3 standard tenets for GVHD pathophysiology, which remain valid today even with rapid advances in this area: (1) donor graft must have immune-competent cells, (2) recipient must be incapable of rejecting the graft, and (3) recipient must have tissue antigens not present in the donor.

To read the full article in PDF:

Click here

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment option for several hematologic malignancies and other congenital diseases including immunodeficiencies or hemoglobinopathies. When the first allografts were performed, most patients given bone marrow (BM) from donors other than homozygotic twins developed skin, gut, and/or liver injury. This disease was defined by Billingham in 1966 as graft-versushost disease (GVHD). He also described 3 standard tenets for GVHD pathophysiology, which remain valid today even with rapid advances in this area: (1) donor graft must have immune-competent cells, (2) recipient must be incapable of rejecting the graft, and (3) recipient must have tissue antigens not present in the donor.

To read the full article in PDF:

Click here

You have spent several days checking on a patient hospitalized for an acute exacerbation of heart failure. You have straightened out her medications and diet and discussed a plan for follow-up with the patient and a family member, and now she is being wheeled out the door. What happens to her next?

Too often, not your desired plan. If she is going home, maybe she understands what she needs to do, maybe not. Maybe she will get your prescriptions filled and take the medications as directed, maybe not. If she is going to a nursing home, maybe the physician covering the nursing home will get your plan, maybe not. There is a good chance she will be back in the emergency room soon, all because of a poor transition of care.

Transitions of care are changes in the level, location, or providers of care as patients move within the health care system. These can be critical junctures in patients’ lives, and if poorly executed can result in many adverse effects—including rehospitalization.¹

Although high rehospitalization rates gained national attention in 2009 after a analysis of Medicare data,² health care providers have known about the lack of coordinated care transitions for more than 50 years.³ Despite some progress, improving care transitions remains a national challenge. As the health system evolves from a fee-for-service financial model to payment-for-value,⁴ it is especially important that health care providers improve care for patients by optimizing care transitions.

In this article, we summarize the factors contributing to poor care transitions, highlight programs that improve them, and discuss strategies for successful transitions.

TRANSITION PROBLEMS ARE COMMON

Transitions of care occur when patients move to short-term and long-term acute care hospitals, skilled nursing facilities, primary and specialty care offices, community health centers, rehabilitation facilities, home health agencies, hospice, and their own homes.⁵ Problems can arise at any of these transitions, but the risk is especially high when patients leave the hospital to receive care in another setting or at home.

In the past decade, one in five Medicare patients was rehospitalized within 30 days of discharge from the hospital,² and up to 25% were rehospitalized after being discharged to a skilled nursing facility.⁶ Some diagnoses (eg, sickle cell anemia, gangrene) and procedures (eg, kidney transplantation, ileostomy) are associated with readmission rates of nearly one in three.^7,8

The desire of policymakers to “bend the cost curve” of health care has led to efforts to enhance care coordination by improving transitions between care venues. Through the Patient Protection and Affordable Care Act, a number of federal initiatives are promoting strategies to improve care transitions and prevent readmissions after hospital discharge.

The Hospital Readmission Reduction Program⁹ drives much of this effort. In fiscal year 2013 (beginning October 1, 2012), more than 2,000 hospitals incurred financial penalties of up to 1% of total Medicare diagnosis-related group payments (about $280 million the first year) for excess readmissions.¹⁰ The penalty’s maximum rose to 2% in fiscal year 2014 and could increase to 3% in 2015. The total penalty for 2014 is projected to be $227 million, with 2,225 hospitals affected.¹¹

The Centers for Medicare and Medicaid Innovation has committed hundreds of millions of dollars to Community-based Care Transitions Programs¹² and more than $200 million to Hospital Engagement Networks¹³ to carry out the goals of the Partnership for Patients,¹⁴ aiming to reduce rehospitalizations and other adverse events.

At first, despite these efforts, readmission rates did not appear to change substantially.¹⁵ However, the Centers for Medicare and Medicaid Services reported that hospital readmission rates for Medicare fee-for-service beneficiaries declined in 2012 to 18.4%,¹⁶ although some believe that the reduction is related to an increase in the number of patients admitted for observation in recent years.¹⁷

TRANSITIONS ARE OFTEN POORLY COORDINATED

Although some readmissions are unavoidable—resulting from the inevitable progression of disease or worsening of chronic conditions¹⁸—they may also result from a fumbled transition between care settings. Our current system of care transition has serious deficiencies that endanger patients. Areas that need improvement include communication between providers, patient education about medications and treatments, monitoring of medication adherence and complications, follow-up of pending tests and procedures after discharge, and outpatient follow-up soon after discharge.^19–21

Traditional health care does not have dependable mechanisms for coordinating care across settings; we are all ensconced in “silos” that generally keep the focus within individual venues.²² Lack of coordination blurs the lines of responsibility for patients in the period between discharge from one location and admission to another, leaving them confused about whom to contact for care, especially if symptoms worsen.^23,24

Gaps in coordination are not surprising, given the complexity of the US health care system and the often remarkable number of physicians caring for an individual patient.⁵ Medicare beneficiaries see an average of two primary care physicians and five specialists during a 2-year period; patients with chronic conditions may see up to 16 physicians in 1 year.²⁵ Coordinating care between so many providers in different settings, combined with possible patient factors such as disadvantaged socioeconomic status, lack of caregiver support, and inadequate health literacy, provides many opportunities for failures.

Research has identified several root causes behind most failed care transitions:

Poor provider communication

Multiple studies associate adverse events after discharge with a lack of timely communication between hospital and outpatient providers.²⁶ One study estimated that 80% of serious medical errors involve miscommunication during the hand-off between medical providers.²⁷ Discharge summaries often lack important information such as test results, hospital course, discharge medications, patient counseling, and follow-up plans. Most adverse drug events after hospital discharge result directly from breakdown in communication between hospital staff and patients or primary care physicians.²⁸ Approximately 40% of patients have test results pending at the time of discharge and 10% of these require some action; yet outpatient physicians and patients are often unaware of them.²¹

Ineffective patient and caregiver education

The Institute of Medicine report, Crossing the Quality Chasm: A New Health System for the 21st Century,²⁹ noted that patients leaving one setting for another receive little information on how to care for themselves, when to resume activities, what medication side effects to watch out for, and how to get answers to questions. Of particular concern is that patients and caregivers are sometimes omitted from transition planning and often must suddenly assume new self-care responsibilities upon going home that hospital staff managed before discharge. Too often, patients are discharged with inadequate understanding of their medical condition, self-care plan,^23,24 and who should manage their care.³⁰

Up to 36% of adults in the United States have inadequate health literacy (defined as the inability to understand basic health information needed to make appropriate decisions), hindering patient education efforts.^31–33 Even if they understand, patients and their caregivers must be engaged or “activated” (ie, able and willing to manage one’s health) if we expect them to adhere to appropriate care and behaviors. A review found direct correlations between patient activation and healthy behavior, better health outcomes (eg, achieving normal hemoglobin A_1c and cholesterol levels), and better care experiences.³⁴ This review also noted that multiple studies have documented improved activation scores as a result of specific interventions.

No follow-up with primary care providers

The risk of hospital readmission is significantly lower for patients with chronic obstructive pulmonary disease or heart failure who receive follow-up within 7 days of discharge.^35–38 Of Medicare beneficiaries readmitted to the hospital within 30 days of discharge in 2003–2004, half had no contact with an outpatient physician in the interval between their discharge and their readmission,² and one in three adult patients discharged from a hospital to the community does not see a physician within 30 days of discharge.³⁹ The dearth of primary care providers in many communities can make follow-up care difficult to coordinate.

Failure to address chronic conditions

Analyses of national data sets reveal that patients are commonly rehospitalized for conditions unrelated to their initial hospitalization. According to the Center for Studying Health System Change, more than a quarter of readmissions in the 30 days after discharge are for conditions unrelated to those identified in the index admission, the proportion rising to more than one-third at 1 year.³⁹ Among Medicare beneficiaries readmitted within 30 days of discharge, the proportion readmitted for the same condition was just 35% after hospitalization for heart failure, 10% after hospitalization for acute myocardial infarction, and 22% after hospitalization for pneumonia.⁴⁰

Lack of community support

Multiple social and environmental factors contribute to adverse postdischarge events.^41–43 For socioeconomically disadvantaged patients, care-transition issues are compounded by insufficient access to outpatient care, lack of social support, and lack of transportation. Some studies indicate that between 40% to 50% of readmissions are linked to social problems and inadequate access to community resources.^44–47 Psychosocial issues such as limited health literacy, poor self-management skills, inadequate social support, and living alone are associated with adverse outcomes, including readmission and death.^48,49 Such factors may help explain high levels of “no-shows” to outpatient follow-up visits.

NATIONAL MODELS OF BEST PRACTICES

Efforts to reduce readmissions have traditionally focused on hospitals, but experts now recognize that multiple factors influence readmissions and must be comprehensively addressed. Several evidence-based models seek to improve patient outcomes with interventions aimed at care transitions:

Project BOOST

Project BOOST (Better Outcomes by Optimizing Safe Transitions)⁵⁰ is a national initiative developed by the Society of Hospital Medicine to standardize and optimize the care of patients discharged from hospital to home. The program includes evidence-based clinical interventions that can easily be adopted by any hospital. Interventions are aimed at:

• Identifying patients at high risk on admission
• Targeting risk-specific situations
• Improving information flow between inpatient and outpatient providers
• Improving patient and caregiver education by using the teach-back method
• Achieving timely follow-up after discharge.

The program includes a year of technical support provided by a physician mentor.

Preliminary results from pilot sites showed a 14% reduction in 30-day readmission rates in units using BOOST compared with control units in the same hospital.⁵¹ Mentored implementation was recognized by the Joint Commission and the National Quality Forum with the 2011 John M. Eisenberg Award for Innovation in Patient Safety and Quality.⁵²

Project RED

Project RED (Re-Engineered Discharge)⁵³ evolved from efforts by Dr. Brian Jack and colleagues to re-engineer the hospital workflow process to improve patient safety and reduce rehospitalization rates at Boston Medical Center. The intervention has 12 mutually reinforcing components aimed at improving the discharge process.

In a randomized controlled trial, Project RED led to a 30% decrease in emergency department visits and readmissions within 30 days of discharge from a general medical service of an urban academic medical center.⁵⁴ This study excluded patients admitted from a skilled nursing facility or discharged to one, but a recent study demonstrated that Project RED also led to a lower rate of hospital admission within 30 days of discharge from a skilled nursing facility.⁵⁵

The STAAR initiative

The STAAR initiative (State Action on Avoidable Re-hospitalizations)⁵⁶ was launched in 2009 by the Institute for Healthcare Improvement with the goal of reducing avoidable readmissions in the states of Massachusetts, Michigan, and Washington. Hospital teams focus on improving:

• Assessment of needs after hospital discharge
• Teaching and learning
• Real-time hand-off communication
• Timely follow-up after hospital discharge.

As yet, no published studies other than case reports show a benefit from STAAR.⁵⁷

The Care Transitions Program

The Care Transitions Program,⁵⁸ under the leadership of Dr. Eric Coleman, aims to empower patients and caregivers, who meet with a “transition coach.” The program provides assistance with medication reconciliation and self-management, a patient-centered record owned and maintained by the patient to facilitate cross-site information transfer, timely outpatient follow-up with primary or specialty care, a list of red flags to indicate a worsening condition, and instructions on proper responses.

A randomized controlled trial of the program demonstrated a reduction in hospital readmissions at 30, 90, and 180 days, and lower hospital costs at 90 and 180 days.⁵⁹ This approach also proved effective in a real-world setting.⁶⁰

The Transitional Care Model

Developed by Dr. Mary Naylor and colleagues, the Transitional Care Model⁶¹ also aims at patient and family empowerment, focusing on patients’ stated goals and priorities and ensuring patient engagement. In the program, a transitional care nurse has the job of enhancing patient and caregiver understanding, facilitating patient self-management, and overseeing medication management and transitional care.

A randomized controlled trial demonstrated improved outcomes after hospital discharge for elderly patients with complex medical illnesses, with overall reductions in medical costs through preventing or delaying rehospitalization.⁶² A subsequent real-world study validated this approach.⁶³

The Bridge Model

The Illinois Transitional Care Consortium’s Bridge Model⁶⁴ is for older patients discharged home after hospitalization. It is led by social workers (“bridge care coordinators”) who address barriers to implementing the discharge plan, coordinate resources, and intervene at three points: before discharge, 2 days after discharge, and 30 days after discharge.

An initial study showed no impact on the 30-day rehospitalization rate,⁶⁵ but larger studies are under way with a modified version.

Guided Care

Developed at the Johns Hopkins Bloomberg School of Public Health, Guided Care⁶⁶ involves nurses who work in partnership with physicians and others in primary care to provide patient-centered, cost-effective care to patients with multiple chronic conditions. Nurses conduct in-home assessments, facilitate care planning, promote patient self-management, monitor conditions, coordinate the efforts of all care professionals, and facilitate access to community resources.

A cluster-randomized controlled trial found that this program had mixed results, reducing the use of home health care but having little effect on the use of other health services in the short run. However, in the subgroup of patients covered by Kaiser-Permanente, those who were randomized to the program accrued, on average, 52% fewer skilled nursing facility days, 47% fewer skilled nursing facility admissions, 49% fewer hospital readmissions, and 17% fewer emergency department visits.⁶⁷

The GRACE model

The GRACE model (Geriatric Resources for Assessment and Care of Elders)⁶⁸ was developed to improve the quality of geriatric care, reduce excess health care use, and prevent long-term nursing home placement. Each patient is assigned a support team consisting of a nurse practitioner and a social worker who make home visits, coordinate health care and community services, and develop an individualized care plan.

In one study,⁶⁹ GRACE reduced hospital admission rates for participants at high risk of hospitalization by 12% in the first year of the program and 44% in the second year. GRACE participants also reported higher quality of life compared with the control group.⁶⁹

INTERACT tools

Led by Dr. Joseph Ouslander, INTERACT (Interventions to Reduce Acute Care Transfers)⁷⁰ is a quality-improvement initiative for skilled nursing facilities, designed to facilitate the early identification, evaluation, documentation, and communication of changes in the status of residents. Visitors to its website can download a set of tools and strategies to help them manage conditions before they become serious enough to require a hospital transfer. The tools assist in promoting important communication among providers and enhancing advance-care planning.

A 6-month study in 25 nursing homes showed a 17% reduction in self-reported hospital admissions with this program compared with the same period the previous year.⁷¹

Additional home-based care interventions

Additional innovations are under way in home-based care.

The Home Health Quality Improvement National Campaign is a patient-centered movement to improve the quality of care received by patients residing at home.⁷² Through its Best Practices Intervention Packages, it offers evidence-based educational tools, resources, and interventions for reducing avoidable hospitalizations, improving medication management, and coordinating transitional care.

The Center for Medicare and Medicaid Innovation Independence at Home Demonstration⁷³ is testing whether home-based comprehensive primary care can improve care and reduce hospitalizations for Medicare beneficiaries with multiple chronic conditions.

