They also suggested that chlorthalidone would reduce the degree of albuminuria over 12 weeks. On the basis of preliminary evidence of an effect on BP in patients with CKD, the study team hypothesized that in patients with advanced CKD and uncontrolled hypertension, chlorthalidone would decrease the 24-hour ambulatory systolic BP. “Chlorthalidone, a thiazide-like diuretic, reduces cardiovascular morbidity, such as the incidence of stroke and heart failure, and cardiovascular mortality. However, its efficacy and safety among patients with advanced chronic kidney disease remain poorly understood.” “Thiazide or thiazide-like diuretics are important agents for lowering blood pressure in patients with essential hypertension,” the authors explained. “The percent change in the urinary albumin-to-creatinine ratio from baseline to 12 weeks was lower in the chlorthalidone group than in the placebo group by 50 percentage points (95% CI, 37 to 60),” the researchers pointed out, adding that hypokalemia, reversible increases in serum creatinine level, hyperglycemia, dizziness, and hyperuricemia occurred more frequently in the chlorthalidone group than in the placebo group.īackground information in the article describes how hypertension, although a common risk factor for both cardiovascular disease and CKD, is often poorly controlled, especially in patients with advanced CKD. That means that the between-group difference was 10.5 mmHg (95% CI, 14.6 to 6.4) ( P <.001). The adjusted change in 24-hour systolic BP from baseline to 12 weeks was 11.0 mmHg (95% confidence interval, 13.9 to 8.1) in the chlorthalidone group and 0.5 mmHg (95% CI, 3.5 to 2.5) in the placebo group. The mean (±SD) estimated glomerular filtration rate (GFR) was 23.2 ± 4.2 mL per minute per 1.73 m 2 of body-surface area at baseline, and the mean number of antihypertensive medications prescribed was 3.4 ± 1.4.Īt randomization, the mean 24-hour ambulatory systolic BP was 142.6☘.1 mmHg in the chlorthalidone group and 140.1☘.1 mmHg in the placebo group, with mean 24-hour ambulatory diastolic BP of 74.6 ± 10.1 mmHg and 72.8 ± 9.3 mmHg, respectively. The study team randomized 160 patients, of whom 121 (76%) had diabetes mellitus and 96 (60%) were receiving loop diuretics. The primary outcome was the change in 24-hour ambulatory systolic BP from baseline to 12 weeks, with secondary outcomes including the change from baseline to 12 weeks in the urinary albumin-to-creatinine ratio, N-terminal pro–B-type natriuretic peptide (NT-proBNP) level, plasma renin and aldosterone levels, and total body volume. Randomization was stratified according to previous use of loop diuretics.
The chlorthalidone dosage was increased every 4 weeks, if necessary, to a maximum of 50 mg per day. Researchers randomly assigned patients with stage 4 CKD and poorly controlled hypertension, as confirmed by 24-hour ambulatory BP monitoring, in a 1:1 ratio to receive chlorthalidone at an initial dosage of 12.5 mg per day or placebo. Indiana University School of Medicine–led researchers determined that in patients with advanced CKD and poorly controlled hypertension, chlorthalidone therapy improved blood-pressure (BP) control at 12 weeks compared with placebo.
That may have changed with a new study published in the New England Journal of Medicine. Indianapolis, IN-In general, scant evidence has been available to promote the use of thiazide diuretics to treat hypertension in patients with advanced chronic kidney disease (CKD).