Kidney Week

Abstract: SA-PO179

Cast Nephropathy from Gamma Heavy-Chain Disease

Session Information

• Onconephrology: Kidney Outcomes during Cancer Treatment and Nephropathies
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Onconephrology

• 1700 Onconephrology

Authors

• Desikan, Sai Prasad, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Sai Prasad Desikan, MD

• Desikan, Raman, White River Health System Inc, Batesville, Arkansas, United States

Raman Desikan, MD

Introduction

In heavy chain disease, frame shift, point mutations, or somatic hypermutations result in the loss of portions of the heavy chain responsible for binding light chains. Gamma heavy chain disease in particular is uncommon. Here we present a patient with gamma heavy chain disease with nephrotic range proteinuria and heavy chain cast nephropathy.

Case Description

A 70-year old male presented with pancytopenia and declining renal function. CBC consisted of WBC of 1.6 x 10³ /μL, Hgb 10.2 g/dL, and PLT of 90 x 10³ / μL. Cr was 2.1 mg/dL. IgG was elevated at 2784 mg/dl. IgM and IgA were both low. 24 hour urine protein was elevated 8g/24 hours. Ig heavy chain made up 7.5g/24hr period. Bone marrow aspirate and biopsy evaluation was notable for 40% plasma cells on immunohistochemistry. Flow cytometry revealed 14.7% plasma cells , cytoplasmic lambda light chain restricted CD38 bright plasma cells. FISH revealed loss of IgH and FGFR3 genes. Renal biopsy revealed cast nephropathy with IgH and severe arteriolar nephrosclerosis. He received the VDT-ACE, Daratumumab protocol. Autologous SCT was performed. On follow up, proteinuria was significantly diminished at 150mg/24 hours and . Monoclonal protein was absent. Bone marrow biopsy revealed normocellular bone marrow 1% plasma cells observed in aspirate and 5-10% plasma cells in core biopsy. Minimal residual disease assessed by flow cytometric analysis was positive. He received velcade, revlimid and dexamethasone as well as stem cell infusion. Course complicated by pancytopenia. Upon recovery he received further consolidation with daratumumab and dexamethasone. He achieved MRD negativity. Cr continues to be elevated at 1.9 mg/dL.

Discussion

Our patient presented with the rare combination of gamma heavy chain disease, nephrotic range proteinuria, and cast nephropathy. Cast nephropathy is usually a result of light chains binding uromodulin; however, this is the first reported case of heavy chains resulting in cast nephropathy. This patient was successfully treated with induction, autologous transplant, and post transplant consolidation. To date, this is the first patient with gamma heavy chain disease managed with autologous transplant.