ArticleJournal of the American Society of Nephrology : JASN2009
The calcium-sensing receptor promotes urinary acidification to prevent nephrolithiasis.
Article in Journal of the American Society of Nephrology : JASN, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.
- The G allele of CaSR R990G polymorphism increases susceptibility to urolithiasis and hypercalciuria: evidences from a comprehensive meta-analysis.BioMed research international · 2015Pooled it
- Clinical and Genetic Profile of Chinese Familial Hypocalciuric Hypercalcemia Type 1 (FHH1): A Retrospective Study.Endocrine · 2026Article
- CaSR regulates SLC26A6 expression via the PKA-FOXO4 signaling axis to promote experimental calcium oxalate kidney stone formation in rats.Frontiers in cell and developmental biology · 2026Article
- A pharmacovigilance study on clinical factors of active vitamin DScientific reports · 2024Article
- Functional analysis reveals calcium-sensing receptor gene regulating cell-cell junction in renal tubular epithelial cells.International urology and nephrology · 2024Article
- A novel mouse model for familial hypocalciuric hypercalcemia (FHH1) reveals PTH-dependent and independent CaSR defects.Pflugers Archiv : European journal of physiology · 2024Article
- Urinary Acidification Does Not Explain the Absence of Nephrocalcinosis in a Mouse Model of Familial Hypomagnesaemia with Hypercalciuria and Nephrocalcinosis (FHHNC).International journal of molecular sciences · 2024Article
- Calcium sensing receptor regulate claudin-14 via PKA-STAT3 pathway in rat model of nephrolithiasis.Frontiers in pharmacology · 2024Article
- Kidney Stone Risk in Normocalcemic Hyperparathyroidism before and after Parathyroid Surgery.Case reports in endocrinology · 2024Article
- Association of TRPV5, CASR, and CALCR genetic variants with kidney stone disease susceptibility in Egyptians through main effects and gene-gene interactions.Urolithiasis · 2022Article
- The role of calcium-sensing receptor signaling in regulating transepithelial calcium transport.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Calcilytic NPSP795 Increases Plasma Calcium and PTH in an Autosomal Dominant Hypocalcemia Type 1 Mouse Model.JBMR plus · 2020Article
- Review
- International Union of Basic and Clinical Pharmacology. CVIII. Calcium-Sensing Receptor Nomenclature, Pharmacology, and Function.Pharmacological reviews · 2020Review
- The rs1256328 (ALPL) and rs12654812 (RGS14) Polymorphisms are Associated with Susceptibility to Calcium Nephrolithiasis in a Taiwanese population.Scientific reports · 2019Article
- Renal CaInternational journal of molecular sciences · 2019Review
- Calcium-sensing receptor: evidence and hypothesis for its role in nephrolithiasis.Urolithiasis · 2019Review
- Furosemide reduces BK-αβ4-mediated KAmerican journal of physiology. Renal physiology · 2019Article
- The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases.Nature reviews. Endocrinology · 2018Review
- Calcium-sensing receptor (CaSR) modulates vacuolar HClinical and experimental nephrology · 2018Article
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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
Hypercalciuria increases the risk for urolithiasis, but renal adaptive mechanisms reduce this risk. For example, transient receptor potential vanilloid 5 knockout (TPRV5(-/-)) mice lack kidney stones despite urinary calcium (Ca(2+)) wasting and hyperphosphaturia, perhaps as a result of their significant polyuria and urinary acidification. Here, we investigated the mechanisms linking hypercalciuria with these adaptive mechanisms. Exposure of dissected mouse outer medullary collecting ducts to high (5.0 mM) extracellular Ca(2+) stimulated H(+)-ATPase activity. In TRPV5(-/-) mice, activation of the renal Ca(2+)-sensing receptor promoted H(+)-ATPase-mediated H(+) excretion and downregulation of aquaporin 2, leading to urinary acidification and polyuria, respectively. Gene ablation of the collecting duct-specific B1 subunit of H(+)-ATPase in TRPV5(-/-) mice abolished the enhanced urinary acidification, which resulted in severe tubular precipitations of Ca(2+)-phosphate in the renal medulla. In conclusion, activation of Ca(2+)-sensing receptor by increased luminal Ca(2+) leads to urinary acidification and polyuria. These beneficial adaptations facilitate the excretion of large amounts of soluble Ca(2+), which is crucial to prevent the formation of kidney stones.
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