Kidney-limited IgG3κ-PGNMID: A case report and narrative review

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare form of monoclonal gammopathy of renal significance, most commonly associated with IgG3-restricted deposits. In many patients, however, a circulating monoclonal protein or clonal plasma cell disorder cannot be identified, complicating therapeutic decision-making. We report the case of a 70-year-old woman presenting with nephrotic syndrome and progressive kidney dysfunction. Kidney biopsy demonstrated a membranoproliferative pattern with IgG3κ-restricted glomerular deposits, establishing the diagnosis of IgG3κ-PGNMID. Extensive hematologic evaluation including serum and urine immunofixation, serum free light chains, bone marrow biopsy with flow cytometry and cytogenetics, fluorescence in situ hybridization, and PET–CT revealed no detectable clonal plasma cell disorder. Despite optimized supportive therapy, kidney function deteriorated rapidly, with serum creatinine rising to 4.45 mg/dL and proteinuria exceeding 10 g/g. Empirical clone-directed therapy with daratumumab, bortezomib, melphalan, and prednisone (Dara-VMP) was initiated. An improvement in kidney function was observed, with proteinuria decreasing to 0.7 g/day after nine treatment cycles and stabilization of serum creatinine at approximately 2.0 mg/dL. Maintenance daratumumab therapy was subsequently continued. At 17 months of follow-up, the patient remains in partial renal remission with stable kidney function. This case supports the potential role of daratumumab-based therapy in patients with progressive PGNMID even when extensive hematologic evaluation fails to identify a clonal disorder.