NO SINGLE INTERVENTION: MULTIPLE STRATEGIES NEEDED

A 2011 review found no single intervention that regularly reduced the 30-day risk of re-hospitalization.⁷⁴ However, other studies have shown that multifaceted interventions can reduce 30-day readmission rates. Randomized controlled trials in short-stay, acute care hospitals indicate that improvement in the following areas can directly reduce hospital readmission rates:

• Comprehensive planning and risk assessment throughout hospitalization
• Quality of care during the initial admission
• Communication with patients, their caregivers, and their clinicians
• Patient education
• Predischarge assessment
• Coordination of care after discharge.

In randomized trials, successful programs reduced the 30-day readmission rates by 20% to 40%,^{54,62,75–79} and a 2011 meta-analysis of randomized clinical trials found evidence that interventions associated with discharge planning helped to reduce readmission rates.⁸⁰

Methods developed by the national care transition models described above can help hospitals optimize patient transitions (Table 1). Although every model has its unique attributes, they have several strategies in common:

Engage a team of key stakeholders that may include patients and caregivers, hospital staff (physicians, nurses, case managers, social workers, and pharmacists), community physicians (primary care, medical homes, and specialists), advance practice providers (physician assistants and nurse practitioners), and postacute care facilities and services (skilled nursing facilities, home health agencies, assisted living residences, hospice, and rehabilitation facilities).

Develop a comprehensive transition plan throughout hospitalization that includes attention to factors that may affect self-care, such as health literacy, chronic conditions, medications, and social support.

Enhance medication reconciliation and management. Obtain the best possible medication history on admission, and ensure that patients understand changes in their medications, how to take each medicine correctly, and important side effects.

Institute daily interdisciplinary communication and care coordination by everyone on the health care team with an emphasis on the care plan, discharge planning, and safety issues.⁸¹

Standardize transition plans, procedures and forms. All discharging physicians should use a standard discharge summary template that includes pertinent diagnoses, active issues, a reconciled medication list with changes highlighted, results from important tests and consultations, pending test results, planned follow-up and required services, warning signs of a worsening condition, and actions needed if a problem arises.

Always send discharge summaries directly to the patient’s primary care physician or next care setting at the time of discharge.

Give the patient a discharge plan that is easy to understand. Enhance patient and family education using health literacy standards⁸² and interactive methods such as teach-back,⁸³ in which patients demonstrate comprehension and skills required for self-care immediately after being taught. Such tools actively teach patients and caregivers to follow a care plan, including managing medications.

Follow up and coordinate support in a timely manner after a patient leaves the care setting. Follow-up visits should be arranged before discharge. Within 1 to 3 days after discharge, the patient should be called or visited by a case manager, social worker, nurse, or other health care provider.

CHALLENGES TO IMPROVING TRANSITIONS

Although several models demonstrated significant reductions of hospital readmissions in trials, challenges remain. Studies do not identify which features of the models are necessary or sufficient, or how applicable they are to different hospital and patient characteristics. A 2012 analysis⁸⁴ of a program designed to reduce readmissions in three states identified key obstacles to successfully improving care transitions:

Collaborative relationships across settings are critical, but very difficult to achieve. It takes time to develop the relationships and trust among providers, and little incentive exists for skilled nursing facilities and physicians outside the hospital to engage in the process.

Infrastructure is lacking, as is experience to implement quality improvements.

We lack proof that models work on a large scale. Confusion exists about which readmissions are preventable and which are not. More evidence is needed to help guide hospitals’ efforts to improve transitions of care and reduce readmissions.

You have spent several days checking on a patient hospitalized for an acute exacerbation of heart failure. You have straightened out her medications and diet and discussed a plan for follow-up with the patient and a family member, and now she is being wheeled out the door. What happens to her next?

Too often, not your desired plan. If she is going home, maybe she understands what she needs to do, maybe not. Maybe she will get your prescriptions filled and take the medications as directed, maybe not. If she is going to a nursing home, maybe the physician covering the nursing home will get your plan, maybe not. There is a good chance she will be back in the emergency room soon, all because of a poor transition of care.

Transitions of care are changes in the level, location, or providers of care as patients move within the health care system. These can be critical junctures in patients’ lives, and if poorly executed can result in many adverse effects—including rehospitalization.¹

Although high rehospitalization rates gained national attention in 2009 after a analysis of Medicare data,² health care providers have known about the lack of coordinated care transitions for more than 50 years.³ Despite some progress, improving care transitions remains a national challenge. As the health system evolves from a fee-for-service financial model to payment-for-value,⁴ it is especially important that health care providers improve care for patients by optimizing care transitions.

In this article, we summarize the factors contributing to poor care transitions, highlight programs that improve them, and discuss strategies for successful transitions.

TRANSITION PROBLEMS ARE COMMON

Transitions of care occur when patients move to short-term and long-term acute care hospitals, skilled nursing facilities, primary and specialty care offices, community health centers, rehabilitation facilities, home health agencies, hospice, and their own homes.⁵ Problems can arise at any of these transitions, but the risk is especially high when patients leave the hospital to receive care in another setting or at home.

In the past decade, one in five Medicare patients was rehospitalized within 30 days of discharge from the hospital,² and up to 25% were rehospitalized after being discharged to a skilled nursing facility.⁶ Some diagnoses (eg, sickle cell anemia, gangrene) and procedures (eg, kidney transplantation, ileostomy) are associated with readmission rates of nearly one in three.^7,8

The desire of policymakers to “bend the cost curve” of health care has led to efforts to enhance care coordination by improving transitions between care venues. Through the Patient Protection and Affordable Care Act, a number of federal initiatives are promoting strategies to improve care transitions and prevent readmissions after hospital discharge.

The Hospital Readmission Reduction Program⁹ drives much of this effort. In fiscal year 2013 (beginning October 1, 2012), more than 2,000 hospitals incurred financial penalties of up to 1% of total Medicare diagnosis-related group payments (about $280 million the first year) for excess readmissions.¹⁰ The penalty’s maximum rose to 2% in fiscal year 2014 and could increase to 3% in 2015. The total penalty for 2014 is projected to be $227 million, with 2,225 hospitals affected.¹¹

The Centers for Medicare and Medicaid Innovation has committed hundreds of millions of dollars to Community-based Care Transitions Programs¹² and more than $200 million to Hospital Engagement Networks¹³ to carry out the goals of the Partnership for Patients,¹⁴ aiming to reduce rehospitalizations and other adverse events.

At first, despite these efforts, readmission rates did not appear to change substantially.¹⁵ However, the Centers for Medicare and Medicaid Services reported that hospital readmission rates for Medicare fee-for-service beneficiaries declined in 2012 to 18.4%,¹⁶ although some believe that the reduction is related to an increase in the number of patients admitted for observation in recent years.¹⁷

TRANSITIONS ARE OFTEN POORLY COORDINATED

Although some readmissions are unavoidable—resulting from the inevitable progression of disease or worsening of chronic conditions¹⁸—they may also result from a fumbled transition between care settings. Our current system of care transition has serious deficiencies that endanger patients. Areas that need improvement include communication between providers, patient education about medications and treatments, monitoring of medication adherence and complications, follow-up of pending tests and procedures after discharge, and outpatient follow-up soon after discharge.^19–21

Traditional health care does not have dependable mechanisms for coordinating care across settings; we are all ensconced in “silos” that generally keep the focus within individual venues.²² Lack of coordination blurs the lines of responsibility for patients in the period between discharge from one location and admission to another, leaving them confused about whom to contact for care, especially if symptoms worsen.^23,24

Gaps in coordination are not surprising, given the complexity of the US health care system and the often remarkable number of physicians caring for an individual patient.⁵ Medicare beneficiaries see an average of two primary care physicians and five specialists during a 2-year period; patients with chronic conditions may see up to 16 physicians in 1 year.²⁵ Coordinating care between so many providers in different settings, combined with possible patient factors such as disadvantaged socioeconomic status, lack of caregiver support, and inadequate health literacy, provides many opportunities for failures.

Research has identified several root causes behind most failed care transitions:

Poor provider communication

Multiple studies associate adverse events after discharge with a lack of timely communication between hospital and outpatient providers.²⁶ One study estimated that 80% of serious medical errors involve miscommunication during the hand-off between medical providers.²⁷ Discharge summaries often lack important information such as test results, hospital course, discharge medications, patient counseling, and follow-up plans. Most adverse drug events after hospital discharge result directly from breakdown in communication between hospital staff and patients or primary care physicians.²⁸ Approximately 40% of patients have test results pending at the time of discharge and 10% of these require some action; yet outpatient physicians and patients are often unaware of them.²¹

Ineffective patient and caregiver education

The Institute of Medicine report, Crossing the Quality Chasm: A New Health System for the 21st Century,²⁹ noted that patients leaving one setting for another receive little information on how to care for themselves, when to resume activities, what medication side effects to watch out for, and how to get answers to questions. Of particular concern is that patients and caregivers are sometimes omitted from transition planning and often must suddenly assume new self-care responsibilities upon going home that hospital staff managed before discharge. Too often, patients are discharged with inadequate understanding of their medical condition, self-care plan,^23,24 and who should manage their care.³⁰

Up to 36% of adults in the United States have inadequate health literacy (defined as the inability to understand basic health information needed to make appropriate decisions), hindering patient education efforts.^31–33 Even if they understand, patients and their caregivers must be engaged or “activated” (ie, able and willing to manage one’s health) if we expect them to adhere to appropriate care and behaviors. A review found direct correlations between patient activation and healthy behavior, better health outcomes (eg, achieving normal hemoglobin A_1c and cholesterol levels), and better care experiences.³⁴ This review also noted that multiple studies have documented improved activation scores as a result of specific interventions.

No follow-up with primary care providers

The risk of hospital readmission is significantly lower for patients with chronic obstructive pulmonary disease or heart failure who receive follow-up within 7 days of discharge.^35–38 Of Medicare beneficiaries readmitted to the hospital within 30 days of discharge in 2003–2004, half had no contact with an outpatient physician in the interval between their discharge and their readmission,² and one in three adult patients discharged from a hospital to the community does not see a physician within 30 days of discharge.³⁹ The dearth of primary care providers in many communities can make follow-up care difficult to coordinate.

Failure to address chronic conditions

Analyses of national data sets reveal that patients are commonly rehospitalized for conditions unrelated to their initial hospitalization. According to the Center for Studying Health System Change, more than a quarter of readmissions in the 30 days after discharge are for conditions unrelated to those identified in the index admission, the proportion rising to more than one-third at 1 year.³⁹ Among Medicare beneficiaries readmitted within 30 days of discharge, the proportion readmitted for the same condition was just 35% after hospitalization for heart failure, 10% after hospitalization for acute myocardial infarction, and 22% after hospitalization for pneumonia.⁴⁰

Lack of community support

Multiple social and environmental factors contribute to adverse postdischarge events.^41–43 For socioeconomically disadvantaged patients, care-transition issues are compounded by insufficient access to outpatient care, lack of social support, and lack of transportation. Some studies indicate that between 40% to 50% of readmissions are linked to social problems and inadequate access to community resources.^44–47 Psychosocial issues such as limited health literacy, poor self-management skills, inadequate social support, and living alone are associated with adverse outcomes, including readmission and death.^48,49 Such factors may help explain high levels of “no-shows” to outpatient follow-up visits.

NATIONAL MODELS OF BEST PRACTICES

Efforts to reduce readmissions have traditionally focused on hospitals, but experts now recognize that multiple factors influence readmissions and must be comprehensively addressed. Several evidence-based models seek to improve patient outcomes with interventions aimed at care transitions:

Project BOOST

Project BOOST (Better Outcomes by Optimizing Safe Transitions)⁵⁰ is a national initiative developed by the Society of Hospital Medicine to standardize and optimize the care of patients discharged from hospital to home. The program includes evidence-based clinical interventions that can easily be adopted by any hospital. Interventions are aimed at:

• Identifying patients at high risk on admission
• Targeting risk-specific situations
• Improving information flow between inpatient and outpatient providers
• Improving patient and caregiver education by using the teach-back method
• Achieving timely follow-up after discharge.

The program includes a year of technical support provided by a physician mentor.

Preliminary results from pilot sites showed a 14% reduction in 30-day readmission rates in units using BOOST compared with control units in the same hospital.⁵¹ Mentored implementation was recognized by the Joint Commission and the National Quality Forum with the 2011 John M. Eisenberg Award for Innovation in Patient Safety and Quality.⁵²

Project RED

Project RED (Re-Engineered Discharge)⁵³ evolved from efforts by Dr. Brian Jack and colleagues to re-engineer the hospital workflow process to improve patient safety and reduce rehospitalization rates at Boston Medical Center. The intervention has 12 mutually reinforcing components aimed at improving the discharge process.

In a randomized controlled trial, Project RED led to a 30% decrease in emergency department visits and readmissions within 30 days of discharge from a general medical service of an urban academic medical center.⁵⁴ This study excluded patients admitted from a skilled nursing facility or discharged to one, but a recent study demonstrated that Project RED also led to a lower rate of hospital admission within 30 days of discharge from a skilled nursing facility.⁵⁵

The STAAR initiative

The STAAR initiative (State Action on Avoidable Re-hospitalizations)⁵⁶ was launched in 2009 by the Institute for Healthcare Improvement with the goal of reducing avoidable readmissions in the states of Massachusetts, Michigan, and Washington. Hospital teams focus on improving:

• Assessment of needs after hospital discharge
• Teaching and learning
• Real-time hand-off communication
• Timely follow-up after hospital discharge.

As yet, no published studies other than case reports show a benefit from STAAR.⁵⁷

The Care Transitions Program

The Care Transitions Program,⁵⁸ under the leadership of Dr. Eric Coleman, aims to empower patients and caregivers, who meet with a “transition coach.” The program provides assistance with medication reconciliation and self-management, a patient-centered record owned and maintained by the patient to facilitate cross-site information transfer, timely outpatient follow-up with primary or specialty care, a list of red flags to indicate a worsening condition, and instructions on proper responses.

A randomized controlled trial of the program demonstrated a reduction in hospital readmissions at 30, 90, and 180 days, and lower hospital costs at 90 and 180 days.⁵⁹ This approach also proved effective in a real-world setting.⁶⁰

The Transitional Care Model

Developed by Dr. Mary Naylor and colleagues, the Transitional Care Model⁶¹ also aims at patient and family empowerment, focusing on patients’ stated goals and priorities and ensuring patient engagement. In the program, a transitional care nurse has the job of enhancing patient and caregiver understanding, facilitating patient self-management, and overseeing medication management and transitional care.

A randomized controlled trial demonstrated improved outcomes after hospital discharge for elderly patients with complex medical illnesses, with overall reductions in medical costs through preventing or delaying rehospitalization.⁶² A subsequent real-world study validated this approach.⁶³

The Bridge Model

The Illinois Transitional Care Consortium’s Bridge Model⁶⁴ is for older patients discharged home after hospitalization. It is led by social workers (“bridge care coordinators”) who address barriers to implementing the discharge plan, coordinate resources, and intervene at three points: before discharge, 2 days after discharge, and 30 days after discharge.

