Hemato-Renal Profile of Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits

Abstract

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare entity classified under the umbrella of monoclonal gammopathy of renal significance. The clinical implications of circulating monoclonal immunoglobulin (MIg), light chain restriction on immunofluorescence (IF) microscopy, histopathological pattern, and type of therapy on renal outcomes are not clearly defined. Sixteen patients of PGNMID diagnosed between 2013 and 2020 were included from a biopsy registry of 11,459 patients at a single center. Follow-up data was collected from electronic medical records until June 2021. The mean age of the cohort was 41.7 ± 13.5 years. Forty-four (7/16) percent showed monoclonal protein on serum or urine electrophoresis, 25% (3/12) had IgG kappa by serum immunofixation electrophoresis (IFE) and 38% (5/13) had abnormal kappa: lambda free light chain (FLC) ratio. The predominant light microscopy pattern, membranoproliferative glomerulonephritis (MPGN) was seen in 7/16 (43.7%) patients. The predominant heavy chain detected by IF microscopy was IgG (13/16, 81.3%). Kappa and lambda light chain restriction were seen in 56.3 (9/16) and 43.8 (7/16) percent of patients respectively. Circulating monoclonal kappa light chains were detected in 50 and 29% of kappa-PGNMID patients by IFE and FLC assay respectively. None of the lambda-PGNMID patients had detectable circulating monoclonal lambda light chains. Patients with circulating MIg had more proteinuria, lower estimated glomerular filtration rate, and a higher percentage of plasma cells on bone marrow biopsy. Thirty-eight percent of our cohort (5/13) progressed to kidney failure over a median (range) period of 3 (IQR, 1-7) months. Of these, 4/5 received immunosuppression, and 1/5 were treated with plasma cell-targeted chemotherapy. PGNMID is a rare disease with a biopsy incidence of 0.1%. Only a quarter of patients with PGNMID have circulating MIg. Presence of circulating MIg, type of monoclonal light chain restriction in kidney biopsy, and type of therapy did not predict renal outcomes. Patients with MPGN pattern had favorable renal outcomes despite a higher degree of proteinuria at presentation.