Chlorthalidone Therapy Improves Blood Pressure in Patients with CKD, Hypertension

Rajiv Agarwal, MD

Little evidence to support the use of thiazide diuretics in the treatment of hypertension in patients with advanced chronic kidney disease (CKD) has led to a new study to determine its effect.

Led by Rajiv Agarwal, MD, Division of Nephrology, Indiana University School of Medicine, observed an improvement in blood-pressure control using chlorthalidone therapy in patients with advanced CKD and poorly controlled hypertension.

Methods

Agarwal and colleagues randomly assigned patients with stage 4 CKD and poorly controlled hypertension, confirmed by 24-hour ambulatory blood-pressure monitoring, in a 1:1 ratio to receive chlorthalidone.

Dosage started at 12.5 mg per day, with increases every 4 weeks if needed to a maximum dose of 50 mg per day, or placebo. Then, the randomization was stratified according to the previous use of loop diuretics.

The primary outcome in the study was identified as the change in 24-hour ambulatory systolic blood pressure was baseline to 12 weeks.

Additionally, secondary outcomes included the change from baseline to 12 weeks in the urinary albumin-to-creatinine ratio, N-terminal pro–B-type natriuretic peptide level, plasma renin and aldosterone levels, and total body volume.

Findings

Data show a total of 160 patients underwent randomization, of which 121 (76%) had diabetes mellitus and 96 (60%) were receiving loop diuretics.

They observed a baseline measurement of estimated glomerular filtration rate was 23.2±4.2 mL per minute per 1.73 m2of body-surface area. Additionally, the mean number of antihypertensive medications prescribed was 3.4±1.4.

During randomization, the mean 24-hour ambulatory systolic blood pressure was 142.6±8.1 mm Hg in the chlorthalidone group and 140.1±8.1 mm Hg in the placebo group. Data show the respective mean 24-hour ambulatory diastolic blood pressure was 74.6±10.1 mm Hg and 72.8±9.3 mm Hg.

From baseline to 12 weeks, the adjusted change in 24-hour systolic blood pressure was -11.0 mm Hg (95% CI, -13.9 to -8.1) in the chlorthalidone group and -0.5 mm Hg (95% CI, -3.5 to 2.5) in the placebo group. A between-group difference of -10.5 mm Hg (95% CI, -14.6 to -6.4, P <.001) was observed.

The team noted the percent change in the urinary albumin-to-creatinine ratio from baseline to 12 weeks was lower in the chlorthalidone group in the placebo group by 50 percentage points (95% CI, 37 - 60).

In the chlorthalidone group, hypokalemia, reversible increases in serum creatinine level, hyperglycemia, dizziness, and hyperuricemia occurred more frequently in the chlorthalidone group, compared to the placebo group.

Takeaways

“Among patients with advanced chronic kidney disease and poorly controlled hypertension, chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo,” investigators wrote.

The study, “Chlorthalidone for Hypertension in Advanced Chronic Kidney Disease,” was published in the New England Journal of Medicine.