背景:降低特定血压(BP)治疗对肾移植后患者重要结局的比较效果尚不确定。我们2009年的Cochrane综述发现,钙通道阻滞剂(CCB)改善了移植物功能并防止了移植物丢失,而其他降BP治疗的证据有限.这是2009年Cochrane审查的更新。
目的:比较不同种类和组合的抗高血压药物对肾移植受者的益处和危害。
方法:我们联系了信息专家,并使用与本评论相关的搜索词搜索了截至2024年7月3日的Cochrane肾脏和移植研究注册。登记册中的研究是通过对CENTRAL的搜索确定的,MEDLINE,EMBASE,会议记录,国际临床试验注册平台(ICTRP)搜索门户,和ClinicalTrials.gov.
方法:随机对照试验(RCTs)和准RCTs评估任何降低血压的药物在有功能的肾移植受者中至少2周是合格的。
方法:两位作者独立评估偏倚风险并提取数据。使用随机效应模型总结治疗估计值,并以95%置信区间(CI)表示为相对风险(RR)或平均差(MD)。使用推荐等级评估证据确定性,评估,开发和评估(等级)过程。主要结果包括全因死亡,移植物丢失,和肾功能。
结果:纳入了97项研究(8706名参与者)。一项研究评估了儿童的治疗。所有领域的总体偏倚风险尚不清楚。与安慰剂或标准护理相比,CCB可能减少全因死亡(23项研究,3327名参与者:RR0.83,95%CI0.72至0.95;I2=0%;中度确定性证据)和移植物丢失(24项研究,3577名参与者:RR0.84,95%CI0.75至0.95;I2=0%;中等确定性证据)。CCB可能对估计的肾小球滤过率(eGFR)影响很小或没有影响(11项研究,2250名参与者:MD1.89mL/min/1.73m2,95%CI-0.70至4.48;I2=48%;低确定性证据)和急性排斥(13项研究,906名参与者:RR10.8,95%CI0.85至1.35;I2=0%;中等确定性证据)。CCB可能会降低收缩压(SBP)(3项研究,329名参与者:MD-5.83mmHg,95%CI-10.24至-1.42;I2=13%;低确定性证据)和舒张压血压(DBP)(3项研究,329名参与者:MD-3.98mmHg,95%CI-5.98至-1.99;I2=0%;低确定性证据)。CCB对蛋白尿的影响不确定。与安慰剂或标准护理相比,血管紧张素转换酶抑制剂(ACEi)可能对全因死亡几乎没有影响(7项研究,702名参与者:RR1.13,95%CI0.58至2.21;I2=0%;低确定性证据),移植物丢失(6项研究,718名参与者:RR0.75,95%CI0.49至1.13;I2=0%;低确定性证据),eGFR(4项研究,509名参与者:MD-2.46mL/min/1.73m2,95%CI-7.66至2.73;I2=64%;低确定性证据)和急性排斥(4项研究,388名参与者:RR1.75,95%CI0.76至4.04;I2=0%;低确定性证据)。ACEi可以减少蛋白尿(5项研究,441名参与者:MD-0.33g/24小时,95%CI-0.64至-0.01;I2=67%;低确定性证据),但对SBP和DBP的影响不确定。与安慰剂或标准护理相比,血管紧张素受体阻滞剂(ARB)可能对全因死亡几乎没有影响(6项研究,1041名参与者:RR0.69,95%CI0.36至1.31;I2=0%;低确定性证据),eGRF(5项研究,300名参与者:MD-1.91mL/min/1.73m2,95%CI-6.20至2.38;I2=57%;低确定性证据),和急性排斥反应(4项研究,323名参与者:RR1.00,95%CI0.44至2.29;I2=0%;低确定性证据)。ARB可以减少移植物损失(6项研究,892名参与者:RR0.35,95%CI0.15至0.84;I2=0%;低确定性证据),SBP(10项研究,1239名参与者:MD-3.73mmHg,95%CI-7.02至-0.44;I2=63%;中度确定性证据)和DBP(9项研究,1086名参与者:MD-2.75mmHg,95%CI-4.32至-1.18;I2=47%;中等确定性证据),但对蛋白尿有不确定的影响。CCB的影响,ACEi或ARB与安慰剂或单独标准治疗相比心血管结局(包括致死性或非致死性心肌梗死,致死性或非致死性卒中)或其他不良事件不确定。ACEi加ARB双重治疗的比较效果,α-受体阻滞剂,盐皮质激素受体拮抗剂与安慰剂或单独标准治疗相比,很少进行评估。ACEi的头对头比较,ARB或噻嗪类与CCB,ACEi对ARB,CCB或ACEi与α-或β-受体阻滞剂,或ACEi加CCB双重治疗与ACEi或CCB单药治疗比较少见。没有研究报告癌症或生命参与的结果数据。
结论:对于肾移植受者,与单独使用安慰剂或标准治疗相比,使用CCB治疗降低BP可能会减少死亡和移植物损失,而ARB可以减少移植物损失。与安慰剂或标准治疗相比,ACEi和ARB对其他以患者为中心的结局的影响尚不确定。双重治疗的效果,α-受体阻滞剂,和盐皮质激素受体拮抗剂与安慰剂或单独标准治疗相比,以及不同治疗方法的比较效果不确定。
BACKGROUND: The comparative effects of specific blood pressure (BP) lowering treatments on patient-important outcomes following kidney transplantation are uncertain. Our 2009 Cochrane review found that calcium channel blockers (CCBs) improved graft function and prevented graft loss, while the evidence for other BP-lowering treatments was limited. This is an update of the 2009 Cochrane review.
