Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, China.
JAMA Netw Open. 2022 Jun 1;5(6):e2215217. doi: 10.1001/jamanetworkopen.2022.15217.
Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown.
To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant.
DESIGN, SETTING, AND PARTICIPANTS: This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population.
Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 μg/kg/h intraoperatively and 0.1 μg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine.
The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30.
Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit.
This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants.
Chinese Clinical Trial Registry Identifier: ChiCTR1900025493.
延迟移植物功能（DGF）是肾移植后急性排斥和移植物失功的一个风险因素。先前的研究表明，右美托咪定可能具有肾保护作用，但使用右美托咪定是否能改善肾移植功能尚不清楚。
研究心脏死亡后供体（DCD）肾移植围手术期使用右美托咪定对 DGF 的影响。
设计、地点和参与者：这是一项在中国苏州大学附属第一医院进行的单中心、双盲、安慰剂对照随机临床试验。纳入计划接受 DCD 肾移植的成年人（18 岁或以上），于 2019 年 9 月 1 日至 2021 年 1 月 28 日入组，并随机分为接受右美托咪定或生理盐水（安慰剂）组。记录术后 1 年的结果。所有分析均基于改良意向治疗人群。
随机分配至右美托咪定组的患者接受 24 小时围手术期右美托咪定静脉输注（术中 0.4 μg/kg/h，术后 0.1 μg/kg/h）。随机分配至生理盐水组的患者接受相同剂量方案的安慰剂静脉输注。
主要结局为 DGF 的发生率，定义为移植后第 1 周需要透析。预设的次要结局包括移植后第 1 周内再次透析、院内急性排斥反应以及术后第 30 天的血肌酐、血清胱抑素 C、估算肾小球滤过率、透析需要和患者生存。
纳入的 114 例患者中，111 例完成了研究（平均[标准差]年龄，43.4[10.8]岁；64 例男性患者[57.7%]），其中 56 例随机分配至右美托咪定组，55 例随机分配至生理盐水组。与生理盐水输注相比，右美托咪定输注降低了 DGF 的发生率（17.9%比 34.5%；比值比[OR]，0.41；95%置信区间[CI]，0.17-0.98；P=0.04）和重复透析（12.5%比 30.9%；OR，0.32；95%CI，0.13-0.88；P=0.02，经多次测试校正后无统计学意义），但对其他次要结局无显著影响。与生理盐水输注相比，右美托咪定输注使术后第 1 天（9.9[4.9-21.2]mL/min 比 7.9[2.0-10.4]mL/min）和第 2 天（29.6[9.7-67.4]mL/min 比 14.6[3.8-45.1]mL/min）的肌酐清除率中位数（IQR）更高，且术后第 2 天（106.5[66.3-175.6]mL/h 比 82.9[27.1-141.9]mL/h）和第 7 天（126.1[98.0-151.3]mL/h 比 107.0[82.5-137.5]mL/h）以及出院时（110.4[92.8-121.9]mL/h 比 97.1[77.5-113.8]mL/h）的尿量中位数（IQR）更高。生理盐水组有 3 例（5.5%）患者在术后 1 年的随访中发生移植物失功。
这项随机临床试验发现，DCD 肾移植围手术期 24 小时使用右美托咪定可降低 DGF 的发生率。研究结果支持在肾移植中使用右美托咪定。
中国临床试验注册中心标识符：ChiCTR1900025493。
