Proliferative glomerulonephritis with monoclonal IgG deposits

J Am Soc Nephrol. 2009 Sep;20(9):2055-64. doi: 10.1681/ASN.2009010110. Epub 2009 May 21.

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 IgG3kappa (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / immunology
  • Biopsy
  • Female
  • Fluorescent Antibody Technique
  • Follow-Up Studies
  • Glomerulonephritis, Membranoproliferative / drug therapy
  • Glomerulonephritis, Membranoproliferative / immunology*
  • Glomerulonephritis, Membranoproliferative / pathology*
  • Humans
  • Immunoglobulin G / immunology*
  • Immunologic Factors / therapeutic use
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / ultrastructure
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Paraproteinemias / immunology*
  • Paraproteinemias / pathology*
  • Retrospective Studies
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Immunologic Factors