ArticleThe Journal of clinical investigation2020
Claudin-2 deficiency associates with hypercalciuria in mice and human kidney stone disease.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
46 citing papers in PubMed, 3 syntheses or guidelines pooled it, 104 citations in OpenAlex.
- X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements.Nature communications · 2024Pooled it
- Metabolic changes in kidney stone disease.Frontiers in immunology · 2023Pooled it
- Unravelling the Complex Relationship between Diet and Nephrolithiasis: The Role of Nutrigenomics and Nutrigenetics.Nutrients · 2022Pooled it
- Novel insights into the role of the renal interstitial microenvironment in Randall's plaque formation (Review).International journal of molecular medicine · 2026Review
- Inflammation-Induced Claudin-2 Up-Regulation Limits Pancreatitis Development by Enhancing Pancreatic Ductal Transport.Gastroenterology · 2026Article
- Novel associations of Claudin gene variants with kidney stone disease.Clinical kidney journal · 2026Article
- Disruption of Claudin-2 and Trpv6 Results in Hypocalcemia, Hypercalciuria, and Altered Bone Microarchitecture in Mice.Acta physiologica (Oxford, England) · 2026Article
- Tight junction structure, assembly and (dys)function.Nature reviews. Molecular cell biology · 2026Review
- Intestinal Microbiota Mediates the Beneficial Effects of γ-Polyglutamic Acid on Calcium Homeostasis and Bone Properties in Lambs.International journal of molecular sciences · 2026Article
- Claudin-2 deficiency reveals a corticomedullary calcium gradient driving kidney stone formation.The Journal of clinical investigation · 2025Article
- Functional landscape of mechanistic diversity in 27 claudin family members at tight junctions.Science advances · 2025Article
- Life in the fast lane: Functional consequences of male-female dynamic differences in the renal auto-regulation of flow.bioRxiv : the preprint server for biology · 2025Article
- Biology of calcium homeostasis regulation in intestine and kidney.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Prebiotics as modulators of colonic calcium and magnesium uptake.Acta physiologica (Oxford, England) · 2025Review
- Dietary sodium intake and all-cause mortality in kidney stone patients: a retrospective cohort study.Frontiers in nutrition · 2025Article
- Peroxisome Proliferator-Activated Receptor Alpha Stimulation Preserves Renal Tight Junction Components in a Rat Model of Early-Stage Diabetic Nephropathy.International journal of molecular sciences · 2024Article
- Paracellular Transport and Renal Tubule Calcium Handling: Emerging Roles in Kidney Stone Disease.Journal of the American Society of Nephrology : JASN · 2024Review
- Expression Profiles of Claudin Gene Family Members in Patients With Recurrent Calcium Oxalate Kidney Stones.Cureus · 2024Article
- miR-148b-5p regulates hypercalciuria and calcium-containing nephrolithiasis.Cellular and molecular life sciences : CMLS · 2024Article
- Calcium signalling and transport in the kidney.Nature reviews. Nephrology · 2024Review
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Authors and funding
16 authors at 8 institutions in 4 countries.
Funding
Abstract
The major risk factor for kidney stone disease is idiopathic hypercalciuria. Recent evidence implicates a role for defective calcium reabsorption in the renal proximal tubule. We hypothesized that claudin-2, a paracellular cation channel protein, mediates proximal tubule calcium reabsorption. We found that claudin-2-null mice have hypercalciuria due to a primary defect in renal tubule calcium transport and papillary nephrocalcinosis that resembles the intratubular plugs in kidney stone formers. Our findings suggest that a proximal tubule defect in calcium reabsorption predisposes to papillary calcification, providing support for the vas washdown hypothesis. Claudin-2-null mice were also found to have increased net intestinal calcium absorption, but reduced paracellular calcium permeability in the colon, suggesting that this was due to reduced intestinal calcium secretion. Common genetic variants in the claudin-2 gene were associated with decreased tissue expression of claudin-2 and increased risk of kidney stones in 2 large population-based studies. Finally, we describe a family in which males with a rare missense variant in claudin-2 have marked hypercalciuria and kidney stone disease. Our findings indicate that claudin-2 is a key regulator of calcium excretion and a potential target for therapies to prevent kidney stones.
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