Influence of donor pretreatment with N-acetylcysteine on ischemia/reperfusion injury in rat kidney grafts.

PURPOSE

N-acetylcysteine (NAC) has been shown to ameliorate ischemic acute renal failure. We determined the effect of donor pretreatment with NAC on ischemia reperfusion (I/R) injury in rat kidney grafts.

MATERIALS AND METHODS

Lewis rats were divided into 3 groups (8 per group) and treated with saline, mannitol (1 gm/kg) or NAC (1 gm/kg intravenously) prior to donor nephrectomy. Cold stored kidneys (24 hours in UW solution) were transplanted into bilaterally nephrectomized recipients. Blood and graft tissue samples were taken 24 hours after transplantation for assessment of metabolic changes, histological damage and renal function. Metabolites associated with renal I/R injury were quantified in blood and renal tissue by magnetic resonance spectroscopy.

RESULTS

The degree of histological damage was similar between the treatment groups. Of the counted tubules 60%were mildly damaged, whereas 40% showed moderate damage. Measurement of the metabolites allantoin and trimethylamine-N-oxide (TMAO) indicated a beneficial effect of NAC treatment. In graft tissue and recipient blood allantoin, a uric acid metabolite, was significantly lower in the NAC group vs the mannitol and saline groups (p <0.05). In recipient blood TMAO, an established marker of renal medullary injury, was significantly decreased in the NAC group vs mannitol and saline (p <0.05). Serum creatinine levels were not different between treatment groups.

CONCLUSIONS

Donor pretreatment with NAC preserves renal metabolism and may improve outcomes of I/R injured kidney transplants. Allantoin and TMAO are sensitive metabolic markers of renal I/R injury that can be detected before the onset of functional and morphological changes.