ArticlePloS one2013
Potentiation of the effect of thiazide derivatives by carbonic anhydrase inhibitors: molecular mechanisms and potential clinical implications.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Acetazolamide therapy in patients with acute heart failure: a systematic review and meta-analysis of randomized controlled trials.Heart failure reviews · 2024Pooled it
- Acetazolamide as an Adjunctive Diuretic Therapy for Patients with Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024 · on this mapPooled it
- Trial
- Acetazolamide as Add-on Diuretic Therapy in Exacerbations of Chronic Heart Failure: a Pilot Study.Clinical drug investigation · 2017Trial
- Loop Diuretic Dose Intensification versus Adjuvant Thiazide for Diuretic Resistance in Acute Heart Failure: Mechanistic Randomized Controlled Trial.Journal of the American Society of Nephrology : JASN · 2026Article
- Use of acetazolamide in volume overload: start at the beginning.Clinical kidney journal · 2026Review
- Diuretics in patients with chronic kidney disease.Nature reviews. Nephrology · 2025Review
- The Changing Role of Loop Diuretics in Heart Failure Management across the Last Century.Journal of clinical medicine · 2024Review
- Serum Chloride and Heart Failure.Kidney medicine · 2023Review
- Effect of Acetazolamide as Add-On Diuretic Therapy in Patients With Heart Failure: A Meta-Analysis.Cureus · 2023 · on this mapReview
- New Strategies for Volume Control in Patients with Diabetes Mellitus, a Narrative Review.Pharmaceutics · 2022Review
- The Effect of Add-on Acetazolamide to Conventional Diuretics for Diuretic-resistant Edema Complicated with Hypercapnia: A Report of Two Cases.Internal medicine (Tokyo, Japan) · 2022Article
- Review
- Usefulness of acetazolamide in the management of diuretic resistance.Proceedings (Baylor University. Medical Center) · 2020Article
- Acetazolamide Therapy in Patients with Heart Failure: A Meta-Analysis.Journal of clinical medicine · 2019Article
- Brain Edema Formation and Functional Outcome After Surgical Decompression in Murine Closed Head Injury Are Modulated by Acetazolamide Administration.Frontiers in neurology · 2019Article
- Tuberous sclerosis complex exhibits a new renal cystogenic mechanism.Physiological reports · 2019Article
- Nephrotic Syndrome: Oedema Formation and Its Treatment With Diuretics.Frontiers in physiology · 2018Review
- Probenecid Pre-treatment Downregulates the Kidney ClFrontiers in physiology · 2018Article
- SGLT-2 Inhibitors in Heart Failure: Implications for the Kidneys.Current heart failure reports · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCarbonic anhydrase inhibitors (CAI) are mild diuretics, hence not widely used in fluid overloaded states. They are however the treatment of choice for certain non-kidney conditions. Thiazides, specific inhibitors of Na-Cl cotransport (NCC), are mild agents and the most widely used diuretics in the world for control of mild hypertension. HYPOTHESIS: In addition to inhibiting the salt reabsorption in the proximal tubule, CAIs down-regulate pendrin, therefore leaving NCC as the major salt absorbing transporter in the distal nephron, and hence allowing for massive diuresis by the inhibitors of NCC in the setting of increased delivery of salt from the proximal tubule. EXPERIMENTAL PROTOCOLS AND
resultsDaily treatment of rats with acetazolamide (ACTZ), a known CAI, for 10 days caused mild diuresis whereas daily treatment with hydrochlorothiazide (HCTZ) for 4 days caused hardly any diuresis. However, treatment of rats that were pretreated with ACTZ for 6 days with a combination of ACTZ plus HCTZ for 4 additional days increased the urine output by greater than 2 fold (p<0.001, n = 5) compared to ACTZ-treated animals. Sodium excretion increased by 80% in the ACTZ plus HCTZ group and animals developed significant volume depletion, metabolic alkalosis and pre-renal failure. Molecular studies demonstrated ∼75% reduction in pendrin expression by ACTZ. The increased urine output in ACTZ/HCTZ treated rats was associated with a significant reduction in urine osmolality and reduced membrane localization of AQP-2 (aquaporin2).
conclusionsThese results indicate that ACTZ down-regulates pendrin expression and leaves NCC as the major salt absorbing transporter in the distal nephron in the setting of increased delivery of salt from the proximal tubule. Despite being considered mild agents individually, we propose that the combination of ACTZ and HCTZ is a powerful diuretic regimen.
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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.