Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits is associated with high rate of early recurrence in the allograft

Kidney Int. 2018 Jul;94(1):159-169. doi: 10.1016/j.kint.2018.01.028. Epub 2018 Apr 30.

Abstract

The characteristics of allograft proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID) are not well defined. To better characterize this disease we retrospectively identified 26 patients with allograft PGNMID, including 16 followed with early protocol biopsies. PGNMID was found to be a recurrent disease in most (89%) patients. A diagnostic biopsy was done for proteinuria and/or increased creatinine in most patients. Median time from transplant to diagnostic biopsy was 5.5 months, with detection within three to four months post-transplant in 86% of patients. Mesangial proliferative glomerulonephritis was the most common pattern on the diagnostic biopsy with 89% of cases showing immunoglobulin G3 subtype restriction. A detectable serum paraprotein was present in 20% of patients. During a mean follow up of 87 months from implantation, 11 of 25 patients lost their allograft largely due to PGNMID within a mean of 36 months from diagnosis. Median graft survival was 92 months. Independent predictors of graft loss were a higher degree of peak proteinuria and longer time from implantation to diagnosis. Sixteen patients were treated with immunosuppressive therapy which resulted in over 50% reduction in proteinuria in 60%, and improvement of glomerular pathology in nine of 13 patients. However, 44% of responders subsequently relapsed. Thus, PGNMID has a high recurrence rate in renal allografts occurring early with detection enhanced by protocol biopsies. Graft outcome is guarded as nearly half of patients lose their graft within three years from diagnosis. Hence, there is a need for better treatment strategies for this disease.

Keywords: PGNMID; membranoproliferative glomerulonephritis; monoclonal gammopathy; recurrent glomerulonephritis; renal allograft.

MeSH terms

  • Adult
  • Aged
  • Allografts / immunology
  • Allografts / pathology*
  • Antibodies, Monoclonal / immunology*
  • Biopsy
  • Female
  • Follow-Up Studies
  • Glomerulonephritis, Membranoproliferative / immunology
  • Glomerulonephritis, Membranoproliferative / pathology*
  • Glomerulonephritis, Membranoproliferative / therapy
  • Graft Survival / immunology
  • Humans
  • Immunoglobulin G / immunology*
  • Immunosuppression Therapy / methods
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / pathology*
  • Kidney Transplantation
  • Male
  • Middle Aged
  • Recurrence
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin G