Summary
Hydrochlorothiazide has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Chronic Kidney Disease would be drug repurposing rather than first-in-human development. This does not mean it is approved for Chronic Kidney Disease. ClinicalTrials.gov lists 8 registered trials linking Hydrochlorothiazide to Chronic Kidney Disease: 3 are currently recruiting; 4 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT02646397). It plans or enrolled 508 participants. Registration activity spans 2010 to 2025. The literature layer holds 7 publications for this pair: 1 Cochrane review, 1 meta-analysis and 5 clinical trial publications. Publication years run from 2017 to 2026. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Chronic Kidney Disease ranks 534 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: GFR decline averages 2-5 mL/min/year on standard care (ACE/ARB + blood pressure control); progression to end-stage renal disease (ESRD) in ~20-30% at 10 years for moderate CKD; reversal essentially impossible once structural fibrosis established.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 69.0 (trials 30.0, literature 19.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 3 recruiting, 0 active / not yet recruiting, 4 completed, 1 other |
| Linked publications | 7 (5 clinical trial publications, 1 Cochrane review, 1 meta-analysis) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | Not recorded |
| Data sources | DGIdb |
| Linked via biomarker / target | AGTR1 |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT05171686 | Diuretics and Volume Overload in Early CKD 2023 | completed | Phase 4 | 49 |
| NCT02875886 | DD-study: Diet or Diuretics for Salt-sensitivity in Chronic Kidney Disease 2016 | completed | Phase 4 | 28 |
| NCT03170336 | A New Application of Amiloride in the Treatment of Patient With Chronic Kidney Disease In Reducing Urinary PROtein 2018 | completed | Phase 4 | 40 |
| NCT07271420 | Blood Pressure Control With Thiazide Diuretics in Peritoneal Dialysis Patients 2020 | recruiting | Phase 4 | 40 |
| NCT02646397 | Benidipine and Hydrochlorothiazide in Fosinopril Treated Chronic Kidney Disease Patients With Hypertension 2016 | status unknown | Phase 4 | 508 |
| NCT01087749 | Pharmacokinetic Study in Patients With Chronic Kidney Disease and Healthy Volunteers 2010 | completed | Phase 1 | 24 |
| NCT07020104 | The Role of Skin Sodium Accumulation in Chronic Kidney Disease 2025 | recruiting | Not applicable | 60 |
| NCT06841692 | Diuretic Testing in Chronic Kidney Disease 2025 | recruiting | Not applicable | 86 |
Published literature
- Clinical trial publication The urine metabolomic signature of distal diuretics and diuretic-induced hyponatremia in patients with chronic kidney diseaseRudolphi CF, Musterd-Bhaggoe U, Ruijter GJG et al. · American journal of physiology. Renal physiology · 2026 · PMID 41962959
- Clinical trial publication Chlorthalidone vs Hydrochlorothiazide and Kidney Outcomes in Patients With Hypertension: A Secondary Analysis of a Randomized Clinical TrialIshani A, Hau C, Raju S et al. · JAMA network open · 2024 · PMID 39656458
- Cochrane review Altered dietary salt intake for preventing diabetic kidney disease and its progressionHodson EM, Cooper TE · The Cochrane database of systematic reviews · 2023 · PMID 36645291
- Clinical trial publication A Randomized Trial of Distal Diuretics versus Dietary Sodium Restriction for Hypertension in Chronic Kidney DiseaseBovée DM, Visser WJ, Middel I et al. · Journal of the American Society of Nephrology : JASN · 2020 · PMID 31996411
- Clinical trial publication Long-term efficacy and tolerability of azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide in chronic kidney diseaseBakris GL, Zhao L, Kupfer S et al. · Journal of clinical hypertension (Greenwich, Conn.) · 2018 · PMID 29504252
- Clinical trial publication Renoprotective RAAS inhibition does not affect the association between worse renal function and higher plasma aldosterone levelsGant CM, Laverman GD, Vogt L et al. · BMC nephrology · 2017 · PMID 29262813
- Meta-analysis Olmesartan-based monotherapy vs combination therapy in hypertension: A meta-analysis based on age and chronic kidney disease statusDeedwania P, Weber M, Reimitz PE et al. · Journal of clinical hypertension (Greenwich, Conn.) · 2017 · PMID 29067756
Mechanism and notes
No mechanism of action is recorded for this pair in the source databases.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target AGTR1. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Hydrochlorothiazide approved for Chronic Kidney Disease?
Hydrochlorothiazide has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Chronic Kidney Disease would be drug repurposing rather than first-in-human development. This does not mean it is approved for Chronic Kidney Disease. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Hydrochlorothiazide in clinical trials for Chronic Kidney Disease?
ClinicalTrials.gov lists 8 registered trials linking Hydrochlorothiazide to Chronic Kidney Disease: 3 are currently recruiting; 4 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT02646397). It plans or enrolled 508 participants. Registration activity spans 2010 to 2025.
What does the evidence show for Hydrochlorothiazide in Chronic Kidney Disease?
Hydrochlorothiazide has both completed registered trials and synthesis-level publications linked to Chronic Kidney Disease. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target AGTR1. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.