The aims of this study were (1) to investigate the effect of
R 75231, a
nucleoside transport inhibitor, on
renin-
angiotensin release after renal
ischemia-reperfusion and (2) to establish a possible protective effect of this
drug on renal function. We used a canine model for auto-
transplantation of kidneys that had been subjected to 30 min of
warm ischemia and subsequently to 24h of cold storage in HTK preservation
solution, with immediate contralateral
nephrectomy.
R 75231 was injected intravenously into six dogs in two equal portions of 0.05 mg/kg both 30 min and 10 min before reanastomosis was established. Another six dogs were used as a control group. At 2 weeks post-
transplantation, five out of six dogs in the
R 75231 group and one out of six in the control group were still alive. Starting on day 4, serum
creatinine was lower in the
R 75231 group than in the control group (p < 0.005). In contrast to the control group, an inversion of the median preischemia
adenosine/
inosine ratio was observed in the
R 75231 group after reperfusion (0.4 preischemia vs 4.0 after 60 min of reperfusion). Reperfusion of the graft resulted in an immediate increase in
renin,
angiotensin I, and
angiotensin II venous blood levels in the control group. In the
R 75231 group,
renin, angiotension I, and
angiotensin II levels were significantly lower. We conclude that administration of
R 75231 before reperfusion has a protective effect on post-transplant function of kidneys that have been subjected to prolonged
warm ischemia. This effect may, at least in part, be ascribed to inhibition of the breakdown and disposal of endogenous
adenosine which, in turn, inhibits the excessive stimulation of the renin-angiotensin system in the early phase of reperfusion.