ArticleThe Journal of clinical investigation2013
α-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01880281 (Effect of a Meat Versus Vegetarian Diet in 12 Healthy Volunteers on the Excretion of Alpha-ketoglutarate Measured in 24-hours Urine), which is not on this map. Cited by 51 papers.
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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.
Effect of a Meat Versus Vegetarian Diet in 12 Healthy Volunteers on the Excretion of Alpha-ketoglutarate Measured in 24-hours Urine
Who cites it
51 citing papers in PubMed, 77 citations in OpenAlex.
- SGLT2 inhibitors preserve serum chloride in non-diabetic CKD: a propensity-matched and LASSO regression analysis.Renal failure · 2026Article
- Structural insights into ligand recognition and activation of the human oxoglutarate receptor OXGR1.Nature communications · 2026Article
- Molecular architecture of OXGR1 reveals an evolutionary conserved mechanisms for metabolite surveillance.The EMBO journal · 2026Article
- Loss of OXGR1 function uncouples intrarenal RAS activation from pendrin and αENaC regulation and blunts angiotensin II-induced hypertension.Frontiers in pharmacology · 2026Article
- Molecular insights into ligand recognition and signaling of OXGR1.Nature communications · 2025Article
- Roles of sensory receptors in non-sensory organs: the kidney and beyond.Nature reviews. Nephrology · 2025Review
- OXGR1-Dependent (Pro)Renin Receptor Upregulation in Collecting Ducts of the Clipped Kidney Contributes to NaInternational journal of molecular sciences · 2024Article
- Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes.Circulation · 2023Review
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- The immunometabolite itaconate stimulates OXGR1 to promote mucociliary clearance during the pulmonary innate immune response.The Journal of clinical investigation · 2023Article
- OXGR1 is a candidate disease gene for human calcium oxalate nephrolithiasis.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- Corn silk polysaccharides attenuate diabetic nephropathy through restoration of the gut microbial ecosystem and metabolic homeostasis.Frontiers in endocrinology · 2023Article
- The proximal tubule through an NBCe1-dependent mechanism regulates collecting duct phenotypic and remodeling responses to acidosis.American journal of physiology. Renal physiology · 2023Article
- AKG/OXGR1 promotes skeletal muscle blood flow and metabolism by relaxing vascular smooth muscle.Life metabolism · 2022Article
- Smooth muscle AKG/OXGR1 signaling regulates epididymal fluid acid-base balance and sperm maturation.Life metabolism · 2022Article
- Activation of 2-oxoglutarate receptor 1 (OXGR1) by α-ketoglutarate (αKG) does not detectably stimulate Pendrin-mediated anion exchange in Xenopus oocytes.Physiological reports · 2022Article
- Disrupted Alpha-Ketoglutarate Homeostasis: Understanding Kidney Diseases from the View of Metabolism and Beyond.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Review
- Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases.Biomolecules · 2021Review
- Landscape of GPCR expression along the mouse nephron.American journal of physiology. Renal physiology · 2021Article
- α-Ketoglutarate Upregulates Collecting Duct (Pro)renin Receptor Expression, Tubular Angiotensin II Formation, and NaFrontiers in cardiovascular medicine · 2021Article
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Paracrine communication between different parts of the renal tubule is increasingly recognized as an important determinant of renal function. Previous studies have shown that changes in dietary acid-base load can reverse the direction of apical α-ketoglutarate (αKG) transport in the proximal tubule and Henle's loop from reabsorption (acid load) to secretion (base load). Here we show that the resulting changes in the luminal concentrations of αKG are sensed by the αKG receptor OXGR1 expressed in the type B and non-A-non-B intercalated cells of the connecting tubule (CNT) and the cortical collecting duct (CCD). The addition of 1 mM αKG to the tubular lumen strongly stimulated Cl(-)-dependent HCO(3)(-) secretion and electroneutral transepithelial NaCl reabsorption in microperfused CCDs of wild-type mice but not Oxgr1(-/-) mice. Analysis of alkali-loaded mice revealed a significantly reduced ability of Oxgr1(-/-) mice to maintain acid-base balance. Collectively, these results demonstrate that OXGR1 is involved in the adaptive regulation of HCO(3)(-) secretion and NaCl reabsorption in the CNT/CCD under acid-base stress and establish αKG as a paracrine mediator involved in the functional coordination of the proximal and the distal parts of the renal tubule.
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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.