OBJECTIVE: To compare the benefits and harms of different classes and combinations of antihypertensive drugs in kidney transplant recipients.
METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 3 July 2024 using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.
METHODS: Randomised controlled trials (RCTs) and quasi-RCTs evaluating any BP-lowering agent in recipients of a functioning kidney transplant for at least two weeks were eligible.
METHODS: Two authors independently assessed the risks of bias and extracted data. Treatment estimates were summarised using the random-effects model and expressed as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CI). Evidence certainty was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) processes. The primary outcomes included all-cause death, graft loss, and kidney function.
RESULTS: Ninety-seven studies (8706 participants) were included. One study evaluated treatment in children. The overall risk of bias was unclear to high across all domains. Compared to placebo or standard care alone, CCBs probably reduce all-cause death (23 studies, 3327 participants: RR 0.83, 95% CI 0.72 to 0.95; I2 = 0%; moderate certainty evidence) and graft loss (24 studies, 3577 participants: RR 0.84, 95% CI 0.75 to 0.95; I2 = 0%; moderate certainty evidence). CCBs may make little or no difference to estimated glomerular filtration rate (eGFR) (11 studies, 2250 participants: MD 1.89 mL/min/1.73 m2, 95% CI -0.70 to 4.48; I2 = 48%; low certainty evidence) and acute rejection (13 studies, 906 participants: RR 10.8, 95% CI 0.85 to 1.35; I2 = 0%; moderate certainty evidence). CCBs may reduce systolic BP (SBP) (3 studies, 329 participants: MD -5.83 mm Hg, 95% CI -10.24 to -1.42; I2 = 13%; low certainty evidence) and diastolic BP (DBP) (3 studies, 329 participants: MD -3.98 mm Hg, 95% CI -5.98 to -1.99; I2 = 0%; low certainty evidence). CCBs have uncertain effects on proteinuria. Compared to placebo or standard care alone, angiotensin-converting-enzyme inhibitors (ACEi) may make little or no difference to all-cause death (7 studies, 702 participants: RR 1.13, 95% CI 0.58 to 2.21; I2 = 0%; low certainty evidence), graft loss (6 studies, 718 participants: RR 0.75, 95% CI 0.49 to 1.13; I2 = 0%; low certainty evidence), eGFR (4 studies, 509 participants: MD -2.46 mL/min/1.73 m2, 95% CI -7.66 to 2.73; I2 = 64%; low certainty evidence) and acute rejection (4 studies, 388 participants: RR 1.75, 95% CI 0.76 to 4.04; I2 = 0%; low certainty evidence). ACEi may reduce proteinuria (5 studies, 441 participants: MD -0.33 g/24 hours, 95% CI -0.64 to -0.01; I2 = 67%; low certainty evidence) but had uncertain effects on SBP and DBP. Compared to placebo or standard care alone, angiotensin receptor blockers (ARB) may make little or no difference to all-cause death (6 studies, 1041 participants: RR 0.69, 95% CI 0.36 to 1.31; I2 = 0%; low certainty evidence), eGRF (5 studies, 300 participants: MD -1.91 mL/min/1.73 m2, 95% CI -6.20 to 2.38; I2 = 57%; low certainty evidence), and acute rejection (4 studies, 323 participants: RR 1.00, 95% CI 0.44 to 2.29; I2 = 0%; low certainty evidence). ARBs may reduce graft loss (6 studies, 892 participants: RR 0.35, 95% CI 0.15 to 0.84; I2 = 0%; low certainty evidence), SBP (10 studies, 1239 participants: MD -3.73 mm Hg, 95% CI -7.02 to -0.44; I2 = 63%; moderate certainty evidence) and DBP (9 studies, 1086 participants: MD -2.75 mm Hg, 95% CI -4.32 to -1.18; I2 = 47%; moderate certainty evidence), but has uncertain effects on proteinuria. The effects of CCBs, ACEi or ARB compared to placebo or standard care alone on cardiovascular outcomes (including fatal or nonfatal myocardial infarction, fatal or nonfatal stroke) or other adverse events were uncertain. The comparative effects of ACEi plus ARB dual therapy, alpha-blockers, and mineralocorticoid receptor antagonists compared to placebo or standard care alone were rarely evaluated. Head-to-head comparisons of ACEi, ARB or thiazide versus CCB, ACEi versus ARB, CCB or ACEi versus alpha- or beta-blockers, or ACEi plus CCB dual therapy versus ACEi or CCB monotherapy were scarce. No studies reported outcome data for cancer or life participation.
CONCLUSIONS: For kidney transplant recipients, the use of CCB therapy to reduce BP probably reduces death and graft loss compared to placebo or standard care alone, while ARB may reduce graft loss. The effects of ACEi and ARB compared to placebo or standard care on other patient-centred outcomes were uncertain. The effects of dual therapy, alpha-blockers, and mineralocorticoid receptor antagonists compared to placebo or standard care alone and the comparative effects of different treatments were uncertain.