Nephrology

Phosphorus is essential for life. However, both low and high levels of phosphorus in the body have consequences, and its concentration in the blood is tightly regulated through dietary absorption, bone flux, and renal excretion and is influenced by calcitriol (1,25 hydroxyvitamin D₃), parathyroid hormone, and fibroblast growth factor 23 (FGF23).

See related articles by M. Shetty and A. Sekar

Sekar et al,¹ in this issue of the Journal, provide an extensive review of the pathophysiology of phosphorus metabolism and strategies to control phosphorus levels in patients with hyperphosphatemia and end-stage kidney disease.

PHOSPHORUS OR PHOSPHATE?

What's in a name? That which we call a rose
By any other word would smell as sweet.
—Shakespeare, Romeo and Juliet

The terms phosphate and phosphorus are often used interchangeably, though most writers still prefer phosphate over phosphorus.

The serum concentrations of phosphate and phosphorus are the same when expressed in millimoles per liter, as every mole of phosphate contains 1 mole of phosphorus, but not the same when expressed in milligrams per deciliter.² The molecular weight of phosphorus is 30.97, whereas the molecular weight of the phosphate ion (PO₄^3–) is 94.97—more than 3 times higher. Therefore, using these terms interchangeably in this context can lead to numerical error.³

Phosphorus, being highly reactive, does not exist by itself in nature and is typically present as phosphates in biologic systems. When describing phosphorus metabolism, the term phosphates should ideally be used because phosphates are the actual participants in the bodily processes. But in the clinical laboratory, all methods that measure serum phosphorus in fact measure inorganic phosphate and are expressed in terms of milligrams of phosphorus per deciliter rather than milligrams of phosphate per deciliter, and using these 2 terms interchangeably in clinical practice should not be of concern.⁴

THE PROBLEM

US adults typically ingest 1,200 mg of phosphorus each day, and about 60% to 70% of the ingested phosphorus is absorbed both by passive paracellular diffusion via tight junctions and by active transcellular transport via sodium-phosphate cotransport. The kidneys must excrete the same amount daily to maintain a steady state. As kidney function declines, phosphorus accumulates in the blood, leading to hyperphosphatemia.

Hyperphosphatemia is often asymptomatic, but it can cause generalized itching, red eyes, and adverse effects on the bone and parathyroid glands. Higher serum phosphorus levels have been shown to be associated with vascular calcification,⁵ cardiovascular events, and higher all-cause mortality rates in the general population,⁶ in patients with diabetes,⁷ and in those with chronic kidney disease.⁸ This association between higher serum phosphorus levels and the all-cause mortality rate led to the assumption that lowering serum phosphorus levels in these patients could reduce the rates of cardiovascular events and death, and to efforts to correct hyperphosphatemia.

Research into FGF23 continues, especially its role in cardiovascular complications of chronic kidney disease, as both phosphorus and FGF23 levels are elevated in chronic kidney disease and are implicated in poor clinical outcomes in these patients. However, both FGF23 and parathyroid hormone levels rise early in the course of kidney disease, long before overt hyperphosphatemia develops. Further, FGF23 rises earlier than parathyroid hormone and has been found to be an independent risk factor for cardiovascular events and death from any cause in end-stage kidney disease.⁹

Whether hyperphosphatemia is the culprit or merely an epiphenomenon of metabolic complications of chronic kidney disease is still unclear, as more molecules are being identified in the complex process of cardiovascular calcification.¹⁰

However, one thing is clear: vascular calcification is not just a simple precipitation of calcium and phosphorus. Instead, it is an active process that involves many regulators of mineral metabolism.¹⁰ The complex nature of this process is likely one of the reasons that evidence is conflicting¹¹ about the benefits of phosphorus binders in terms of cardiovascular events or all-cause mortality in these patients.

Reducing intake

Dietary phosphorus restriction is the first step in controlling serum phosphorus. But reducing phosphorus intake while otherwise trying to optimize the nutritional status can be challenging.

The recommended daily protein intake is 1.0 to 1.2 g/kg. But phosphorus is typically found in foods rich in proteins, and restricting protein severely can compromise nutritional status and may be as bad as elevated phosphate levels in terms of outcomes.

Although plant-based foods contain more phosphate per gram of protein (ie, they have a higher ratio of phosphorus to protein) than animal-based foods, the bioavailability of phosphorus from plant foods is lower. Phosphorus in plant-based foods is mainly in the form of phytate. Humans cannot hydrolyze phytate because we lack the phytase enzyme; hence, the phosphorus in plant-based foods is not well absorbed. Therefore, a vegetarian diet may be preferable and beneficial in patients with chronic kidney disease. A small study in humans showed that a vegetarian diet resulted in lower serum phosphorus and FGF23 levels, but the study was limited by its small sample size.¹²

Patients should be advised to avoid foods that have a high phosphate content, such as processed foods, fast foods, and cola beverages, which often have phosphate-based food additives.

Further, one should be cautious about using supplements with healthy-sounding names. A case in point is “vitamin water”: 12 oz of this fruit punch-flavored beverage contains 392 mg of phosphorus,¹³ and this alone would require 12 to 15 phosphate binder tablets to bind its phosphorus content.

In addition, many prescription drugs have significant amounts of phosphorus, and this is often unrecognized.

Sherman et al¹⁴ reviewed 200 of the most commonly prescribed drugs in dialysis patients and found that 23 (11.5%) of the drug labels listed phosphorus-containing ingredients, but the actual amount of phosphorus was not listed. The phosphorus content ranged from 1.4 mg (clonidine 0.2 mg, Blue Point Laboratories, Dublin, Ireland) to 111.5 mg (paroxetine 40 mg, GlaxoSmith Kline, Philadelphia, PA). The phosphorus content was inconsistent and varied with the dose of the agent, type of formulation (tablet or syrup), branded or generic formulation, and manufacturer.

Branded lisinopril (Merck, Kenilworth, NJ) had 21.4 mg of phosphorus per 10-mg dose, while a generic product (Blue Point Laboratories, Dublin, Ireland) had 32.6 mg. Different brands of generic amlodipine 10 mg varied in their phosphorus content from 8.6 mg (Lupin Pharmaceuticals, Mumbai, India) to 27.8 mg (Greenstone LLC, Peapack, NJ) to 40.1 mg (Qualitest Pharmaceuticals, Huntsville, AL. Rena-Vite (Cypress Pharmaceuticals, Madison, MS), a multivitamin marketed to patients with kidney disease, had 37.7 mg of phosphorus per tablet. Thus, just to bind the phosphorus content of these 3 tablets (lisinopril, amlodipine, and Rena-Vite), a patient could need at least 3 to 4 extra doses of phosphate binder.

The phosphate content of medications should be considered when prescribing. For example, Reno Caps (Nnodum Pharmaceuticals, Cincinnati, OH), another vitamin supplement, has only 1.7 mg of phosphorus per tablet and should be considered, especially in patients with poorly controlled serum phosphorus levels. However, the challenge is that medication labels do not provide the phosphorus content.

Reducing phosphorus absorption

Although these agents reduce serum phosphorus and help reduce symptoms, an important quality-of-life measure, it is uncertain whether they improve clinical outcomes.¹¹ To date, no specific phosphorus binder offers a survival benefit over placebo.¹¹

Based on the limited and conflicting evidence, the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, recently updated, suggest that oral phosphorus binders should be used in patients with hyperphosphatemia to lower serum phosphorus levels toward the normal range.¹⁵ They further recommend not exceeding 1,500 mg of elemental calcium per day if a calcium-based binder is used, and they recommend avoiding calcium-based binders in patients with hypercalcemia, adynamic bone disease, or vascular calcification.

Phosphorus binders may account for up to 50% of the daily pill burden and may contribute to poor medication adherence.¹⁶ Dialysis patients need to take a lot of these drugs: by weight, 5 to 6 pounds per year.

These drugs can bind and interfere with the absorption of other vital medications and so should be taken with meals and separately from other medications.

Removing phosphorus

Removal of phosphorus by adequate dialysis or kidney transplant is the final strategy.

New agents under study

To improve phosphorus control, other agents that inhibit absorption of phosphate are being investigated.

Nicotinamide reduces expression of the sodium-phosphorus cotransporter NTP2b. Its use in combination with a low-phosphorus diet and phosphorus binders may maximize reductions in phosphorus absorption and is being studied in the CKD Optimal Management With Binders and Nicotinamide (COMBINE) study.

Tenapanor, an inhibitor of the sodium-hydrogen transporter NHE3, has been shown in animal studies to increase fecal phosphate excretion and decrease urinary phosphate excretion17 but requires further evaluation.

Phosphorus is essential for life. However, both low and high levels of phosphorus in the body have consequences, and its concentration in the blood is tightly regulated through dietary absorption, bone flux, and renal excretion and is influenced by calcitriol (1,25 hydroxyvitamin D₃), parathyroid hormone, and fibroblast growth factor 23 (FGF23).

See related articles by M. Shetty and A. Sekar

Sekar et al,¹ in this issue of the Journal, provide an extensive review of the pathophysiology of phosphorus metabolism and strategies to control phosphorus levels in patients with hyperphosphatemia and end-stage kidney disease.

PHOSPHORUS OR PHOSPHATE?

What's in a name? That which we call a rose
By any other word would smell as sweet.
—Shakespeare, Romeo and Juliet

The terms phosphate and phosphorus are often used interchangeably, though most writers still prefer phosphate over phosphorus.

The serum concentrations of phosphate and phosphorus are the same when expressed in millimoles per liter, as every mole of phosphate contains 1 mole of phosphorus, but not the same when expressed in milligrams per deciliter.² The molecular weight of phosphorus is 30.97, whereas the molecular weight of the phosphate ion (PO₄^3–) is 94.97—more than 3 times higher. Therefore, using these terms interchangeably in this context can lead to numerical error.³

Phosphorus, being highly reactive, does not exist by itself in nature and is typically present as phosphates in biologic systems. When describing phosphorus metabolism, the term phosphates should ideally be used because phosphates are the actual participants in the bodily processes. But in the clinical laboratory, all methods that measure serum phosphorus in fact measure inorganic phosphate and are expressed in terms of milligrams of phosphorus per deciliter rather than milligrams of phosphate per deciliter, and using these 2 terms interchangeably in clinical practice should not be of concern.⁴

THE PROBLEM

US adults typically ingest 1,200 mg of phosphorus each day, and about 60% to 70% of the ingested phosphorus is absorbed both by passive paracellular diffusion via tight junctions and by active transcellular transport via sodium-phosphate cotransport. The kidneys must excrete the same amount daily to maintain a steady state. As kidney function declines, phosphorus accumulates in the blood, leading to hyperphosphatemia.

Hyperphosphatemia is often asymptomatic, but it can cause generalized itching, red eyes, and adverse effects on the bone and parathyroid glands. Higher serum phosphorus levels have been shown to be associated with vascular calcification,⁵ cardiovascular events, and higher all-cause mortality rates in the general population,⁶ in patients with diabetes,⁷ and in those with chronic kidney disease.⁸ This association between higher serum phosphorus levels and the all-cause mortality rate led to the assumption that lowering serum phosphorus levels in these patients could reduce the rates of cardiovascular events and death, and to efforts to correct hyperphosphatemia.

