雷帕霉素对肾移植患者术后肾功能的影响

Effect of rapamycin on kidney function after kidney transplanation

目的探讨国产雷帕霉素(rapamycin,RPM)联合环孢菌素A(cyclosporineA,CsA)、激素(steroid,ST)对肾移植患者术后肾功能的影响。方法本实验为随机开放、与硫唑嘌呤(azathioprine,AZA)平行对照的多中心Ⅱ期临床研究,观察期24周;172例首次接受同种异体肾移植的患者术后72小时内随机平均分配进入两组:RPM组,应用RPM、CsA和ST;AZA组,应用AZA、CsA和ST。对术后24周内的肾功能指标[肌酐(SCr)、尿素氮(BUN)、尿酸(UA)以及肾功能首次恢复时间]和相关的不良事件进行客观评价。结果与AZA组术后肾功能首次恢复时间(23.63±39.24)天相比,RPM组术后肾功能首次恢复时间(17.05±36.31)天更早。术后24周,RPM组和AZA组的SCr分别为(93.75±26.40)μmol/Lvs(102.39±44.61)μmol/L,P=0.145;BUN分别为(6.16±1.68)mmol/Lvs(7.05±1.56)mmol/L,P=0.001;UA分别为(329.09±76.25)mmol/Lvs(360.06±74.82)mmol/L,P=0.013,各项肾功能试验室指标RPM组均低于AZA组。发生肾功能相关的不良事件,RPM组7例(8.14%),AZA组18例(20.93%),其中高尿酸血症AZA组多于RPM组(17例,19.77%vs3例,3.49%),P=0.001。结论RPM、CsA和Pred联合应用于同种肾移植,更有利于术后移植肾功能的恢复,且无肾毒性。

Objective To explore the effect of rapamycin(RPM) combined with cyclosporine A(CsA) and steroid(ST) on renal function of recipients after renal transplanation. Methods This was a randomized,open-label,multicentre phase Ⅱ study which was compared with azathioprine parallel.Within 72 hours post-transplant,172 recipients of primary renal allografts were randomized in two groups:RPM group,treated with RPM-CsA-ST;and AZA group,treated with AZA-CsA-ST.The indexes of renal function(serum creatinine,blood urea nitrogen,serum uric acid and the first recovered time of renal function) within 24 weeks after transplant,as well as correlative adverse events were evaluated.Results Compared with AZA group ( 23.63 ± 39.24 ) d,the first recovered time of renal function in RPM group ( 17.05 ± 36.31 ) d was earlier.At 24 weeks post-transplant,the values of SCr were ( 93.75 ± 26.40 ) μmol/L vs ( 102.39 ± 44.61 ) μmol/L for RPM group and AZA group, P = 0.145 ;the values of BUN were ( 6.16 ± 1.68 ) mmol/L vs ( 7.05 ± 1.56 ) mmol/L respectively, P = 0.001 ;the values of uric acid(UA) were ( 329.09 ± 76.25 ) mmol/L vs ( 360.06 ± 74.82 ) mmol/L respectively, P = 0.013 .All laboratory levels of renal function in RPM group were lower than those of AZA group. For the correlative adverse events of renal function,there were 7 patients( 8.14 %) in RPM group and 18 patients( 20.93 %) in AZA group,and that hyperuricemia occurred statistically more frequently in patients treated with AZA(17 patients, 19.77 % vs 3 patients, 3.49 %, P = 0.001 ). Conclusion The treatment of rapamycin in combination with cyclosporine and steroid is more favorable for the recovery of renal function post-transplant,and no nephrotoxicity.