Polyethylene Glycol Reduces Early and Long-Term Cold Ischemia-Reperfusion and Renal Medulla Injury

Abstract

Ischemia-reperfusion injury (IRI) after transplantation is a major cause of delayed graft function, which has a negative impact on early and late graft function and improve acute rejection. We have previously shown that polyethylene glycol (PEG) and particularly PEG 20M has a protective effect against cold ischemia and reperfusion injury in an isolated perfused pig and rat kidney model. We extended those observations to investigate the role of PEG using different doses (30g or 50g/l) added (ICPEG30 or ICPEG50) or not (IC) to a simplified preservation solution to reduce IRI after prolonged cold storage (48-h) of pig kidneys when compared with Euro-Collins and University of Wisconsin solutions. The study of renal function and medulla injury was performed with biochemical methods and proton NMR spectroscopy. Histological and inflammatory cell studies were performed after reperfusion (30 -40 min) and on days 7 and 14 and weeks 4, 8, and 12. Peripheral-type benzodiazepine receptor (PBR), a mitochondrial protein involved in cholesterol homeostasis, was also studied. The results demonstrated that ICPEG30 improved renal function and reduced medulla injury. ICPEG30 also improved tubular function and strongly protect mitochondrial integrity. Post-IRI inflammation was strongly reduced in this group, particularly lymphocytes TCD4 ϩ , PBR expression was influenced by IRI in the early period and during the development of chronic dysfunction. This study clearly shows that PEG has a beneficial effect in renal preservation and suggests a role of PBR as a marker IRI and repair processes.

Cold Preservation Mediated Renal Injury: Involvement of Mitochondrial Oxidative Stress

“…The adverse effects of extended periods of cold renal preservation have been demonstrated using animal [16,17,32,33] and cellular [14,15,34,35] models. Cells exposed to cold storage have been shown to sustain mitochondrial injury and cell death.…”

Protective Effect of PEG 35 000 Da on Renal Cells: Paradoxical Activation of JNK Signaling Pathway During Cold Storage

“…We showed, in an extensive way, the beneficial effect of a simple modified Krebs solution containing a 20 000 Da polyethylene glycol (PEG20) on an autotransplanted pig kidney model (15,16). These transplanted kidneys exhibited less marked tubular cell damage than kidneys cold-flushed with UW (17).…”

The Mitochondria-Targeted Antioxidant Mitoquinone Protects against Cold Storage Injury of Renal Tubular Cells and Rat Kidneys

“…Some reports suggest that the addition of bioflavonoids and trophic factor supplementation to preservation solutions should be explored further because these compounds prevented lipid peroxidation, mitochondrial dysfunction, and loss of cell viability during CS of porcine and canine renal tubular cells (Ahlenstiel et al, 2006;Kwon et al, 2007). The addition of polyethylene glycol and trimetazidine to preservation solutions reduced interstitial and peritubular inflammation, infiltration, and renal dysfunction of pig kidneys after cold ischemia/reperfusion (I/R) (Hauet et al, 2000;Faure et al, 2002). The addition of the antioxidant deferoxamine to the University of Wisconsin (UW) preservation solution has been shown to improve glomerular filtration rate and decrease cell death in a syngeneic rat kidney transplant model .…”