Chlorthalidone no better than hydrochlorothiazide for kidney health

In the treatment of patients with hypertension, the use of chlorthalidone does not appear to yield superior kidney outcomes when compared with hydrochlorothiazide but is associated with an increased risk of hypokalemia, as reported in a study.

Secondary analysis of the Diuretic Comparison Project showed that over a mean follow-up of 3.9 years, chlorthalidone did not significantly reduce the incidence of chronic kidney disease (CKD) progression, the primary outcome, compared with hydrochlorothiazide (6.0 percent vs 6.4 percent; hazard ratio [HR], 0.94, 95 percent confidence interval [CI], 0.81–1.08; p=0.37). [JAMA Netw Open 2024;7:e2449576]

CKD progression was defined as doubling of serum creatinine level from baseline, a terminal eGFR of less than 15 mL/min, or dialysis initiation. Similar results were obtained when doubling of creatinine was replaced with at least a 40-percent reduction in eGFR (12.7 percent vs 13.3 percent; HR, 0.96, 95 percent CI, 0.87–1.06; p=0.39), according to the investigators.

Likewise, chlorthalidone showed no significant beneficial effect on the incidence of CKD (21.3 percent vs 20.8 percent; p=0.59) or acute kidney injury requiring hospitalization (6.4 percent vs 6.2 percent; p=0.63) compared with hydrochlorothiazide.

However, patients treated with chlorthalidone were more likely to experience hypokalemia than those treated with hydrochlorothiazide (8.9 percent vs 6.9 percent; p<0.001).

“Thiazide diuretics have been demonstrated to reduce blood pressure and the incidence of cardiovascular outcomes in those with hypertension. They are recommended as first-line agents by numerous hypertension guidelines for the general population and in those with CKD and no proteinuria,” the investigators said. [Hypertension 2018;71:e13-e115; J Hypertens 2023;41:1874-2071; Kidney Int 2021;99:S1-S87]

Due to concerns about their limited ability to reach the distal convoluted tubule in CKD patients, thiazide diuretics were historically considered less effective for blood pressure management in this population, they continued. “Given the findings [from the present study], clinicians should feel more confident in using either agent for the treatment of hypertension.”

The analysis included 12,265 older adults (median age 71 years, 96.8 percent male, 45.9 percent had diabetes) with systolic blood pressure (SBP) of at least 120 mm Hg, active hydrochlorothiazide prescription of 25 or 50 mg/d, and had a baseline and at least one follow-up creatinine measurements. At baseline, the median SPB was 139 mm Hg, the median eGFR was 71.2 mL/min/1.73 m², and 26.3 percent of patients had CKD.

The participants were randomly assigned to continue hydrochlorothiazide (n=6,147) or switch to chlorthalidone (n=6,118). The median doses used were 12.3 mg/d for chlorthalidone and 23.0 mg/d for hydrochlorothiazide, with a mean medication possession ratio of 79.7 percent and 79.4 percent, respectively.