An initial study showed no impact on the 30-day rehospitalization rate,⁶⁵ but larger studies are under way with a modified version.

Guided Care

Developed at the Johns Hopkins Bloomberg School of Public Health, Guided Care⁶⁶ involves nurses who work in partnership with physicians and others in primary care to provide patient-centered, cost-effective care to patients with multiple chronic conditions. Nurses conduct in-home assessments, facilitate care planning, promote patient self-management, monitor conditions, coordinate the efforts of all care professionals, and facilitate access to community resources.

A cluster-randomized controlled trial found that this program had mixed results, reducing the use of home health care but having little effect on the use of other health services in the short run. However, in the subgroup of patients covered by Kaiser-Permanente, those who were randomized to the program accrued, on average, 52% fewer skilled nursing facility days, 47% fewer skilled nursing facility admissions, 49% fewer hospital readmissions, and 17% fewer emergency department visits.⁶⁷

The GRACE model

The GRACE model (Geriatric Resources for Assessment and Care of Elders)⁶⁸ was developed to improve the quality of geriatric care, reduce excess health care use, and prevent long-term nursing home placement. Each patient is assigned a support team consisting of a nurse practitioner and a social worker who make home visits, coordinate health care and community services, and develop an individualized care plan.

In one study,⁶⁹ GRACE reduced hospital admission rates for participants at high risk of hospitalization by 12% in the first year of the program and 44% in the second year. GRACE participants also reported higher quality of life compared with the control group.⁶⁹

INTERACT tools

Led by Dr. Joseph Ouslander, INTERACT (Interventions to Reduce Acute Care Transfers)⁷⁰ is a quality-improvement initiative for skilled nursing facilities, designed to facilitate the early identification, evaluation, documentation, and communication of changes in the status of residents. Visitors to its website can download a set of tools and strategies to help them manage conditions before they become serious enough to require a hospital transfer. The tools assist in promoting important communication among providers and enhancing advance-care planning.

A 6-month study in 25 nursing homes showed a 17% reduction in self-reported hospital admissions with this program compared with the same period the previous year.⁷¹

Additional home-based care interventions

Additional innovations are under way in home-based care.

The Home Health Quality Improvement National Campaign is a patient-centered movement to improve the quality of care received by patients residing at home.⁷² Through its Best Practices Intervention Packages, it offers evidence-based educational tools, resources, and interventions for reducing avoidable hospitalizations, improving medication management, and coordinating transitional care.

The Center for Medicare and Medicaid Innovation Independence at Home Demonstration⁷³ is testing whether home-based comprehensive primary care can improve care and reduce hospitalizations for Medicare beneficiaries with multiple chronic conditions.

NO SINGLE INTERVENTION: MULTIPLE STRATEGIES NEEDED

A 2011 review found no single intervention that regularly reduced the 30-day risk of re-hospitalization.⁷⁴ However, other studies have shown that multifaceted interventions can reduce 30-day readmission rates. Randomized controlled trials in short-stay, acute care hospitals indicate that improvement in the following areas can directly reduce hospital readmission rates:

• Comprehensive planning and risk assessment throughout hospitalization
• Quality of care during the initial admission
• Communication with patients, their caregivers, and their clinicians
• Patient education
• Predischarge assessment
• Coordination of care after discharge.

In randomized trials, successful programs reduced the 30-day readmission rates by 20% to 40%,^{54,62,75–79} and a 2011 meta-analysis of randomized clinical trials found evidence that interventions associated with discharge planning helped to reduce readmission rates.⁸⁰

Methods developed by the national care transition models described above can help hospitals optimize patient transitions (Table 1). Although every model has its unique attributes, they have several strategies in common:

Engage a team of key stakeholders that may include patients and caregivers, hospital staff (physicians, nurses, case managers, social workers, and pharmacists), community physicians (primary care, medical homes, and specialists), advance practice providers (physician assistants and nurse practitioners), and postacute care facilities and services (skilled nursing facilities, home health agencies, assisted living residences, hospice, and rehabilitation facilities).

Develop a comprehensive transition plan throughout hospitalization that includes attention to factors that may affect self-care, such as health literacy, chronic conditions, medications, and social support.

Enhance medication reconciliation and management. Obtain the best possible medication history on admission, and ensure that patients understand changes in their medications, how to take each medicine correctly, and important side effects.

Institute daily interdisciplinary communication and care coordination by everyone on the health care team with an emphasis on the care plan, discharge planning, and safety issues.⁸¹

Standardize transition plans, procedures and forms. All discharging physicians should use a standard discharge summary template that includes pertinent diagnoses, active issues, a reconciled medication list with changes highlighted, results from important tests and consultations, pending test results, planned follow-up and required services, warning signs of a worsening condition, and actions needed if a problem arises.

Always send discharge summaries directly to the patient’s primary care physician or next care setting at the time of discharge.

Give the patient a discharge plan that is easy to understand. Enhance patient and family education using health literacy standards⁸² and interactive methods such as teach-back,⁸³ in which patients demonstrate comprehension and skills required for self-care immediately after being taught. Such tools actively teach patients and caregivers to follow a care plan, including managing medications.

Follow up and coordinate support in a timely manner after a patient leaves the care setting. Follow-up visits should be arranged before discharge. Within 1 to 3 days after discharge, the patient should be called or visited by a case manager, social worker, nurse, or other health care provider.

CHALLENGES TO IMPROVING TRANSITIONS

Although several models demonstrated significant reductions of hospital readmissions in trials, challenges remain. Studies do not identify which features of the models are necessary or sufficient, or how applicable they are to different hospital and patient characteristics. A 2012 analysis⁸⁴ of a program designed to reduce readmissions in three states identified key obstacles to successfully improving care transitions:

Collaborative relationships across settings are critical, but very difficult to achieve. It takes time to develop the relationships and trust among providers, and little incentive exists for skilled nursing facilities and physicians outside the hospital to engage in the process.

Infrastructure is lacking, as is experience to implement quality improvements.

We lack proof that models work on a large scale. Confusion exists about which readmissions are preventable and which are not. More evidence is needed to help guide hospitals’ efforts to improve transitions of care and reduce readmissions.

You have spent several days checking on a patient hospitalized for an acute exacerbation of heart failure. You have straightened out her medications and diet and discussed a plan for follow-up with the patient and a family member, and now she is being wheeled out the door. What happens to her next?

Too often, not your desired plan. If she is going home, maybe she understands what she needs to do, maybe not. Maybe she will get your prescriptions filled and take the medications as directed, maybe not. If she is going to a nursing home, maybe the physician covering the nursing home will get your plan, maybe not. There is a good chance she will be back in the emergency room soon, all because of a poor transition of care.

Transitions of care are changes in the level, location, or providers of care as patients move within the health care system. These can be critical junctures in patients’ lives, and if poorly executed can result in many adverse effects—including rehospitalization.¹

Although high rehospitalization rates gained national attention in 2009 after a analysis of Medicare data,² health care providers have known about the lack of coordinated care transitions for more than 50 years.³ Despite some progress, improving care transitions remains a national challenge. As the health system evolves from a fee-for-service financial model to payment-for-value,⁴ it is especially important that health care providers improve care for patients by optimizing care transitions.

In this article, we summarize the factors contributing to poor care transitions, highlight programs that improve them, and discuss strategies for successful transitions.

TRANSITION PROBLEMS ARE COMMON

Transitions of care occur when patients move to short-term and long-term acute care hospitals, skilled nursing facilities, primary and specialty care offices, community health centers, rehabilitation facilities, home health agencies, hospice, and their own homes.⁵ Problems can arise at any of these transitions, but the risk is especially high when patients leave the hospital to receive care in another setting or at home.

In the past decade, one in five Medicare patients was rehospitalized within 30 days of discharge from the hospital,² and up to 25% were rehospitalized after being discharged to a skilled nursing facility.⁶ Some diagnoses (eg, sickle cell anemia, gangrene) and procedures (eg, kidney transplantation, ileostomy) are associated with readmission rates of nearly one in three.^7,8

The desire of policymakers to “bend the cost curve” of health care has led to efforts to enhance care coordination by improving transitions between care venues. Through the Patient Protection and Affordable Care Act, a number of federal initiatives are promoting strategies to improve care transitions and prevent readmissions after hospital discharge.

The Hospital Readmission Reduction Program⁹ drives much of this effort. In fiscal year 2013 (beginning October 1, 2012), more than 2,000 hospitals incurred financial penalties of up to 1% of total Medicare diagnosis-related group payments (about $280 million the first year) for excess readmissions.¹⁰ The penalty’s maximum rose to 2% in fiscal year 2014 and could increase to 3% in 2015. The total penalty for 2014 is projected to be $227 million, with 2,225 hospitals affected.¹¹

The Centers for Medicare and Medicaid Innovation has committed hundreds of millions of dollars to Community-based Care Transitions Programs¹² and more than $200 million to Hospital Engagement Networks¹³ to carry out the goals of the Partnership for Patients,¹⁴ aiming to reduce rehospitalizations and other adverse events.

At first, despite these efforts, readmission rates did not appear to change substantially.¹⁵ However, the Centers for Medicare and Medicaid Services reported that hospital readmission rates for Medicare fee-for-service beneficiaries declined in 2012 to 18.4%,¹⁶ although some believe that the reduction is related to an increase in the number of patients admitted for observation in recent years.¹⁷

TRANSITIONS ARE OFTEN POORLY COORDINATED

Although some readmissions are unavoidable—resulting from the inevitable progression of disease or worsening of chronic conditions¹⁸—they may also result from a fumbled transition between care settings. Our current system of care transition has serious deficiencies that endanger patients. Areas that need improvement include communication between providers, patient education about medications and treatments, monitoring of medication adherence and complications, follow-up of pending tests and procedures after discharge, and outpatient follow-up soon after discharge.^19–21

Traditional health care does not have dependable mechanisms for coordinating care across settings; we are all ensconced in “silos” that generally keep the focus within individual venues.²² Lack of coordination blurs the lines of responsibility for patients in the period between discharge from one location and admission to another, leaving them confused about whom to contact for care, especially if symptoms worsen.^23,24

Gaps in coordination are not surprising, given the complexity of the US health care system and the often remarkable number of physicians caring for an individual patient.⁵ Medicare beneficiaries see an average of two primary care physicians and five specialists during a 2-year period; patients with chronic conditions may see up to 16 physicians in 1 year.²⁵ Coordinating care between so many providers in different settings, combined with possible patient factors such as disadvantaged socioeconomic status, lack of caregiver support, and inadequate health literacy, provides many opportunities for failures.

Research has identified several root causes behind most failed care transitions:

Poor provider communication

Multiple studies associate adverse events after discharge with a lack of timely communication between hospital and outpatient providers.²⁶ One study estimated that 80% of serious medical errors involve miscommunication during the hand-off between medical providers.²⁷ Discharge summaries often lack important information such as test results, hospital course, discharge medications, patient counseling, and follow-up plans. Most adverse drug events after hospital discharge result directly from breakdown in communication between hospital staff and patients or primary care physicians.²⁸ Approximately 40% of patients have test results pending at the time of discharge and 10% of these require some action; yet outpatient physicians and patients are often unaware of them.²¹

Ineffective patient and caregiver education

The Institute of Medicine report, Crossing the Quality Chasm: A New Health System for the 21st Century,²⁹ noted that patients leaving one setting for another receive little information on how to care for themselves, when to resume activities, what medication side effects to watch out for, and how to get answers to questions. Of particular concern is that patients and caregivers are sometimes omitted from transition planning and often must suddenly assume new self-care responsibilities upon going home that hospital staff managed before discharge. Too often, patients are discharged with inadequate understanding of their medical condition, self-care plan,^23,24 and who should manage their care.³⁰

Up to 36% of adults in the United States have inadequate health literacy (defined as the inability to understand basic health information needed to make appropriate decisions), hindering patient education efforts.^31–33 Even if they understand, patients and their caregivers must be engaged or “activated” (ie, able and willing to manage one’s health) if we expect them to adhere to appropriate care and behaviors. A review found direct correlations between patient activation and healthy behavior, better health outcomes (eg, achieving normal hemoglobin A_1c and cholesterol levels), and better care experiences.³⁴ This review also noted that multiple studies have documented improved activation scores as a result of specific interventions.

No follow-up with primary care providers

The risk of hospital readmission is significantly lower for patients with chronic obstructive pulmonary disease or heart failure who receive follow-up within 7 days of discharge.^35–38 Of Medicare beneficiaries readmitted to the hospital within 30 days of discharge in 2003–2004, half had no contact with an outpatient physician in the interval between their discharge and their readmission,² and one in three adult patients discharged from a hospital to the community does not see a physician within 30 days of discharge.³⁹ The dearth of primary care providers in many communities can make follow-up care difficult to coordinate.

Failure to address chronic conditions

Analyses of national data sets reveal that patients are commonly rehospitalized for conditions unrelated to their initial hospitalization. According to the Center for Studying Health System Change, more than a quarter of readmissions in the 30 days after discharge are for conditions unrelated to those identified in the index admission, the proportion rising to more than one-third at 1 year.³⁹ Among Medicare beneficiaries readmitted within 30 days of discharge, the proportion readmitted for the same condition was just 35% after hospitalization for heart failure, 10% after hospitalization for acute myocardial infarction, and 22% after hospitalization for pneumonia.⁴⁰

Lack of community support

Multiple social and environmental factors contribute to adverse postdischarge events.^41–43 For socioeconomically disadvantaged patients, care-transition issues are compounded by insufficient access to outpatient care, lack of social support, and lack of transportation. Some studies indicate that between 40% to 50% of readmissions are linked to social problems and inadequate access to community resources.^44–47 Psychosocial issues such as limited health literacy, poor self-management skills, inadequate social support, and living alone are associated with adverse outcomes, including readmission and death.^48,49 Such factors may help explain high levels of “no-shows” to outpatient follow-up visits.

NATIONAL MODELS OF BEST PRACTICES

Efforts to reduce readmissions have traditionally focused on hospitals, but experts now recognize that multiple factors influence readmissions and must be comprehensively addressed. Several evidence-based models seek to improve patient outcomes with interventions aimed at care transitions:

Project BOOST

Project BOOST (Better Outcomes by Optimizing Safe Transitions)⁵⁰ is a national initiative developed by the Society of Hospital Medicine to standardize and optimize the care of patients discharged from hospital to home. The program includes evidence-based clinical interventions that can easily be adopted by any hospital. Interventions are aimed at:

• Identifying patients at high risk on admission
• Targeting risk-specific situations
• Improving information flow between inpatient and outpatient providers
• Improving patient and caregiver education by using the teach-back method
• Achieving timely follow-up after discharge.

The program includes a year of technical support provided by a physician mentor.

