Proliferative Glomerulonephritis with Monoclonal IgG Deposits

Abstract

Dysproteinemias that result in monoclonal glomerular deposits of IgG are relatively uncommon. Here, we report the largest series of proliferative glomerulonephritis with monoclonal IgG deposits, a form of renal involvement by monoclonal gammopathy that mimics immune-complex glomerulonephritis. We retrospectively identified 37 patients, most of whom were white (81%), female (62%), or older than 50 yr (65%). At presentation, 49% had nephrotic syndrome, 68% had renal insufficiency, and 77% had hematuria. In 30% of the patients, we identified a monoclonal serum protein with the same heavy-and light-chain isotypes as the glomerular deposits (mostly IgG1 or IgG2), but only one patient had myeloma. Histologic patterns were predominantly membranoproliferative (57%) or endocapillary proliferative (35%) with membranous features. Electron microscopy revealed granular, nonorganized deposits, and immunofluorescence demonstrated glomerular deposits that stained for a single light-chain isotype and a single heavy-chain subtype, most commonly IgG3 (53%). During an average of 30.3 mo of follow-up for 32 patients with available data, 38% had complete or partial recovery, 38% had persistent renal dysfunction, and 22% progressed to ESRD. Correlates of ESRD on univariate analysis were higher creatinine at biopsy, percentage of glomerulosclerosis, and degree of interstitial fibrosis but not immunomodulatory treatment or presence of a monoclonal spike. On multivariate analysis, higher percentage of glomerulosclerosis was the only independent predictor of ESRD. Only one patient lacking a monoclonal spike at presentation subsequently developed a monoclonal spike and no patient with a monoclonal spike at presentation subsequently developed a hematologic malignancy. We conclude that proliferative glomerulonephritis with monoclonal IgG deposits does not seem to be a precursor of myeloma in the vast majority of patients.

Rituximab–cyclophosphamide‐dexamethasone is highly effective in patients with monoclonal Ig deposit‐related glomerulopathy and indolent non‐Hodgkin lymphomas

“…Less commonly, iNHLs may also promote glomerulonephritis associated with monoclonal deposits [3,12,13], with extremely heterogeneous pathologic pattern as exemplified in our series.…”

“…Among the 12 patients who received RCD as a first-line therapy, eight (67%) obtained a complete renal response. Among the nine patients with a complete haematological response, six (67%) reached a complete renal response (median time between haematological and renal complete response was 3 months [1][2][3][4][5][6][7][8][9][10]), compared with two that did not reach a complete haematological response (not significant). A significant reduction in 24-hr proteinuria was observed over time following RCD therapy as shown in Fig.…”

“…To date, most published series on glomerulopathy with monoclonal Ig deposits have been based on pathologic patterns [3,6,[12][13][14][15]. Because of the wide heterogeneity of treatments in these series (e.g., no treatment, steroids only, rituximab, or combined chemotherapy), no firm recommendations for iNHL treatment are available.…”

“…Renal complications of circulating monoclonal immunoglobulin may result from light chains, light and heavy chains, or heavy-chain deposition, Type-I cryoglobulinemic glomerulonephritis, or light-chain proximal tubulopathy [1,2]. Monoclonal Ig-dependent glomerulonephritis (mIgGN) can occur in a membranous, membranoproliferative, diffuse proliferative, cryoglobulinemic, amyloidosic, or crescentic pattern [3][4][5].…”

Determination of primary versus secondary membranous glomerulopathy utilizing phospholipase A2 receptor staining in renal biopsies

“…However, there are rare cases with light chain restriction, usually k. These cases have more recently been included within the spectrum of 'proliferative glomerulonephritis with monoclonal IgG deposits' (Nasr Disease). 20 The majority of the reported cases are idiopathic in nature without a known secondary lymphoproliferative disorder. 21 There is, however, one report of this form of membranous glomerulopathy in the setting of lymphoma.…”