Bennett W M, Carpenter C B, Shapiro M E, Strom T B, Hefty D, Tillman M, Abrams J, Ryan D, Kelley V R
Division of Nephrology, Hypertension and Clinical Pharmacology, Oregon Health Sciences University, Portland 97201.
Transplantation. 1995 Feb 15;59(3):352-6.
An earlier reported trial suggests that omega-3 fatty acids in fish oil supplements at 6 g/day with administration commencing at the time of engraftment may reduce acute CsA renal dysfunction. When started at the time of renal transplant, there are improvements in renal hemodynamics and blood pressure, and a decrease in rejection episodes. To examine the effect of later introduction of omega-3 fatty acids, 133 cadaver renal transplant recipients received CsA, prednisone, and AZA for 16 weeks (period 1). If patients were stable without rejection or infection activity, they were randomized to 9 g of eicosapentanoic acid (EPA), 18 g of EPA, 9 g of corn oil, or 18 g of corn oil in 1-g capsules as supplements. Glomerular filtration rate, renal blood flow, number of rejection episodes, blood pressure, and episodes of CsA nephrotoxicity were followed for 26 weeks in a double-blind manner (period 2). Ninety patients were evaluable and completed the protocol. There were 50 corn oil placebo patients, 22 low dose EPA patients, and 18 high dose EPA patients. In period 1, there were 27 rejection episodes in 21 patients without differences among subsequent treatment groups. In period 2, there were 13 rejection episodes in 4 patients. No patient with an EPA level in plasma statistically higher than placebo had a rejection episode. All allografts functioned for the entire 6 months with none lost to rejection. All 5 episodes of acute CsA nephrotoxicity occurred in placebo-treated patients without differences in whole blood CsA among toxic patients, other placebo patients, and EPA-treated recipients. At the end of the study, there were no differences in glomerular filtration rate, renal blood flow, or creatinine clearance among groups. Diastolic blood pressure fell by 9 mmHg during period 2 in high dose fish oil recipients and by 10 mmHg in low dose fish oil recipients (P < 0.05), while it rose by 2 mmHg in placebo patients. No serious adverse effects of EPA supplements were noted, although compliance based on plasma EPA was erratic. Based on our experience and that in the literature, administration of omega-3 fatty acids for purposes of kidney protection would seem to be most useful when started early after surgery. Late administration in our study was associated with minor clinical benefits.
一项较早报道的试验表明，移植时开始每天服用6克鱼油补充剂中的ω-3脂肪酸可能会降低环孢素A（CsA）所致的急性肾功能障碍。肾移植时开始服用，可改善肾脏血流动力学和血压，并减少排斥反应发作次数。为了研究较晚引入ω-3脂肪酸的效果，133例尸体肾移植受者接受CsA、泼尼松和硫唑嘌呤治疗16周（第1阶段）。如果患者病情稳定，没有排斥反应或感染活动，则将他们随机分为服用1克胶囊形式的9克二十碳五烯酸（EPA）、18克EPA、9克玉米油或18克玉米油作为补充剂。以双盲方式随访26周，观察肾小球滤过率、肾血流量、排斥反应发作次数、血压和CsA肾毒性发作情况（第2阶段）。90例患者可评估并完成了方案。有50例玉米油安慰剂患者、22例低剂量EPA患者和18例高剂量EPA患者。在第1阶段，21例患者中有27次排斥反应发作，后续治疗组之间无差异。在第2阶段，4例患者中有13次排斥反应发作。血浆中EPA水平在统计学上高于安慰剂的患者均无排斥反应发作。所有同种异体移植在整个6个月内均发挥功能，无因排斥反应而丢失的情况。所有5例急性CsA肾毒性发作均发生在安慰剂治疗的患者中，中毒患者、其他安慰剂患者和EPA治疗的受者之间全血CsA无差异。研究结束时，各组之间的肾小球滤过率、肾血流量或肌酐清除率无差异。高剂量鱼油受者在第2阶段舒张压下降9 mmHg，低剂量鱼油受者下降10 mmHg（P<0.05），而安慰剂患者上升2 mmHg。尽管基于血浆EPA的依从性不稳定，但未观察到EPA补充剂有严重不良反应。根据我们的经验以及文献中的经验，为保护肾脏而服用ω-3脂肪酸似乎在术后早期开始时最有用。在我们的研究中较晚服用仅带来了轻微的临床益处。
