TY - JOUR
T1 - A Trial of the Prostaglandin E1 Analogue, Enisoprost, to Reverse Chronic Cyclosporine-Associated Renal Dysfunction
AU - Pollak, R.
AU - Knight, R.
AU - Mozes, M. F.
AU - Maddux, M.
AU - Veremis, S.
AU - Van Buren, C.
AU - Lewis, R.
AU - Scott, E.
AU - Cole, M.
AU - Hyndman, V.
AU - Moran, M.
AU - Kahan, B. D.
N1 - Funding Information:
Received October 22, 1991; accepted in revised form June 2, 1992. Supported by a grant from G. D. Searle and Company. Presented in abstract form at the 10th Scientific Meeting of the American Society of Transplant Physicians, Chicago, IL, May 1991. Address reprint requests to Raymond Pollak, MB, FRCS, FACS, Chief, Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Box 6998 (M/C 958), Chicago, IL 60680. © 1992 by the National Kidney Foundation, Inc. 0272-6386/92/2004-0003$3.00;0
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
KW - Cyclosporine
KW - enisoprost
KW - prostaglandins
KW - renal transplantation
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U2 - 10.1016/S0272-6386(12)70295-0
DO - 10.1016/S0272-6386(12)70295-0
M3 - Article
C2 - 1415200
AN - SCOPUS:0026616850
SN - 0272-6386
VL - 20
SP - 336
EP - 341
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 4
ER -