Increase of Proliferating Renal Progenitor Cells in Acute Tubular Necrosis Underlying Delayed Graft Function

Abstract

Background. Delayed graft function (DGF) is associated with acute tubular necrosis. In this setting, surviving tubular cells may proliferate and replace injured cells. CD133⁺Pax-2⁺cells may play a role in the regeneration of tubular damage. The aim of this study was to demonstrate the presence of these cells in human kidneys before transplantation and in grafts with DGF. Methods. Ten normal kidneys (group 1) and pretransplant biopsy of 25 deceased donors (group 2) were examined. The latter group included 10 kidneys with early graft function (2A) and 15 with DGF (2B). Group 2B patients received a second biopsy during DGF (2C). CD133, Pax-2, and Ki-67 protein expression was investigated by confocal microscopy. Results. CD133⁺Pax-2⁺ and CD133⁻Pax-2⁺cells were present within the Bowman’s capsule and proximal tubules in all groups except group 2B. Number of CD133⁺Pax-2⁺ and CD133⁻Pax-2⁺cells at tubular level was similar in groups 1 and 2A. Within group 2B we observed a striking reduction in both cell types. There was a significant increase of both cell populations within group 2C, compared with group 2B. CD133⁺Pax-2⁺ and CD133⁻Pax-2⁺cell number in group 2 correlated inversely with cold ischemia time. Pax-2⁺Ki-67⁺cells were absent from group 1 and 2B samples, and increased significantly in groups 2A and 2C. Proliferating CD133⁺ cells increased significantly in group 2C. Conclusions. Our data suggest that regenerative response in posttransplant acute tubular necrosis, underlying DGF, is characterized by an increase in proliferating renal progenitor/stem cells CD133⁺Pax-2⁺ and CD133⁻Pax-2⁺ cells involved in repairing tubular damage.