Early Macrophage Infiltration and Sustained Inflammation in Kidneys From Deceased Donors Are Associated With Long-Term Renal Function

Am J Transplant. 2017 Mar;17(3):733-743. doi: 10.1111/ajt.13998. Epub 2016 Sep 15.

Abstract

Kidney transplants from living donors (LDs) have a better outcome than those from deceased donors (DDs). Different factors have been suggested to justify the different outcome. In this study, we analyzed the infiltration and phenotype of monocytes/macrophages and the expression of inflammatory and fibrotic markers in renal biopsy specimens from 94 kidney recipients (60 DDs and 34 LDs) at baseline and 4 months after transplantation. We evaluated their association with medium- and long-term renal function. At baseline, inflammatory gene expression was higher in DDs than in LDs. These results were confirmed by the high number of CD68-positive cells in DD kidneys, which correlated negatively with long-term renal function. Expression of the fibrotic markers vimentin, fibronectin, and α-smooth muscle actin was more elevated in biopsy specimens from DDs at 4 months than in those from LDs. Gene expression of inflammatory and fibrotic markers at 4 months and difference between 4 months and baseline correlated negatively with medium- and long-term renal function in DDs. Multivariate analysis point to transforming growth factor-β1 as the best predictor of long-term renal function in DDs. We conclude that early macrophage infiltration, sustained inflammation, and transforming growth factor-β1 expression, at least for the first 4 months, contribute significantly to the difference in DD and LD transplant outcome.

Keywords: basic (laboratory) research/science; biopsy; donors and donation; fibrosis; graft survival; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; molecular biology; translational research/science.

Publication types

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

MeSH terms

  • Adult
  • Cadaver
  • Delayed Graft Function
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / etiology*
  • Graft Rejection / pathology
  • Graft Survival / immunology*
  • Humans
  • Inflammation / etiology*
  • Inflammation / pathology
  • Kidney Failure, Chronic / surgery
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Macrophages / immunology*
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Tissue Donors*
  • Tissue and Organ Procurement / methods*