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

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 4degreesC. 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.