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

Abstract

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, -2.8mmHg).

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/1.73m²; mean systolic blood pressure [SBP], 151±12mmHg).

Intervention: Amlodipine (5-10mg) and chlorthalidone (12.5-25mg) 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>140mmHg 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±13mmHg; effect size, -4.2 [95% CI, -7.3 to 1.1] mmHg). 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.

Keywords: Calcineurin inhibitors (CNIs); ambulatory blood pressure monitoring (ABPM); amlodipine; blood pressure; chlorthalidone; clinical trial; edema; end-stage renal disease (ESRD); hypertension; kidney function; kidney transplantation; proteinuria; sodium-chloride cotransporter (NCC); thiazide diuretics.