Varied Presentations and Clinical Outcomes of Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposit: An Indian Series of Five Patients

A BSTRACT Background: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMIDs) is a unique and rare entity which can have a variety of presentations ranging from nephrotic syndrome to rapidly progressive renal failure (RPRF). The data about this entity are sparse worldwide and there is hardly any robust literature from India. Methods: A retrospective analysis of 320 patients undergoing native kidney biopsy from August 2021 to August 2024 in the Department of Nephrology, AIIMS Jodhpur, was done and 5 cases of PGNMID constituting 1.25% of the native kidney biopsies and 33% of biopsy proven monoclonal gammopathy of renal significance (15 cases) were analyzed. Results: The mean age of presentation was 48 years with a female preponderance (80%). The mean estimated glomerular filtration rate at presentation was 34.6 ml/min/1.73 m 2 with 60% patients presenting as RPRF, the mean proteinuria being 5.8 g/day. None of the patients had paraproteinemia. On histopathology, membranoproliferative glomerulonephritis was seen in 2 (40%), endocapillary hypercellularity in 2 (40%) and membranous pattern in 1 (20%), with 3 (60%) patients showing crescents. Immunofluorescence showed deposits of immunoglobulin G (IgG) kappa in 4 (80%) and IgG lambda restriction in 1 (20%). Electron microscopy done in 2 of the 5 patients showed subepithelial deposits in one and subendothelial deposits in the other. Therapeutic response was varied. The patient with membranous pattern had an indolent course with just anti-proteinuric measures. Cyclophosphamide–bortezomib–dexamethasone was administered in two patients, being ineffective in both. Rituximab resulted in complete remission in one patient. The outcome in others were unfavorable, 2 (40%) had persistent renal dysfunction while 2 (40%) progressed to end-stage renal disease. Conclusion: PGNMID is a distinct entity whose clinical profile may be varied. Chemotherapy has been found to improve outcomes, however, larger prospective randomized multicenter studies are mandated to define the optimal therapeutic approach and duration of treatment.