Renal auto-transplantation promotes cortical microvascular network remodeling in a preclinical porcine model

PLoS One. 2017 Jul 13;12(7):e0181067. doi: 10.1371/journal.pone.0181067. eCollection 2017.

Abstract

The vascular network is a major target of ischemia-reperfusion, but has been poorly investigated in renal transplantation. The aim of this study was to characterize the remodeling of the renal vascular network that follows ischemia-reperfusion along with the most highly affected cortex section in a preclinical renal transplantation model. There were two experimental groups. The first was a grafted kidney group consisting of large white pigs for which the left kidney was harvested, cold flushed, preserved for 24 h in the University of Wisconsin's preservation solution, and then auto-transplanted (n = 5); the right kidney was removed to mimic the situation of human kidney transplantation. The second group (uni-nephrectomized kidney group) consisted of animals that underwent only right nephrectomy, but not left renal transplantation (n = 5). Three months after autotransplantation, the kidneys were studied by X-ray microcomputed tomography. Vessel morphology and density and tortuosity of the network were analyzed using a 3D image analysis method. Cortical blood flow was determined by laser doppler analysis and renal function and tissue injury assessed by plasma creatinine levels and histological analysis. Renal ischemia-reperfusion led to decreased vascular segment volume associated with fewer vessels of less than 30 μm, particularly in the inner cortex:0.79 ± 0.54% in grafted kidneys vs. 7.06 ± 1.44% in uni-nephrectomized kidneys, p < 0.05. Vessels showed higher connectivity throughout the cortex (the arborescence factor of the whole cortex was less in grafted than uni-nephrectomized kidneys 0.90 ± 0.04 vs. 1.07 ± 0.05, p < 0.05, with an increase in the number of bifurcations). Furthermore, cortical blood flow decreased early in kidney grafts and remained low three months after auto-transplantation. The decrease in microvasculature correlated with a deterioration of renal function, proteinuria, and tubular dysfunction, and was associated with the development of fibrous tissue. This work provides new evidence concerning the impact of ischemia-reperfusion injuries on the spectrum of renal vascular diseases and could potentially guide future therapy to preserve microvessels in transplantation ischemia-reperfusion injury.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Graft Survival
  • Humans
  • Kidney / blood supply*
  • Kidney / diagnostic imaging
  • Kidney Transplantation / methods*
  • Microvessels / diagnostic imaging*
  • Organ Preservation
  • Reperfusion Injury / diagnostic imaging*
  • Swine
  • Transplantation, Autologous
  • X-Ray Microtomography / methods*

Grants and funding

This study was supported by funding from Inserm (http://www.inserm.fr) and University of Poitiers (http://www.univ-poitiers.fr). All the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Professor T Hauet and F Favreau received a salary from University of Poitiers, but they worked independently from University of Poitiers in this research study.