Textor S C, Burnett J C, Romero J C, Canzanello V J, Taler S J, Wiesner R, Porayko M, Krom R, Gores G, Hay E
Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Kidney Int. 1995 May;47(5):1426-33. doi: 10.1038/ki.1995.200.
Transplant immunosuppression using either cyclosporine (CsA) or FK506 leads to renal vasoconstriction. To examine the role of endothelin (ET) in this process, we measured plasma and urinary ET before and at intervals for two years after liver transplantation. Urinary prostacyclin (as 6-keto-PG-F1 alpha), thromboxane, glomerular filtration rate and renal plasma flow were also measured. Forty-four patients were treated with CsA-based regimens and 31 patients with FK506-based regimens. Prednisone doses after one year were lower with FK506 (5.5 +/- 0.5 vs. 10.5 +/- 0.5 mg/day) by study design. Circulating plasma ET remained above normal, but not different from pre-transplant levels. Urinary ET was elevated before transplant (24.6 +/- 3.4 ng/day vs. normal 16 +/- 1.5 ng/day, P < 0.05) and rose further after transplantation (48.5 +/- 13 ng/day, P < 0.05), remaining elevated for two years. 6-keto-PG-F1 alpha fell from 2567 +/- 338 ng/day to subnormal levels and remained suppressed (1158 +/- 128 ng/day, P < 0.01). Over the same period GFR fell (84 +/- 3 ml/min to 60 +/- 3 ml/min, P < 0.01) and renal vascular resistance index rose (11,119 +/- 561 to 23,279 +/- 1692 d.s.cm-5.m-2, P < 0.01). Similar changes were observed both with CsA and FK506-based immunosuppression. No changes in ET were attributable to dihydropyridine calcium channel blockers. These results demonstrate that urinary ET changes independently from plasma ET after transplantation. Elevated ET and suppression of endothelium-derived prostacyclin persist with intense renal vasoconstriction for at least two years after transplant.
使用环孢素（CsA）或他克莫司（FK506）进行移植免疫抑制会导致肾血管收缩。为了研究内皮素（ET）在此过程中的作用，我们在肝移植前及移植后两年期间定期测量血浆和尿液中的ET。同时还测量了尿前列环素（以6-酮-前列腺素F1α表示）、血栓素、肾小球滤过率和肾血浆流量。44例患者接受基于CsA的方案治疗，31例患者接受基于FK506的方案治疗。根据研究设计，一年后使用FK506的患者泼尼松剂量较低（5.5±0.5 vs. 10.5±0.5 mg/天）。循环血浆ET仍高于正常水平，但与移植前水平无差异。移植前尿ET升高（24.6±3.4 ng/天 vs. 正常16±1.5 ng/天，P<0.05），移植后进一步升高（48.5±13 ng/天，P<0.05），并持续升高两年。6-酮-前列腺素F1α从2567±338 ng/天降至低于正常水平并持续受到抑制（1158±128 ng/天，P<0.01）。同期肾小球滤过率下降（84±3 ml/分钟至60±3 ml/分钟，P<0.01），肾血管阻力指数升高（11,119±561至23,279±1692 d.s.cm-5.m-2，P<0.01）。基于CsA和FK506的免疫抑制均观察到类似变化。ET的变化与二氢吡啶钙通道阻滞剂无关。这些结果表明，移植后尿ET与血浆ET独立变化。移植后至少两年内，ET升高和内皮源性前列环素的抑制与强烈的肾血管收缩持续存在。
