New insights regarding chronic antibody-mediated rejection and its progression to transplant glomerulopathy

Curr Opin Nephrol Hypertens. 2014 Nov;23(6):611-8. doi: 10.1097/MNH.0000000000000070.


Purpose of this review: To discuss new insights regarding chronic antibody-mediated rejection (CAMR) and its progression to transplant glomerulopathy. We will describe the progression to transplant glomerulopathy from a histologic perspective and provide updates on what is known about its pathophysiology, prognosis, and potential therapy.

Recent findings: Transplant glomerulopathy is a major contributor to long-term renal allograft loss and is most often associated with CAMR. On the basis of protocol biopsies, we have found that 3.5% of conventional transplants and 27.5% of positive crossmatch kidney transplants have transplant glomerulopathy at 1 year. The pathophysiology of the process is largely unknown, but complement activation was previously thought to be essential. However, CAMR appears to develop despite terminal complement blockade and many C4d negative cases of CAMR have been identified. Thus, complement independent mechanisms, such as direct endothelial cell activation and the infiltration of natural killer cells and monocytes, are likely key to the development of transplant glomerulopathy.

Summary: Transplant glomerulopathy is often the result of CAMR and leads to allograft loss. It is characterized by distinctive histologic changes, and its pathophysiology is a multifaceted process involving both innate and adaptive immunity. Despite advances in the understanding of this condition, no effective therapy exists.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chronic Disease
  • Disease Progression
  • Glomerulonephritis / diagnosis
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / physiopathology
  • Glomerulonephritis / therapy
  • Graft Rejection / diagnosis
  • Graft Rejection / immunology*
  • Graft Rejection / physiopathology
  • Graft Rejection / therapy
  • Graft Survival
  • Histocompatibility*
  • Humans
  • Isoantibodies / immunology*
  • Kidney / immunology*
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney Transplantation / adverse effects*
  • Treatment Outcome


  • Isoantibodies