Preliminary results from pilot sites showed a 14% reduction in 30-day readmission rates in units using BOOST compared with control units in the same hospital.⁵¹ Mentored implementation was recognized by the Joint Commission and the National Quality Forum with the 2011 John M. Eisenberg Award for Innovation in Patient Safety and Quality.⁵²

Project RED

Project RED (Re-Engineered Discharge)⁵³ evolved from efforts by Dr. Brian Jack and colleagues to re-engineer the hospital workflow process to improve patient safety and reduce rehospitalization rates at Boston Medical Center. The intervention has 12 mutually reinforcing components aimed at improving the discharge process.

In a randomized controlled trial, Project RED led to a 30% decrease in emergency department visits and readmissions within 30 days of discharge from a general medical service of an urban academic medical center.⁵⁴ This study excluded patients admitted from a skilled nursing facility or discharged to one, but a recent study demonstrated that Project RED also led to a lower rate of hospital admission within 30 days of discharge from a skilled nursing facility.⁵⁵

The STAAR initiative

The STAAR initiative (State Action on Avoidable Re-hospitalizations)⁵⁶ was launched in 2009 by the Institute for Healthcare Improvement with the goal of reducing avoidable readmissions in the states of Massachusetts, Michigan, and Washington. Hospital teams focus on improving:

• Assessment of needs after hospital discharge
• Teaching and learning
• Real-time hand-off communication
• Timely follow-up after hospital discharge.

As yet, no published studies other than case reports show a benefit from STAAR.⁵⁷

The Care Transitions Program

The Care Transitions Program,⁵⁸ under the leadership of Dr. Eric Coleman, aims to empower patients and caregivers, who meet with a “transition coach.” The program provides assistance with medication reconciliation and self-management, a patient-centered record owned and maintained by the patient to facilitate cross-site information transfer, timely outpatient follow-up with primary or specialty care, a list of red flags to indicate a worsening condition, and instructions on proper responses.

A randomized controlled trial of the program demonstrated a reduction in hospital readmissions at 30, 90, and 180 days, and lower hospital costs at 90 and 180 days.⁵⁹ This approach also proved effective in a real-world setting.⁶⁰

The Transitional Care Model

Developed by Dr. Mary Naylor and colleagues, the Transitional Care Model⁶¹ also aims at patient and family empowerment, focusing on patients’ stated goals and priorities and ensuring patient engagement. In the program, a transitional care nurse has the job of enhancing patient and caregiver understanding, facilitating patient self-management, and overseeing medication management and transitional care.

A randomized controlled trial demonstrated improved outcomes after hospital discharge for elderly patients with complex medical illnesses, with overall reductions in medical costs through preventing or delaying rehospitalization.⁶² A subsequent real-world study validated this approach.⁶³

The Bridge Model

The Illinois Transitional Care Consortium’s Bridge Model⁶⁴ is for older patients discharged home after hospitalization. It is led by social workers (“bridge care coordinators”) who address barriers to implementing the discharge plan, coordinate resources, and intervene at three points: before discharge, 2 days after discharge, and 30 days after discharge.

An initial study showed no impact on the 30-day rehospitalization rate,⁶⁵ but larger studies are under way with a modified version.

Guided Care

Developed at the Johns Hopkins Bloomberg School of Public Health, Guided Care⁶⁶ involves nurses who work in partnership with physicians and others in primary care to provide patient-centered, cost-effective care to patients with multiple chronic conditions. Nurses conduct in-home assessments, facilitate care planning, promote patient self-management, monitor conditions, coordinate the efforts of all care professionals, and facilitate access to community resources.

A cluster-randomized controlled trial found that this program had mixed results, reducing the use of home health care but having little effect on the use of other health services in the short run. However, in the subgroup of patients covered by Kaiser-Permanente, those who were randomized to the program accrued, on average, 52% fewer skilled nursing facility days, 47% fewer skilled nursing facility admissions, 49% fewer hospital readmissions, and 17% fewer emergency department visits.⁶⁷

The GRACE model

The GRACE model (Geriatric Resources for Assessment and Care of Elders)⁶⁸ was developed to improve the quality of geriatric care, reduce excess health care use, and prevent long-term nursing home placement. Each patient is assigned a support team consisting of a nurse practitioner and a social worker who make home visits, coordinate health care and community services, and develop an individualized care plan.

In one study,⁶⁹ GRACE reduced hospital admission rates for participants at high risk of hospitalization by 12% in the first year of the program and 44% in the second year. GRACE participants also reported higher quality of life compared with the control group.⁶⁹

INTERACT tools

Led by Dr. Joseph Ouslander, INTERACT (Interventions to Reduce Acute Care Transfers)⁷⁰ is a quality-improvement initiative for skilled nursing facilities, designed to facilitate the early identification, evaluation, documentation, and communication of changes in the status of residents. Visitors to its website can download a set of tools and strategies to help them manage conditions before they become serious enough to require a hospital transfer. The tools assist in promoting important communication among providers and enhancing advance-care planning.

A 6-month study in 25 nursing homes showed a 17% reduction in self-reported hospital admissions with this program compared with the same period the previous year.⁷¹

Additional home-based care interventions

Additional innovations are under way in home-based care.

The Home Health Quality Improvement National Campaign is a patient-centered movement to improve the quality of care received by patients residing at home.⁷² Through its Best Practices Intervention Packages, it offers evidence-based educational tools, resources, and interventions for reducing avoidable hospitalizations, improving medication management, and coordinating transitional care.

The Center for Medicare and Medicaid Innovation Independence at Home Demonstration⁷³ is testing whether home-based comprehensive primary care can improve care and reduce hospitalizations for Medicare beneficiaries with multiple chronic conditions.

NO SINGLE INTERVENTION: MULTIPLE STRATEGIES NEEDED

A 2011 review found no single intervention that regularly reduced the 30-day risk of re-hospitalization.⁷⁴ However, other studies have shown that multifaceted interventions can reduce 30-day readmission rates. Randomized controlled trials in short-stay, acute care hospitals indicate that improvement in the following areas can directly reduce hospital readmission rates:

• Comprehensive planning and risk assessment throughout hospitalization
• Quality of care during the initial admission
• Communication with patients, their caregivers, and their clinicians
• Patient education
• Predischarge assessment
• Coordination of care after discharge.

In randomized trials, successful programs reduced the 30-day readmission rates by 20% to 40%,^{54,62,75–79} and a 2011 meta-analysis of randomized clinical trials found evidence that interventions associated with discharge planning helped to reduce readmission rates.⁸⁰

Methods developed by the national care transition models described above can help hospitals optimize patient transitions (Table 1). Although every model has its unique attributes, they have several strategies in common:

Engage a team of key stakeholders that may include patients and caregivers, hospital staff (physicians, nurses, case managers, social workers, and pharmacists), community physicians (primary care, medical homes, and specialists), advance practice providers (physician assistants and nurse practitioners), and postacute care facilities and services (skilled nursing facilities, home health agencies, assisted living residences, hospice, and rehabilitation facilities).

Develop a comprehensive transition plan throughout hospitalization that includes attention to factors that may affect self-care, such as health literacy, chronic conditions, medications, and social support.

Enhance medication reconciliation and management. Obtain the best possible medication history on admission, and ensure that patients understand changes in their medications, how to take each medicine correctly, and important side effects.

Institute daily interdisciplinary communication and care coordination by everyone on the health care team with an emphasis on the care plan, discharge planning, and safety issues.⁸¹

Standardize transition plans, procedures and forms. All discharging physicians should use a standard discharge summary template that includes pertinent diagnoses, active issues, a reconciled medication list with changes highlighted, results from important tests and consultations, pending test results, planned follow-up and required services, warning signs of a worsening condition, and actions needed if a problem arises.

Always send discharge summaries directly to the patient’s primary care physician or next care setting at the time of discharge.

Give the patient a discharge plan that is easy to understand. Enhance patient and family education using health literacy standards⁸² and interactive methods such as teach-back,⁸³ in which patients demonstrate comprehension and skills required for self-care immediately after being taught. Such tools actively teach patients and caregivers to follow a care plan, including managing medications.

Follow up and coordinate support in a timely manner after a patient leaves the care setting. Follow-up visits should be arranged before discharge. Within 1 to 3 days after discharge, the patient should be called or visited by a case manager, social worker, nurse, or other health care provider.

CHALLENGES TO IMPROVING TRANSITIONS

Although several models demonstrated significant reductions of hospital readmissions in trials, challenges remain. Studies do not identify which features of the models are necessary or sufficient, or how applicable they are to different hospital and patient characteristics. A 2012 analysis⁸⁴ of a program designed to reduce readmissions in three states identified key obstacles to successfully improving care transitions:

Collaborative relationships across settings are critical, but very difficult to achieve. It takes time to develop the relationships and trust among providers, and little incentive exists for skilled nursing facilities and physicians outside the hospital to engage in the process.

Infrastructure is lacking, as is experience to implement quality improvements.

We lack proof that models work on a large scale. Confusion exists about which readmissions are preventable and which are not. More evidence is needed to help guide hospitals’ efforts to improve transitions of care and reduce readmissions.

Accountable-care organizations are becoming more prominent in the United States, and therefore health care systems in the near future will be reimbursed on the basis of their ability to care for patient populations rather than individual patients. As a result, primary care physicians will need to be well versed in the care of patients with common chronic diseases such as chronic kidney disease (CKD). By one estimate, patients with CKD constitute 14% of the US population age 20 and older, or more than 31 million people.¹

An earlier article in this journal reviewed how to identify patients with CKD and how to interpret the estimated glomerular filtration rate (GFR).² This article examines the care of patients with advanced CKD, how to manage their health risks, and how to optimize their care by coordinating with nephrologists.

GOALS OF CKD CARE

CKD is defined either as renal damage (which is most commonly manifested by proteinuria, but which may include pathologic changes on biopsy or other markers of damage on serum, urine, or imaging studies), or as a GFR less than 60 mL/min/1.73 m² for at least 3 months.³ It is divided into five stages (Table 1).

Since most patients with CKD never reach end-stage renal disease, much of their care is aimed at slowing the progression of renal dysfunction and addressing medical issues that arise as a result of CKD. To these ends, it is important to detect CKD early and refer these patients to a nephrology team in a timely manner. Their care can be separated into several important tasks:

• Identify the cause of CKD, if possible; address potentially reversible causes such as obstruction or medication-related causes. If a primarily glomerular process (marked by heavy proteinuria and dysmorphic red blood cells and red blood cell casts in the urine sediment) or interstitial nephritis (manifested by white blood cells in the urine) is suspected, refer to a nephrologist early.
• Provide treatment to correct the specific cause (if one is present) or slow the deterioration of renal function.
• Address cardiovascular risk factors.
• Address metabolic abnormalities related to CKD.
• If the CKD is advanced, educate the patient about end-stage renal disease and its treatment options, and guide the patient through the transition to end-stage renal disease.

WHEN SHOULD A NEPHROLOGIST BE CONSULTED?

The ideal timing of referral to a nephrologist is not well defined and depends on the comfort level of the primary care provider.

Treatments to slow the progression of CKD and decrease cardiovascular risk should begin early in CKD (ie, in stage 3) and can be managed by the primary care provider with guidance from a nephrologist. Patients referred to a nephrologist while in stage 3 have been shown to go longer without CKD progression than those referred in later stages.⁴ Early referral to a nephrologist has also been associated with a decreased mortality rate.⁵ The studies that found these trends, however, were limited by the fact that patients with stage 3 CKD are less likely to progress to end-stage renal disease or to die of cardiovascular disease than patients with stage 4 or 5 CKD.

Once stage 4 CKD develops, the nephrologist should take a more active role in the care plan. In this stage, cardiovascular risk rises, and the risk of developing end-stage renal disease rises dramatically.⁶ With comprehensive care in a CKD clinic, even patients with advanced CKD are more likely to have a stabilization of renal function.⁷ Kinchen et al⁸ found that patients referred to a nephrologist within 4 months of starting dialysis had a lower survival rate than those referred earlier. Therefore, if a nephrologist was not involved in the patient’s care prior to stage 4, then a referral must be made.

Recommendation. Patients with stage 3 CKD can be referred for an initial evaluation and development of a treatment plan, but most of the responsibility for their care can remain with the primary care provider. Once stage 4 CKD develops, the nephrologist should assume an increasing role. However, if glomerular disease is suspected, we recommend referral to a nephrologist regardless of the estimated GFR.

ELEVATED CARDIOVASCULAR RISK

Patients with stage 3 CKD are 20 times more likely to die of a cardiovascular event than to reach end-stage renal disease.⁶ This increased risk does not quite reach the status of a cardiovascular disease risk equivalent, as does diabetes,^9,10 but cardiovascular risk reduction should be a primary focus of care for the CKD patient.

The cardiovascular risk in part is attributed to a high prevalence of traditional cardiovascular risk factors, including diabetes mellitus, hypertension, and hyperlipidemia.^11,12 About two-thirds of CKD patients have metabolic syndrome, which is a risk factor for cardiovascular disease and is associated with more rapid progression of CKD.¹³ In addition, renal dysfunction, proteinuria, and hyperphosphatemia are also risk factors for cardiovascular disease.^14–19

The risk of death from a cardiovascular event increases as kidney function declines, with reported 5-year death rates of 19.5% in stage 2, 24.3% in stage 3, and 45.7% in stage 4 CKD. However, imbalance between mortality risk and progression to end-stage renal disease may be age-dependent.²⁰ Younger patients (age 45 and younger) are more likely to progress to end-stage renal disease, whereas in older patients (over age 65), the relative risk of dying of cardiovascular disease is higher.

Aggressive lipid management

Hyperlipidemia is a common risk factor for cardiovascular morbidity and mortality in CKD.²¹ However, until recently, all studies of outcomes of patients treated for hyperlipidemia excluded patients with CKD. Post hoc analyses of these studies ^22–27 showed statins to be beneficial in primary and secondary cardiovascular prevention in patents with “normal” serum creatinine values but estimated GFR levels of 50 to 59 mL/min/1.73 m².

The SHARP trial²⁸ was the first prospective trial to study lipid-lowering therapy in patients with CKD. In this trial, patients with various stages of CKD, including advanced CKD, had fewer major vascular events if they received the combination of low-dose simvastatin (Zocor) and ezetimibe (Zetia). However, the evidence does not suggest that statin therapy slows the progression of CKD.^28–31

Recommendation. Manage hyperlipidemia aggressively using statin therapy with or without ezetimibe, with a target low-density lipoprotein cholesterol level below 100 mg/dL.³²

Manage other cardiovascular risk factors

Because hypertension and proteinuria are risk factors not only for cardiovascular disease but also for progression of CKD, they are discussed in the section below.

ATTEMPT TO PREVENT WORSENING OF RENAL FUNCTION

Medications to avoid

It is important to review a CKD patient’s medication list—prescription and over-the-counter drugs—to identify any that may contribute to a worsening of renal function. CKD patients need to be informed about avoiding medications such as nonsteroidal anti-inflammatory drugs, proton pump inhibitors, and herbal supplements because they can cause further renal injury. In addition, other medications (eg, metformin) are contraindicated in CKD because of side effects that may occur in CKD.

