Evidence map›Paper›PMID 34739197›Full record

Trial reportThe New England journal of medicine2021

Chlorthalidone for Hypertension in Advanced Chronic Kidney Disease.

Rajiv Agarwal, Arjun D Sinha, Andrew E Cramer, Mary Balmes-Fenwick, Jazmyn H Dickinson, Fangqian Ouyang, Wanzhu Tu

2 registry-linked trialsOpen access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 114 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 7 pooled it
32.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02841280 phase2completednot on this map

Chlorthalidone in Chronic Kidney Disease

TypeinterventionalSponsorIndiana UniversityRan2016 to 2021Enrolled160ConditionsRenal Insufficiency, Chronic, HypertensionArmsChlorthalidone, Placebo
NCT07271420 phase4recruitingnot on this map

Blood Pressure Control With Thiazide Diuretics in Peritoneal Dialysis Patients

TypeinterventionalSponsorChinese University of Hong KongRan2020 to 2027Enrolled40ConditionsHypertension, Peritoneal Dialysis, End Stage Kidney Disease (ESRD)ArmsHydrochlorothiazide 25mg once per day
3 · Its place in the literature

Who cites it

114 citing papers in PubMed, 7 syntheses or guidelines pooled it, 266 citations in OpenAlex.

  1. The Japanese Society of Hypertension Guidelines for the management of elevated blood pressure and hypertension 2025 (JSH2025).Hypertension research : official journal of the Japanese Society of Hypertension · 2026
    Guideline
  2. Guideline
  3. Guideline
  4. Guideline
  5. Guideline
  6. A European Renal Association (ERA) synopsis for nephrology practice of the 2023 European Society of Hypertension (ESH) Guidelines for the Management of Arterial Hypertension.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024
    Guideline
  7. Pooled it
  8. Trial
  9. Trial
  10. Trial
  11. Review
  12. Diuretics in Cardiovascular Disease: For How Long and at What Dose?Journal of cardiovascular development and disease · 2026
    Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Pitfalls in the pharmacotherapy of hypertension.Clinical medicine (London, England) · 2026
    Review
  19. Management of hypertension in chronic kidney disease.Clinical medicine (London, England) · 2026
    Review
  20. Review

54 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Rajiv AgarwalFrom 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.ORCID 0000-0001-8355-7100
Arjun D SinhaFrom 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.
Andrew E CramerFrom 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.
Mary Balmes-FenwickFrom 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.
Jazmyn H DickinsonFrom 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.
Fangqian OuyangFrom 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.
Wanzhu TuFrom 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.
Richard L. Roudebush VA Medical Center · USRegenstrief Institute · US

Funding

ChLorthalidone In Chronic Kidney Disease (CLICK) StudyR01HL126903 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI AGARWAL, RAJIV · 2016 to 2020
$3.2M
NHLBI NIH HHS R01 HL126903NHLBI NIH HHS R01HL126903
6 · The paper itself

Abstract

backgroundLittle evidence has been available to support the use of thiazide diuretics to treat hypertension in patients with advanced chronic kidney disease.

methodsWe randomly assigned patients with stage 4 chronic kidney disease and poorly controlled hypertension, as confirmed by 24-hour ambulatory blood-pressure monitoring, in a 1:1 ratio to receive chlorthalidone at an initial dose of 12.5 mg per day, with increases every 4 weeks if needed to a maximum dose of 50 mg per day, or placebo; randomization was stratified according to previous use of loop diuretics. The primary outcome was the change in 24-hour ambulatory systolic blood pressure from baseline to 12 weeks. Secondary outcomes were 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. Safety was also assessed.

resultsA total of 160 patients underwent randomization, of whom 121 (76%) had diabetes mellitus and 96 (60%) were receiving loop diuretics. At baseline, the mean (±SD) estimated glomerular filtration rate was 23.2±4.2 ml per minute per 1.73 m

conclusionsAmong patients with advanced chronic kidney disease and poorly controlled hypertension, chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo. (Funded by the National Heart, Lung, and Blood Institute and the Indiana Institute of Medical Research; CLICK ClinicalTrials.gov number, NCT02841280.).

Indexed as

AgedAlbuminuriaBlood PressureChlorthalidoneCreatinineDiureticsDouble-Blind MethodFemaleGlomerular Filtration RateHumansHypertensionMaleMiddle AgedNatriuretic Peptide, BrainPeptide FragmentsRenal Insufficiency, ChronicChlorthalidoneCreatinineDiureticsNatriuretic Peptide, BrainPeptide Fragmentspro-brain natriuretic peptide (1-76)Sodium Chloride Symporter Inhibitors

Identifiers

PMID34739197
PMCPMC9119310
OpenAlexW3210606186

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.