Repeat Kidney Biopsy to Inform Escalation and Discontinuation of Therapy in Light- and Heavy-Chain Deposition Disease.

Abstract

Persistent renal dysfunction after haematologic remission in monoclonal immunoglobulin deposition disease creates uncertainty regarding treatment intensity when clinical parameters do not distinguish reversible injury from established structural remodelling. We report a 34-year-old man with light- and heavy-chain deposition disease who presented with serum creatinine 1.8 mg/dL and heavy proteinuria (urine protein-to-creatinine ratio 5.0 g/gCr). After cyclophosphamide, bortezomib and dexamethasone therapy, haematologic parameters improved and proteinuria decreased; however, renal function continued to worsen, and serum creatinine increased to 4.1 mg/dL before autologous stem cell transplantation. Despite a deep haematologic response after transplantation, serum creatinine remained elevated at 2.7 mg/dL. A second kidney biopsy demonstrated persistent proliferative glomerular lesions with limited global sclerosis (1/56 glomeruli). Minimal residual disease remained detectable at 0.0029%, supporting additional clone-directed therapy. Following CD38-directed treatment, proteinuria resolved and minimal residual disease became undetectable, yet serum creatinine remained approximately 1.9 mg/dL with persistent microscopic haematuria. Because laboratory findings could not determine whether residual dysfunction reflected ongoing activity or fixed chronic change, a third kidney biopsy was performed. This biopsy revealed resolution of active glomerular lesions with predominance of chronic remodelling (5/32 globally sclerotic glomeruli). Therapy was discontinued, and renal function subsequently improved gradually to 1.1 mg/dL, remaining stable for more than 5 years without further therapy. Serial kidney biopsies informed two distinct therapeutic decisions-treatment escalation and subsequent discontinuation-when clinical parameters alone were insufficient to guide management.