PROTECTION OF CANINE RENAL GRAFTS BY RENIN-ANGIOTENSIN INHIBITION THROUGH NUCLEOSIDE TRANSPORT BLOCKADE

The aims of this study were (1) to investigate the effect of R 75231, a nucleoside transport inhibitor, on renin-angiotensin release after r enal ischemia-reperfusion and (2) to establish a possible protective e ffect of this drug on renal function. We used a canine model for autot ransplantation of kidneys that had been subjected to 30 min of warm is chemia and subsequently to 24 h of cold storage in HTK preservation so lution, 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 do gs 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 contro l group were still alive. Starting on day 4, serum creatinine was lowe r in the R 75231 group than in the control group (p < 0.05). In contra st to the control group, an inversion of the median preischemia adenos ine/inosine ratio was observed in the R 75231 group after reperfusion (0.4 preischemia vs 4.0 after 60 min of reperfusion). Reperfusion of t he graft resulted in an immediate increase in renin, angiotensin I, an d angiotensin II venous blood levels in the control group. In the R 75 231 group, renin, angiotension I, and angiotensin II levels were signi ficantly lower. We conclude that administration of R 75231 before repe rfusion 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 disp osal of endogenous adenosine which, in turn, inhibits the excessive st imulation of the renin-angiotensin system in the early phase of reperf usion.