Proliferative Glomerulonephritis With Fibrils, Monoclonal κ Light Chain, and C3 Deposits

Am J Kidney Dis. 2021 Sep;78(3):459-463. doi: 10.1053/j.ajkd.2021.01.014. Epub 2021 Mar 25.

Abstract

There is increasing recognition of monoclonal gammopathy as a cause of proliferative glomerulonephritis (GN), including cases in which glomerular deposition of monoclonal immunoglobulin is demonstrated. Recently, proliferative GN with monoclonal immunoglobulin deposits (PGNMID) has incorporated a light chain variant of the disease (termed PGNMID-LC). Intriguingly, glomerular co-deposition of C3 is found in addition to monotypic light chain, implying complement activation via the alternative pathway (AP). We present a unique case of proliferative GN in a 42-year-old man who presented with nephrotic syndrome and was found to have κ light chain multiple myeloma. Immune staining of the glomerulus was positive only for κ light chain and C3, with the striking appearance of nonamyloid fibrils on electron microscopy. Following clonally targeted therapy for myeloma, the renal clinical abnormalities resolved completely. We present detailed molecular studies for light chain and complement and consider local mechanisms whereby monoclonal κ light chain fibrils may have triggered AP activation within the glomerulus.

Keywords: B-cell disorder; C3 glomerulopathy; Case report; Complement; Fibrils; Immunotactoid; Kidney biopsy; Light chain; Membranoproliferative glomerulonephritis (MPGN); Monoclonal gammopathy of renal significance (MGRS); Multiple myeloma; PGNMID.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Biopsy
  • Complement C3 / metabolism*
  • Fibrosis / diagnosis
  • Fibrosis / immunology
  • Fibrosis / metabolism
  • Glomerulonephritis, Membranoproliferative / diagnosis*
  • Glomerulonephritis, Membranoproliferative / immunology
  • Glomerulonephritis, Membranoproliferative / metabolism
  • Humans
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / metabolism
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / ultrastructure*
  • Male
  • Microscopy, Electron

Substances

  • Complement C3
  • Immunoglobulin G