title: 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.
  
  
  METHODS
  Randomized noninferiority crossover trial (noninferiority margin, -2.8mmHg).
  
  
  METHODS
  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).
  
  
  METHODS
  Amlodipine (5-10mg) and chlorthalidone (12.5-25mg) for 8 weeks (separated by 2-week washout).
  
  
  RESULTS
  Average daytime (9 am to 9 pm) ambulatory SBP.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Open-label design, short follow-up, per-protocol analysis.
  
  
  CONCLUSIONS
  Chlorthalidone is an antihypertensive drug equally effective as amlodipine after kidney transplantation.
authors.affiliation: Division of Nephrology & Transplantation, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Moes
authors.affiliation: Division of Nephrology & Transplantation, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Hesselink
authors.affiliation: Division of Vascular Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Anton H
authors.initials: AH
authors.lastname: van den Meiracker
authors.affiliation: Division of Nephrology & Transplantation, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Zietse
authors.affiliation: Division of Nephrology & Transplantation, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. Electronic address: e.j.hoorn@erasmusmc.nl.
authors.forename: Ewout J
authors.initials: EJ
authors.lastname: Hoorn
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D018660:Blood Pressure Monitoring, Ambulatory; D002752:Chlorthalidone / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004487:Edema; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000150:complications / Q000601:surgery*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011507:Proteinuria; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D007166:Immunosuppressive Agents; D017311:Amlodipine; D002752:Chlorthalidone; D016559:Tacrolimus
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