Patients should be encouraged to discuss any changes in their medications, including over-the-counter products, with their primary care physicians.

Manage hypertension aggressively

Many patients with CKD also have hypertension,^33,34 possibly because they have a higher frequency of underlying essential hypertension or because CKD often worsens preexisting hypertension. Moreover, uncontrolled hypertension is associated with a further decline in renal function.^35,36

The ACCORD trial³⁷ found no benefit in lowering systolic blood pressure to less than 120 mm Hg compared with less than 140 mm Hg in patients with diabetes mellitus. (The patients in this study did not necessarily have CKD.)

A meta-analysis³⁸ of trials of antihypertensive treatment in patients with CKD found that the optimal target systolic blood pressure for decreasing the progression of CKD was 110 to 129 mm Hg. The relative risk of progression of renal dysfunction was:

• 1.83 (95% confidence interval [CI] 0.97–3.44) at 130 mm to 139 mm Hg, vs
• 3.14 (95% CI 1.64–5.99) at 160 mm Hg or higher.

There is also evidence that blood pressure control can be relaxed as patients age. While the exact age differs among published guidelines, the evidence supports a goal blood pressure of less than 150/90 mm Hg once a patient reaches the age of 70, regardless of CKD or proteinuria.

Recommendation. Current evidence suggests the following blood pressure goals in CKD patients:

• With diabetes mellitus or proteinuria: < 130/80 mm Hg
• Without proteinuria: < 140/90 mm Hg
• Age 70 and older: <150/90 mm Hg.³⁹

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are the preferred antihypertensive drugs in patients with diabetes or proteinuria (see below).

Manage proteinuria

Proteinuria is also associated with progression of CKD. AASK,⁴⁰ a study that included nondiabetic African American patients whose estimated GFRs were between 20 and 60 mL/min/1.73 m², showed that higher levels of proteinuria were associated with a higher risk of decline in GFR and a higher risk of end-stage renal disease. Findings were similar to those in studies of other CKD populations.^41–43 Proteinuria is also an independent risk factor for cardiovascular disease and death. Multiple large studies^16,17,44,45 have found associations between higher levels of albumin excretion and risk of major cardiovascular events, cardiovascular death, and death from any cause in people with and without diabetes.

Reducing proteinuria has been shown to both slow progression of renal dysfunction and reduce the cardiovascular risk.^44,45 In a substudy of the IDNT⁴⁶ in patients with diabetic nephropathy, each 50% reduction in urinary protein excretion was associated with a 56% reduction in risk of progression of CKD. Similar effects have been shown in nondiabetic CKD patients.⁴⁷

ACE inhibitors and ARBs are the preferred treatments for proteinuria in patients with CKD.^48–50 Combination therapy with an ACE inhibitor and an ARB has been used,^51–53 with a better response in proteinuria reduction. However, combination therapy with these drugs cannot currently be recommended, as the only prospective study of this regimen to date suggested worse renal and overall outcomes in patients at high cardiovascular risk.⁵⁴ These drugs may also have renoprotective effects independent of their effects on blood pressure and proteinuria.³⁸ Dietary salt restriction and diuretic therapy can further increase the efficacy of proteinuria reduction by ACE inhibitors or ARBs.^55,56

On the other hand, stopping ACE inhibitors or ARBs may be beneficial as the patient nears end-stage renal disease. Ahmed et al⁵⁷ demonstrated that stopping ACE inhibitors or ARBs in advanced stage 4 CKD (mean estimated GFR 16 mL/min/1.73 m²) was associated with improved GFR and delayed onset of renal replacement therapy. This improvement may be due to regaining the slight decrease in GFR that occurred when these medications were started.

Nondihydropyridine calcium channel blockers such as diltiazem (Cardizem) and verapamil (Calan) have also been shown to be useful for reducing proteinuria,⁵⁸ whereas dihydropyridine calcium channel blockers such as amlodipine (Norvasc) and nifedipine (Procardia), when used without ACE inhibitors or ARBs, can worsen proteinuria.^58,59

Correct metabolic acidosis

The kidneys play an important role in maintaining acid-base balance, keeping the blood from becoming too acidic both by reabsorbing bicarbonate filtered into the urine by the glomerulus and by excreting the daily acid load. Metabolic acidosis can develop when these functions break down at more advanced stages of CKD, most often when the estimated GFR declines to less than 20 mL/min/1.73 m².

Bicarbonate levels of 22 mmol/L or less have been associated with a higher risk of worsening renal function.⁶⁰ When such patients were treated with sodium bicarbonate to achieve a serum bicarbonate of at least 23 mmol/L, they had an 80% lower rate of progression to end-stage renal disease without any increase in edema, admission for congestive heart failure, or change in blood pressure.⁶¹

Susantitaphong et al⁶² reviewed six randomized trials of bicarbonate supplementation in CKD and found that it was associated with improved kidney function and a 79% lower rate of progression to end-stage renal disease.

The proposed mechanism behind this benefit lies in the increase in ammonia production that each surviving nephron must undertake to handle the daily acid load. The increased ammonia is thought to play a role in activating the alternative complement pathway,⁶³ causing renal inflammation and injury.

Recommendation. Bicarbonate therapy should be used to maintain serum bicarbonate levels above 22 mmol/L in CKD.⁶⁴

OTHER ASPECTS OF CKD CARE

Bone mineral disorders

Patients with CKD develop secondary hyperparathyroidism, hyperphosphatemia, and (in advanced CKD) hypocalcemia, all leading to disorders of bone mineral metabolism.

Traditionally, it has been thought that decreased production of 1,25-dihydroxyvitamin D by dysfunctional kidneys leads to decreased suppression of the parathyroid gland and to secondary hyperparathyroidism. The major long-term adverse effect of this is a weakened bone matrix resulting from increased calcium and phosphorus efflux from bones (renal osteodystrophy).

The discovery of fibroblast growth factor 23 (FGF-23) has improved our understanding of the physiology behind disordered bone mineral metabolism in CKD. FGF-23, produced by osteoblasts and osteocytes, acts directly on the kidney to increase renal phosphate excretion. It also suppresses 1,25-dihydroxyvitamin D levels by inhibiting 1-alpha-hydroxylase,⁶⁵ and it stimulates parathyroid hormone secretion. FGF-23 levels rise much earlier in CKD than do parathyroid hormone levels, suggesting that abnormalities in phosphorus balance and FGF-23 may be the earliest pathophysiologic changes.⁶⁶

The initial treatment of bone mineral disorders is to some extent guided by laboratory values. Phosphate levels higher than 3.5 or 4 mg/dL and elevated FGF-23 levels have been associated with increased mortality rates in CKD patients.^{18,19,67–69} All patients should also have their 1,25-dihydroxyvitamin D level checked and supplemented if deficient. In many patients with early stage 3 CKD, this may correct secondary hyperparathyroidism.⁷⁰

Serum phosphorus levels should be kept in the normal range in stage 3 and 4 CKD,⁷¹ either by restricting dietary phosphorus intake (< 800 or < 1,000 mg/day) or by using a phosphate binder, which is taken with meals to prevent phosphorus absorption from the gastrointestinal tract. Current US recommendations are to allow graded increases in parathyroid hormone based on the stage of CKD (Table 2).⁷¹ However, these targets are still an area of uncertainty, with some guidelines suggesting that wider variations in parathyroid hormone can be allowed, so there may be wider variation in clinical practice in this area.⁷² If the serum phosphorus level is in the goal range but parathyroid hormone levels are still high, an activated vitamin D analogue such as calcitriol is recommended, although with the emerging role of FGF-23, some experts also call for early use of a phosphate binder in this group.

The treatment of bone mineral disorders in CKD is fairly complex, and we recommend that it be done by or with the close direction of a nephrologist.

Recommendations on bone disorders

• Check levels of calcium, phosphorus, 25-hydroxyvitamin D, and parathyroid hormone in all patients whose estimated GFR is less than 60 mL/min/1.73 m², with frequency of measurements based on the stage of CKD.⁷¹
• Replace vitamin D if deficient.
• Treat elevated phosphorus levels with a protein-restricted diet (nutrition referral) and a phosphate binder.
• Treat elevated hyperparathyroid hormone levels with a vitamin D analogue once phosphorus levels have been controlled.
• Refer patients with an elevated phosphorus or parathyroid hormone level to a nephrology service for consultation before initiating medical therapy.

Anemia is common, treatment controversial

The treatment of anemia attributed to CKD has been a topic of controversy over the past decade, and we recommend that it be done with the guidance of a nephrologist.

Anemia is common in CKD, and declining kidney function is an independent predictor of anemia.⁷³ Anemia is a risk factor for left ventricular hypertrophy, cardiovascular disease,⁷⁴ and death in CKD.⁷⁵

The anemia of CKD is attributed to relative erythropoietin deficiency and bone marrow resistance to erythropoietin, but this is a diagnosis of exclusion, and other causes of anemia must be ruled out. Iron deficiency is a common cause of anemia in CKD, and treatment of iron deficiency may correct anemia in more than one-third of these patients.^76,77

Erythropoiesis-stimulating agents such as epoetin alfa (Procrit) and darbepoetin (Aranesp) are used to treat renal anemia. However, the target hemoglobin level has been a subject of debate. Three prospective trials^78–80 found no benefit in raising the hemoglobin level to normal ranges using these agents, and several found an association with higher rates of stroke and venous thrombosis. The US Food and Drug Administration suggests that the only role for these agents in CKD is to avoid the need for transfusions. They should not be used to normalize the hemoglobin level. The target, although not explicitly specified, is suggested to be around 10 g/dL.⁸¹

PREPARE FOR END-STAGE RENAL DISEASE

Discuss the options

Because the risk of developing end-stage renal disease rises dramatically once CKD reaches stage 4, all such patients should have a discussion about renal replacement therapy. They should be educated about their options for treatment (hemodialysis, peritoneal dialysis, and transplantation, as well as not proceeding with renal replacement therapy), often in a formal class. They should then be actively engaged in the decision about how to proceed. Survival and quality of life should be discussed, particularly with patients who are over age 80, who are severely ill, or who are living in a nursing facility, as these groups get limited survival benefit from starting dialysis, and quality of life may actually decrease with dialysis.^82,83

The Renal Physicians Association has created clinical practice guidelines for shared decision-making, consisting of 10 practice recommendations that outline a systematic approach to patients needing renal replacement therapy.⁸⁴

Consider preemptive kidney transplantation

Any patient thought to be a suitable candidate for renal transplantation should be referred to a transplantation center for evaluation. Studies have shown that kidney transplantation offers a survival advantage compared with chronic dialysis and should preferably be done preemptively, ie, before dialysis is required.^85–90 Therefore, patients with estimated GFRs in the low 20s should be referred for a transplantation evaluation.

If a living donor is available, the transplantation team usually waits to perform the procedure until the patient is closer to needing dialysis, often when the estimated GFR is around 15 to 16 mL/min/1.73 m². If no living donor is available, the patient can earn time on the deceased-donor waiting list once his or her estimated GFR falls to below 20 mL/min/1.7 m².

Plan for dialysis access

Patients starting hemodialysis first need to undergo a procedure to provide access to the blood. The three options are an arteriovenous fistula, an arteriovenous graft, and a central venous catheter (Figure 1).

An arteriovenous fistula is the best option, being the most durable, followed by a graft and then a catheter.⁹¹ Arteriovenous fistulas also have the lowest rates of infection,⁹² thrombosis,⁹³ and intervention to maintain patency.⁹³

The fistula is created by ligating a vein draining an extremity, most often the nondominant arm, and anastomosing the vein to an artery. The higher arterial pressure causes the vein to dilate and thicken (“arterialize”), thus making it able to withstand repeated cannulation necessary for hemodialysis.

An arteriovenous fistula typically takes 1 to 3 months to “mature” to the point where it can be used,^94,95 and, depending on the patient and experience of the vascular surgeon, a significant number may never mature. Thus, it is important to discuss hemodialysis access before the patient reaches end-stage renal disease so that he or she can be referred to a vascular surgeon early, when the estimated GFR is about 20 mL/min/1.73 m².

An arteriovenous graft. Not all patients have suitable vessels for creation of an arteriovenous fistula. In such patients, an arteriovenous graft, typically made of polytetrafluoroethylene, is the next best option. The graft is typically ready to use in 2 weeks and thus does not require as much advance planning. Grafts tend to narrow more often than fistulas and require more procedures to keep them patent.

A central venous catheter is most often inserted into the internal jugular vein and tunneled under the skin to exit in an area covered by the patient’s shirt.

Tunneled dialysis catheters are associated with higher rates of infection, thrombosis, and overall mortality and are therefore the least preferred choice. They are reserved for patients who have not had advance planning for end-stage renal disease, who do not have acceptable vessels for an arteriovenous fistula or graft, or who have refused surgical access.

Protect the fistula arm. It is recommended that venipuncture, intravenous lines, and blood pressure measurements be avoided in the nondominant upper arm of patients with stage 4 and 5 CKD to protect those veins for the potential creation of an arteriovenous fistula.⁹⁶ For the same reason, peripherally inserted central catheter lines and subclavian catheters should be avoided in these patients. If an arteriovenous fistula has already been placed, this arm must be protected from such procedures at all times.

Studies have shown that late referral to a nephrologist is associated with a lower incidence of starting dialysis with a permanent vascular access.^97,98

If the patient wishes to start peritoneal dialysis, the peritoneal dialysis catheter can usually be used 2 weeks after being inserted.

Starting dialysis

The appropriate time for starting dialysis remains controversial, especially in elderly patients with multiple comorbid conditions.

The IDEAL study⁹⁹ found no benefit in starting dialysis at a GFR of 10 to 14 mL/min compared with 5 to 7 mL/min. Thus, there is no single estimated GFR at which dialysis should be started. Rather, the development of early uremic symptoms and the patient’s quality of life should guide this decision.^{82,83,99–101}

Hemodialysis involves three sessions per week, each taking about 4 hours. Evidence suggests that longer sessions or more sessions per week may offer benefits, especially in terms of blood pressure, volume, and dietary management. This has led to an increase in the popularity of home and in-center nocturnal hemodialysis programs across the United States.

Peritoneal dialysis?

Peritoneal dialysis is an excellent choice for patients who are motivated, can care for themselves at home, and have a support system available to assist them if needed. It allows for daily dialysis, less fluid restriction, and less dietary restriction, and it gives the patient an opportunity to stay independent. It also spares the veins in the arms, which may be needed for vascular access later in life if hemodialysis is needed.

Recommendation. We recommend that peritoneal dialysis be offered to any suitable patient who is approaching end-stage renal disease.

A COMPREHENSIVE, COLLABORATIVE APPROACH

Chronic kidney disease is a multisystem disorder, and its management requires a comprehensive approach (Table 3). Early detection and interventions are key to reducing cardiovascular events and progression to kidney failure.

