A Twisted Tale of Monoclonal Gammopathy of Renal Significance

Introduction: Monoclonal Gammopathy of Renal Significance (MGRS) can vary in kidney manifestations. We report a case of worsening kidney disease in a patient who initially responded well to daratumumab, bortezomib, cyclophosphamide, dexamethasone (DaraCyBorD) for biopsy proven light chain deposition disease (LCDD). Case Description: 52-year-old female with hypertension, smoking, chronic kidney disease 3b diagnosed with LCDD seven months prior to presentation. Initial labs: IgG lambda on immunofixation (IFE), 0.7 g/dL M-spike, serum free light chain (SFLC) kappa 8.11 mg/dL, lambda 7.91 mg/dL and ratio 1.03, normocellular bone marrow. DaraCyBorD treatment was started and, after 3 cycles, had a good hematologic response 0.16 g/dL M-spike, kappa 3.59 mg/dL, lambda 2.01 mg/dL and ratio 1.79. Renal function and proteinuria worsened prompting further evaluation. At presentation, labs showed Cr 4.8 mg/dL (from baseline of ~2.4 mg/dl), UPCR 6.2g/g, IgG Kappa on IFE (likely from Daratumumab), 0.1 g/dL M-spike, kappa 3.64mg/dL, lambda 2.57 mg/dL and ratio 1.04. Repeat kidney biopsy (Figure) showed two concurrent clonal processes causing MGRS: 1) proliferative glomerulonephritis with monotypic immunoglobulin deposition with IgG3 kappa deposits characterized by diffuse proliferative glomerular injury with 20-25% cellular crescents and focal necrotizing lesions, and 2) heavy/light chain deposition disease with IgG1 lambda deposits. She was treated with high-dose steroids, but chemotherapy was deferred pending bone marrow biopsy results. Discussion: Dual concurrent clonal processes causing MGRS is rare. Typically, non-amyloid MGRS responds to initial treatment in 72% of patients. A second MGRS may represent treatment failure or a previously undetected clone. Clinicians should have a low threshold for repeat kidney biopsy in patients with worsening renal function and proteinuria despite good response to chemotherapy.