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An Unprecedented Case of AL and Apolipoprotein A-IV Renal Amyloidosis
Background
Whereas light chain (AL) amyloid is the most common cause of amyloidosis, Apolipoprotein A-IV (AApoAIV) amyloid is rare. Here we describe the first case of renal amyloidosis with pathology demonstrating concurrent deposition of AL and AApoAIV amyloid.
Case Presentation
A 79-year-old man presented with bilateral leg swelling and was diagnosed with nephrotic syndrome with preserved renal function. Serum protein electrophoresis and immunofixation showed no measurable monoclonal protein. Serum lambda free light chains were elevated at 97.72 mg/L, and kappa:lambda ratio was 0.22. Pathology from renal biopsy showed focal deposits of Congo red staining. Liquid chromatography tandem mass spectrometry identified both fibrillogenic ApoIV signal sequence peptides and a peptide profile consistent with AL amyloid deposition.
Further testing showed mild Bence Jones proteinuria, mildly elevated beta-2 microglobulin, elevated cardiac troponin T, normal NT-pro-B-type natriuretic peptide, and normal Factor X activity. Echocardiogram and FDG PET CT were unremarkable. Bone marrow biopsy demonstrated a lambda-restricted monotypic plasma cell population comprising 10% of plasma cells by immunohistochemistry. Although the Congo red stain was indeterminate, IGH::CCND1 fusion was detected by FISH.
Treatment was initiated with daratumumab, cyclophosphamide, bortezomib, and dexamethasone. Serum lambda light chains normalized after one cycle. Urine protein:creatinine ratio improved from 7.0 to 3.0 by the end of cycle 3. The patient will soon complete cycle 4 and undergo reassessment.
Discussion
While there are rare reports of AApoAIV renal amyloidosis and more prevalent cases of AL renal amyloidosis, the presence of both types of amyloid in the same patient has not been previously reported. AApoAIV renal amyloidosis has no established treatment and tends to present with rising serum creatinine as opposed to proteinuria. Given our patient’s clinical presentation with nephrotic syndrome and current light chain response to treatment, AL amyloidosis may be predominantly driving the disease.
Conclusions
Given the rarity of renal amyloidosis involving both AL and AApoAIV amyloid, the clinical course and optimal treatments are not established. The cumulative knowledge gained from individual case studies can serve as a basis for ongoing investigation and management of similar cases in the future.
Background
Whereas light chain (AL) amyloid is the most common cause of amyloidosis, Apolipoprotein A-IV (AApoAIV) amyloid is rare. Here we describe the first case of renal amyloidosis with pathology demonstrating concurrent deposition of AL and AApoAIV amyloid.
Case Presentation
A 79-year-old man presented with bilateral leg swelling and was diagnosed with nephrotic syndrome with preserved renal function. Serum protein electrophoresis and immunofixation showed no measurable monoclonal protein. Serum lambda free light chains were elevated at 97.72 mg/L, and kappa:lambda ratio was 0.22. Pathology from renal biopsy showed focal deposits of Congo red staining. Liquid chromatography tandem mass spectrometry identified both fibrillogenic ApoIV signal sequence peptides and a peptide profile consistent with AL amyloid deposition.
Further testing showed mild Bence Jones proteinuria, mildly elevated beta-2 microglobulin, elevated cardiac troponin T, normal NT-pro-B-type natriuretic peptide, and normal Factor X activity. Echocardiogram and FDG PET CT were unremarkable. Bone marrow biopsy demonstrated a lambda-restricted monotypic plasma cell population comprising 10% of plasma cells by immunohistochemistry. Although the Congo red stain was indeterminate, IGH::CCND1 fusion was detected by FISH.
Treatment was initiated with daratumumab, cyclophosphamide, bortezomib, and dexamethasone. Serum lambda light chains normalized after one cycle. Urine protein:creatinine ratio improved from 7.0 to 3.0 by the end of cycle 3. The patient will soon complete cycle 4 and undergo reassessment.
Discussion
While there are rare reports of AApoAIV renal amyloidosis and more prevalent cases of AL renal amyloidosis, the presence of both types of amyloid in the same patient has not been previously reported. AApoAIV renal amyloidosis has no established treatment and tends to present with rising serum creatinine as opposed to proteinuria. Given our patient’s clinical presentation with nephrotic syndrome and current light chain response to treatment, AL amyloidosis may be predominantly driving the disease.
Conclusions
Given the rarity of renal amyloidosis involving both AL and AApoAIV amyloid, the clinical course and optimal treatments are not established. The cumulative knowledge gained from individual case studies can serve as a basis for ongoing investigation and management of similar cases in the future.
Background
Whereas light chain (AL) amyloid is the most common cause of amyloidosis, Apolipoprotein A-IV (AApoAIV) amyloid is rare. Here we describe the first case of renal amyloidosis with pathology demonstrating concurrent deposition of AL and AApoAIV amyloid.
Case Presentation
A 79-year-old man presented with bilateral leg swelling and was diagnosed with nephrotic syndrome with preserved renal function. Serum protein electrophoresis and immunofixation showed no measurable monoclonal protein. Serum lambda free light chains were elevated at 97.72 mg/L, and kappa:lambda ratio was 0.22. Pathology from renal biopsy showed focal deposits of Congo red staining. Liquid chromatography tandem mass spectrometry identified both fibrillogenic ApoIV signal sequence peptides and a peptide profile consistent with AL amyloid deposition.
Further testing showed mild Bence Jones proteinuria, mildly elevated beta-2 microglobulin, elevated cardiac troponin T, normal NT-pro-B-type natriuretic peptide, and normal Factor X activity. Echocardiogram and FDG PET CT were unremarkable. Bone marrow biopsy demonstrated a lambda-restricted monotypic plasma cell population comprising 10% of plasma cells by immunohistochemistry. Although the Congo red stain was indeterminate, IGH::CCND1 fusion was detected by FISH.
Treatment was initiated with daratumumab, cyclophosphamide, bortezomib, and dexamethasone. Serum lambda light chains normalized after one cycle. Urine protein:creatinine ratio improved from 7.0 to 3.0 by the end of cycle 3. The patient will soon complete cycle 4 and undergo reassessment.
Discussion
While there are rare reports of AApoAIV renal amyloidosis and more prevalent cases of AL renal amyloidosis, the presence of both types of amyloid in the same patient has not been previously reported. AApoAIV renal amyloidosis has no established treatment and tends to present with rising serum creatinine as opposed to proteinuria. Given our patient’s clinical presentation with nephrotic syndrome and current light chain response to treatment, AL amyloidosis may be predominantly driving the disease.
Conclusions
Given the rarity of renal amyloidosis involving both AL and AApoAIV amyloid, the clinical course and optimal treatments are not established. The cumulative knowledge gained from individual case studies can serve as a basis for ongoing investigation and management of similar cases in the future.