Early referral to a nephrologist and team collaboration between the primary care provider, the nephrologist, and other health care providers are essential. Early in the course of CKD, it may be appropriate for a nephrologist to evaluate the patient and recommend a set of treatment goals. Follow-up may be infrequent or unnecessary.

As CKD progresses, especially as the patient reaches an estimated GFR of 30 mL/min/1.73 m², the nephrologist will take a more active role in the patient’s care and medical decision-making. In some circumstances, it may even be appropriate for the nephrologist to be the patient’s source of primary care, with the primary care provider as a consultant.

Caring for patients with CKD includes not only strategies to preserve renal function and prolong survival, but also making critical decisions about starting dialysis and about the need for transplantation. Early involvement of a nephrologist and early preparation for end-stage renal disease with preemptive transplantation and arteriovenous fistula placement are associated with better patient outcomes. Key to this is collaboration between the primary care provider and the nephrologist, with levels of responsibility for patient care that adapt to the patient’s degree of renal dysfunction and other comorbidities. Such strategies to select patients for timely nephrology referral may help improve outcomes in this vulnerable population.

Accountable-care organizations are becoming more prominent in the United States, and therefore health care systems in the near future will be reimbursed on the basis of their ability to care for patient populations rather than individual patients. As a result, primary care physicians will need to be well versed in the care of patients with common chronic diseases such as chronic kidney disease (CKD). By one estimate, patients with CKD constitute 14% of the US population age 20 and older, or more than 31 million people.¹

An earlier article in this journal reviewed how to identify patients with CKD and how to interpret the estimated glomerular filtration rate (GFR).² This article examines the care of patients with advanced CKD, how to manage their health risks, and how to optimize their care by coordinating with nephrologists.

GOALS OF CKD CARE

CKD is defined either as renal damage (which is most commonly manifested by proteinuria, but which may include pathologic changes on biopsy or other markers of damage on serum, urine, or imaging studies), or as a GFR less than 60 mL/min/1.73 m² for at least 3 months.³ It is divided into five stages (Table 1).

Since most patients with CKD never reach end-stage renal disease, much of their care is aimed at slowing the progression of renal dysfunction and addressing medical issues that arise as a result of CKD. To these ends, it is important to detect CKD early and refer these patients to a nephrology team in a timely manner. Their care can be separated into several important tasks:

• Identify the cause of CKD, if possible; address potentially reversible causes such as obstruction or medication-related causes. If a primarily glomerular process (marked by heavy proteinuria and dysmorphic red blood cells and red blood cell casts in the urine sediment) or interstitial nephritis (manifested by white blood cells in the urine) is suspected, refer to a nephrologist early.
• Provide treatment to correct the specific cause (if one is present) or slow the deterioration of renal function.
• Address cardiovascular risk factors.
• Address metabolic abnormalities related to CKD.
• If the CKD is advanced, educate the patient about end-stage renal disease and its treatment options, and guide the patient through the transition to end-stage renal disease.

WHEN SHOULD A NEPHROLOGIST BE CONSULTED?

The ideal timing of referral to a nephrologist is not well defined and depends on the comfort level of the primary care provider.

Treatments to slow the progression of CKD and decrease cardiovascular risk should begin early in CKD (ie, in stage 3) and can be managed by the primary care provider with guidance from a nephrologist. Patients referred to a nephrologist while in stage 3 have been shown to go longer without CKD progression than those referred in later stages.⁴ Early referral to a nephrologist has also been associated with a decreased mortality rate.⁵ The studies that found these trends, however, were limited by the fact that patients with stage 3 CKD are less likely to progress to end-stage renal disease or to die of cardiovascular disease than patients with stage 4 or 5 CKD.

Once stage 4 CKD develops, the nephrologist should take a more active role in the care plan. In this stage, cardiovascular risk rises, and the risk of developing end-stage renal disease rises dramatically.⁶ With comprehensive care in a CKD clinic, even patients with advanced CKD are more likely to have a stabilization of renal function.⁷ Kinchen et al⁸ found that patients referred to a nephrologist within 4 months of starting dialysis had a lower survival rate than those referred earlier. Therefore, if a nephrologist was not involved in the patient’s care prior to stage 4, then a referral must be made.

Recommendation. Patients with stage 3 CKD can be referred for an initial evaluation and development of a treatment plan, but most of the responsibility for their care can remain with the primary care provider. Once stage 4 CKD develops, the nephrologist should assume an increasing role. However, if glomerular disease is suspected, we recommend referral to a nephrologist regardless of the estimated GFR.

ELEVATED CARDIOVASCULAR RISK

Patients with stage 3 CKD are 20 times more likely to die of a cardiovascular event than to reach end-stage renal disease.⁶ This increased risk does not quite reach the status of a cardiovascular disease risk equivalent, as does diabetes,^9,10 but cardiovascular risk reduction should be a primary focus of care for the CKD patient.

The cardiovascular risk in part is attributed to a high prevalence of traditional cardiovascular risk factors, including diabetes mellitus, hypertension, and hyperlipidemia.^11,12 About two-thirds of CKD patients have metabolic syndrome, which is a risk factor for cardiovascular disease and is associated with more rapid progression of CKD.¹³ In addition, renal dysfunction, proteinuria, and hyperphosphatemia are also risk factors for cardiovascular disease.^14–19

The risk of death from a cardiovascular event increases as kidney function declines, with reported 5-year death rates of 19.5% in stage 2, 24.3% in stage 3, and 45.7% in stage 4 CKD. However, imbalance between mortality risk and progression to end-stage renal disease may be age-dependent.²⁰ Younger patients (age 45 and younger) are more likely to progress to end-stage renal disease, whereas in older patients (over age 65), the relative risk of dying of cardiovascular disease is higher.

Aggressive lipid management

Hyperlipidemia is a common risk factor for cardiovascular morbidity and mortality in CKD.²¹ However, until recently, all studies of outcomes of patients treated for hyperlipidemia excluded patients with CKD. Post hoc analyses of these studies ^22–27 showed statins to be beneficial in primary and secondary cardiovascular prevention in patents with “normal” serum creatinine values but estimated GFR levels of 50 to 59 mL/min/1.73 m².

The SHARP trial²⁸ was the first prospective trial to study lipid-lowering therapy in patients with CKD. In this trial, patients with various stages of CKD, including advanced CKD, had fewer major vascular events if they received the combination of low-dose simvastatin (Zocor) and ezetimibe (Zetia). However, the evidence does not suggest that statin therapy slows the progression of CKD.^28–31

Recommendation. Manage hyperlipidemia aggressively using statin therapy with or without ezetimibe, with a target low-density lipoprotein cholesterol level below 100 mg/dL.³²

Manage other cardiovascular risk factors

Because hypertension and proteinuria are risk factors not only for cardiovascular disease but also for progression of CKD, they are discussed in the section below.

ATTEMPT TO PREVENT WORSENING OF RENAL FUNCTION

Medications to avoid

It is important to review a CKD patient’s medication list—prescription and over-the-counter drugs—to identify any that may contribute to a worsening of renal function. CKD patients need to be informed about avoiding medications such as nonsteroidal anti-inflammatory drugs, proton pump inhibitors, and herbal supplements because they can cause further renal injury. In addition, other medications (eg, metformin) are contraindicated in CKD because of side effects that may occur in CKD.

Patients should be encouraged to discuss any changes in their medications, including over-the-counter products, with their primary care physicians.

Manage hypertension aggressively

Many patients with CKD also have hypertension,^33,34 possibly because they have a higher frequency of underlying essential hypertension or because CKD often worsens preexisting hypertension. Moreover, uncontrolled hypertension is associated with a further decline in renal function.^35,36

The ACCORD trial³⁷ found no benefit in lowering systolic blood pressure to less than 120 mm Hg compared with less than 140 mm Hg in patients with diabetes mellitus. (The patients in this study did not necessarily have CKD.)

A meta-analysis³⁸ of trials of antihypertensive treatment in patients with CKD found that the optimal target systolic blood pressure for decreasing the progression of CKD was 110 to 129 mm Hg. The relative risk of progression of renal dysfunction was:

• 1.83 (95% confidence interval [CI] 0.97–3.44) at 130 mm to 139 mm Hg, vs
• 3.14 (95% CI 1.64–5.99) at 160 mm Hg or higher.

There is also evidence that blood pressure control can be relaxed as patients age. While the exact age differs among published guidelines, the evidence supports a goal blood pressure of less than 150/90 mm Hg once a patient reaches the age of 70, regardless of CKD or proteinuria.

Recommendation. Current evidence suggests the following blood pressure goals in CKD patients:

• With diabetes mellitus or proteinuria: < 130/80 mm Hg
• Without proteinuria: < 140/90 mm Hg
• Age 70 and older: <150/90 mm Hg.³⁹

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are the preferred antihypertensive drugs in patients with diabetes or proteinuria (see below).

Manage proteinuria

Proteinuria is also associated with progression of CKD. AASK,⁴⁰ a study that included nondiabetic African American patients whose estimated GFRs were between 20 and 60 mL/min/1.73 m², showed that higher levels of proteinuria were associated with a higher risk of decline in GFR and a higher risk of end-stage renal disease. Findings were similar to those in studies of other CKD populations.^41–43 Proteinuria is also an independent risk factor for cardiovascular disease and death. Multiple large studies^16,17,44,45 have found associations between higher levels of albumin excretion and risk of major cardiovascular events, cardiovascular death, and death from any cause in people with and without diabetes.

Reducing proteinuria has been shown to both slow progression of renal dysfunction and reduce the cardiovascular risk.^44,45 In a substudy of the IDNT⁴⁶ in patients with diabetic nephropathy, each 50% reduction in urinary protein excretion was associated with a 56% reduction in risk of progression of CKD. Similar effects have been shown in nondiabetic CKD patients.⁴⁷

ACE inhibitors and ARBs are the preferred treatments for proteinuria in patients with CKD.^48–50 Combination therapy with an ACE inhibitor and an ARB has been used,^51–53 with a better response in proteinuria reduction. However, combination therapy with these drugs cannot currently be recommended, as the only prospective study of this regimen to date suggested worse renal and overall outcomes in patients at high cardiovascular risk.⁵⁴ These drugs may also have renoprotective effects independent of their effects on blood pressure and proteinuria.³⁸ Dietary salt restriction and diuretic therapy can further increase the efficacy of proteinuria reduction by ACE inhibitors or ARBs.^55,56

On the other hand, stopping ACE inhibitors or ARBs may be beneficial as the patient nears end-stage renal disease. Ahmed et al⁵⁷ demonstrated that stopping ACE inhibitors or ARBs in advanced stage 4 CKD (mean estimated GFR 16 mL/min/1.73 m²) was associated with improved GFR and delayed onset of renal replacement therapy. This improvement may be due to regaining the slight decrease in GFR that occurred when these medications were started.

Nondihydropyridine calcium channel blockers such as diltiazem (Cardizem) and verapamil (Calan) have also been shown to be useful for reducing proteinuria,⁵⁸ whereas dihydropyridine calcium channel blockers such as amlodipine (Norvasc) and nifedipine (Procardia), when used without ACE inhibitors or ARBs, can worsen proteinuria.^58,59

Correct metabolic acidosis

The kidneys play an important role in maintaining acid-base balance, keeping the blood from becoming too acidic both by reabsorbing bicarbonate filtered into the urine by the glomerulus and by excreting the daily acid load. Metabolic acidosis can develop when these functions break down at more advanced stages of CKD, most often when the estimated GFR declines to less than 20 mL/min/1.73 m².

Bicarbonate levels of 22 mmol/L or less have been associated with a higher risk of worsening renal function.⁶⁰ When such patients were treated with sodium bicarbonate to achieve a serum bicarbonate of at least 23 mmol/L, they had an 80% lower rate of progression to end-stage renal disease without any increase in edema, admission for congestive heart failure, or change in blood pressure.⁶¹

Susantitaphong et al⁶² reviewed six randomized trials of bicarbonate supplementation in CKD and found that it was associated with improved kidney function and a 79% lower rate of progression to end-stage renal disease.

The proposed mechanism behind this benefit lies in the increase in ammonia production that each surviving nephron must undertake to handle the daily acid load. The increased ammonia is thought to play a role in activating the alternative complement pathway,⁶³ causing renal inflammation and injury.

Recommendation. Bicarbonate therapy should be used to maintain serum bicarbonate levels above 22 mmol/L in CKD.⁶⁴

OTHER ASPECTS OF CKD CARE

Bone mineral disorders

Patients with CKD develop secondary hyperparathyroidism, hyperphosphatemia, and (in advanced CKD) hypocalcemia, all leading to disorders of bone mineral metabolism.

Traditionally, it has been thought that decreased production of 1,25-dihydroxyvitamin D by dysfunctional kidneys leads to decreased suppression of the parathyroid gland and to secondary hyperparathyroidism. The major long-term adverse effect of this is a weakened bone matrix resulting from increased calcium and phosphorus efflux from bones (renal osteodystrophy).

The discovery of fibroblast growth factor 23 (FGF-23) has improved our understanding of the physiology behind disordered bone mineral metabolism in CKD. FGF-23, produced by osteoblasts and osteocytes, acts directly on the kidney to increase renal phosphate excretion. It also suppresses 1,25-dihydroxyvitamin D levels by inhibiting 1-alpha-hydroxylase,⁶⁵ and it stimulates parathyroid hormone secretion. FGF-23 levels rise much earlier in CKD than do parathyroid hormone levels, suggesting that abnormalities in phosphorus balance and FGF-23 may be the earliest pathophysiologic changes.⁶⁶

The initial treatment of bone mineral disorders is to some extent guided by laboratory values. Phosphate levels higher than 3.5 or 4 mg/dL and elevated FGF-23 levels have been associated with increased mortality rates in CKD patients.^{18,19,67–69} All patients should also have their 1,25-dihydroxyvitamin D level checked and supplemented if deficient. In many patients with early stage 3 CKD, this may correct secondary hyperparathyroidism.⁷⁰

Serum phosphorus levels should be kept in the normal range in stage 3 and 4 CKD,⁷¹ either by restricting dietary phosphorus intake (< 800 or < 1,000 mg/day) or by using a phosphate binder, which is taken with meals to prevent phosphorus absorption from the gastrointestinal tract. Current US recommendations are to allow graded increases in parathyroid hormone based on the stage of CKD (Table 2).⁷¹ However, these targets are still an area of uncertainty, with some guidelines suggesting that wider variations in parathyroid hormone can be allowed, so there may be wider variation in clinical practice in this area.⁷² If the serum phosphorus level is in the goal range but parathyroid hormone levels are still high, an activated vitamin D analogue such as calcitriol is recommended, although with the emerging role of FGF-23, some experts also call for early use of a phosphate binder in this group.

The treatment of bone mineral disorders in CKD is fairly complex, and we recommend that it be done by or with the close direction of a nephrologist.

