An integrated view of molecular changes, histopathology and outcomes in kidney transplants

Am J Transplant. 2010 Oct;10(10):2223-30. doi: 10.1111/j.1600-6143.2010.03268.x.


Data-driven approaches to deteriorating kidney transplants, incorporating histologic, molecular and HLA antibody findings, have created a new understanding of transplant pathology and why transplants fail. Transplant dysfunction is best understood in terms of three elements: diseases, the active injury-repair response and the cumulative burden of injury. Progression to failure is mainly attributable to antibody-mediated rejection, nonadherence and glomerular disease. Antibody-mediated rejection usually develops late due to de novo HLA antibodies, particularly anti-class II, and is often C4d negative. Pure treated T cell-mediated rejection does not predispose to graft loss because it responds well, even with endothelialitis, but it may indicate nonadherence. The cumulative burden of injury results in atrophy-fibrosis (nephron loss), arterial fibrous intimal thickening and arteriolar hyalinosis, but these are not progressive without ongoing disease/injury, and do not explain progression. Calcineurin inhibitor toxicity has been overestimated because burden-of-injury lesions invite this default diagnosis when diseases such as antibody-mediated rejection are missed. Disease/injury triggers a stereotyped active injury-repair response, including de-differentiation, cell cycling and apoptosis. The active injury-repair response is the strongest correlate of organ function and future progression to failure, but should always prompt a search for the initiating injury or disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • Cost of Illness
  • Disease Progression
  • Fibrosis
  • Graft Rejection / immunology*
  • Humans
  • Kidney / immunology
  • Kidney / pathology
  • Kidney Transplantation / immunology*
  • Patient Compliance
  • Phenotype
  • Treatment Outcome