重组人促红细胞生成素 -b作为肾移植中的组织保护剂：一项前瞻性随机对照试验
rhErythropoietin-b as a tissue protective agent in kidney transplantation: a pilot randomized controlled trial.
作者信息
Coupes Beatrice, de Freitas Declan G, Roberts Stephen A, Read Ian, Riad Hany, Brenchley Paul E C, Picton Michael L
机构信息
Department of Renal Medicine, Manchester Royal Infirmary, Oxford Rd, Manchester, M13 9WL, UK.
Centre for Biostatistics, University of Manchester, Manchester, M13 9PL, UK.
出版信息
BMC Res Notes. 2015 Feb 3;8:21. doi: 10.1186/s13104-014-0964-0.
BACKGROUND
Extended criteria donor (ECD) and donation after circulatory death (DCD) kidneys are at increased risk of delayed graft function (DGF). Experimental evidence suggests that erythropoietin (EPO) attenuates renal damage in acute kidney injury. This study piloted the administration of high dose recombinant human EPO-beta at implantation of ECD and DCD kidneys, and evaluated biomarkers of kidney injury post-transplant.
METHODS
Forty patients were randomly assigned to receive either rhEPO-b (100,000 iu) (n = 19 in the intervention group, as 1 patient was un-transplantable post randomisation), or placebo (n = 20) in this, double blind, placebo-controlled trial at Manchester Royal Infirmary from August 2007 to June 2009. Participants received either an ECD (n = 17) or DCD (n = 22) kidney. Adverse events, renal function, haematopoietic markers, and rejections were recorded out to 90 days post-transplant. Biomarkers of kidney injury (neutrophil gelatinase-associated lipocalin, Kidney Injury Molecule-1 and IL-18) were measured in blood and urine during the first post-operative week.
RESULTS
The incidence of DGF (53% vs 55%) (RR = 1.0; CI = 0.5-1.6; p = 0.93) and slow graft function (SGF) (32% vs 25%) (RR = 1.1; CI = 0.5-1.9; p = 0.73) respectively, serum creatinine, eGFR, haemoglobin and haematocrit, blood pressure, and acute rejection were similar in the 2 study arms. High dose rhEPO-b had little effect on the temporal profiles of the biomarkers.
CONCLUSIONS
High dose rhEPO-b appears to be safe and well tolerated in the early post- transplant period in this study, but has little effect on delayed or slow graft function in recipients of kidneys from DCD and ECD donors. Comparing the profiles of biomarkers of kidney injury (NGAL, IL-18 and KIM-1) showed little difference between the rhEPO-b treated and placebo groups. A meta-analysis of five trials yielded an overall estimate of the RR for DGF of 0.89 (CI = 0.73; 1.07), a modest effect favouring EPO but not a significant difference. A definitive trial based on this estimate would require 1000-2500 patients per arm for populations with base DGF rates of 50-30% and 90% power. Such a trial is clearly unfeasible.
TRIAL REGISTRATION
EudraCT Number 2006-005373-22 ISRCTN ISRCTN85447324 registered 19/08/09.
背景
扩大标准供体（ECD）肾脏及心脏死亡后捐献（DCD）肾脏发生移植肾功能延迟恢复（DGF）的风险增加。实验证据表明，促红细胞生成素（EPO）可减轻急性肾损伤中的肾损害。本研究在ECD和DCD肾脏植入时试用高剂量重组人EPO-β，并评估移植后肾损伤的生物标志物。
方法
在2007年8月至2009年6月于曼彻斯特皇家医院进行的这项双盲、安慰剂对照试验中，40例患者被随机分配接受rhEPO-b（100,000国际单位）（干预组n = 19，因为随机分组后有1例患者无法进行移植）或安慰剂（n = 20）。参与者接受ECD肾脏（n = 17）或DCD肾脏（n = 22）。记录移植后90天内的不良事件、肾功能、造血标志物和排斥反应情况。在术后第一周测定血液和尿液中的肾损伤生物标志物（中性粒细胞明胶酶相关脂质运载蛋白、肾损伤分子-1和IL-18）。
结果
DGF的发生率（53%对55%）（RR = 1.0；CI = 0.5 - 1.6；p = 0.93）和移植肾功能缓慢恢复（SGF）的发生率（32%对25%）（RR = 1.1；CI = 0.5 - 1.9；p = 0.73），2个研究组的血清肌酐、估算肾小球滤过率（eGFR）、血红蛋白和血细胞比容、血压及急性排斥反应情况相似。高剂量rhEPO-b对生物标志物的时间变化曲线影响不大。
结论
在本研究中，高剂量rhEPO-b在移植后早期似乎安全且耐受性良好，但对DCD和ECD供体肾脏受者的移植肾功能延迟或缓慢恢复影响不大。比较肾损伤生物标志物（中性粒细胞明胶酶相关脂质运载蛋白、IL-18和肾损伤分子-1）的变化曲线显示，rhEPO-b治疗组和安慰剂组之间差异不大。对5项试验的荟萃分析得出DGF的RR总体估计值为0.89（CI = 0.73；1.07），EPO有一定益处但无显著差异。基于该估计值进行确定性试验，对于基础DGF发生率为50% - 30%且检验效能为90%的人群，每组需要1000 - 2500例患者。这样的试验显然不可行。
试验注册
欧盟临床试验编号2006 - 005373 - 22，国际标准随机对照试验编号ISRCTN85447324，于2009年8月19日注册。
Zotero 插件