Antihypertensive treatment for kidneytransplant recipients

Rationale The comparative effects of specific blood pressure (BP) lowering treatments on patient-important outcomes following kidney transplantation are uncertain. Our 2009 Cochranereview found that calcium channel blockers (CCBs) improved graft function and preventedgraft loss, while the evidence for other BP-lowering treatments was limited. This is anupdate of the 2009 Cochrane review. Objectives To compare the benefits and harms of different classes and combinations ofantihypertensive drugs in kidney transplant recipients. Search methods We contacted the Information Specialist and searched the Cochrane Kidney and TransplantRegister of Studies up to 3 July 2024 using search terms relevant to this review. Studies inthe Register were identified through searches of CENTRAL, MEDLINE, EMBASE,conference proceedings, the International Clinical Trials Registry Platform (ICTRP) SearchPortal, and ClinicalTrials.gov. Eligibility criteria Randomised controlled trials (RCTs) and quasi-RCTs evaluating any BP-lowering agent inrecipients of a functioning kidney transplant for at least two weeks were eligible. Synthesis 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 wasassessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) processes. The primary outcomes included all-cause death, graft loss, and kidney function. 01/08/2024, 14:02 RevMan - Antihypertensive treatment for kidney transplant recipients Synthesis of results Ninety-seven studies (8706 participants) were included. One study evaluated treatment inchildren. 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 (23studies, 3327 participants: RR 0.83, 95% CI 0.72 to 0.95; I = 0%; moderate certaintyevidence) and graft loss (24 studies, 3577 participants: RR 0.84, 95% CI 0.75 to 0.95; I =0%; moderate certainty evidence). CCBs may make little or no difference to estimatedglomerular filtration rate (eGFR) (11 studies, 2250 participants: MD 1.89 mL/min/1.73 m ,95% CI -0.70 to 4.48; I = 48%; low certainty evidence) and acute rejection (13 studies, 906participants: RR 10.8, 95% CI 0.85 to 1.35; I = 0%; moderate certainty evidence). CCBsmay reduce systolic BP (SBP) (3 studies, 329 participants: MD -5.83 mm Hg, 95% CI -10.24to -1.42; I = 13%; low certainty evidence) and diastolic BP (DBP) (3 studies, 329participants: MD -3.98 mm Hg, 95% CI -5.98 to -1.99; I = 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: RR1.13, 95% CI 0.58 to 2.21; I = 0%; low certainty evidence), graft loss (6 studies, 718participants: RR 0.75, 95% CI 0.49 to 1.13; I = 0%; low certainty evidence), eGFR (4studies, 509 participants: MD -2.46 mL/min/1.73 m , 95% CI -7.66 to 2.73; I = 64%; lowcertainty evidence) and acute rejection (4 studies, 388 participants: RR 1.75, 95% CI 0.76 to4.04; I = 0%; low certainty evidence). ACEi may reduce proteinuria (5 studies, 441participants: MD -0.33 g/24 hours, 95% CI -0.64 to -0.01; I = 67%; low certainty evidence)but had uncertain effects on SBP and DBP. Compared to placebo or standard care alone, angiotensin receptor blockers (ARB) maymake little or no difference to all-cause death (6 studies, 1041 participants: RR 0.69, 95% CI0.36 to 1.31; I = 0%; low certainty evidence), eGRF (5 studies, 300 participants: MD -1.91mL/min/1.73 m , 95% CI -6.20 to 2.38; I = 57%; low certainty evidence), and acuterejection (4 studies, 323 participants: RR 1.00, 95% CI 0.44 to 2.29; I = 0%; low certaintyevidence). ARBs may reduce graft loss (6 studies, 892 participants: RR 0.35, 95% CI 0.15to 0.84; I = 0%; low certainty evidence), SBP (10 studies, 1239 participants: MD -3.73 mmHg, 95% CI -7.02 to -0.44; I = 63%; moderate certainty evidence) and DBP (9 studies,1086 participants: MD -2.75 mm Hg, 95% CI -4.32 to -1.18; I = 47%; moderate certaintyevidence), but has uncertain effects on proteinuria. The effects of CCBs, ACEi or ARB compared to placebo or standard care alone oncardiovascular outcomes (including fatal or nonfatal myocardial infarction, fatal or nonfatalstroke) or other adverse events were uncertain. The comparative effects of ACEi plus ARB dual therapy, alpha-blockers, andmineralocorticoid receptor antagonists compared to placebo or standard care alone wererarely evaluated. Head-to-head comparisons of ACEi, ARB or thiazide versus CCB, ACEi versus ARB, CCBor ACEi versus alpha- or beta-blockers, or ACEi plus CCB dual therapy versus ACEi or CCBmonotherapy were scarce. No studies reported outcome data for cancer or life participation. Authors' conclusions For kidney transplant recipients, the use of CCB therapy to reduce BP probably reducesdeath and graft loss compared to placebo or standard care alone, while ARB may reducegraft loss. The effects of ACEi and ARB compared to placebo or standard care on other 01/08/2024, 14:02 RevMan - Antihypertensive treatment for kidney transplant recipients https://revman.cochrane.org/696001041914312138/dashboard/htmlView/9.5.3?revertEnabled=true 4/92 patient-centred outcomes were uncertain. The effects of dual therapy, alpha-blockers, andmineralocorticoid receptor antagonists compared to placebo or standard care alone and thecomparative effects of different treatments were uncertain.