Nephrotic Syndrome Due to Heavy-Chain Amyloidosis

Introduction: Amyloidosis is a multi-system disorder that can affect the kidneys caused by deposition of insoluble amyloid fibrils. Ig heavy chain-associated (AH) amyloidosis is a very rare form of monoclonal Ig-related amyloidosis that is characterized by amyloid fibril deposition originating from fragments from the Ig heavy chain. There is limited published literature regarding AH amyloidosis given the rarity of the disease. It is noted that the presentation of AH amyloidosis including its organ involvement, clinical course, and response to therapy tends to be similar to AL amyloidosis. This pattern includes most often the involvement of the kidneys, heart, and nerves. Case Description: A 63-year-old male with a history of chronic pancreatitis presented to the clinic with generalized edema and weight gain over the past 3 months. He was found to have 24-hour urine protein of 13.4g, Serum albumin of 1.9, and Serum Creatinine of 1.0. The kappa/lambda ratio, complement levels, serum IgA and IgG were normal. On account of his proteinuria, the patient underwent a renal biopsy, which was consistent with amyloid nephropathy AH type, IgA restricted. He underwent a bone marrow biopsy that was consistent with a monoclonal B-cell lymphocytosis. He underwent chemotherapy with Dara-CyBorD with plan for 3-4 cycles before being referred for autologous stem cell transplant. Within 3 months of his presentation, he had an interval decrease of his proteinuria to 1.6g/day, albumin increased to 2.1, and improvement of edema. Discussion: AH amyloidosis is a very rare type of amyloidosis with limited published literature. The renal presentation is similar to AL amyloidosis, including nephrotic syndrome with or without renal insufficiency. AH amyloidosis patients tend to have lower frequency of cardiac involvement. Treatment revolves around suppressing the stimulus of the monoclonal protein, lowering proteinuria, and reducing the risk of advancement to late-stage kidney disease. Like AL amyloidosis, AH amyloidosis is typically treated with chemotherapeutic agents approved for multiple myeloma, which typically include Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone. Given this fact, early referral to oncology is important to ensure expertise for further workup and management of this disease. Eventual evaluation and referral for autologous stem-cell transplantation should take place as the most definitive treatment.