Polyethylene glycol reduces the inflammatory injury due to cold ischemia/reperfusion in autotransplanted pig kidneys

Abstract

Background: The conditions of storage of donor kidney may influence the deleterious consequences of ischemia/reperfusion injury (IRI) on delayed graft function. Since polyethylene glycol (PEG) can protect renal tubule cells against cold injury, we tested the effects of adding PEG 20 kD to ice-cold preservation solutions on the IRI of autotransplanted pig kidneys.

Methods: The pigs' left kidneys were removed, cold-flushed with University of Wisconsin (UW) or simplified high K+ or high Na+ solutions with or without 30 g/L PEG 20M and stored for 48 hours at 4 degrees C. The kidneys were then autotransplanted and the contralateral kidneys were removed. Kidney biopsies were then performed and renal function parameters were analyzed over 8 to 12 weeks following surgery.

Results: The kidneys cold-flushed with PEG-supplemented solutions on day 7 post-transplantation were better preserved and exhibited less marked nuclear tubular cell damage than the kidneys cold-flushed with the UW solution alone. PEG also almost completely inhibited the overexpression of major histocompatibility complex class II that was detected in epithelial tubule cells from kidneys cold-flushed with the UW solution. PEG also significantly reduced the number of CD4+ T lymphocytes and limited the infiltration of macrophages/monocytes and the progression of interstitial fibrosis in the 8- to 12-week post-transplanted kidneys. Moreover, pigs autotransplanted with kidneys flushed with PEG-supplemented solutions had the best renal function and the lowest levels of proteinuria.

Conclusions: These findings indicate that PEG inhibits the early inflammatory response due to IRI, improves renal function, and may prevent the progression of interstitial fibrosis in the long-term autotransplanted pig kidney.