Chlorthalidone in Chronic Kidney Disease
Summary
It is estimated that in the United States there are approximately 8 million individuals who have moderate to severe chronic kidney disease (CKD). Among them hypertension is common and is often poorly controlled due to an expanded volume state; diuretics are frequently prescribed. Loop diuretics are potent and effective in lowering blood pressure (BP) but their use is associated with acute kidney injury. Thiazide diuretics, on the other hand, are less potent, their use may be associated with less acute kidney injury, but as yet there are no firm data to support that thiazide diuretic therapy can improve BP among subjects with advanced CKD. The investigators found 13 studies on the use of thiazide diuretics in advanced CKD either alone or in combination with loop diuretics and concluded that thiazides may be useful. Thiazides cause a negative Na balance, increase Na excretion by 10-15% and weight loss by 1-2 kg in observational studies. Observational data show that thiazides lead to an improvement in seated clinic BP of about 10-15 mmHg systolic and 5-10 mmHg diastolic whereas randomized trials show about a 15 mmHg reduction in mean BP. Randomized trials had only between 7 and 23 subjects each; accordingly, larger studies are needed to evaluate their safety and efficacy in moderate to advanced CKD.
Timeline
- Start
- 2016-07
- Primary completion
- 2021-04
- Completion
- 2021-04
Publications
- Agarwal R, Sinha AD, Tu W. Mechanisms of Antihypertensive Effect of Chlorthalidone in Advanced Chronic Kidney Disease: A Causal Mediation Analysis. Clin J Am Soc Nephrol. 2024 Aug 1;19(8):1025-1032. doi: 10.2215/CJN.0000000000000484. Epub 2024 Jun 12.
- Agarwal R, Sinha AD, Cramer AE, Balmes-Fenwick M, Dickinson JH, Ouyang F, Tu W. Chlorthalidone for Hypertension in Advanced Chronic Kidney Disease. N Engl J Med. 2021 Dec 30;385(27):2507-2519. doi: 10.1056/NEJMoa2110730. Epub 2021 Nov 5.
- Agarwal R, Cramer AE, Balmes-Fenwick M, Sinha AD, Ouyang F, Tu W. Design and Baseline Characteristics of the Chlorthalidone in Chronic Kidney Disease (CLICK) Trial. Am J Nephrol. 2020;51(7):542-552. doi: 10.1159/000508700. Epub 2020 Jul 14.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Chlorthalidone | Other / unclassified | 50 mg | — |