Recommendations on bone disorders

• Check levels of calcium, phosphorus, 25-hydroxyvitamin D, and parathyroid hormone in all patients whose estimated GFR is less than 60 mL/min/1.73 m², with frequency of measurements based on the stage of CKD.⁷¹
• Replace vitamin D if deficient.
• Treat elevated phosphorus levels with a protein-restricted diet (nutrition referral) and a phosphate binder.
• Treat elevated hyperparathyroid hormone levels with a vitamin D analogue once phosphorus levels have been controlled.
• Refer patients with an elevated phosphorus or parathyroid hormone level to a nephrology service for consultation before initiating medical therapy.

Anemia is common, treatment controversial

The treatment of anemia attributed to CKD has been a topic of controversy over the past decade, and we recommend that it be done with the guidance of a nephrologist.

Anemia is common in CKD, and declining kidney function is an independent predictor of anemia.⁷³ Anemia is a risk factor for left ventricular hypertrophy, cardiovascular disease,⁷⁴ and death in CKD.⁷⁵

The anemia of CKD is attributed to relative erythropoietin deficiency and bone marrow resistance to erythropoietin, but this is a diagnosis of exclusion, and other causes of anemia must be ruled out. Iron deficiency is a common cause of anemia in CKD, and treatment of iron deficiency may correct anemia in more than one-third of these patients.^76,77

Erythropoiesis-stimulating agents such as epoetin alfa (Procrit) and darbepoetin (Aranesp) are used to treat renal anemia. However, the target hemoglobin level has been a subject of debate. Three prospective trials^78–80 found no benefit in raising the hemoglobin level to normal ranges using these agents, and several found an association with higher rates of stroke and venous thrombosis. The US Food and Drug Administration suggests that the only role for these agents in CKD is to avoid the need for transfusions. They should not be used to normalize the hemoglobin level. The target, although not explicitly specified, is suggested to be around 10 g/dL.⁸¹

PREPARE FOR END-STAGE RENAL DISEASE

Discuss the options

Because the risk of developing end-stage renal disease rises dramatically once CKD reaches stage 4, all such patients should have a discussion about renal replacement therapy. They should be educated about their options for treatment (hemodialysis, peritoneal dialysis, and transplantation, as well as not proceeding with renal replacement therapy), often in a formal class. They should then be actively engaged in the decision about how to proceed. Survival and quality of life should be discussed, particularly with patients who are over age 80, who are severely ill, or who are living in a nursing facility, as these groups get limited survival benefit from starting dialysis, and quality of life may actually decrease with dialysis.^82,83

The Renal Physicians Association has created clinical practice guidelines for shared decision-making, consisting of 10 practice recommendations that outline a systematic approach to patients needing renal replacement therapy.⁸⁴

Consider preemptive kidney transplantation

Any patient thought to be a suitable candidate for renal transplantation should be referred to a transplantation center for evaluation. Studies have shown that kidney transplantation offers a survival advantage compared with chronic dialysis and should preferably be done preemptively, ie, before dialysis is required.^85–90 Therefore, patients with estimated GFRs in the low 20s should be referred for a transplantation evaluation.

If a living donor is available, the transplantation team usually waits to perform the procedure until the patient is closer to needing dialysis, often when the estimated GFR is around 15 to 16 mL/min/1.73 m². If no living donor is available, the patient can earn time on the deceased-donor waiting list once his or her estimated GFR falls to below 20 mL/min/1.7 m².

Plan for dialysis access

Patients starting hemodialysis first need to undergo a procedure to provide access to the blood. The three options are an arteriovenous fistula, an arteriovenous graft, and a central venous catheter (Figure 1).

An arteriovenous fistula is the best option, being the most durable, followed by a graft and then a catheter.⁹¹ Arteriovenous fistulas also have the lowest rates of infection,⁹² thrombosis,⁹³ and intervention to maintain patency.⁹³

The fistula is created by ligating a vein draining an extremity, most often the nondominant arm, and anastomosing the vein to an artery. The higher arterial pressure causes the vein to dilate and thicken (“arterialize”), thus making it able to withstand repeated cannulation necessary for hemodialysis.

An arteriovenous fistula typically takes 1 to 3 months to “mature” to the point where it can be used,^94,95 and, depending on the patient and experience of the vascular surgeon, a significant number may never mature. Thus, it is important to discuss hemodialysis access before the patient reaches end-stage renal disease so that he or she can be referred to a vascular surgeon early, when the estimated GFR is about 20 mL/min/1.73 m².

An arteriovenous graft. Not all patients have suitable vessels for creation of an arteriovenous fistula. In such patients, an arteriovenous graft, typically made of polytetrafluoroethylene, is the next best option. The graft is typically ready to use in 2 weeks and thus does not require as much advance planning. Grafts tend to narrow more often than fistulas and require more procedures to keep them patent.

A central venous catheter is most often inserted into the internal jugular vein and tunneled under the skin to exit in an area covered by the patient’s shirt.

Tunneled dialysis catheters are associated with higher rates of infection, thrombosis, and overall mortality and are therefore the least preferred choice. They are reserved for patients who have not had advance planning for end-stage renal disease, who do not have acceptable vessels for an arteriovenous fistula or graft, or who have refused surgical access.

Protect the fistula arm. It is recommended that venipuncture, intravenous lines, and blood pressure measurements be avoided in the nondominant upper arm of patients with stage 4 and 5 CKD to protect those veins for the potential creation of an arteriovenous fistula.⁹⁶ For the same reason, peripherally inserted central catheter lines and subclavian catheters should be avoided in these patients. If an arteriovenous fistula has already been placed, this arm must be protected from such procedures at all times.

Studies have shown that late referral to a nephrologist is associated with a lower incidence of starting dialysis with a permanent vascular access.^97,98

If the patient wishes to start peritoneal dialysis, the peritoneal dialysis catheter can usually be used 2 weeks after being inserted.

Starting dialysis

The appropriate time for starting dialysis remains controversial, especially in elderly patients with multiple comorbid conditions.

The IDEAL study⁹⁹ found no benefit in starting dialysis at a GFR of 10 to 14 mL/min compared with 5 to 7 mL/min. Thus, there is no single estimated GFR at which dialysis should be started. Rather, the development of early uremic symptoms and the patient’s quality of life should guide this decision.^{82,83,99–101}

Hemodialysis involves three sessions per week, each taking about 4 hours. Evidence suggests that longer sessions or more sessions per week may offer benefits, especially in terms of blood pressure, volume, and dietary management. This has led to an increase in the popularity of home and in-center nocturnal hemodialysis programs across the United States.

Peritoneal dialysis?

Peritoneal dialysis is an excellent choice for patients who are motivated, can care for themselves at home, and have a support system available to assist them if needed. It allows for daily dialysis, less fluid restriction, and less dietary restriction, and it gives the patient an opportunity to stay independent. It also spares the veins in the arms, which may be needed for vascular access later in life if hemodialysis is needed.

Recommendation. We recommend that peritoneal dialysis be offered to any suitable patient who is approaching end-stage renal disease.

A COMPREHENSIVE, COLLABORATIVE APPROACH

Chronic kidney disease is a multisystem disorder, and its management requires a comprehensive approach (Table 3). Early detection and interventions are key to reducing cardiovascular events and progression to kidney failure.

Early referral to a nephrologist and team collaboration between the primary care provider, the nephrologist, and other health care providers are essential. Early in the course of CKD, it may be appropriate for a nephrologist to evaluate the patient and recommend a set of treatment goals. Follow-up may be infrequent or unnecessary.

As CKD progresses, especially as the patient reaches an estimated GFR of 30 mL/min/1.73 m², the nephrologist will take a more active role in the patient’s care and medical decision-making. In some circumstances, it may even be appropriate for the nephrologist to be the patient’s source of primary care, with the primary care provider as a consultant.

Caring for patients with CKD includes not only strategies to preserve renal function and prolong survival, but also making critical decisions about starting dialysis and about the need for transplantation. Early involvement of a nephrologist and early preparation for end-stage renal disease with preemptive transplantation and arteriovenous fistula placement are associated with better patient outcomes. Key to this is collaboration between the primary care provider and the nephrologist, with levels of responsibility for patient care that adapt to the patient’s degree of renal dysfunction and other comorbidities. Such strategies to select patients for timely nephrology referral may help improve outcomes in this vulnerable population.

Accountable-care organizations are becoming more prominent in the United States, and therefore health care systems in the near future will be reimbursed on the basis of their ability to care for patient populations rather than individual patients. As a result, primary care physicians will need to be well versed in the care of patients with common chronic diseases such as chronic kidney disease (CKD). By one estimate, patients with CKD constitute 14% of the US population age 20 and older, or more than 31 million people.¹

An earlier article in this journal reviewed how to identify patients with CKD and how to interpret the estimated glomerular filtration rate (GFR).² This article examines the care of patients with advanced CKD, how to manage their health risks, and how to optimize their care by coordinating with nephrologists.

GOALS OF CKD CARE

CKD is defined either as renal damage (which is most commonly manifested by proteinuria, but which may include pathologic changes on biopsy or other markers of damage on serum, urine, or imaging studies), or as a GFR less than 60 mL/min/1.73 m² for at least 3 months.³ It is divided into five stages (Table 1).

Since most patients with CKD never reach end-stage renal disease, much of their care is aimed at slowing the progression of renal dysfunction and addressing medical issues that arise as a result of CKD. To these ends, it is important to detect CKD early and refer these patients to a nephrology team in a timely manner. Their care can be separated into several important tasks:

• Identify the cause of CKD, if possible; address potentially reversible causes such as obstruction or medication-related causes. If a primarily glomerular process (marked by heavy proteinuria and dysmorphic red blood cells and red blood cell casts in the urine sediment) or interstitial nephritis (manifested by white blood cells in the urine) is suspected, refer to a nephrologist early.
• Provide treatment to correct the specific cause (if one is present) or slow the deterioration of renal function.
• Address cardiovascular risk factors.
• Address metabolic abnormalities related to CKD.
• If the CKD is advanced, educate the patient about end-stage renal disease and its treatment options, and guide the patient through the transition to end-stage renal disease.

WHEN SHOULD A NEPHROLOGIST BE CONSULTED?

The ideal timing of referral to a nephrologist is not well defined and depends on the comfort level of the primary care provider.

Treatments to slow the progression of CKD and decrease cardiovascular risk should begin early in CKD (ie, in stage 3) and can be managed by the primary care provider with guidance from a nephrologist. Patients referred to a nephrologist while in stage 3 have been shown to go longer without CKD progression than those referred in later stages.⁴ Early referral to a nephrologist has also been associated with a decreased mortality rate.⁵ The studies that found these trends, however, were limited by the fact that patients with stage 3 CKD are less likely to progress to end-stage renal disease or to die of cardiovascular disease than patients with stage 4 or 5 CKD.

Once stage 4 CKD develops, the nephrologist should take a more active role in the care plan. In this stage, cardiovascular risk rises, and the risk of developing end-stage renal disease rises dramatically.⁶ With comprehensive care in a CKD clinic, even patients with advanced CKD are more likely to have a stabilization of renal function.⁷ Kinchen et al⁸ found that patients referred to a nephrologist within 4 months of starting dialysis had a lower survival rate than those referred earlier. Therefore, if a nephrologist was not involved in the patient’s care prior to stage 4, then a referral must be made.

Recommendation. Patients with stage 3 CKD can be referred for an initial evaluation and development of a treatment plan, but most of the responsibility for their care can remain with the primary care provider. Once stage 4 CKD develops, the nephrologist should assume an increasing role. However, if glomerular disease is suspected, we recommend referral to a nephrologist regardless of the estimated GFR.

ELEVATED CARDIOVASCULAR RISK

Patients with stage 3 CKD are 20 times more likely to die of a cardiovascular event than to reach end-stage renal disease.⁶ This increased risk does not quite reach the status of a cardiovascular disease risk equivalent, as does diabetes,^9,10 but cardiovascular risk reduction should be a primary focus of care for the CKD patient.

The cardiovascular risk in part is attributed to a high prevalence of traditional cardiovascular risk factors, including diabetes mellitus, hypertension, and hyperlipidemia.^11,12 About two-thirds of CKD patients have metabolic syndrome, which is a risk factor for cardiovascular disease and is associated with more rapid progression of CKD.¹³ In addition, renal dysfunction, proteinuria, and hyperphosphatemia are also risk factors for cardiovascular disease.^14–19

The risk of death from a cardiovascular event increases as kidney function declines, with reported 5-year death rates of 19.5% in stage 2, 24.3% in stage 3, and 45.7% in stage 4 CKD. However, imbalance between mortality risk and progression to end-stage renal disease may be age-dependent.²⁰ Younger patients (age 45 and younger) are more likely to progress to end-stage renal disease, whereas in older patients (over age 65), the relative risk of dying of cardiovascular disease is higher.

Aggressive lipid management

Hyperlipidemia is a common risk factor for cardiovascular morbidity and mortality in CKD.²¹ However, until recently, all studies of outcomes of patients treated for hyperlipidemia excluded patients with CKD. Post hoc analyses of these studies ^22–27 showed statins to be beneficial in primary and secondary cardiovascular prevention in patents with “normal” serum creatinine values but estimated GFR levels of 50 to 59 mL/min/1.73 m².

The SHARP trial²⁸ was the first prospective trial to study lipid-lowering therapy in patients with CKD. In this trial, patients with various stages of CKD, including advanced CKD, had fewer major vascular events if they received the combination of low-dose simvastatin (Zocor) and ezetimibe (Zetia). However, the evidence does not suggest that statin therapy slows the progression of CKD.^28–31

Recommendation. Manage hyperlipidemia aggressively using statin therapy with or without ezetimibe, with a target low-density lipoprotein cholesterol level below 100 mg/dL.³²

Manage other cardiovascular risk factors

Because hypertension and proteinuria are risk factors not only for cardiovascular disease but also for progression of CKD, they are discussed in the section below.

ATTEMPT TO PREVENT WORSENING OF RENAL FUNCTION

Medications to avoid

It is important to review a CKD patient’s medication list—prescription and over-the-counter drugs—to identify any that may contribute to a worsening of renal function. CKD patients need to be informed about avoiding medications such as nonsteroidal anti-inflammatory drugs, proton pump inhibitors, and herbal supplements because they can cause further renal injury. In addition, other medications (eg, metformin) are contraindicated in CKD because of side effects that may occur in CKD.

Patients should be encouraged to discuss any changes in their medications, including over-the-counter products, with their primary care physicians.

Manage hypertension aggressively

Many patients with CKD also have hypertension,^33,34 possibly because they have a higher frequency of underlying essential hypertension or because CKD often worsens preexisting hypertension. Moreover, uncontrolled hypertension is associated with a further decline in renal function.^35,36

The ACCORD trial³⁷ found no benefit in lowering systolic blood pressure to less than 120 mm Hg compared with less than 140 mm Hg in patients with diabetes mellitus. (The patients in this study did not necessarily have CKD.)

A meta-analysis³⁸ of trials of antihypertensive treatment in patients with CKD found that the optimal target systolic blood pressure for decreasing the progression of CKD was 110 to 129 mm Hg. The relative risk of progression of renal dysfunction was:

• 1.83 (95% confidence interval [CI] 0.97–3.44) at 130 mm to 139 mm Hg, vs
• 3.14 (95% CI 1.64–5.99) at 160 mm Hg or higher.

