ArticleJournal of the American Society of Nephrology : JASN2012
Deficiency of the calcium-sensing receptor in the kidney causes parathyroid hormone-independent hypocalciuria.
Article in Journal of the American Society of Nephrology : JASN, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 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.
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Who cites it
62 citing papers in PubMed, 144 citations in OpenAlex.
- MBX 2109, A Once-Weekly Parathyroid Hormone Replacement Therapy Prodrug: Phase 1, First-In-Human, Randomized Trial.The Journal of clinical endocrinology and metabolism · 2025Trial
- Immunohistochemical Expression of CaSR, VDR, and AMA in Parathyroid Tumors in Relation to Hypercalcemia Severity in Primary Hyperparathyroidism.Current issues in molecular biology · 2026Article
- Article
- Hypercalcemia's Hidden Regulator: Calcium-Sensing Receptor and the Kidney's Secret Weapon.Journal of the American Society of Nephrology : JASN · 2025Article
- Calcium-Sensing Receptor in the Thick Ascending Limb and Renal Response to Hypercalcemia.Journal of the American Society of Nephrology : JASN · 2025Article
- Calcium-sensing receptor- and ADAM10-mediated klotho shedding is regulated by tetraspanin 5.FEBS letters · 2025Article
- Paracellular Transport and Renal Tubule Calcium Handling: Emerging Roles in Kidney Stone Disease.Journal of the American Society of Nephrology : JASN · 2024Review
- How the kidney regulates magnesium: a modelling study.Royal Society open science · 2024Article
- Exploring Adaptive Phenotypes for the Human Calcium-Sensing Receptor Polymorphism R990G.Molecular biology and evolution · 2024Article
- Unlocking the mysteries of n-oxPTH: implications for CKD patients.Frontiers in endocrinology · 2024Review
- Contribution of thick ascending limb and distal convoluted tubule to glucose-induced hypercalciuria in healthy controls.American journal of physiology. Renal physiology · 2023Article
- Distinct and targetable role of calcium-sensing receptor in leukaemia.Nature communications · 2023Article
- Nephrocalcinosis in a 3-year-old child with hypocalcemia: Answers.Pediatric nephrology (Berlin, Germany) · 2023Article
- 24-h Urinary Calcium Excretion and Renal Outcomes in Hospitalized Patients with and without Chronic Kidney Disease.Journal of clinical medicine · 2023Article
- NHE3 in the thick ascending limb is required for sustained but not acute furosemide-induced urinary acidification.American journal of physiology. Renal physiology · 2022Article
- The importance of kidney calcium handling in the homeostasis of extracellular fluid calcium.Pflugers Archiv : European journal of physiology · 2022Review
- Molecular mechanisms altering tubular calcium reabsorption.Pediatric nephrology (Berlin, Germany) · 2022Review
- Acute kidney injury in cancer patients.Clinical and experimental nephrology · 2022Review
- Association study ofOpen life sciences · 2022Article
- Physiologic Regulation of Systemic Klotho Levels by Renal CaSR Signaling in Response to CaSR Ligands and pH o.Journal of the American Society of Nephrology : JASN · 2021Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Rare loss-of-function mutations in the calcium-sensing receptor (Casr) gene lead to decreased urinary calcium excretion in the context of parathyroid hormone (PTH)-dependent hypercalcemia, but the role of Casr in the kidney is unknown. Using animals expressing Cre recombinase driven by the Six2 promoter, we generated mice that appeared grossly normal but had undetectable levels of Casr mRNA and protein in the kidney. Baseline serum calcium, phosphorus, magnesium, and PTH levels were similar to control mice. When challenged with dietary calcium supplementation, however, these mice had significantly lower urinary calcium excretion than controls (urinary calcium to creatinine, 0.31±0.03 versus 0.63±0.14; P=0.001). Western blot analysis on whole-kidney lysates suggested an approximately four-fold increase in activated Na(+)-K(+)-2Cl(-) cotransporter (NKCC2). In addition, experimental animals exhibited significant downregulation of Claudin14, a negative regulator of paracellular cation permeability in the thick ascending limb, and small but significant upregulation of Claudin16, a positive regulator of paracellular cation permeability. Taken together, these data suggest that renal Casr regulates calcium reabsorption in the thick ascending limb, independent of any change in PTH, by increasing the lumen-positive driving force for paracellular Ca(2+) transport.
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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.