Should we CLICK on chlorthalidone for treatment-resistant hypertension in chronic kidney disease?

Treatment-resistant hypertension is common among patients with advanced chronic kidney disease (CKD). In people with preserved kidney function, spironolactone is an evidence-based treatment. However, the risk for hyperkalemia limits its use in people with more advanced CKD. In the Chlorthalidone in Chronic Kidney Disease (CLICK) trial, 160 patients with stage 4 CKD and poorly controlled hypertension as confirmed by 24-hour ambulatory blood pressure (ABP) monitoring were randomly assigned to either placebo or chlorthalidone 12.5 mg daily in a 1:1 ratio stratified by prior loop diuretic use. The primary endpoint was the change in 24-hour systolic ABP from baseline to 12 weeks. The trial showed a treatment-induced reduction of 24-hour systolic ABP by 10.5 mmHg. Of the 160 patients randomized, 113 (71%) had resistant hypertension, of which 90 (80%) were on loop diuretics and the mean number of antihypertensive medications prescribed was 4.1 (standard deviation 1.1). In this subgroup of patients with treatment-resistant hypertension, the adjusted change from baseline to 12 weeks in the between-group difference in 24-hour systolic ABP was -13.9 mmHg (95% CI -19.4 to -8.4;

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Published by Oxford University Press on behalf of the ERA 2023.

Déclaration de conflit d'intérêts

R.A. reports personal fees and nonfinancial support from Bayer Healthcare Pharmaceuticals, Akebia Therapeutics, Boehringer Ingelheim, Eli Lilly and Vifor Pharma; personal fees from Lexicon and Reata; is a member of data safety monitoring committees for Vertex and Chinook; a member of steering committees of randomized trials for Akebia Therapeutics, Bayer and Relypsa; a member of adjudication committees for Bayer; has served as Associate Editor of the American Journal of Nephrology and Nephrology Dialysis and Transplantation and has been an author for UpToDate; and has received research grants from the National Institutes of Health and the U.S. Veterans Administration.