Chlorthalidone, a drug approved by the FDA in 1960, significantly improves systolic blood pressure (SBP) control at 12 weeks compared with placebo in patients with advanced chronic kidney disease (CKD) and poorly controlled hypertension, according to data presented at the American Society of Nephrology’s Kidney Week 2021 and published concomitantly in the New England Journal of Medicine.

“This study establishes the efficacy of low dose chlorthalidone as an effective drug to treat hypertension in patients with stage 4 CKD,” lead investigator Rajiv Agarwal, MD, MS, professor of medicine at the Indiana University School of Medicine in Indianapolis, told Renal & Urology News.

The double-blind Chlorthalidone in Chronic Kidney Disease (CLICK) Trial included 160 patients with stage 4 CKD randomly assigned to receive chlorthalidone at an initial dose of 12.5 mg per day, with increases every 4 weeks if needed to a maximum of 50 mg per day, or placebo. At randomization, the mean 24-hour ambulatory SBP was 142.6 mm Hg in the chlorthalidone group and 140.1 mm Hg in the placebo group.


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From baseline to 12 weeks, mean SBP declined by 11.0 mm Hg in the chlorthalidone group and 0.5 mm Hg in the placebo group, a significant 10.5 mm Hg lower SBP in the chlorthalidone group.

Further, the urinary albumin-to-creatinine ratio at 12 weeks was 50% lower in the chlorthalidone group than in the placebo group, which Dr Agarwal said suggests that chlorthalidone protects patients from kidney failure.

The investigators noted that chlorthalidone should be used with caution in patients receiving loop diuretics, particularly because of the risk for an increase in serum creatinine level. Hypokalemia, reversible increases in serum creatinine level, hyperglycemia, dizziness, and hyperuricemia occurred more frequently in the chlorthalidone group than in the placebo.

“Among those with stage 4 CKD who are also treated with either an ACE inhibitor, angiotensin receptor blocker, or a beta blocker, the drug can lower the BP effectively,” Dr Agarwal said. “There are potential side effects of the drug, typically those that we have known about, and it is important to monitor the patients.”

The study showed that chlorthalidone-treated patients had a 37% lower risk for progressing to dialysis compared with placebo recipients, although this was not statistically significant. “A larger study is needed to answer the question of kidney protection,” Dr Agarwal said. “However, we are continuing to follow these patients and will be able to say in the future if there is an association between chlorthalidone use and kidney protection.”

References

Agarwal R, Sinha AD, Cramer AE, et al. Chlorthalidone for hypertension in advanced CKD (CLICK): A randomized double-blind trial. Presented at: Kidney Week 2021, November 2-7, 2021. Abstract FR-OR68.

Agarwal R, Sinha AD, Cramer AE, et al. Chlorthalidone for hypertension in advanced chronic kidney disease. N Engl J Med. Published online November 5, 2021. doi:10.1056/NEJMoa2110730