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Review
. 2022 Dec 20;16(5):793-796.
doi: 10.1093/ckj/sfac272. eCollection 2023 May.

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

Rajiv Agarwal  1
Affiliations
Review

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

Rajiv Agarwal. Clin Kidney J. .

Abstract

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; P < .0001). Furthermore, compared with placebo, the urine albumin:creatinine ratio in the chlorthalidone group at 12 weeks was 54% lower (95% CI -65 to -40). Following randomization, hypokalemia, reversible increases in serum creatinine, hyperglycemia, dizziness, orthostatic hypotension and hyperuricemia occurred more frequently in the chlorthalidone group. Chlorthalidone has the potential to improve BP control among patients with advanced CKD and treatment-resistant hypertension. However, caution is advised when treating patients, especially when they are on loop diuretics.

Keywords: albuminuria; ambulatory blood pressure monitoring; chronic renal failure; creatinine; diuretics; hypertension.

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Conflict of interest statement

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.

Figures

Figure 1:
Figure 1:
Efficacy, safety and dosing of spironolactone and chlorthalidone in CKD.
See this image and copyright information in PMC

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