Research into FGF23 continues, especially its role in cardiovascular complications of chronic kidney disease, as both phosphorus and FGF23 levels are elevated in chronic kidney disease and are implicated in poor clinical outcomes in these patients. However, both FGF23 and parathyroid hormone levels rise early in the course of kidney disease, long before overt hyperphosphatemia develops. Further, FGF23 rises earlier than parathyroid hormone and has been found to be an independent risk factor for cardiovascular events and death from any cause in end-stage kidney disease.⁹

Whether hyperphosphatemia is the culprit or merely an epiphenomenon of metabolic complications of chronic kidney disease is still unclear, as more molecules are being identified in the complex process of cardiovascular calcification.¹⁰

However, one thing is clear: vascular calcification is not just a simple precipitation of calcium and phosphorus. Instead, it is an active process that involves many regulators of mineral metabolism.¹⁰ The complex nature of this process is likely one of the reasons that evidence is conflicting¹¹ about the benefits of phosphorus binders in terms of cardiovascular events or all-cause mortality in these patients.

Reducing intake

Dietary phosphorus restriction is the first step in controlling serum phosphorus. But reducing phosphorus intake while otherwise trying to optimize the nutritional status can be challenging.

The recommended daily protein intake is 1.0 to 1.2 g/kg. But phosphorus is typically found in foods rich in proteins, and restricting protein severely can compromise nutritional status and may be as bad as elevated phosphate levels in terms of outcomes.

Although plant-based foods contain more phosphate per gram of protein (ie, they have a higher ratio of phosphorus to protein) than animal-based foods, the bioavailability of phosphorus from plant foods is lower. Phosphorus in plant-based foods is mainly in the form of phytate. Humans cannot hydrolyze phytate because we lack the phytase enzyme; hence, the phosphorus in plant-based foods is not well absorbed. Therefore, a vegetarian diet may be preferable and beneficial in patients with chronic kidney disease. A small study in humans showed that a vegetarian diet resulted in lower serum phosphorus and FGF23 levels, but the study was limited by its small sample size.¹²

Patients should be advised to avoid foods that have a high phosphate content, such as processed foods, fast foods, and cola beverages, which often have phosphate-based food additives.

Further, one should be cautious about using supplements with healthy-sounding names. A case in point is “vitamin water”: 12 oz of this fruit punch-flavored beverage contains 392 mg of phosphorus,¹³ and this alone would require 12 to 15 phosphate binder tablets to bind its phosphorus content.

In addition, many prescription drugs have significant amounts of phosphorus, and this is often unrecognized.

Sherman et al¹⁴ reviewed 200 of the most commonly prescribed drugs in dialysis patients and found that 23 (11.5%) of the drug labels listed phosphorus-containing ingredients, but the actual amount of phosphorus was not listed. The phosphorus content ranged from 1.4 mg (clonidine 0.2 mg, Blue Point Laboratories, Dublin, Ireland) to 111.5 mg (paroxetine 40 mg, GlaxoSmith Kline, Philadelphia, PA). The phosphorus content was inconsistent and varied with the dose of the agent, type of formulation (tablet or syrup), branded or generic formulation, and manufacturer.

Branded lisinopril (Merck, Kenilworth, NJ) had 21.4 mg of phosphorus per 10-mg dose, while a generic product (Blue Point Laboratories, Dublin, Ireland) had 32.6 mg. Different brands of generic amlodipine 10 mg varied in their phosphorus content from 8.6 mg (Lupin Pharmaceuticals, Mumbai, India) to 27.8 mg (Greenstone LLC, Peapack, NJ) to 40.1 mg (Qualitest Pharmaceuticals, Huntsville, AL. Rena-Vite (Cypress Pharmaceuticals, Madison, MS), a multivitamin marketed to patients with kidney disease, had 37.7 mg of phosphorus per tablet. Thus, just to bind the phosphorus content of these 3 tablets (lisinopril, amlodipine, and Rena-Vite), a patient could need at least 3 to 4 extra doses of phosphate binder.

The phosphate content of medications should be considered when prescribing. For example, Reno Caps (Nnodum Pharmaceuticals, Cincinnati, OH), another vitamin supplement, has only 1.7 mg of phosphorus per tablet and should be considered, especially in patients with poorly controlled serum phosphorus levels. However, the challenge is that medication labels do not provide the phosphorus content.

Reducing phosphorus absorption

Although these agents reduce serum phosphorus and help reduce symptoms, an important quality-of-life measure, it is uncertain whether they improve clinical outcomes.¹¹ To date, no specific phosphorus binder offers a survival benefit over placebo.¹¹

Based on the limited and conflicting evidence, the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, recently updated, suggest that oral phosphorus binders should be used in patients with hyperphosphatemia to lower serum phosphorus levels toward the normal range.¹⁵ They further recommend not exceeding 1,500 mg of elemental calcium per day if a calcium-based binder is used, and they recommend avoiding calcium-based binders in patients with hypercalcemia, adynamic bone disease, or vascular calcification.

Phosphorus binders may account for up to 50% of the daily pill burden and may contribute to poor medication adherence.¹⁶ Dialysis patients need to take a lot of these drugs: by weight, 5 to 6 pounds per year.

These drugs can bind and interfere with the absorption of other vital medications and so should be taken with meals and separately from other medications.

Removing phosphorus

Removal of phosphorus by adequate dialysis or kidney transplant is the final strategy.

New agents under study

To improve phosphorus control, other agents that inhibit absorption of phosphate are being investigated.

Nicotinamide reduces expression of the sodium-phosphorus cotransporter NTP2b. Its use in combination with a low-phosphorus diet and phosphorus binders may maximize reductions in phosphorus absorption and is being studied in the CKD Optimal Management With Binders and Nicotinamide (COMBINE) study.

Tenapanor, an inhibitor of the sodium-hydrogen transporter NHE3, has been shown in animal studies to increase fecal phosphate excretion and decrease urinary phosphate excretion17 but requires further evaluation.

Phosphorus is essential for life. However, both low and high levels of phosphorus in the body have consequences, and its concentration in the blood is tightly regulated through dietary absorption, bone flux, and renal excretion and is influenced by calcitriol (1,25 hydroxyvitamin D₃), parathyroid hormone, and fibroblast growth factor 23 (FGF23).

See related articles by M. Shetty and A. Sekar

Sekar et al,¹ in this issue of the Journal, provide an extensive review of the pathophysiology of phosphorus metabolism and strategies to control phosphorus levels in patients with hyperphosphatemia and end-stage kidney disease.

PHOSPHORUS OR PHOSPHATE?

What's in a name? That which we call a rose
By any other word would smell as sweet.
—Shakespeare, Romeo and Juliet

The terms phosphate and phosphorus are often used interchangeably, though most writers still prefer phosphate over phosphorus.

The serum concentrations of phosphate and phosphorus are the same when expressed in millimoles per liter, as every mole of phosphate contains 1 mole of phosphorus, but not the same when expressed in milligrams per deciliter.² The molecular weight of phosphorus is 30.97, whereas the molecular weight of the phosphate ion (PO₄^3–) is 94.97—more than 3 times higher. Therefore, using these terms interchangeably in this context can lead to numerical error.³

Phosphorus, being highly reactive, does not exist by itself in nature and is typically present as phosphates in biologic systems. When describing phosphorus metabolism, the term phosphates should ideally be used because phosphates are the actual participants in the bodily processes. But in the clinical laboratory, all methods that measure serum phosphorus in fact measure inorganic phosphate and are expressed in terms of milligrams of phosphorus per deciliter rather than milligrams of phosphate per deciliter, and using these 2 terms interchangeably in clinical practice should not be of concern.⁴

THE PROBLEM

US adults typically ingest 1,200 mg of phosphorus each day, and about 60% to 70% of the ingested phosphorus is absorbed both by passive paracellular diffusion via tight junctions and by active transcellular transport via sodium-phosphate cotransport. The kidneys must excrete the same amount daily to maintain a steady state. As kidney function declines, phosphorus accumulates in the blood, leading to hyperphosphatemia.

Hyperphosphatemia is often asymptomatic, but it can cause generalized itching, red eyes, and adverse effects on the bone and parathyroid glands. Higher serum phosphorus levels have been shown to be associated with vascular calcification,⁵ cardiovascular events, and higher all-cause mortality rates in the general population,⁶ in patients with diabetes,⁷ and in those with chronic kidney disease.⁸ This association between higher serum phosphorus levels and the all-cause mortality rate led to the assumption that lowering serum phosphorus levels in these patients could reduce the rates of cardiovascular events and death, and to efforts to correct hyperphosphatemia.

Research into FGF23 continues, especially its role in cardiovascular complications of chronic kidney disease, as both phosphorus and FGF23 levels are elevated in chronic kidney disease and are implicated in poor clinical outcomes in these patients. However, both FGF23 and parathyroid hormone levels rise early in the course of kidney disease, long before overt hyperphosphatemia develops. Further, FGF23 rises earlier than parathyroid hormone and has been found to be an independent risk factor for cardiovascular events and death from any cause in end-stage kidney disease.⁹

Whether hyperphosphatemia is the culprit or merely an epiphenomenon of metabolic complications of chronic kidney disease is still unclear, as more molecules are being identified in the complex process of cardiovascular calcification.¹⁰

However, one thing is clear: vascular calcification is not just a simple precipitation of calcium and phosphorus. Instead, it is an active process that involves many regulators of mineral metabolism.¹⁰ The complex nature of this process is likely one of the reasons that evidence is conflicting¹¹ about the benefits of phosphorus binders in terms of cardiovascular events or all-cause mortality in these patients.

Reducing intake

Dietary phosphorus restriction is the first step in controlling serum phosphorus. But reducing phosphorus intake while otherwise trying to optimize the nutritional status can be challenging.

The recommended daily protein intake is 1.0 to 1.2 g/kg. But phosphorus is typically found in foods rich in proteins, and restricting protein severely can compromise nutritional status and may be as bad as elevated phosphate levels in terms of outcomes.

Although plant-based foods contain more phosphate per gram of protein (ie, they have a higher ratio of phosphorus to protein) than animal-based foods, the bioavailability of phosphorus from plant foods is lower. Phosphorus in plant-based foods is mainly in the form of phytate. Humans cannot hydrolyze phytate because we lack the phytase enzyme; hence, the phosphorus in plant-based foods is not well absorbed. Therefore, a vegetarian diet may be preferable and beneficial in patients with chronic kidney disease. A small study in humans showed that a vegetarian diet resulted in lower serum phosphorus and FGF23 levels, but the study was limited by its small sample size.¹²

Patients should be advised to avoid foods that have a high phosphate content, such as processed foods, fast foods, and cola beverages, which often have phosphate-based food additives.

Further, one should be cautious about using supplements with healthy-sounding names. A case in point is “vitamin water”: 12 oz of this fruit punch-flavored beverage contains 392 mg of phosphorus,¹³ and this alone would require 12 to 15 phosphate binder tablets to bind its phosphorus content.

In addition, many prescription drugs have significant amounts of phosphorus, and this is often unrecognized.

Sherman et al¹⁴ reviewed 200 of the most commonly prescribed drugs in dialysis patients and found that 23 (11.5%) of the drug labels listed phosphorus-containing ingredients, but the actual amount of phosphorus was not listed. The phosphorus content ranged from 1.4 mg (clonidine 0.2 mg, Blue Point Laboratories, Dublin, Ireland) to 111.5 mg (paroxetine 40 mg, GlaxoSmith Kline, Philadelphia, PA). The phosphorus content was inconsistent and varied with the dose of the agent, type of formulation (tablet or syrup), branded or generic formulation, and manufacturer.

