Chlorthalidone for Hypertension in Advanced Chronic Kidney Disease

Little proof has been needed to support the usage of thiazide diuretics to deal with high blood pressure in sufferers with superior chronic kidney disease.


We randomly assigned sufferers with level 4 chronic kidney ailment and poorly managed hypertension, as showed by using 24-hour ambulatory blood-strain tracking, in a 1:1 ratio to receive chlorthalidone at an initial dose of 12.5 mg in line with day, with will increase every four weeks if had to the most quantity of fifty mg in step with day, or placebo; randomization was stratified in stage with previous use of loop diuretics. The number one outcome changed the 24-hour ambulatory systolic blood strain from baseline to 12 weeks. Secondary consequences alternate from baseline to 12 weeks in the urinary albumin-to-creatinine ratio, N-terminal seasoned–B-type natriuretic peptide degree, plasma renin, aldosterone levels, and general body volume. Safety was also assessed.


An overall of a hundred and sixty sufferers underwent randomization, of whom 121 (76%) had diabetes mellitus, and 96 (60%) received loop diuretics. At baseline, the implied (±SD) predicted glomerular filtration charge became 23.2±four.2 ml in keeping with minute consistent with 1. Seventy-three m2 of the body-surface region and the mean range of antihypertensive medications prescribed was 3.4±1.Four. At randomization, the mean 24-hour ambulatory systolic blood pressure becomes 142.6±8.1 mm Hg inside the chlorthalidone group and a hundred and forty.1±eight.1 mm Hg within the placebo organization and the suggested 24-hour ambulatory diastolic blood stress was 74.6±10.1 mm Hg and 72.Eight±nine.3 mm Hg, respectively. The adjusted change in 24-hour systolic blood pressure from baseline to twelve weeks becomes −11.0 mm Hg (95% confidence interval [CI], −thirteen. Nine to −eight.1) within the chlorthalidone group −zero. Five mm Hg (95% CI, −3.Five to two.5) in the placebo group. The between-organization distinction became −10. Five mm Hg (ninety-five% CI, −14.6 to −6.4) (P<zero.001). The percentage alternate within the urinary albumin-to-creatinine ratio from baseline to twelve weeks decreased within the chlorthalidone organization than inside the placebo group by using 50 percentage points (95% CI, 37 to 60). Hypokalemia, reversible increases in serum creatinine stage, hyperglycemia, dizziness, and hyperuricemia occurred more frequently within the chlorthalidone group than within the placebo group.


Among patients with superior chronic kidney disorder and poorly managed hypertension, chlorthalidone therapy advanced blood-stress manipulation at 12 weeks compared with placebo. (Funded by using the National Heart, Lung, and Blood Institute and the Indiana Institute of Medical Research; CLICK ClinicalTrials.Gov wide variety, NCT02841280. It opens in a new tab.)

They are supported by the National Heart, Lung, and Blood Institute (grant R01 HL126903) and the Indiana Institute of Medical Research. Disclosure paperwork furnished by the authors is available with the total text at NEJM.Org.

This article was posted on November 5, 2021, and updated on November 8, 2021, at NEJM.Org. A record-sharing declaration provided using the authors is available with the full-textual content at NEJM.Org.

We thank the sufferers who participated in the trial; Leroy Rhea, R.Ph., the research pharmacist; Robert V. Considine, Ph.D., for help with the evaluation of renin and aldosterone ranges; and the participants of the records and protection monitoring board for their oversight.
Author Affiliations

From the Division of Nephrology, Department of Medicine (R.A., A.D.S., A.E.C., M.B.-F., J.H.D.), and the Department of Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health (F.O., W.T.), Indiana University School of Medicine, Richard L. Roudebush Veterans Affairs Medical Center (R.A., A.D.S., A.E.C., M.B.-F., J.H.D.), and Indiana University Center for Aging Research, Regenstrief Institute (W.T.) — all in Indianapolis.

Dr. Agarwal can be contacted at ragarwal@iu.Edu or Richard L. Roudebush Veterans Affairs Medical Center, 1481 W. Tenth St., 111N, Indianapolis, IN 46202.

Dorothy R. Ferry

Coffee trailblazer. Unapologetic student. Freelance communicator. Travel nerd. Music fan. Spoke at an international conference about donating magma for farmers. Had some great experience promoting saliva on the black market. Spent 2002-2009 lecturing about basketballs in Pensacola, FL. In 2009 I was writing about Magic 8-Balls in Miami, FL. Earned praised for my work importing crayon art in Hanford, CA. At the moment I'm managing sausage in West Palm Beach, FL.

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