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 CKD (CLICK) trial, 160 patients with stage 4 CKD and poorly controlled hypertension as confirmed by 24-hour ambulatory blood pressure (BP) 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 ambulatory BP from baseline to 12 weeks. The trial showed a treatment-induced reduction of 24-hour systolic ambulatory BP 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 (SD) number of antihypertensive medications prescribed was 4.1 (1.1). In this subgroup of patients with treatment-resistant hypertension, the adjusted change from baseline to 12 weeks the between-group difference in 24-hour systolic ambulatory BP was -13.9 (95% CI, -19.4 to -8.4; p < 0.0001) mmHg. Furthermore, compared to placebo, the urine albumin to urine 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.