Branded lisinopril (Merck, Kenilworth, NJ) had 21.4 mg of phosphorus per 10-mg dose, while a generic product (Blue Point Laboratories, Dublin, Ireland) had 32.6 mg. Different brands of generic amlodipine 10 mg varied in their phosphorus content from 8.6 mg (Lupin Pharmaceuticals, Mumbai, India) to 27.8 mg (Greenstone LLC, Peapack, NJ) to 40.1 mg (Qualitest Pharmaceuticals, Huntsville, AL. Rena-Vite (Cypress Pharmaceuticals, Madison, MS), a multivitamin marketed to patients with kidney disease, had 37.7 mg of phosphorus per tablet. Thus, just to bind the phosphorus content of these 3 tablets (lisinopril, amlodipine, and Rena-Vite), a patient could need at least 3 to 4 extra doses of phosphate binder.

The phosphate content of medications should be considered when prescribing. For example, Reno Caps (Nnodum Pharmaceuticals, Cincinnati, OH), another vitamin supplement, has only 1.7 mg of phosphorus per tablet and should be considered, especially in patients with poorly controlled serum phosphorus levels. However, the challenge is that medication labels do not provide the phosphorus content.

Reducing phosphorus absorption

Although these agents reduce serum phosphorus and help reduce symptoms, an important quality-of-life measure, it is uncertain whether they improve clinical outcomes.¹¹ To date, no specific phosphorus binder offers a survival benefit over placebo.¹¹

Based on the limited and conflicting evidence, the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, recently updated, suggest that oral phosphorus binders should be used in patients with hyperphosphatemia to lower serum phosphorus levels toward the normal range.¹⁵ They further recommend not exceeding 1,500 mg of elemental calcium per day if a calcium-based binder is used, and they recommend avoiding calcium-based binders in patients with hypercalcemia, adynamic bone disease, or vascular calcification.

Phosphorus binders may account for up to 50% of the daily pill burden and may contribute to poor medication adherence.¹⁶ Dialysis patients need to take a lot of these drugs: by weight, 5 to 6 pounds per year.

These drugs can bind and interfere with the absorption of other vital medications and so should be taken with meals and separately from other medications.

Removing phosphorus

Removal of phosphorus by adequate dialysis or kidney transplant is the final strategy.

New agents under study

To improve phosphorus control, other agents that inhibit absorption of phosphate are being investigated.

Nicotinamide reduces expression of the sodium-phosphorus cotransporter NTP2b. Its use in combination with a low-phosphorus diet and phosphorus binders may maximize reductions in phosphorus absorption and is being studied in the CKD Optimal Management With Binders and Nicotinamide (COMBINE) study.

Tenapanor, an inhibitor of the sodium-hydrogen transporter NHE3, has been shown in animal studies to increase fecal phosphate excretion and decrease urinary phosphate excretion17 but requires further evaluation.

A 51-year-old man with end-stage renal disease, on peritoneal dialysis for the past 4 years, presented to the emergency department with severe pain in both legs. The pain had started 2 months previously and had progressively worsened. After multiple admissions in the past for hyperkalemia and volume overload due to noncompliance, he had been advised to switch to hemodialysis.

See related article and editorial

Laboratory analysis revealed the following values:

• Serum creatinine 12.62 mg/dL (reference range 0.73–1.22)
• Blood urea nitrogen 159 mg/dL (9–24)
• Serum calcium corrected for serum albumin 8.1 mg/dL (8.4–10.0)
• Serum phosphorus 10.6 mg/dL (2.7–4.8).

His history of end-stage renal disease, failure of peritoneal dialysis, high calcium-phosphorus product (8.1 mg/dL × 10.6 mg/dL = 85.9 mg²/dL ², reference range ≤ 55), and characteristic physical findings led to the diagnosis of calcific uremic arteriolopathy.

CALCIFIC UREMIC ARTERIOLOPATHY

Calcific uremic arteriolopathy or “calciphylaxis,” seen most often in patients with end-stage renal disease, is caused by calcium deposition in the media of the dermo-hypodermic arterioles, leading to infarction of adjacent tissue.^1–3 A high calcium-phosphorus product (> 55) has been implicated in its development; however, the calcium-phosphorus product can be normal despite hyperphosphatemia, which itself may promote ectopic calcification.

Early ischemic manifestations include livedo reticularis and painful retiform purpura on the thighs and other areas of high adiposity. Lesions evolve into violaceous plaquelike subcutaneous nodules that can infarct, become necrotic, ulcerate, and become infected. Punch biopsy demonstrating arteriolar calcification, subintimal fibrosis, and thrombosis confirms the diagnosis.

Differential diagnosis

Warfarin necrosis can cause large, irregular, bloody bullae that ulcerate and turn into eschar that may resemble lesions of calcific uremic arteriolopathy. Our patient, however, had no exposure to warfarin.

Pemphigus foliaceus, an immunoglobulin G4-mediated autoimmune disorder targeted against desmoglein-1, leads to the formation of fragile blisters that easily rupture when rubbed (Nikolsky sign). Lesions evolve into scaling, crusty erosions on an erythematous base. With tender blisters and lack of mucous membrane involvement, pemphigus foliaceus shares similarities with calcific uremic arteriolopathy, but the presence of necrotic eschar surrounded by violaceous plaques in our patient made it an unlikely diagnosis.

Cryofibrinogenemia. In the right clinical scenario, ie, in a patient with vasculitis, malignancy, infection, cryoglobulinemia, or collagen diseases, cryofibrinogen-mediated cold-induced occlusive lesions may mimic calcific uremic arteriolopathy, with painful or pruritic erythema, purpura, livedo reticularis, necrosis, and ulceration.⁴ Our patient had no color changes with exposure to cold, nor any history of Raynaud phenomenon or joint pain, making the diagnosis of cryofibrinogenemia less likely.

Nephrogenic systemic fibrosis. Gadolinium contrast medium in magnetic resonance imaging can cause nephrogenic systemic fibrosis, characterized by erythematous papules that coalesce into brawny plaques with surrounding woody induration, which may resemble lesions of calcific uremic arteriolopathy.⁵ However, our patient had not been exposed to gadolinium.

Management

Management is multidisciplinary and includes the following¹:

• Hemodialysis, modified to optimize calcium balance²
• Intravenous sodium thiosulfate: the exact mechanism of action remains unclear, but it is thought to play a role in chelating calcium from tissue deposits, thus decreasing pain and promoting regression of skin lesions³
• Wound care, including chemical debridement agents, negative-pressure wound therapy, and surgical debridement for infected wounds⁶
• Pain management with opioid analgesics.

The patient was treated with all these measures. However, he died of sudden cardiac arrest during the same admission.

A 51-year-old man with end-stage renal disease, on peritoneal dialysis for the past 4 years, presented to the emergency department with severe pain in both legs. The pain had started 2 months previously and had progressively worsened. After multiple admissions in the past for hyperkalemia and volume overload due to noncompliance, he had been advised to switch to hemodialysis.

See related article and editorial

Laboratory analysis revealed the following values:

• Serum creatinine 12.62 mg/dL (reference range 0.73–1.22)
• Blood urea nitrogen 159 mg/dL (9–24)
• Serum calcium corrected for serum albumin 8.1 mg/dL (8.4–10.0)
• Serum phosphorus 10.6 mg/dL (2.7–4.8).

His history of end-stage renal disease, failure of peritoneal dialysis, high calcium-phosphorus product (8.1 mg/dL × 10.6 mg/dL = 85.9 mg²/dL ², reference range ≤ 55), and characteristic physical findings led to the diagnosis of calcific uremic arteriolopathy.

CALCIFIC UREMIC ARTERIOLOPATHY

Calcific uremic arteriolopathy or “calciphylaxis,” seen most often in patients with end-stage renal disease, is caused by calcium deposition in the media of the dermo-hypodermic arterioles, leading to infarction of adjacent tissue.^1–3 A high calcium-phosphorus product (> 55) has been implicated in its development; however, the calcium-phosphorus product can be normal despite hyperphosphatemia, which itself may promote ectopic calcification.

Early ischemic manifestations include livedo reticularis and painful retiform purpura on the thighs and other areas of high adiposity. Lesions evolve into violaceous plaquelike subcutaneous nodules that can infarct, become necrotic, ulcerate, and become infected. Punch biopsy demonstrating arteriolar calcification, subintimal fibrosis, and thrombosis confirms the diagnosis.

Differential diagnosis

Warfarin necrosis can cause large, irregular, bloody bullae that ulcerate and turn into eschar that may resemble lesions of calcific uremic arteriolopathy. Our patient, however, had no exposure to warfarin.

Pemphigus foliaceus, an immunoglobulin G4-mediated autoimmune disorder targeted against desmoglein-1, leads to the formation of fragile blisters that easily rupture when rubbed (Nikolsky sign). Lesions evolve into scaling, crusty erosions on an erythematous base. With tender blisters and lack of mucous membrane involvement, pemphigus foliaceus shares similarities with calcific uremic arteriolopathy, but the presence of necrotic eschar surrounded by violaceous plaques in our patient made it an unlikely diagnosis.

Cryofibrinogenemia. In the right clinical scenario, ie, in a patient with vasculitis, malignancy, infection, cryoglobulinemia, or collagen diseases, cryofibrinogen-mediated cold-induced occlusive lesions may mimic calcific uremic arteriolopathy, with painful or pruritic erythema, purpura, livedo reticularis, necrosis, and ulceration.⁴ Our patient had no color changes with exposure to cold, nor any history of Raynaud phenomenon or joint pain, making the diagnosis of cryofibrinogenemia less likely.

Nephrogenic systemic fibrosis. Gadolinium contrast medium in magnetic resonance imaging can cause nephrogenic systemic fibrosis, characterized by erythematous papules that coalesce into brawny plaques with surrounding woody induration, which may resemble lesions of calcific uremic arteriolopathy.⁵ However, our patient had not been exposed to gadolinium.

Management

Management is multidisciplinary and includes the following¹:

• Hemodialysis, modified to optimize calcium balance²
• Intravenous sodium thiosulfate: the exact mechanism of action remains unclear, but it is thought to play a role in chelating calcium from tissue deposits, thus decreasing pain and promoting regression of skin lesions³
• Wound care, including chemical debridement agents, negative-pressure wound therapy, and surgical debridement for infected wounds⁶
• Pain management with opioid analgesics.

The patient was treated with all these measures. However, he died of sudden cardiac arrest during the same admission.

A 51-year-old man with end-stage renal disease, on peritoneal dialysis for the past 4 years, presented to the emergency department with severe pain in both legs. The pain had started 2 months previously and had progressively worsened. After multiple admissions in the past for hyperkalemia and volume overload due to noncompliance, he had been advised to switch to hemodialysis.

See related article and editorial

Laboratory analysis revealed the following values:

• Serum creatinine 12.62 mg/dL (reference range 0.73–1.22)
• Blood urea nitrogen 159 mg/dL (9–24)
• Serum calcium corrected for serum albumin 8.1 mg/dL (8.4–10.0)
• Serum phosphorus 10.6 mg/dL (2.7–4.8).

