Mechanisms of antihypertensive effect of chlorthalidone in advanced chronic kidney disease-a causal mediation analysis.
Journal
Clinical journal of the American Society of Nephrology : CJASN
ISSN: 1555-905X
Titre abrégé: Clin J Am Soc Nephrol
Pays: United States
ID NLM: 101271570
Informations de publication
Date de publication:
12 Jun 2024
12 Jun 2024
Historique:
received:
12
02
2024
accepted:
07
06
2024
medline:
12
6
2024
pubmed:
12
6
2024
entrez:
12
6
2024
Statut:
aheadofprint
Résumé
Chlorthalidone in chronic kidney disease (CLICK) randomized trial demonstrated a robust reduction in systolic blood pressure (BP) in stage 4 chronic kidney disease (CKD). Here we explore the mechanisms underlying the antihypertensive effect of chlorthalidone. In this prespecified analysis, we analyzed the contributions of baseline levels of 24-hour urinary sodium and aldosterone and the changes from baseline to 4 weeks in the multiple mediators reflecting volume status in a causal mediation analysis framework. Baseline levels of these mediators served as covariates. No power calculationfor this analysis was performed. Of the 160 patients randomized, 140 (87.5%) were included in this analysis. Compared to placebo, chlorthalidone within 4 weeks reduced weight -1.5 % (95% CI -2.2 to -0.7) and volume -1.4 % (95% CI -2.2 to -0.6), stimulated plasma renin 40.5% (95% CI 25.4 to 57.4%) and serum aldosterone 40.2% (95% CI 11.7% to 76%), and reduced plasma NT-pro BNP levels -19.4% (95% CI -33.8% to -1.9%). Mediation analysis revealed the following results: for weight change, the total effect on systolic BP was -10.8 mmHg (95% CI -16 to -5.7), of which weight change (indirect effect) accounted for -0.9 mmHg (95% CI -4.2 to 2.5) and BP change independent of weight (direct effect) accounted for -10 mmHg (-15.7 to - 4.2). Thus, the percent mediation was 8.1% (95% CI -22.4 to 38.5). Baseline excretion of 24-hour sodium or aldosterone or any of the changes in the above mediators examined accounted for <2 mmHg BP drop and were not significant for any of the mediators. Chlorthalidone improved BP control among patients with advanced CKD independently of baseline urinary sodium, aldosterone, weight loss, or changes in the renin-angiotensin system or NT-pro BNP. (Funded by the National Heart Lung and Blood Institute; CLICK ClinicalTrials.gov number, NCT02841280).
Sections du résumé
BACKGROUND
BACKGROUND
Chlorthalidone in chronic kidney disease (CLICK) randomized trial demonstrated a robust reduction in systolic blood pressure (BP) in stage 4 chronic kidney disease (CKD). Here we explore the mechanisms underlying the antihypertensive effect of chlorthalidone.
METHODS
METHODS
In this prespecified analysis, we analyzed the contributions of baseline levels of 24-hour urinary sodium and aldosterone and the changes from baseline to 4 weeks in the multiple mediators reflecting volume status in a causal mediation analysis framework. Baseline levels of these mediators served as covariates. No power calculationfor this analysis was performed.
RESULTS
RESULTS
Of the 160 patients randomized, 140 (87.5%) were included in this analysis. Compared to placebo, chlorthalidone within 4 weeks reduced weight -1.5 % (95% CI -2.2 to -0.7) and volume -1.4 % (95% CI -2.2 to -0.6), stimulated plasma renin 40.5% (95% CI 25.4 to 57.4%) and serum aldosterone 40.2% (95% CI 11.7% to 76%), and reduced plasma NT-pro BNP levels -19.4% (95% CI -33.8% to -1.9%). Mediation analysis revealed the following results: for weight change, the total effect on systolic BP was -10.8 mmHg (95% CI -16 to -5.7), of which weight change (indirect effect) accounted for -0.9 mmHg (95% CI -4.2 to 2.5) and BP change independent of weight (direct effect) accounted for -10 mmHg (-15.7 to - 4.2). Thus, the percent mediation was 8.1% (95% CI -22.4 to 38.5). Baseline excretion of 24-hour sodium or aldosterone or any of the changes in the above mediators examined accounted for <2 mmHg BP drop and were not significant for any of the mediators.
CONCLUSION
CONCLUSIONS
Chlorthalidone improved BP control among patients with advanced CKD independently of baseline urinary sodium, aldosterone, weight loss, or changes in the renin-angiotensin system or NT-pro BNP. (Funded by the National Heart Lung and Blood Institute; CLICK ClinicalTrials.gov number, NCT02841280).
Identifiants
pubmed: 38865199
doi: 10.2215/CJN.0000000000000484
pii: 01277230-990000000-00405
doi:
Banques de données
ClinicalTrials.gov
['NCT02841280']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Office of Extramural Research, National Institutes of Health
ID : R01HL126903
Informations de copyright
Copyright © 2024 by the American Society of Nephrology.