ArticleClinical and experimental nephrology2019
Hydrochlorothiazide ameliorates polyuria caused by tolvaptan treatment of polycystic kidney disease in PCK rats.
Article in Clinical and experimental nephrology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- The effect of trichlormethiazide in autosomal dominant polycystic kidney disease patients receiving tolvaptan: a randomized crossover controlled trial.Scientific reports · 2021Trial
- Therapeutic potential of urinary extracellular vesicles in delivering functional proteins and modulating gene expression for genetic kidney disease.Biomaterials · 2025Article
- Construction of arginine vasopressin receptor 2-deficient rats by the rGONAD method.Clinical and experimental nephrology · 2025Article
- Article
- Dehydration Accelerates Cytogenesis and Cyst Growth in Pkd1Inflammation · 2023Article
- Combining Metformin and Drug-Loaded Kidney-Targeting Micelles for Polycystic Kidney Disease.Cellular and molecular bioengineering · 2023Article
- Application of nanoparticles in the diagnosis and treatment of chronic kidney disease.Frontiers in medicine · 2023Review
- Thiazide diuretics and the rate of disease progression in autosomal dominant polycystic kidney disease: an observational study.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2021Observational
- Improving kidney targeting: The influence of nanoparticle physicochemical properties on kidney interactions.Journal of controlled release : official journal of the Controlled Release Society · 2021Review
- The effect of size, charge, and peptide ligand length on kidney targeting by small, organic nanoparticles.Bioengineering & translational medicine · 2020Article
- Autosomal dominant polycystic kidney disease: updated perspectives.Therapeutics and clinical risk management · 2019Review
- Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTolvaptan is an effective treatment for polycystic kidney disease (PKD), but also causes unfortunate polyuria. Hydrochlorothiazide (HCTZ) has been shown to reduce urine volume in nephrogenic diabetes insipidus, raising the possibility that HCTZ could also be effective in reducing tolvaptan-induced polyuria. In this study, we examined the combined administration of HCTZ and tolvaptan.
methodsMale PCK rats were divided into four groups of normal chow (Cont), normal chow plus tolvaptan, gavage HCTZ treatment, and tolvaptan + HCTZ. Biochemical examinations of the plasma and urine were performed as well as histological and molecular (mRNA and protein expression) analyses.
resultsGroups treated with tolvaptan had significantly higher 24 h urine excretion, which was significantly reduced in the tolvaptan + HCTZ group after 2 weeks. Cyst size, pERK protein expression, and Cyclin D1 mRNA expression were all significantly reduced in both the tolvaptan and tolvaptan + HCTZ groups, indicating that HCTZ did not affect the beneficial functions of tolvaptan. Notably, aquaporin 2 redistribution from the apical to intracellular domains was observed in tolvaptan-treated rats and was partially reversed in the tolvaptan + HCTZ group. The renal glomerular filtration rate was reduced in the tolvaptan + HCTZ group. Significantly lowered mRNA expression of neuronal nitric oxide synthase, prostaglandin E synthase 2 and renin were also found in the medulla, but not in the cortex.
conclusionHCTZ reduces tolvaptan-induced polyuria without altering its beneficial effects on PKD. This novel therapeutic combination could potentially lead to better PKD treatments and improved quality of life for the affected patients.
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