His history of end-stage renal disease, failure of peritoneal dialysis, high calcium-phosphorus product (8.1 mg/dL × 10.6 mg/dL = 85.9 mg²/dL ², reference range ≤ 55), and characteristic physical findings led to the diagnosis of calcific uremic arteriolopathy.

CALCIFIC UREMIC ARTERIOLOPATHY

Calcific uremic arteriolopathy or “calciphylaxis,” seen most often in patients with end-stage renal disease, is caused by calcium deposition in the media of the dermo-hypodermic arterioles, leading to infarction of adjacent tissue.^1–3 A high calcium-phosphorus product (> 55) has been implicated in its development; however, the calcium-phosphorus product can be normal despite hyperphosphatemia, which itself may promote ectopic calcification.

Early ischemic manifestations include livedo reticularis and painful retiform purpura on the thighs and other areas of high adiposity. Lesions evolve into violaceous plaquelike subcutaneous nodules that can infarct, become necrotic, ulcerate, and become infected. Punch biopsy demonstrating arteriolar calcification, subintimal fibrosis, and thrombosis confirms the diagnosis.

Differential diagnosis

Warfarin necrosis can cause large, irregular, bloody bullae that ulcerate and turn into eschar that may resemble lesions of calcific uremic arteriolopathy. Our patient, however, had no exposure to warfarin.

Pemphigus foliaceus, an immunoglobulin G4-mediated autoimmune disorder targeted against desmoglein-1, leads to the formation of fragile blisters that easily rupture when rubbed (Nikolsky sign). Lesions evolve into scaling, crusty erosions on an erythematous base. With tender blisters and lack of mucous membrane involvement, pemphigus foliaceus shares similarities with calcific uremic arteriolopathy, but the presence of necrotic eschar surrounded by violaceous plaques in our patient made it an unlikely diagnosis.

Cryofibrinogenemia. In the right clinical scenario, ie, in a patient with vasculitis, malignancy, infection, cryoglobulinemia, or collagen diseases, cryofibrinogen-mediated cold-induced occlusive lesions may mimic calcific uremic arteriolopathy, with painful or pruritic erythema, purpura, livedo reticularis, necrosis, and ulceration.⁴ Our patient had no color changes with exposure to cold, nor any history of Raynaud phenomenon or joint pain, making the diagnosis of cryofibrinogenemia less likely.

Nephrogenic systemic fibrosis. Gadolinium contrast medium in magnetic resonance imaging can cause nephrogenic systemic fibrosis, characterized by erythematous papules that coalesce into brawny plaques with surrounding woody induration, which may resemble lesions of calcific uremic arteriolopathy.⁵ However, our patient had not been exposed to gadolinium.

Management

Management is multidisciplinary and includes the following¹:

• Hemodialysis, modified to optimize calcium balance²
• Intravenous sodium thiosulfate: the exact mechanism of action remains unclear, but it is thought to play a role in chelating calcium from tissue deposits, thus decreasing pain and promoting regression of skin lesions³
• Wound care, including chemical debridement agents, negative-pressure wound therapy, and surgical debridement for infected wounds⁶
• Pain management with opioid analgesics.

The patient was treated with all these measures. However, he died of sudden cardiac arrest during the same admission.

MALMO, SWEDEN – Ultrasound of the kidneys and urinary tract in the acute phase of a first urinary tract infection in young children has an unacceptably high false-positive rate, Magdalena Okarska-Napierala, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“Sonography performed 2 weeks after treatment initiation seems to be more reliable,” said Dr. Okarska-Napierala, a pediatrician at the Medical University of Warsaw Children’s Hospital.

Broad agreement exists that imaging is warranted in all children with a first urinary tract infection (UTI), because this infection can be the first signal of a structural abnormality of the kidneys or urinary tract. Abdominal ultrasound is the first-choice imaging modality in this setting because it is noninvasive, widely available, and inexpensive. But there remains controversy – and guidelines differ – regarding when to perform the ultrasound in children with UTI who respond well to therapy. This was the impetus for Dr. Okarska-Napierala and her coinvestigators to launch a prospective, single-center study examining the issue.

“The theory beneath it is the possibility that diffuse inflammation affects the ultrasound picture of the kidneys and urinary tract and may give us false-positive results, so we shouldn’t base our decisions on those results,” she explained.

This theory has been provisionally confirmed by the preliminary results of the study, which is continuing to enroll patients.

To date, the study includes 48 children, mean age 10.4 months, hospitalized for their first UTI. Participation was restricted to patients with no known congenital abnormalities of the kidneys or urinary tract and who were not on antibiotics at enrollment. Of the 48 children, 44 had an Escherichia coli infection. The predominant treatment was a second-generation cephalosporin for a median of 10 days.

On day 1 of treatment all patients underwent an ultrasound exam evaluating kidney size, anterior-posterior renal pelvis diameter, and the urinary tract based upon a grading system for urinary tract dilation developed by multidisciplinary consensus (J Pediatr Urol. 2014 Dec;10[6]:982-98). The ultrasound exam was repeated 2 weeks later, and again 2 weeks after that.

The most striking findings were a significantly increased kidney size and more prevalent urinary tract dilation on the day 1 ultrasound exam than on repeat ultrasound 2 weeks later. The average length of the left and right kidneys was 67.0 and 64.5 mm, respectively, on day 1, dropping off to 64.3 and 62.0 mm at 2 weeks, with a smaller and statistically nonsignificant further drop-off to 61.9 and 60.0 mm on the week 4 ultrasound.

“We saw a strong correlation between initial kidney size and CRP [C-reactive protein] value: The higher the CRP you have initially, the bigger the kidneys. It’s an interesting finding, but not so very practical. The only practical conclusion is that if we perform ultrasound at this stage and the child has big kidneys, it doesn’t mean anything. We have to check it again later,” she said.

Also, the number of renal units with urinary tract dilation went from 29 on day 1 ultrasound to 20 at 2 weeks and 19 at 4 weeks. Of the 48 children, 28 had urinary tract dilation on day 1, compared with 18 at 2 weeks and 16 at 4 weeks.

“If we look at this practically, if we base our decision on the day 1 ultrasound we would qualify half of all children for voiding cystourethrography, which is harmful, but if we wait 2 weeks to do the ultrasound we would reduce this number by six children. So I think we can call this a clinically significant difference,” she continued.

Of the 48 children, 11 have undergone voiding cystourethrography, revealing 2 mild cases of vesicoureteral reflux, which is the most common congenital abnormality of the urinary tract.

“I would like to emphasize that there is no real benefit in performing an ultrasound exam in children in this acute phase of infection. And there is harm in that we have to repeat the exam later, the parents are worried, the doctor is worried,” Dr. Okarska-Napierala concluded.

She reported having no relevant financial conflicts, and the study was conducted free of commercial support.

[email protected]

MALMO, SWEDEN – Ultrasound of the kidneys and urinary tract in the acute phase of a first urinary tract infection in young children has an unacceptably high false-positive rate, Magdalena Okarska-Napierala, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“Sonography performed 2 weeks after treatment initiation seems to be more reliable,” said Dr. Okarska-Napierala, a pediatrician at the Medical University of Warsaw Children’s Hospital.

Broad agreement exists that imaging is warranted in all children with a first urinary tract infection (UTI), because this infection can be the first signal of a structural abnormality of the kidneys or urinary tract. Abdominal ultrasound is the first-choice imaging modality in this setting because it is noninvasive, widely available, and inexpensive. But there remains controversy – and guidelines differ – regarding when to perform the ultrasound in children with UTI who respond well to therapy. This was the impetus for Dr. Okarska-Napierala and her coinvestigators to launch a prospective, single-center study examining the issue.

“The theory beneath it is the possibility that diffuse inflammation affects the ultrasound picture of the kidneys and urinary tract and may give us false-positive results, so we shouldn’t base our decisions on those results,” she explained.

This theory has been provisionally confirmed by the preliminary results of the study, which is continuing to enroll patients.

To date, the study includes 48 children, mean age 10.4 months, hospitalized for their first UTI. Participation was restricted to patients with no known congenital abnormalities of the kidneys or urinary tract and who were not on antibiotics at enrollment. Of the 48 children, 44 had an Escherichia coli infection. The predominant treatment was a second-generation cephalosporin for a median of 10 days.

On day 1 of treatment all patients underwent an ultrasound exam evaluating kidney size, anterior-posterior renal pelvis diameter, and the urinary tract based upon a grading system for urinary tract dilation developed by multidisciplinary consensus (J Pediatr Urol. 2014 Dec;10[6]:982-98). The ultrasound exam was repeated 2 weeks later, and again 2 weeks after that.

The most striking findings were a significantly increased kidney size and more prevalent urinary tract dilation on the day 1 ultrasound exam than on repeat ultrasound 2 weeks later. The average length of the left and right kidneys was 67.0 and 64.5 mm, respectively, on day 1, dropping off to 64.3 and 62.0 mm at 2 weeks, with a smaller and statistically nonsignificant further drop-off to 61.9 and 60.0 mm on the week 4 ultrasound.

“We saw a strong correlation between initial kidney size and CRP [C-reactive protein] value: The higher the CRP you have initially, the bigger the kidneys. It’s an interesting finding, but not so very practical. The only practical conclusion is that if we perform ultrasound at this stage and the child has big kidneys, it doesn’t mean anything. We have to check it again later,” she said.

Also, the number of renal units with urinary tract dilation went from 29 on day 1 ultrasound to 20 at 2 weeks and 19 at 4 weeks. Of the 48 children, 28 had urinary tract dilation on day 1, compared with 18 at 2 weeks and 16 at 4 weeks.

“If we look at this practically, if we base our decision on the day 1 ultrasound we would qualify half of all children for voiding cystourethrography, which is harmful, but if we wait 2 weeks to do the ultrasound we would reduce this number by six children. So I think we can call this a clinically significant difference,” she continued.

Of the 48 children, 11 have undergone voiding cystourethrography, revealing 2 mild cases of vesicoureteral reflux, which is the most common congenital abnormality of the urinary tract.

“I would like to emphasize that there is no real benefit in performing an ultrasound exam in children in this acute phase of infection. And there is harm in that we have to repeat the exam later, the parents are worried, the doctor is worried,” Dr. Okarska-Napierala concluded.

She reported having no relevant financial conflicts, and the study was conducted free of commercial support.

[email protected]

MALMO, SWEDEN – Ultrasound of the kidneys and urinary tract in the acute phase of a first urinary tract infection in young children has an unacceptably high false-positive rate, Magdalena Okarska-Napierala, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“Sonography performed 2 weeks after treatment initiation seems to be more reliable,” said Dr. Okarska-Napierala, a pediatrician at the Medical University of Warsaw Children’s Hospital.

Broad agreement exists that imaging is warranted in all children with a first urinary tract infection (UTI), because this infection can be the first signal of a structural abnormality of the kidneys or urinary tract. Abdominal ultrasound is the first-choice imaging modality in this setting because it is noninvasive, widely available, and inexpensive. But there remains controversy – and guidelines differ – regarding when to perform the ultrasound in children with UTI who respond well to therapy. This was the impetus for Dr. Okarska-Napierala and her coinvestigators to launch a prospective, single-center study examining the issue.

“The theory beneath it is the possibility that diffuse inflammation affects the ultrasound picture of the kidneys and urinary tract and may give us false-positive results, so we shouldn’t base our decisions on those results,” she explained.

