Rare and rapidly progressive crescentic proliferative glomerulonephritis with monoclonal immunoglobulin deposits: a...

Crescentic proliferative glomerulonephritis with monoclonal immunoglobulin deposits (c-PGNMID), defined as >50% glomerular crescents, represents an aggressive and poorly characterized variant of PGNMID - a rare monoclonal gammopathy-related nephropathy first described in 2004. While crescents occur in 30-40% of PGNMID cases, c-PGNMID lacks systematic clinicopathological characterization, with no prior case series reported. This study aims to delineate its clinical spectrum, therapeutic challenges and outcomes.

We retrospectively analyzed four cases of biopsy-proven c-PGNMID from National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine (1 January 2010 to 31 December 2023). Evaluations included laboratory parameters, renal ultrasound status and bone marrow examination. Treatment responses were assessed by serial serum creatinine and 24-hour proteinuria.

The cohort (three males, one female; median age 42 years) presented with rapidly progressive glomerulonephritis (RPGN, median serum creatinine 7.55 mg/dL) and nephrotic-range proteinuria (median 9.05 g/24 h). Hypocomplementemia was observed in three cases. Renal histopathology demonstrated: (1) diffuse crescentic proliferation (53.8-79.5% glomeruli) with membranoproliferative features; (2) monotypic IgG3 deposits (κ-restricted 3/4, λ-restricted 1/4); (3) subendothelial/mesangial/subepithelial electron-dense deposits. Treatment regimens included pulse methylprednisolone (0.25-2.4 g cumulative) and cyclophosphamide (2.4-14.4 g cumulative) with thalidomide + dexamethasone, rituximab or plasma exchange. Despite intensive intervention, all patients progressed to dialysis dependence within 6-34 months.

This single center retrospective study characterizes c-PGNMID in four patients. All cases exhibited IgG3κ/λ-restricted deposits, hypocomplementemia (3/4) and rapid progression to end-stage kidney disease (ESKD) despite aggressive immunosuppression. These findings highlight the need for novel therapies targeting clonal plasma cells or complement-mediated injury.