There is also evidence that blood pressure control can be relaxed as patients age. While the exact age differs among published guidelines, the evidence supports a goal blood pressure of less than 150/90 mm Hg once a patient reaches the age of 70, regardless of CKD or proteinuria.

Recommendation. Current evidence suggests the following blood pressure goals in CKD patients:

• With diabetes mellitus or proteinuria: < 130/80 mm Hg
• Without proteinuria: < 140/90 mm Hg
• Age 70 and older: <150/90 mm Hg.³⁹

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are the preferred antihypertensive drugs in patients with diabetes or proteinuria (see below).

Manage proteinuria

Proteinuria is also associated with progression of CKD. AASK,⁴⁰ a study that included nondiabetic African American patients whose estimated GFRs were between 20 and 60 mL/min/1.73 m², showed that higher levels of proteinuria were associated with a higher risk of decline in GFR and a higher risk of end-stage renal disease. Findings were similar to those in studies of other CKD populations.^41–43 Proteinuria is also an independent risk factor for cardiovascular disease and death. Multiple large studies^16,17,44,45 have found associations between higher levels of albumin excretion and risk of major cardiovascular events, cardiovascular death, and death from any cause in people with and without diabetes.

Reducing proteinuria has been shown to both slow progression of renal dysfunction and reduce the cardiovascular risk.^44,45 In a substudy of the IDNT⁴⁶ in patients with diabetic nephropathy, each 50% reduction in urinary protein excretion was associated with a 56% reduction in risk of progression of CKD. Similar effects have been shown in nondiabetic CKD patients.⁴⁷

ACE inhibitors and ARBs are the preferred treatments for proteinuria in patients with CKD.^48–50 Combination therapy with an ACE inhibitor and an ARB has been used,^51–53 with a better response in proteinuria reduction. However, combination therapy with these drugs cannot currently be recommended, as the only prospective study of this regimen to date suggested worse renal and overall outcomes in patients at high cardiovascular risk.⁵⁴ These drugs may also have renoprotective effects independent of their effects on blood pressure and proteinuria.³⁸ Dietary salt restriction and diuretic therapy can further increase the efficacy of proteinuria reduction by ACE inhibitors or ARBs.^55,56

On the other hand, stopping ACE inhibitors or ARBs may be beneficial as the patient nears end-stage renal disease. Ahmed et al⁵⁷ demonstrated that stopping ACE inhibitors or ARBs in advanced stage 4 CKD (mean estimated GFR 16 mL/min/1.73 m²) was associated with improved GFR and delayed onset of renal replacement therapy. This improvement may be due to regaining the slight decrease in GFR that occurred when these medications were started.

Nondihydropyridine calcium channel blockers such as diltiazem (Cardizem) and verapamil (Calan) have also been shown to be useful for reducing proteinuria,⁵⁸ whereas dihydropyridine calcium channel blockers such as amlodipine (Norvasc) and nifedipine (Procardia), when used without ACE inhibitors or ARBs, can worsen proteinuria.^58,59

Correct metabolic acidosis

The kidneys play an important role in maintaining acid-base balance, keeping the blood from becoming too acidic both by reabsorbing bicarbonate filtered into the urine by the glomerulus and by excreting the daily acid load. Metabolic acidosis can develop when these functions break down at more advanced stages of CKD, most often when the estimated GFR declines to less than 20 mL/min/1.73 m².

Bicarbonate levels of 22 mmol/L or less have been associated with a higher risk of worsening renal function.⁶⁰ When such patients were treated with sodium bicarbonate to achieve a serum bicarbonate of at least 23 mmol/L, they had an 80% lower rate of progression to end-stage renal disease without any increase in edema, admission for congestive heart failure, or change in blood pressure.⁶¹

Susantitaphong et al⁶² reviewed six randomized trials of bicarbonate supplementation in CKD and found that it was associated with improved kidney function and a 79% lower rate of progression to end-stage renal disease.

The proposed mechanism behind this benefit lies in the increase in ammonia production that each surviving nephron must undertake to handle the daily acid load. The increased ammonia is thought to play a role in activating the alternative complement pathway,⁶³ causing renal inflammation and injury.

Recommendation. Bicarbonate therapy should be used to maintain serum bicarbonate levels above 22 mmol/L in CKD.⁶⁴

OTHER ASPECTS OF CKD CARE

Bone mineral disorders

Patients with CKD develop secondary hyperparathyroidism, hyperphosphatemia, and (in advanced CKD) hypocalcemia, all leading to disorders of bone mineral metabolism.

Traditionally, it has been thought that decreased production of 1,25-dihydroxyvitamin D by dysfunctional kidneys leads to decreased suppression of the parathyroid gland and to secondary hyperparathyroidism. The major long-term adverse effect of this is a weakened bone matrix resulting from increased calcium and phosphorus efflux from bones (renal osteodystrophy).

The discovery of fibroblast growth factor 23 (FGF-23) has improved our understanding of the physiology behind disordered bone mineral metabolism in CKD. FGF-23, produced by osteoblasts and osteocytes, acts directly on the kidney to increase renal phosphate excretion. It also suppresses 1,25-dihydroxyvitamin D levels by inhibiting 1-alpha-hydroxylase,⁶⁵ and it stimulates parathyroid hormone secretion. FGF-23 levels rise much earlier in CKD than do parathyroid hormone levels, suggesting that abnormalities in phosphorus balance and FGF-23 may be the earliest pathophysiologic changes.⁶⁶

The initial treatment of bone mineral disorders is to some extent guided by laboratory values. Phosphate levels higher than 3.5 or 4 mg/dL and elevated FGF-23 levels have been associated with increased mortality rates in CKD patients.^{18,19,67–69} All patients should also have their 1,25-dihydroxyvitamin D level checked and supplemented if deficient. In many patients with early stage 3 CKD, this may correct secondary hyperparathyroidism.⁷⁰

Serum phosphorus levels should be kept in the normal range in stage 3 and 4 CKD,⁷¹ either by restricting dietary phosphorus intake (< 800 or < 1,000 mg/day) or by using a phosphate binder, which is taken with meals to prevent phosphorus absorption from the gastrointestinal tract. Current US recommendations are to allow graded increases in parathyroid hormone based on the stage of CKD (Table 2).⁷¹ However, these targets are still an area of uncertainty, with some guidelines suggesting that wider variations in parathyroid hormone can be allowed, so there may be wider variation in clinical practice in this area.⁷² If the serum phosphorus level is in the goal range but parathyroid hormone levels are still high, an activated vitamin D analogue such as calcitriol is recommended, although with the emerging role of FGF-23, some experts also call for early use of a phosphate binder in this group.

The treatment of bone mineral disorders in CKD is fairly complex, and we recommend that it be done by or with the close direction of a nephrologist.

Recommendations on bone disorders

• Check levels of calcium, phosphorus, 25-hydroxyvitamin D, and parathyroid hormone in all patients whose estimated GFR is less than 60 mL/min/1.73 m², with frequency of measurements based on the stage of CKD.⁷¹
• Replace vitamin D if deficient.
• Treat elevated phosphorus levels with a protein-restricted diet (nutrition referral) and a phosphate binder.
• Treat elevated hyperparathyroid hormone levels with a vitamin D analogue once phosphorus levels have been controlled.
• Refer patients with an elevated phosphorus or parathyroid hormone level to a nephrology service for consultation before initiating medical therapy.

Anemia is common, treatment controversial

The treatment of anemia attributed to CKD has been a topic of controversy over the past decade, and we recommend that it be done with the guidance of a nephrologist.

Anemia is common in CKD, and declining kidney function is an independent predictor of anemia.⁷³ Anemia is a risk factor for left ventricular hypertrophy, cardiovascular disease,⁷⁴ and death in CKD.⁷⁵

The anemia of CKD is attributed to relative erythropoietin deficiency and bone marrow resistance to erythropoietin, but this is a diagnosis of exclusion, and other causes of anemia must be ruled out. Iron deficiency is a common cause of anemia in CKD, and treatment of iron deficiency may correct anemia in more than one-third of these patients.^76,77

Erythropoiesis-stimulating agents such as epoetin alfa (Procrit) and darbepoetin (Aranesp) are used to treat renal anemia. However, the target hemoglobin level has been a subject of debate. Three prospective trials^78–80 found no benefit in raising the hemoglobin level to normal ranges using these agents, and several found an association with higher rates of stroke and venous thrombosis. The US Food and Drug Administration suggests that the only role for these agents in CKD is to avoid the need for transfusions. They should not be used to normalize the hemoglobin level. The target, although not explicitly specified, is suggested to be around 10 g/dL.⁸¹

PREPARE FOR END-STAGE RENAL DISEASE

Discuss the options

Because the risk of developing end-stage renal disease rises dramatically once CKD reaches stage 4, all such patients should have a discussion about renal replacement therapy. They should be educated about their options for treatment (hemodialysis, peritoneal dialysis, and transplantation, as well as not proceeding with renal replacement therapy), often in a formal class. They should then be actively engaged in the decision about how to proceed. Survival and quality of life should be discussed, particularly with patients who are over age 80, who are severely ill, or who are living in a nursing facility, as these groups get limited survival benefit from starting dialysis, and quality of life may actually decrease with dialysis.^82,83

The Renal Physicians Association has created clinical practice guidelines for shared decision-making, consisting of 10 practice recommendations that outline a systematic approach to patients needing renal replacement therapy.⁸⁴

Consider preemptive kidney transplantation

Any patient thought to be a suitable candidate for renal transplantation should be referred to a transplantation center for evaluation. Studies have shown that kidney transplantation offers a survival advantage compared with chronic dialysis and should preferably be done preemptively, ie, before dialysis is required.^85–90 Therefore, patients with estimated GFRs in the low 20s should be referred for a transplantation evaluation.

If a living donor is available, the transplantation team usually waits to perform the procedure until the patient is closer to needing dialysis, often when the estimated GFR is around 15 to 16 mL/min/1.73 m². If no living donor is available, the patient can earn time on the deceased-donor waiting list once his or her estimated GFR falls to below 20 mL/min/1.7 m².

Plan for dialysis access

Patients starting hemodialysis first need to undergo a procedure to provide access to the blood. The three options are an arteriovenous fistula, an arteriovenous graft, and a central venous catheter (Figure 1).

An arteriovenous fistula is the best option, being the most durable, followed by a graft and then a catheter.⁹¹ Arteriovenous fistulas also have the lowest rates of infection,⁹² thrombosis,⁹³ and intervention to maintain patency.⁹³

The fistula is created by ligating a vein draining an extremity, most often the nondominant arm, and anastomosing the vein to an artery. The higher arterial pressure causes the vein to dilate and thicken (“arterialize”), thus making it able to withstand repeated cannulation necessary for hemodialysis.

An arteriovenous fistula typically takes 1 to 3 months to “mature” to the point where it can be used,^94,95 and, depending on the patient and experience of the vascular surgeon, a significant number may never mature. Thus, it is important to discuss hemodialysis access before the patient reaches end-stage renal disease so that he or she can be referred to a vascular surgeon early, when the estimated GFR is about 20 mL/min/1.73 m².

An arteriovenous graft. Not all patients have suitable vessels for creation of an arteriovenous fistula. In such patients, an arteriovenous graft, typically made of polytetrafluoroethylene, is the next best option. The graft is typically ready to use in 2 weeks and thus does not require as much advance planning. Grafts tend to narrow more often than fistulas and require more procedures to keep them patent.

A central venous catheter is most often inserted into the internal jugular vein and tunneled under the skin to exit in an area covered by the patient’s shirt.

Tunneled dialysis catheters are associated with higher rates of infection, thrombosis, and overall mortality and are therefore the least preferred choice. They are reserved for patients who have not had advance planning for end-stage renal disease, who do not have acceptable vessels for an arteriovenous fistula or graft, or who have refused surgical access.

Protect the fistula arm. It is recommended that venipuncture, intravenous lines, and blood pressure measurements be avoided in the nondominant upper arm of patients with stage 4 and 5 CKD to protect those veins for the potential creation of an arteriovenous fistula.⁹⁶ For the same reason, peripherally inserted central catheter lines and subclavian catheters should be avoided in these patients. If an arteriovenous fistula has already been placed, this arm must be protected from such procedures at all times.

Studies have shown that late referral to a nephrologist is associated with a lower incidence of starting dialysis with a permanent vascular access.^97,98

If the patient wishes to start peritoneal dialysis, the peritoneal dialysis catheter can usually be used 2 weeks after being inserted.

Starting dialysis

The appropriate time for starting dialysis remains controversial, especially in elderly patients with multiple comorbid conditions.

The IDEAL study⁹⁹ found no benefit in starting dialysis at a GFR of 10 to 14 mL/min compared with 5 to 7 mL/min. Thus, there is no single estimated GFR at which dialysis should be started. Rather, the development of early uremic symptoms and the patient’s quality of life should guide this decision.^{82,83,99–101}

Hemodialysis involves three sessions per week, each taking about 4 hours. Evidence suggests that longer sessions or more sessions per week may offer benefits, especially in terms of blood pressure, volume, and dietary management. This has led to an increase in the popularity of home and in-center nocturnal hemodialysis programs across the United States.

Peritoneal dialysis?

Peritoneal dialysis is an excellent choice for patients who are motivated, can care for themselves at home, and have a support system available to assist them if needed. It allows for daily dialysis, less fluid restriction, and less dietary restriction, and it gives the patient an opportunity to stay independent. It also spares the veins in the arms, which may be needed for vascular access later in life if hemodialysis is needed.

Recommendation. We recommend that peritoneal dialysis be offered to any suitable patient who is approaching end-stage renal disease.

A COMPREHENSIVE, COLLABORATIVE APPROACH

Chronic kidney disease is a multisystem disorder, and its management requires a comprehensive approach (Table 3). Early detection and interventions are key to reducing cardiovascular events and progression to kidney failure.

Early referral to a nephrologist and team collaboration between the primary care provider, the nephrologist, and other health care providers are essential. Early in the course of CKD, it may be appropriate for a nephrologist to evaluate the patient and recommend a set of treatment goals. Follow-up may be infrequent or unnecessary.

As CKD progresses, especially as the patient reaches an estimated GFR of 30 mL/min/1.73 m², the nephrologist will take a more active role in the patient’s care and medical decision-making. In some circumstances, it may even be appropriate for the nephrologist to be the patient’s source of primary care, with the primary care provider as a consultant.

Caring for patients with CKD includes not only strategies to preserve renal function and prolong survival, but also making critical decisions about starting dialysis and about the need for transplantation. Early involvement of a nephrologist and early preparation for end-stage renal disease with preemptive transplantation and arteriovenous fistula placement are associated with better patient outcomes. Key to this is collaboration between the primary care provider and the nephrologist, with levels of responsibility for patient care that adapt to the patient’s degree of renal dysfunction and other comorbidities. Such strategies to select patients for timely nephrology referral may help improve outcomes in this vulnerable population.