This theory has been provisionally confirmed by the preliminary results of the study, which is continuing to enroll patients.

To date, the study includes 48 children, mean age 10.4 months, hospitalized for their first UTI. Participation was restricted to patients with no known congenital abnormalities of the kidneys or urinary tract and who were not on antibiotics at enrollment. Of the 48 children, 44 had an Escherichia coli infection. The predominant treatment was a second-generation cephalosporin for a median of 10 days.

On day 1 of treatment all patients underwent an ultrasound exam evaluating kidney size, anterior-posterior renal pelvis diameter, and the urinary tract based upon a grading system for urinary tract dilation developed by multidisciplinary consensus (J Pediatr Urol. 2014 Dec;10[6]:982-98). The ultrasound exam was repeated 2 weeks later, and again 2 weeks after that.

The most striking findings were a significantly increased kidney size and more prevalent urinary tract dilation on the day 1 ultrasound exam than on repeat ultrasound 2 weeks later. The average length of the left and right kidneys was 67.0 and 64.5 mm, respectively, on day 1, dropping off to 64.3 and 62.0 mm at 2 weeks, with a smaller and statistically nonsignificant further drop-off to 61.9 and 60.0 mm on the week 4 ultrasound.

“We saw a strong correlation between initial kidney size and CRP [C-reactive protein] value: The higher the CRP you have initially, the bigger the kidneys. It’s an interesting finding, but not so very practical. The only practical conclusion is that if we perform ultrasound at this stage and the child has big kidneys, it doesn’t mean anything. We have to check it again later,” she said.

Also, the number of renal units with urinary tract dilation went from 29 on day 1 ultrasound to 20 at 2 weeks and 19 at 4 weeks. Of the 48 children, 28 had urinary tract dilation on day 1, compared with 18 at 2 weeks and 16 at 4 weeks.

“If we look at this practically, if we base our decision on the day 1 ultrasound we would qualify half of all children for voiding cystourethrography, which is harmful, but if we wait 2 weeks to do the ultrasound we would reduce this number by six children. So I think we can call this a clinically significant difference,” she continued.

Of the 48 children, 11 have undergone voiding cystourethrography, revealing 2 mild cases of vesicoureteral reflux, which is the most common congenital abnormality of the urinary tract.

“I would like to emphasize that there is no real benefit in performing an ultrasound exam in children in this acute phase of infection. And there is harm in that we have to repeat the exam later, the parents are worried, the doctor is worried,” Dr. Okarska-Napierala concluded.

She reported having no relevant financial conflicts, and the study was conducted free of commercial support.

[email protected]

Evidence-based recommendations for appropriate nephrology testing in children are the latest installment of the American Board of Internal Medicine Foundation’s “Choosing Wisely” campaign.

[email protected]

Evidence-based recommendations for appropriate nephrology testing in children are the latest installment of the American Board of Internal Medicine Foundation’s “Choosing Wisely” campaign.

[email protected]

Evidence-based recommendations for appropriate nephrology testing in children are the latest installment of the American Board of Internal Medicine Foundation’s “Choosing Wisely” campaign.

[email protected]

The CREDENCE trial, which was investigating whether the antidiabetes drug canagliflozin (Invokana) plus standard of care could safely help prevent or slow chronic kidney disease (CKD) in patients with type 2 diabetes, has been ended early because it has already achieved prespecified efficacy criteria, Janssen announced in a press release. These criteria included risk reduction in the composite endpoint of time to dialysis or kidney transplant, doubling of serum creatinine, and renal or cardiovascular death.

In CANVAS, the cardiovascular outcomes trial for canagliflozin, treatment was linked to reductions in progression of albuminuria and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal replacement therapy, or death from renal causes, compared with placebo, but those didn’t reach statistical significance.

CREDENCE (Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial that enrolled roughly 4,400 patients with type 2 diabetes and established kidney disease who had been receiving ACE inhibitors or angiotensin II receptor blockers for at least 4 weeks prior to randomization.

The decision to halt CREDENCE came about after a review of data by the study’s independent data monitoring committee during a planned interim analysis. The resulting recommendation was based on the efficacy findings, the exact data for which have not yet been released.

Canagliflozin, a sodium-glucose transporter 2 (SGLT2) inhibitor, in conjunction with diet and exercise, can help improve glycemic control. In the context of kidney disease and type 2 diabetes, canagliflozin has been associated with increased risk of dehydration, vaginal or penile yeast infections, and amputations of all or part of the foot or leg. It has also been associated with ketoacidosis, kidney problems, hyperkalemia, hypoglycemia, and urinary tract infections.

More information can be found in the press release. Full prescribing information can be found on the Food and Drug Administration website.

[email protected]

The CREDENCE trial, which was investigating whether the antidiabetes drug canagliflozin (Invokana) plus standard of care could safely help prevent or slow chronic kidney disease (CKD) in patients with type 2 diabetes, has been ended early because it has already achieved prespecified efficacy criteria, Janssen announced in a press release. These criteria included risk reduction in the composite endpoint of time to dialysis or kidney transplant, doubling of serum creatinine, and renal or cardiovascular death.

In CANVAS, the cardiovascular outcomes trial for canagliflozin, treatment was linked to reductions in progression of albuminuria and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal replacement therapy, or death from renal causes, compared with placebo, but those didn’t reach statistical significance.

CREDENCE (Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial that enrolled roughly 4,400 patients with type 2 diabetes and established kidney disease who had been receiving ACE inhibitors or angiotensin II receptor blockers for at least 4 weeks prior to randomization.

The decision to halt CREDENCE came about after a review of data by the study’s independent data monitoring committee during a planned interim analysis. The resulting recommendation was based on the efficacy findings, the exact data for which have not yet been released.

Canagliflozin, a sodium-glucose transporter 2 (SGLT2) inhibitor, in conjunction with diet and exercise, can help improve glycemic control. In the context of kidney disease and type 2 diabetes, canagliflozin has been associated with increased risk of dehydration, vaginal or penile yeast infections, and amputations of all or part of the foot or leg. It has also been associated with ketoacidosis, kidney problems, hyperkalemia, hypoglycemia, and urinary tract infections.

More information can be found in the press release. Full prescribing information can be found on the Food and Drug Administration website.

[email protected]

The CREDENCE trial, which was investigating whether the antidiabetes drug canagliflozin (Invokana) plus standard of care could safely help prevent or slow chronic kidney disease (CKD) in patients with type 2 diabetes, has been ended early because it has already achieved prespecified efficacy criteria, Janssen announced in a press release. These criteria included risk reduction in the composite endpoint of time to dialysis or kidney transplant, doubling of serum creatinine, and renal or cardiovascular death.

In CANVAS, the cardiovascular outcomes trial for canagliflozin, treatment was linked to reductions in progression of albuminuria and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal replacement therapy, or death from renal causes, compared with placebo, but those didn’t reach statistical significance.

CREDENCE (Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial that enrolled roughly 4,400 patients with type 2 diabetes and established kidney disease who had been receiving ACE inhibitors or angiotensin II receptor blockers for at least 4 weeks prior to randomization.

The decision to halt CREDENCE came about after a review of data by the study’s independent data monitoring committee during a planned interim analysis. The resulting recommendation was based on the efficacy findings, the exact data for which have not yet been released.

Canagliflozin, a sodium-glucose transporter 2 (SGLT2) inhibitor, in conjunction with diet and exercise, can help improve glycemic control. In the context of kidney disease and type 2 diabetes, canagliflozin has been associated with increased risk of dehydration, vaginal or penile yeast infections, and amputations of all or part of the foot or leg. It has also been associated with ketoacidosis, kidney problems, hyperkalemia, hypoglycemia, and urinary tract infections.

More information can be found in the press release. Full prescribing information can be found on the Food and Drug Administration website.

[email protected]

AMSTERDAM – Abatacept used on top of the standard of care did not improve the primary endpoint of a complete renal response versus placebo in the ALLURE phase 3 study.

Criteria for a complete renal response (CRR) at 1 year was met by 35.1% of abatacept-treated and 33.5% of placebo-treated patients (P = .73). CRR criteria included having a urine protein to creatinine ratio (UPCR) of less than 0.5, a normal estimated glomerular filtration rate (eGFR) or an eGFR of 85% or more of baseline values, no cellular casts, and a daily corticosteroid dose of 10 mg or less.

Sara Freeman/MDedge News

SOURCE: Furie RA et al. EULAR 2018. Abstract OP0253.

AMSTERDAM – Abatacept used on top of the standard of care did not improve the primary endpoint of a complete renal response versus placebo in the ALLURE phase 3 study.

Criteria for a complete renal response (CRR) at 1 year was met by 35.1% of abatacept-treated and 33.5% of placebo-treated patients (P = .73). CRR criteria included having a urine protein to creatinine ratio (UPCR) of less than 0.5, a normal estimated glomerular filtration rate (eGFR) or an eGFR of 85% or more of baseline values, no cellular casts, and a daily corticosteroid dose of 10 mg or less.

Sara Freeman/MDedge News

SOURCE: Furie RA et al. EULAR 2018. Abstract OP0253.

AMSTERDAM – Abatacept used on top of the standard of care did not improve the primary endpoint of a complete renal response versus placebo in the ALLURE phase 3 study.

Criteria for a complete renal response (CRR) at 1 year was met by 35.1% of abatacept-treated and 33.5% of placebo-treated patients (P = .73). CRR criteria included having a urine protein to creatinine ratio (UPCR) of less than 0.5, a normal estimated glomerular filtration rate (eGFR) or an eGFR of 85% or more of baseline values, no cellular casts, and a daily corticosteroid dose of 10 mg or less.

Sara Freeman/MDedge News

SOURCE: Furie RA et al. EULAR 2018. Abstract OP0253.

A 17-year-old girl seen in a Portuguese dermatology clinic was found to have a nodular basal cell carcinoma on the parietal region of her scalp. The nodule appeared 6 years after she had received a kidney transplant, according to João Borges-Costa, MD, PhD, who submitted the case report.

Since the transplant, the girl had been maintained on immunosuppressive medication of tacrolimus 1 mg twice daily, mycophenolate sodium 360 mg twice daily, and prednisolone 10 mg every other day. The 1-cm nodule was pigmented; dermatoscopy did not yield clarity about whether the lesion was melanocytic. An excisional biopsy with 0.5-cm margins was performed, and histology confirmed that the lesion was a nodular pigmented basal cell carcinoma that had been excised completely.

The case, said Dr. Borges-Costa, shows that skin cancers can develop earlier than the typical 12-18 years after pediatric transplantation. Most reported cases have been squamous cell cancers and melanomas, and often are associated with lack of appropriate sun protection behavior.

The patient, a Caucasian, was a sailor who used sunscreen but did not typically wear a hat while sailing, reported Dr. Borges-Costa, a dermatologist at the University of Lisbon. Her family history was significant for a grandparent with melanoma.

Dr. Borges noted that the parents and patient were given advice regarding the importance of the lifelong use of sun-protective clothing and headgear. “Education of pediatric organ recipients and their parents about sun protection is important because, as occurred with our patient, protective clothing and hats are frequently forgotten.”

Because of the ongoing potential for skin malignancies, early referral “after transplantation to specialized dermatology outpatient clinics, similar to what is now advocated for transplanted adults, could help in surveillance and improve adherence to sun-protective measures,” he added.

