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.
Kakiuchi et al. (Fri,) studied this question.