ReviewNature reviews. Nephrology2015
Urea transporter proteins as targets for small-molecule diuretics.
Review in Nature reviews. Nephrology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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.
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
27 citing papers in PubMed, 44 citations in OpenAlex.
- Comparison of the effects of tolvaptan and furosemide on renal water and sodium excretion in patients with heart failure and advanced chronic kidney disease: a subanalysis of the K-STAR study.Clinical and experimental nephrology · 2018Trial
- Epithelial plasma membrane transporters as drug targets.Physiological reviews · 2026Review
- Urine Recirculation During Normothermic Kidney Preservation Improves Energy Balance Involving the Urea and Citric Acid Cycles.Transplantation direct · 2026Article
- Hotspot pocket-based discovery of urea transporter selective inhibitors.Nature communications · 2026Article
- The Physiological Roles and Pathological Implications of Urea Transporters in the Cardiovascular System.Biomedicines · 2025Review
- Urea Transporters in Cancer: Emerging Roles and Their Clinical Implications.Biomedicines · 2025Review
- Structural characterization of the urea transporter bound to the orally bioavailable inhibitor E3.Acta pharmacologica Sinica · 2025Article
- Identification and Validation of Urea Transporter B Inhibitor fromMolecules (Basel, Switzerland) · 2025Article
- [Research progress of tolvaptan in the treatment of refractory ascites in cirrhosis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Small-Molecule Inhibitors and Drug Discovery of Urea Transporters.Sub-cellular biochemistry · 2025Review
- Physiological Functions of Urea Transporters.Sub-cellular biochemistry · 2025Review
- Structural insights into the mechanisms of urea permeation and distinct inhibition modes of urea transporters.Nature communications · 2024Article
- Systems Biology of the Vasopressin V2 Receptor: New Tools for Discovery of Molecular Actions of a GPCR.Annual review of pharmacology and toxicology · 2022Review
- Urea transport and hydrolysis in the rumen: A review.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2021Review
- Discovery of novel diarylamides as orally active diuretics targeting urea transporters.Acta pharmaceutica Sinica. B · 2021Article
- Urea Derivatives in Modern Drug Discovery and Medicinal Chemistry.Journal of medicinal chemistry · 2020Article
- Urea-aromatic interactions in biology.Biophysical reviews · 2020Review
- Sickle Cell Anemia: Variants in theFrontiers in pharmacology · 2020Article
- Article
- Pharmacokinetics, Tissue Distribution and Excretion of a Novel Diuretic (PU-48) in Rats.Pharmaceutics · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Conventional diuretics such as furosemide and thiazides target salt transporters in kidney tubules, but urea transporters (UTs) have emerged as alternative targets. UTs are a family of transmembrane channels expressed in a variety of mammalian tissues, in particular the kidney. UT knockout mice and humans with UT mutations exhibit reduced maximal urinary osmolality, demonstrating that UTs are necessary for the concentration of urine. Small-molecule screening has identified potent and selective inhibitors of UT-A, the UT protein expressed in renal tubule epithelial cells, and UT-B, the UT protein expressed in vasa recta endothelial cells. Data from UT knockout mice and from rodents administered UT inhibitors support the diuretic action of UT inhibition. The kidney-specific expression of UT-A1, together with high selectivity of the small-molecule inhibitors, means that off-target effects of such small-molecule drugs should be minimal. This Review summarizes the structure, expression and function of UTs, and looks at the evidence supporting the validity of UTs as targets for the development of salt-sparing diuretics with a unique mechanism of action. UT-targeted inhibitors may be useful alone or in combination with conventional diuretics for therapy of various oedemas and hyponatraemias, potentially including those refractory to treatment with current diuretics.
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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.