Protection of autotransplanted pig kidneys from ischemia-reperfusion injury by polyethylene glycol.

BACKGROUND: Ischemia-reperfusion injury (IRI) is often responsible for graft rejection and leads to delayed graft function of cadaveric kidneys. We have shown that adding polyethylene glycol (PEG 20M) to the preservation solutions helps protect isolated perfused pig kidneys against cold ischemia and reperfusion injury. METHODS: We compared the effects of adding PEG to a simplified high-K+ perfusion solution of cold-stored kidneys to Euro-Collins or University of Wisconsin solutions on the function of reperfused autotransplanted pig kidneys. The left kidney was cold-flushed with the preservation solutions and stored for 48 hr at 4 degrees C before reimplantation. Creatinine clearance and fractional excretion of sodium were analyzed 2 days before surgery and over 7 days after transplantation. Histological sections were obtained 40 min after reperfusion and on day 7 after surgery. RESULTS: Adding PEG to the perfusate significantly reduced IRI from autotransplanted pig kidneys. Creatinine clearance was significantly higher and fractional excretion of sodium was significantly lower in pigs transplanted with kidneys cold-flushed with PEG-supplemented perfusate than in those flushed with Euro-Collins or University of Wisconsin solutions. PEG supplementation also better preserved the integrity of kidney cells and markedly reduced interstitial cell infiltrates. CONCLUSION: PEG protects against IRI and reduces early cellular inflammation. PEG may impair the recruitment and migration of leukocytes into retransplanted pig kidneys. Cold preservation of donor organs with PEG-supplemented solutions may therefore help limit IRI in human renal transplantation.

Pharmacological limitation of damage to renal medulla after cold storage and transplantation by trimetazidine.

Delayed graft function remains an important complication after renal transplantation. In this study, we investigated the influence of trimetazidine (TMZ), a cytoprotective agent, on renal medullary damage after prolonged preservation and autotransplantation. Pig kidneys were cold-flushed and preserved (48 h at 4 degrees C) with two standard renal preservation solutions Euro-Collins and University of Wisconsin supplemented or not with TMZ (10(-6) M). Analysis of plasma and urine from 48-h-cold-stored and autotransplanted kidneys was performed with biochemical methods and proton NMR spectroscopy. Histological study by light and electron microscopy was performed after reperfusion (30-40 min) and on day 14. The results showed that the preservation in either Euro-Collins or University of Wisconsin solution containing TMZ improved significantly glomerular filtration rate compared with kidneys preserved without TMZ. TMZ significantly reduced renal medullary damage, evidenced by decreased excretion of trimethylamine-N-oxide, dimethylamine, dimethylglycine, and acetate in urine. Proximal tubular injury in TMZ-free groups was assessed by significantly greater Na(+) excretion, amino aciduria, and lactic aciduria than in TMZ-supplemented groups. Urinary concentrating ability was significantly improved in TMZ-preserved groups compared with TMZ-free groups. In TMZ-supplemented groups, there was also a greater excretion of citrate, which is a citric acid cycle metabolite. An extensive reduction in apical brush border of tubular cells, notably those of the proximal tubules, was noted in TMZ-free groups. This study clearly shows that TMZ has a beneficial action on in vivo renal preservation and its major impact is the vulnerable renal medulla.