Chlorthalidone Versus Amlodipine for Hypertension in Kidney Transplant Recipients Treated With Tacrolimus: A Randomized Crossover Trial

Background: Chlorthalidone is a very effective antihypertensive drug, but it has not been studied prospectively in kidney transplant recipients with hypertension. Recent data indicate that calcineurin inhibitors activate the thiazide-sensitive sodium chloride cotransporter, providing further rationale to test thiazides in this population. Study Design: Randomized noninferiority crossover trial (noninferiority margin, -2.8 mm Hg). Setting & Participants: Hypertensive kidney transplant recipients using tacrolimus (median duration, 2.4 years after transplantation; mean estimated glomerular filtration rate, 63 +/- 27 [SD] mL/min/1.73 m(2); mean systolic blood pressure [SBP], 151 +/- 12 mm Hg). Intervention: Amlodipine (5-10 mg) and chlorthalidone (12.5-25 mg) for 8 weeks (separated by 2-week washout). Outcomes: Average daytime (9 AM to 9 PM) ambulatory SBP. Measurements: Blood pressure and laboratory parameters. Results: 88 patients underwent ambulatory blood pressure monitoring, of whom 49 (56%) with average daytime SBP > 140 mm Hg were enrolled. 41 patients completed the study. Amlodipine and chlorthalidone both reduced ambulatory SBP after 8 weeks (mean changes of 150 +/- 12 to 137 +/- 12 [SD] vs 151 +/- 12 to 141 +/- 13 mm Hg; effect size, -4.2 [95% CI, -7.3 to 1.1] mm Hg). Despite these similar blood pressure responses, chlorthalidone reduced proteinuria by 30% (effect size, -65 [95% CI, -108 to -35] mg/g) and also reduced physician-assessed peripheral edema (22% to 10%; P < 0.05 for both). In contrast, chlorthalidone temporarily reduced kidney function and increased both serum uric acid and glycated hemoglobin levels. Limitations: Open-label design, short follow-up, per-protocol analysis. Conclusions: Chlorthalidone is an antihypertensive drug equally effective as amlodipine after kidney transplantation. (C) 2017 by the National Kidney Foundation, Inc.