Cyclosporine (CYA) reduces the renal synthesis of prostaglandins of the E series (PGE). Analogue of PGE, have been shown to mitigate the vasoconstriction and abnormal renal function of experimental acute CYA nephrotoxicity. We examined the hypothesis that the orally bioavailable PGE analogue enisoprost (EP) would improve renal function in renal transplant recipients chronically exposed to CYA. In a randomized double-blind study, 40 patients at two centers who were being monitored for 3 to 30 months after renal transplantation, were allocated to receive either EP 100 δg orally four times daily or placebo (P) for 2 weeks. CYA dosing was fixed at existing levels. There could be no evidence of concurrent acute renal injury, including that of acute rejection. Glomerular filtration rate (GFR) was measured by the clearance of radiolabeled DTPA, while effective renal plasma flow (ERPF) was measured as the clearance of p-aminohipporic acid (PAH). The acute effects of EP were examined twice, by comparing immediate postdose to predose values for GFR and ERPF on day 1 and again on day 14. Chronic effects were examined by comparing baseline (predose) values only for GFR and ERPF between days 1 and 14 and by an examination of creatinine clearances (CCR) on days 0,14, and 21. At enrollment, patients were well matched for renal function (CCR:EP 47 ± 5 v P 49 ± 4 mL/min/1.73 m2; P = NS). Baseline demographics were similar, although patients treated with EP were older (46 ± 2 v 36 ± 3 years, mean ± SEM, P = 0.003). CYA doses and blood levels did not change significantly. We observed a small acute significant decline in GFR after the initial dose of EP, not observed following 14 days of continual exposure four times daily. A similar pattern of changes was observed for ERPF. The patterns of change in filtration fraction showed no sustained differences between the two groups, while CCR values did not change significantly in either group between pretreatment, day 14, and 1 week posttreatment. We conclude that 2 weeks of therapy with the PGE analogue EP does not improve long-term renal function in CVA-treated renal transplant recipients.
- renal transplantation
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