SOURCE: Borges-Costa J et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13537..

A 17-year-old girl seen in a Portuguese dermatology clinic was found to have a nodular basal cell carcinoma on the parietal region of her scalp. The nodule appeared 6 years after she had received a kidney transplant, according to João Borges-Costa, MD, PhD, who submitted the case report.

Since the transplant, the girl had been maintained on immunosuppressive medication of tacrolimus 1 mg twice daily, mycophenolate sodium 360 mg twice daily, and prednisolone 10 mg every other day. The 1-cm nodule was pigmented; dermatoscopy did not yield clarity about whether the lesion was melanocytic. An excisional biopsy with 0.5-cm margins was performed, and histology confirmed that the lesion was a nodular pigmented basal cell carcinoma that had been excised completely.

The case, said Dr. Borges-Costa, shows that skin cancers can develop earlier than the typical 12-18 years after pediatric transplantation. Most reported cases have been squamous cell cancers and melanomas, and often are associated with lack of appropriate sun protection behavior.

The patient, a Caucasian, was a sailor who used sunscreen but did not typically wear a hat while sailing, reported Dr. Borges-Costa, a dermatologist at the University of Lisbon. Her family history was significant for a grandparent with melanoma.

Dr. Borges noted that the parents and patient were given advice regarding the importance of the lifelong use of sun-protective clothing and headgear. “Education of pediatric organ recipients and their parents about sun protection is important because, as occurred with our patient, protective clothing and hats are frequently forgotten.”

Because of the ongoing potential for skin malignancies, early referral “after transplantation to specialized dermatology outpatient clinics, similar to what is now advocated for transplanted adults, could help in surveillance and improve adherence to sun-protective measures,” he added.

SOURCE: Borges-Costa J et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13537..

A 17-year-old girl seen in a Portuguese dermatology clinic was found to have a nodular basal cell carcinoma on the parietal region of her scalp. The nodule appeared 6 years after she had received a kidney transplant, according to João Borges-Costa, MD, PhD, who submitted the case report.

Since the transplant, the girl had been maintained on immunosuppressive medication of tacrolimus 1 mg twice daily, mycophenolate sodium 360 mg twice daily, and prednisolone 10 mg every other day. The 1-cm nodule was pigmented; dermatoscopy did not yield clarity about whether the lesion was melanocytic. An excisional biopsy with 0.5-cm margins was performed, and histology confirmed that the lesion was a nodular pigmented basal cell carcinoma that had been excised completely.

The case, said Dr. Borges-Costa, shows that skin cancers can develop earlier than the typical 12-18 years after pediatric transplantation. Most reported cases have been squamous cell cancers and melanomas, and often are associated with lack of appropriate sun protection behavior.

The patient, a Caucasian, was a sailor who used sunscreen but did not typically wear a hat while sailing, reported Dr. Borges-Costa, a dermatologist at the University of Lisbon. Her family history was significant for a grandparent with melanoma.

Dr. Borges noted that the parents and patient were given advice regarding the importance of the lifelong use of sun-protective clothing and headgear. “Education of pediatric organ recipients and their parents about sun protection is important because, as occurred with our patient, protective clothing and hats are frequently forgotten.”

Because of the ongoing potential for skin malignancies, early referral “after transplantation to specialized dermatology outpatient clinics, similar to what is now advocated for transplanted adults, could help in surveillance and improve adherence to sun-protective measures,” he added.

SOURCE: Borges-Costa J et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13537..

ORLANDO – Serum uric acid lowering might help prevent kidney disease in children with type 2 diabetes mellitus, according to a 7-year investigation of 539 children.

Every 1-mg/dL climb in baseline serum uric acid increased the risk of subsequent elevated urine albumin excretion 1.23 fold, after adjustment for potential confounders (P = .02).

The finding adds to growing evidence that serum uric acid (SUA) isn’t just a marker of diabetic kidney disease, but a contributor to it. “There is definitely” cross-talk between gout and diabetes, said lead investigator Petter Bjornstad, MD, assistant professor of pediatric endocrinology at the University of Colorado, Aurora.

Elevated SUA is common in both conditions and a risk factor for kidney disease. Newer studies have linked higher levels to nephron number decline and other pathologies, perhaps through renal inflammation. Allopurinol, the traditional uric acid lowering agent in gout, is already under investigation to prevent kidney decline in adults with type 1 diabetes mellitus. There’s also evidence that the potent uric acid lowering agent, febuxostat (Uloric), attenuates hypofiltration in early diabetic kidney disease.

M. Alexander Otto/MDedge News

[email protected]

SOURCE: Bjornstad P et al. ADA 2018, abstract 339-OR.

ORLANDO – Serum uric acid lowering might help prevent kidney disease in children with type 2 diabetes mellitus, according to a 7-year investigation of 539 children.

Every 1-mg/dL climb in baseline serum uric acid increased the risk of subsequent elevated urine albumin excretion 1.23 fold, after adjustment for potential confounders (P = .02).

The finding adds to growing evidence that serum uric acid (SUA) isn’t just a marker of diabetic kidney disease, but a contributor to it. “There is definitely” cross-talk between gout and diabetes, said lead investigator Petter Bjornstad, MD, assistant professor of pediatric endocrinology at the University of Colorado, Aurora.

Elevated SUA is common in both conditions and a risk factor for kidney disease. Newer studies have linked higher levels to nephron number decline and other pathologies, perhaps through renal inflammation. Allopurinol, the traditional uric acid lowering agent in gout, is already under investigation to prevent kidney decline in adults with type 1 diabetes mellitus. There’s also evidence that the potent uric acid lowering agent, febuxostat (Uloric), attenuates hypofiltration in early diabetic kidney disease.

M. Alexander Otto/MDedge News

[email protected]

SOURCE: Bjornstad P et al. ADA 2018, abstract 339-OR.

ORLANDO – Serum uric acid lowering might help prevent kidney disease in children with type 2 diabetes mellitus, according to a 7-year investigation of 539 children.

Every 1-mg/dL climb in baseline serum uric acid increased the risk of subsequent elevated urine albumin excretion 1.23 fold, after adjustment for potential confounders (P = .02).

The finding adds to growing evidence that serum uric acid (SUA) isn’t just a marker of diabetic kidney disease, but a contributor to it. “There is definitely” cross-talk between gout and diabetes, said lead investigator Petter Bjornstad, MD, assistant professor of pediatric endocrinology at the University of Colorado, Aurora.

Elevated SUA is common in both conditions and a risk factor for kidney disease. Newer studies have linked higher levels to nephron number decline and other pathologies, perhaps through renal inflammation. Allopurinol, the traditional uric acid lowering agent in gout, is already under investigation to prevent kidney decline in adults with type 1 diabetes mellitus. There’s also evidence that the potent uric acid lowering agent, febuxostat (Uloric), attenuates hypofiltration in early diabetic kidney disease.

M. Alexander Otto/MDedge News

[email protected]

SOURCE: Bjornstad P et al. ADA 2018, abstract 339-OR.

TORONTO – When Brandy Wicklow, MD, began her pediatric endocrinology fellowship at McGill University in 2006, about 12 per 100,000 children in Manitoba, Canada, were diagnosed with type 2 diabetes mellitus each year. By 2016 that rate had more than doubled, to 26 per 100,000 children.

“If you look just at indigenous youth in our province, it’s probably one of the highest rates ever reported, with 95 per 100,000 Manitoba First Nation children diagnosed with type 2 diabetes,” said Dr. Wicklow, a pediatric endocrinologist at the University of Manitoba and the Children’s Hospital Research Institute of Manitoba.

Many indigenous populations also face an increased risk for primary renal disease. One study reviewed the charts 90 of Canadian First Nation children and adolescents with T2DM (Diabetes Care. 2009;32[5]:786-90). Of 10 who had renal biopsies performed, nine had immune complex disease/glomerulosclerosis, two had mild diabetes-related lesions, and seven had focal segmental glomerulosclerosis (FSGS); yet none had classic nephropathy. An analysis of Chinese youth that included 216 renal biopsies yielded similar findings (Intl Urol Nephrol. 2012;45[1]:173-9).

It’s also known that early-onset T2DM is associated with substantially increased incidence of end-stage renal disease (ESRD) and mortality in middle age. For example, one study of Pima Indians found that those who were diagnosed with T2DM earlier than 20 years of age had a one in five chance of developing ESRD, while those who were diagnosed at age 20 years or older had a one in two chance of ESRD (JAMA. 2006;296[4]:421-6). In a separate analysis, researchers estimated the remaining lifetime risks for ESRD among Aboriginal people in Australia with and without diabetes (Diabetes Res Clin Pract. 2014;103[3]:e24-6). The value for young adults with diabetes was high, about one in two at the age of 30 years, while it decreased with age to one in seven at 60 years.

“One of the first biomarkers we see in terms of renal disease in kids with T2DM is albuminuria,” Dr. Wicklow said at the Pediatric Academic Societies meeting. “The question is, why do kids with type 2 get more renal disease than kids with type 1 diabetes?” The SEARCH for Diabetes in Youth (SEARCH) study from 2006 found that hypertension, increased body mass index, increased weight circumference, and increased lipids were factors, while the SEARCH study from 2015 found that ethnicity, increased weight to height ratio, and mean arterial pressure were factors.

“Insulin resistance is significantly associated with albuminuria,” Dr. Wicklow continued. “It’s also been shown to be associated with hyperfiltration. Some of the markers of insulin resistance are important but they make up about 19% of the variance between type 1 and type 2, which means there are other variables that we’re not measuring.”

Enter ICARE (Improving Renal Complications in Adolescents with Type 2 Diabetes through Research), an ongoing prospective cohort study that Dr. Wicklow and her associates launched in 2014 at eight centers in Canada. It aims to examine the biopsychosocial risk factors for albuminuria in youth with T2DM and the mechanisms for renal injury. “Our theoretical framework was that biological exposures that we are aware of, such as glycemic control, hypertension, and lipids, would all be important in the development of albuminuria and renal disease in kids,” said Dr. Wicklow, who is the study’s coprimary investigator along with Allison Dart, MD. “But what we thought was novel was that psychological exposures either as socioeconomic status or as mental health factors would also directly impinge on renal health with respect to chronic inflammation in the body, inflammation in the kidneys, and long-term kidney damage.”

Courtesy Dr. Brandy Wicklow

Courtesy Dr. Brandy Wicklow

Courtesy Dr. Brandy Wicklow

[email protected]

TORONTO – When Brandy Wicklow, MD, began her pediatric endocrinology fellowship at McGill University in 2006, about 12 per 100,000 children in Manitoba, Canada, were diagnosed with type 2 diabetes mellitus each year. By 2016 that rate had more than doubled, to 26 per 100,000 children.

“If you look just at indigenous youth in our province, it’s probably one of the highest rates ever reported, with 95 per 100,000 Manitoba First Nation children diagnosed with type 2 diabetes,” said Dr. Wicklow, a pediatric endocrinologist at the University of Manitoba and the Children’s Hospital Research Institute of Manitoba.

Many indigenous populations also face an increased risk for primary renal disease. One study reviewed the charts 90 of Canadian First Nation children and adolescents with T2DM (Diabetes Care. 2009;32[5]:786-90). Of 10 who had renal biopsies performed, nine had immune complex disease/glomerulosclerosis, two had mild diabetes-related lesions, and seven had focal segmental glomerulosclerosis (FSGS); yet none had classic nephropathy. An analysis of Chinese youth that included 216 renal biopsies yielded similar findings (Intl Urol Nephrol. 2012;45[1]:173-9).

