Renal allograft fibrosis: biology and therapeutic targets

Am J Transplant. 2015 Apr;15(4):863-86. doi: 10.1111/ajt.13180. Epub 2015 Feb 17.

Abstract

Renal tubulointerstitial fibrosis is the final common pathway of progressive renal diseases. In allografts, it is assessed with tubular atrophy as interstitial fibrosis/tubular atrophy (IF/TA). IF/TA occurs in about 40% of kidney allografts at 3-6 months after transplantation, increasing to 65% at 2 years. The origin of renal fibrosis in the allograft is complex and includes donor-related factors, in particular in case of expanded criteria donors, ischemia-reperfusion injury, immune-mediated damage, recurrence of underlying diseases, hypertensive damage, nephrotoxicity of immunosuppressants, recurrent graft infections, postrenal obstruction, etc. Based largely on studies in the non-transplant setting, there is a large body of literature on the role of different cell types, be it intrinsic to the kidney or bone marrow derived, in mediating renal fibrosis, and the number of mediator systems contributing to fibrotic changes is growing steadily. Here we review the most important cellular processes and mediators involved in the progress of renal fibrosis, with a focus on the allograft situation, and discuss some of the challenges in translating experimental insights into clinical trials, in particular fibrosis biomarkers or imaging modalities.

Keywords: basic (laboratory) research/science; biomarker; fibrosis; immunosuppressant; kidney transplantation/nephrology; molecular biology; pathology/histopathology; translational research/science.

Publication types

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

MeSH terms

  • Fibrosis / etiology*
  • Humans
  • Kidney Transplantation / adverse effects*
  • Transplantation, Homologous / adverse effects*