ArticleScientific reports2020
Renal cyst growth is attenuated by a combination treatment of tolvaptan and pioglitazone, while pioglitazone treatment alone is not effective.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02697617 (Use of Low Dose Pioglitazone to Treat Autosomal Dominant Polycystic Kidney), which is not on this map. Cited by 15 papers.
What it found
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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.
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.
Use of Low Dose Pioglitazone to Treat Autosomal Dominant Polycystic Kidney
Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Effects of Hydrochlorothiazide and Metformin on Aquaresis and Nephroprotection by a Vasopressin V2 Receptor Antagonist in ADPKD: A Randomized Crossover Trial.Clinical journal of the American Society of Nephrology : CJASN · 2022Trial
- Advances in the Treatment of Autosomal Dominant Polycystic Kidney Disease and Novel Therapeutic Targets.Current issues in molecular biology · 2026Review
- Kcnn4/KCa3.1 inhibition blunts polycystic kidney disease progression in mouse models.JCI insight · 2025Article
- Pharmacotherapy in kidney disease: what it takes to move from general guidance to specific recommendations to stratified subgroups of patients - the tale of autosomal dominant polycystic kidney disease (ADPKD).Expert opinion on drug metabolism & toxicology · 2025Review
- A Patient-Derived 3D Cyst Model of Polycystic Kidney Disease That Mimics Disease Development and Responds to Repurposing Candidates.Clinical and translational science · 2025Article
- Short salsalate administration affects cell proliferation, metabolism, and inflammation in polycystic kidney disease.iScience · 2023Article
- Combining Metformin and Drug-Loaded Kidney-Targeting Micelles for Polycystic Kidney Disease.Cellular and molecular bioengineering · 2023Article
- Vascular Dysfunction in Polycystic Kidney Disease: A Mini-Review.Journal of vascular research · 2023Review
- Preclinical evaluation of tolvaptan and salsalate combination therapy in aFrontiers in molecular biosciences · 2023Article
- Contributions of afferent and sympathetic renal nerves to cystogenesis and arterial pressure regulation in a preclinical model of autosomal recessive polycystic kidney disease.American journal of physiology. Renal physiology · 2022Article
- Autosomal Dominant Polycystic Kidney Disease: From Pathophysiology of Cystogenesis to Advances in the Treatment.International journal of molecular sciences · 2022Review
- Therapeutic advances in ADPKD: the future awaits.Journal of nephrology · 2022Review
- Drug repurposing in autosomal dominant polycystic kidney disease: back to the future with pioglitazone.Clinical kidney journal · 2021Article
- Insights Into the Molecular Mechanisms of Polycystic Kidney Diseases.Frontiers in physiology · 2021Review
- Autosomal dominant polycystic kidney disease and pioglitazone for its therapy: a comprehensive review with an emphasis on the molecular pathogenesis and pharmacological aspects.Molecular medicine (Cambridge, Mass.) · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common monogenic disorders, characterized by the progressive formation of fluid-filled cysts. Tolvaptan is an approved drug for ADPKD patients, but is also associated with multiple side effects. The peroxisome proliferator-activator receptor gamma (PPARγ) agonist pioglitazone slows disease progression in the PCK rat model for PKD. Here, we tested whether a combination treatment of relevant doses of tolvaptan and pioglitazone leads to improved efficacy in an adult-onset PKD mouse model. Tolvaptan indeed slowed PKD progression, but the combination treatment was not more effective than tolvaptan alone. In addition, although pioglitazone raised plasma levels of its surrogate drug marker adiponectin, the drug unexpectedly failed to slow PKD progression. The pioglitazone target PPARγ was expressed at surprisingly low levels in mouse, rat and human kidneys. Other pioglitazone targets were more abundantly expressed, but this pattern was comparable across various species. The data suggest that several potential pharmacokinetic and pharmacodynamic (PK/PD) differences between different species may underlie whether or not pioglitazone is able to slow PKD progression. The ongoing phase II clinical trial with low-dose pioglitazone treatment (NCT02697617) will show whether pioglitazone is a suitable drug candidate for ADPKD treatment.
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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.