It’s also known that early-onset T2DM is associated with substantially increased incidence of end-stage renal disease (ESRD) and mortality in middle age. For example, one study of Pima Indians found that those who were diagnosed with T2DM earlier than 20 years of age had a one in five chance of developing ESRD, while those who were diagnosed at age 20 years or older had a one in two chance of ESRD (JAMA. 2006;296[4]:421-6). In a separate analysis, researchers estimated the remaining lifetime risks for ESRD among Aboriginal people in Australia with and without diabetes (Diabetes Res Clin Pract. 2014;103[3]:e24-6). The value for young adults with diabetes was high, about one in two at the age of 30 years, while it decreased with age to one in seven at 60 years.

“One of the first biomarkers we see in terms of renal disease in kids with T2DM is albuminuria,” Dr. Wicklow said at the Pediatric Academic Societies meeting. “The question is, why do kids with type 2 get more renal disease than kids with type 1 diabetes?” The SEARCH for Diabetes in Youth (SEARCH) study from 2006 found that hypertension, increased body mass index, increased weight circumference, and increased lipids were factors, while the SEARCH study from 2015 found that ethnicity, increased weight to height ratio, and mean arterial pressure were factors.

“Insulin resistance is significantly associated with albuminuria,” Dr. Wicklow continued. “It’s also been shown to be associated with hyperfiltration. Some of the markers of insulin resistance are important but they make up about 19% of the variance between type 1 and type 2, which means there are other variables that we’re not measuring.”

Enter ICARE (Improving Renal Complications in Adolescents with Type 2 Diabetes through Research), an ongoing prospective cohort study that Dr. Wicklow and her associates launched in 2014 at eight centers in Canada. It aims to examine the biopsychosocial risk factors for albuminuria in youth with T2DM and the mechanisms for renal injury. “Our theoretical framework was that biological exposures that we are aware of, such as glycemic control, hypertension, and lipids, would all be important in the development of albuminuria and renal disease in kids,” said Dr. Wicklow, who is the study’s coprimary investigator along with Allison Dart, MD. “But what we thought was novel was that psychological exposures either as socioeconomic status or as mental health factors would also directly impinge on renal health with respect to chronic inflammation in the body, inflammation in the kidneys, and long-term kidney damage.”

Courtesy Dr. Brandy Wicklow

Courtesy Dr. Brandy Wicklow

Courtesy Dr. Brandy Wicklow

[email protected]

TORONTO – When Brandy Wicklow, MD, began her pediatric endocrinology fellowship at McGill University in 2006, about 12 per 100,000 children in Manitoba, Canada, were diagnosed with type 2 diabetes mellitus each year. By 2016 that rate had more than doubled, to 26 per 100,000 children.

“If you look just at indigenous youth in our province, it’s probably one of the highest rates ever reported, with 95 per 100,000 Manitoba First Nation children diagnosed with type 2 diabetes,” said Dr. Wicklow, a pediatric endocrinologist at the University of Manitoba and the Children’s Hospital Research Institute of Manitoba.

Many indigenous populations also face an increased risk for primary renal disease. One study reviewed the charts 90 of Canadian First Nation children and adolescents with T2DM (Diabetes Care. 2009;32[5]:786-90). Of 10 who had renal biopsies performed, nine had immune complex disease/glomerulosclerosis, two had mild diabetes-related lesions, and seven had focal segmental glomerulosclerosis (FSGS); yet none had classic nephropathy. An analysis of Chinese youth that included 216 renal biopsies yielded similar findings (Intl Urol Nephrol. 2012;45[1]:173-9).

It’s also known that early-onset T2DM is associated with substantially increased incidence of end-stage renal disease (ESRD) and mortality in middle age. For example, one study of Pima Indians found that those who were diagnosed with T2DM earlier than 20 years of age had a one in five chance of developing ESRD, while those who were diagnosed at age 20 years or older had a one in two chance of ESRD (JAMA. 2006;296[4]:421-6). In a separate analysis, researchers estimated the remaining lifetime risks for ESRD among Aboriginal people in Australia with and without diabetes (Diabetes Res Clin Pract. 2014;103[3]:e24-6). The value for young adults with diabetes was high, about one in two at the age of 30 years, while it decreased with age to one in seven at 60 years.

“One of the first biomarkers we see in terms of renal disease in kids with T2DM is albuminuria,” Dr. Wicklow said at the Pediatric Academic Societies meeting. “The question is, why do kids with type 2 get more renal disease than kids with type 1 diabetes?” The SEARCH for Diabetes in Youth (SEARCH) study from 2006 found that hypertension, increased body mass index, increased weight circumference, and increased lipids were factors, while the SEARCH study from 2015 found that ethnicity, increased weight to height ratio, and mean arterial pressure were factors.

“Insulin resistance is significantly associated with albuminuria,” Dr. Wicklow continued. “It’s also been shown to be associated with hyperfiltration. Some of the markers of insulin resistance are important but they make up about 19% of the variance between type 1 and type 2, which means there are other variables that we’re not measuring.”

Enter ICARE (Improving Renal Complications in Adolescents with Type 2 Diabetes through Research), an ongoing prospective cohort study that Dr. Wicklow and her associates launched in 2014 at eight centers in Canada. It aims to examine the biopsychosocial risk factors for albuminuria in youth with T2DM and the mechanisms for renal injury. “Our theoretical framework was that biological exposures that we are aware of, such as glycemic control, hypertension, and lipids, would all be important in the development of albuminuria and renal disease in kids,” said Dr. Wicklow, who is the study’s coprimary investigator along with Allison Dart, MD. “But what we thought was novel was that psychological exposures either as socioeconomic status or as mental health factors would also directly impinge on renal health with respect to chronic inflammation in the body, inflammation in the kidneys, and long-term kidney damage.”

Courtesy Dr. Brandy Wicklow

Courtesy Dr. Brandy Wicklow

Courtesy Dr. Brandy Wicklow

[email protected]

Alaska is a vast state—larger than Texas, Montana, and California combined. It is also home to the highest percentage of American Indian (AI) and Alaska Native (AN) persons in the United States. These two populations—collectively referred to as Native Americans—have been served by the Indian Health Services (IHS) since it was established through the Snyder Act of 1921, in response to the dismal health conditions of the indigenous tribes in this country.¹ Across the US (not only in Alaska), the IHS has partnered with AI/AN peoples to decrease health disparities in a culturally acceptable manner that honors and protects their traditions and values.

The IHS—which in 2016 comprised 2,500 nurses, 750 physicians, 700 pharmacists, 200 PAs and NPs, and 280 dentists, as well as nutritionists, diabetes educators, administrators, and other professionals—has made huge advances in decreasing health disparities in their populations. Among them: decreased rates of tuberculosis and of maternal and infant deaths.

However, life expectancy among Native Americans remains four years shorter than that of the rest of the US population. This disparity can be traced to three recalcitrant factors: unintentional injuries, liver disease, and diabetes.

The IHS practitioners decided to tackle diabetes with a multipronged approach. And what they achieved is astonishing.

WHAT THEY DID

Worldwide, diabetes is the most common cause of kidney failure; identifying patients with diabetes and early-stage chronic kidney disease allows for aggressive treatment that can slow progression to kidney failure and dialysis.

The IHS providers knew when they decided to tackle the problem of diabetes in the AI/AN population that the incidence was 16%—and the rate of diabetes leading to kidney failure in this population was the highest for any ethnic group in the US.^2,3 And yet …

From 1996 to 2013, the rate of diabetes-related kidney failure among Native Americans dropped by 54%.³ Yes—the group of patients with the highest percentage of diabetes diagnoses has had the greatest improvement in prevention of kidney failure.⁴

Continue to: Some of the clinical achievements that contributed to...

Some of the clinical achievements that contributed to this significant change include

• Increased use of ACE inhibitors or angiotensin receptor blockers (ARBs) (from 42% to 74% over a five-year period)
• Reduced average blood pressure among hypertensive patients (to 133/76 mm Hg)
• Improved blood glucose control (by 10%)
• Increased testing for kidney disease among older patients (50% higher than the rest of the Medicare diabetes population).³

HOW THEY DID IT

This is not rocket science. The IHS staff integrated both population- and team-based approaches to achieve a more impressive decrease than ever could have been expected. In retrospect, perhaps this success should not come as such a surprise—many religious beliefs held by Native Americans focus around society, communal harmony, kinship, and cooperation.

The population health approach focused on promoting the wellness of the entire community and connecting people to local resources, including healthy food, transportation, housing, and mental health care. In the team approach, IHS medical experts implemented strategies to improve patient education, community outreach, care coordination, health outcome tracking, and access to a wide variety of health care providers.^3,5

In a place like Alaska—where the northernmost city, Barrow, is more than 700 miles (two hours by plane) from Anchorage, and the southeastern Annette Island is more than 1,000 miles (six hours by plane) from the capital—this can be an especially challenging prospect. To reduce travel burden for rural patients, the IHS sponsors a diabetes team that travels from village to village. Nephrology services are not included in these field visits, however, so the kidney team relies heavily on telehealth. This requires extensive clinic staff coordination, as well as equipment and knowledgeable information systems support teams.

Other challenges require educational and logistical solutions. As noted, the use of ACE inhibitors and ARBs increased through the IHS’s efforts—and contributed to the delayed progression of diabetic kidney disease—but those additional prescriptions necessitate patient education. Understanding of these medications can be limited; many rural patients trust that when the bottle is empty, their practitioner has treated and cured their disease—mistakenly believing that no refills are needed. And even when the need to continue the prescription is understood, rural clinics may have difficulty tracking appointments and prescriptions written by providers at specialty clinics in Anchorage, making ongoing refills an issue.

Continue to: The necessary dietary changes can also be...

The necessary dietary changes can also be difficult for AI/AN populations. For example, in rural Alaska, tap water may not be safe to drink, and soda costs less than bottled water. Fresh produce is expensive and has often begun to spoil by the time it reaches local stores. The Native villagers often prefer their usual diets of gathered berries, fish, and red meat from subsistence hunting, making implementation of dietary changes difficult.

However, as the success of the IHS initiative shows, challenges can be met and overcome by practitioners who see a need, formulate a solution individualized to the circumstance, and think outside the box. One of the keys is developing a trusting relationship with patients. Another is to recognize informational needs and utilize available resources to educate patients. For example, visual representations of kidney function tend to be helpful in explaining the nature and course of disease; the National Kidney Disease Education Program uses an illustration similar to a gas gauge to demonstrate glomerular filtration rate (which would otherwise seem abstract and hard to understand for some patients; see below).⁶ When you understand your patient population and their needs, it makes addressing the challenging aspects of health care and prevention easier.

CONCLUSION

The results that the IHS achieved should serve as an example for all Americans with diabetes and their health care providers. We must be open to delivery of care via different approaches and practitioners in order to successfully help patients of different backgrounds and circumstances. This is the individualization of care that we hear so much about.

In 2016, the costs of caring for the kidney failure population were greater than the entire budget of the NIH. By aggressively identifying and treating patients at risk for kidney failure, we can slow disease progression—saving society money, but more importantly allowing our patients many more years of life free from the constraints of dialysis. —MET, RB

Mandy E. Thompson, PA-C
Kidney Center of Denver Health

Robin Bassett, DNP
Nephrology and Hypertension Associates, Anchorage
Adjunct Professor, NP program, University of Alaska, Anchorage

Alaska is a vast state—larger than Texas, Montana, and California combined. It is also home to the highest percentage of American Indian (AI) and Alaska Native (AN) persons in the United States. These two populations—collectively referred to as Native Americans—have been served by the Indian Health Services (IHS) since it was established through the Snyder Act of 1921, in response to the dismal health conditions of the indigenous tribes in this country.¹ Across the US (not only in Alaska), the IHS has partnered with AI/AN peoples to decrease health disparities in a culturally acceptable manner that honors and protects their traditions and values.

The IHS—which in 2016 comprised 2,500 nurses, 750 physicians, 700 pharmacists, 200 PAs and NPs, and 280 dentists, as well as nutritionists, diabetes educators, administrators, and other professionals—has made huge advances in decreasing health disparities in their populations. Among them: decreased rates of tuberculosis and of maternal and infant deaths.

However, life expectancy among Native Americans remains four years shorter than that of the rest of the US population. This disparity can be traced to three recalcitrant factors: unintentional injuries, liver disease, and diabetes.

The IHS practitioners decided to tackle diabetes with a multipronged approach. And what they achieved is astonishing.

WHAT THEY DID

Worldwide, diabetes is the most common cause of kidney failure; identifying patients with diabetes and early-stage chronic kidney disease allows for aggressive treatment that can slow progression to kidney failure and dialysis.

The IHS providers knew when they decided to tackle the problem of diabetes in the AI/AN population that the incidence was 16%—and the rate of diabetes leading to kidney failure in this population was the highest for any ethnic group in the US.^2,3 And yet …

From 1996 to 2013, the rate of diabetes-related kidney failure among Native Americans dropped by 54%.³ Yes—the group of patients with the highest percentage of diabetes diagnoses has had the greatest improvement in prevention of kidney failure.⁴

Continue to: Some of the clinical achievements that contributed to...

Some of the clinical achievements that contributed to this significant change include

• Increased use of ACE inhibitors or angiotensin receptor blockers (ARBs) (from 42% to 74% over a five-year period)
• Reduced average blood pressure among hypertensive patients (to 133/76 mm Hg)
• Improved blood glucose control (by 10%)
• Increased testing for kidney disease among older patients (50% higher than the rest of the Medicare diabetes population).³

HOW THEY DID IT

This is not rocket science. The IHS staff integrated both population- and team-based approaches to achieve a more impressive decrease than ever could have been expected. In retrospect, perhaps this success should not come as such a surprise—many religious beliefs held by Native Americans focus around society, communal harmony, kinship, and cooperation.

The population health approach focused on promoting the wellness of the entire community and connecting people to local resources, including healthy food, transportation, housing, and mental health care. In the team approach, IHS medical experts implemented strategies to improve patient education, community outreach, care coordination, health outcome tracking, and access to a wide variety of health care providers.^3,5

In a place like Alaska—where the northernmost city, Barrow, is more than 700 miles (two hours by plane) from Anchorage, and the southeastern Annette Island is more than 1,000 miles (six hours by plane) from the capital—this can be an especially challenging prospect. To reduce travel burden for rural patients, the IHS sponsors a diabetes team that travels from village to village. Nephrology services are not included in these field visits, however, so the kidney team relies heavily on telehealth. This requires extensive clinic staff coordination, as well as equipment and knowledgeable information systems support teams.

Other challenges require educational and logistical solutions. As noted, the use of ACE inhibitors and ARBs increased through the IHS’s efforts—and contributed to the delayed progression of diabetic kidney disease—but those additional prescriptions necessitate patient education. Understanding of these medications can be limited; many rural patients trust that when the bottle is empty, their practitioner has treated and cured their disease—mistakenly believing that no refills are needed. And even when the need to continue the prescription is understood, rural clinics may have difficulty tracking appointments and prescriptions written by providers at specialty clinics in Anchorage, making ongoing refills an issue.

Continue to: The necessary dietary changes can also be...

The necessary dietary changes can also be difficult for AI/AN populations. For example, in rural Alaska, tap water may not be safe to drink, and soda costs less than bottled water. Fresh produce is expensive and has often begun to spoil by the time it reaches local stores. The Native villagers often prefer their usual diets of gathered berries, fish, and red meat from subsistence hunting, making implementation of dietary changes difficult.

However, as the success of the IHS initiative shows, challenges can be met and overcome by practitioners who see a need, formulate a solution individualized to the circumstance, and think outside the box. One of the keys is developing a trusting relationship with patients. Another is to recognize informational needs and utilize available resources to educate patients. For example, visual representations of kidney function tend to be helpful in explaining the nature and course of disease; the National Kidney Disease Education Program uses an illustration similar to a gas gauge to demonstrate glomerular filtration rate (which would otherwise seem abstract and hard to understand for some patients; see below).⁶ When you understand your patient population and their needs, it makes addressing the challenging aspects of health care and prevention easier.

CONCLUSION

The results that the IHS achieved should serve as an example for all Americans with diabetes and their health care providers. We must be open to delivery of care via different approaches and practitioners in order to successfully help patients of different backgrounds and circumstances. This is the individualization of care that we hear so much about.

In 2016, the costs of caring for the kidney failure population were greater than the entire budget of the NIH. By aggressively identifying and treating patients at risk for kidney failure, we can slow disease progression—saving society money, but more importantly allowing our patients many more years of life free from the constraints of dialysis. —MET, RB

Mandy E. Thompson, PA-C
Kidney Center of Denver Health

Robin Bassett, DNP
Nephrology and Hypertension Associates, Anchorage
Adjunct Professor, NP program, University of Alaska, Anchorage

Alaska is a vast state—larger than Texas, Montana, and California combined. It is also home to the highest percentage of American Indian (AI) and Alaska Native (AN) persons in the United States. These two populations—collectively referred to as Native Americans—have been served by the Indian Health Services (IHS) since it was established through the Snyder Act of 1921, in response to the dismal health conditions of the indigenous tribes in this country.¹ Across the US (not only in Alaska), the IHS has partnered with AI/AN peoples to decrease health disparities in a culturally acceptable manner that honors and protects their traditions and values.

The IHS—which in 2016 comprised 2,500 nurses, 750 physicians, 700 pharmacists, 200 PAs and NPs, and 280 dentists, as well as nutritionists, diabetes educators, administrators, and other professionals—has made huge advances in decreasing health disparities in their populations. Among them: decreased rates of tuberculosis and of maternal and infant deaths.

However, life expectancy among Native Americans remains four years shorter than that of the rest of the US population. This disparity can be traced to three recalcitrant factors: unintentional injuries, liver disease, and diabetes.

The IHS practitioners decided to tackle diabetes with a multipronged approach. And what they achieved is astonishing.

WHAT THEY DID

Worldwide, diabetes is the most common cause of kidney failure; identifying patients with diabetes and early-stage chronic kidney disease allows for aggressive treatment that can slow progression to kidney failure and dialysis.

The IHS providers knew when they decided to tackle the problem of diabetes in the AI/AN population that the incidence was 16%—and the rate of diabetes leading to kidney failure in this population was the highest for any ethnic group in the US.^2,3 And yet …

From 1996 to 2013, the rate of diabetes-related kidney failure among Native Americans dropped by 54%.³ Yes—the group of patients with the highest percentage of diabetes diagnoses has had the greatest improvement in prevention of kidney failure.⁴

Continue to: Some of the clinical achievements that contributed to...

Some of the clinical achievements that contributed to this significant change include

• Increased use of ACE inhibitors or angiotensin receptor blockers (ARBs) (from 42% to 74% over a five-year period)
• Reduced average blood pressure among hypertensive patients (to 133/76 mm Hg)
• Improved blood glucose control (by 10%)
• Increased testing for kidney disease among older patients (50% higher than the rest of the Medicare diabetes population).³

HOW THEY DID IT

This is not rocket science. The IHS staff integrated both population- and team-based approaches to achieve a more impressive decrease than ever could have been expected. In retrospect, perhaps this success should not come as such a surprise—many religious beliefs held by Native Americans focus around society, communal harmony, kinship, and cooperation.

The population health approach focused on promoting the wellness of the entire community and connecting people to local resources, including healthy food, transportation, housing, and mental health care. In the team approach, IHS medical experts implemented strategies to improve patient education, community outreach, care coordination, health outcome tracking, and access to a wide variety of health care providers.^3,5

In a place like Alaska—where the northernmost city, Barrow, is more than 700 miles (two hours by plane) from Anchorage, and the southeastern Annette Island is more than 1,000 miles (six hours by plane) from the capital—this can be an especially challenging prospect. To reduce travel burden for rural patients, the IHS sponsors a diabetes team that travels from village to village. Nephrology services are not included in these field visits, however, so the kidney team relies heavily on telehealth. This requires extensive clinic staff coordination, as well as equipment and knowledgeable information systems support teams.

Other challenges require educational and logistical solutions. As noted, the use of ACE inhibitors and ARBs increased through the IHS’s efforts—and contributed to the delayed progression of diabetic kidney disease—but those additional prescriptions necessitate patient education. Understanding of these medications can be limited; many rural patients trust that when the bottle is empty, their practitioner has treated and cured their disease—mistakenly believing that no refills are needed. And even when the need to continue the prescription is understood, rural clinics may have difficulty tracking appointments and prescriptions written by providers at specialty clinics in Anchorage, making ongoing refills an issue.

Continue to: The necessary dietary changes can also be...

The necessary dietary changes can also be difficult for AI/AN populations. For example, in rural Alaska, tap water may not be safe to drink, and soda costs less than bottled water. Fresh produce is expensive and has often begun to spoil by the time it reaches local stores. The Native villagers often prefer their usual diets of gathered berries, fish, and red meat from subsistence hunting, making implementation of dietary changes difficult.

However, as the success of the IHS initiative shows, challenges can be met and overcome by practitioners who see a need, formulate a solution individualized to the circumstance, and think outside the box. One of the keys is developing a trusting relationship with patients. Another is to recognize informational needs and utilize available resources to educate patients. For example, visual representations of kidney function tend to be helpful in explaining the nature and course of disease; the National Kidney Disease Education Program uses an illustration similar to a gas gauge to demonstrate glomerular filtration rate (which would otherwise seem abstract and hard to understand for some patients; see below).⁶ When you understand your patient population and their needs, it makes addressing the challenging aspects of health care and prevention easier.

CONCLUSION

The results that the IHS achieved should serve as an example for all Americans with diabetes and their health care providers. We must be open to delivery of care via different approaches and practitioners in order to successfully help patients of different backgrounds and circumstances. This is the individualization of care that we hear so much about.

In 2016, the costs of caring for the kidney failure population were greater than the entire budget of the NIH. By aggressively identifying and treating patients at risk for kidney failure, we can slow disease progression—saving society money, but more importantly allowing our patients many more years of life free from the constraints of dialysis. —MET, RB

Mandy E. Thompson, PA-C
Kidney Center of Denver Health

Robin Bassett, DNP
Nephrology and Hypertension Associates, Anchorage
Adjunct Professor, NP program, University of Alaska, Anchorage