ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 291 papers, 4 of them syntheses that pooled it.
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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.
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Who cites it
291 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD).The Cochrane database of systematic reviews · 2025Pooled it
- Correlation between soluble klotho and chronic kidney disease-mineral and bone disorder in chronic kidney disease: a meta-analysis.Scientific reports · 2024Pooled it
- Genetic Variants Associated with Circulating Fibroblast Growth Factor 23.Journal of the American Society of Nephrology : JASN · 2018Pooled it
- Correlation between SolubleBioMed research international · 2018Pooled it
- Trial
- A Controlled Increase in Dietary Phosphate Elevates BP in Healthy Human Subjects.Journal of the American Society of Nephrology : JASN · 2018Trial
- Changes in Serum Concentrations of Fibroblast Growth Factor 23 and Soluble Klotho in Hemodialysis Patients after Total Parathyroidectomy.BioMed research international · 2016Trial
- Reduction of Oxidative Stress in Chronic Kidney Disease Does Not Increase Circulating α-Klotho Concentrations.PloS one · 2016Trial
- Klotho revisited: tubular heterogeneity reshapes mineral metabolism, aging, and CKD.Pflugers Archiv : European journal of physiology · 2026Review
- Klotho in the kidney distal convolution regulates urinary Klotho excretion and kidney calcium reabsorption, but not phosphate homeostasis.Kidney international · 2026Article
- Molecular Basis of Rare Inherited Tubulopathies of the Kidney: A Primer for Clinicians.International journal of molecular sciences · 2026Review
- Integrative Approaches to Treating Cellular Senescence in Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The Impact of Hyperphosphatemia on Mineral and Bone Metabolism: Implications for Bone and Vascular Health.International journal of molecular sciences · 2026Review
- Sex-Related Expression of Klotho in Rat Kidneys: Species Differences Between Rats and Mice.International journal of molecular sciences · 2026Article
- Follicular Klotho in the Ovarian Microenvironment: Exploring Its Role in IVF Outcome Prediction.Medicina (Kaunas, Lithuania) · 2026Article
- Multi-omics and machine learning identify FN1 and ALDH2 as diagnostic biomarkers and therapeutic targets in early and late diabetic kidney disease.Renal failure · 2025Article
- Advances in noninvasive diagnosis of renal osteodystrophy.Renal failure · 2025Review
- Associations between klotho levels and mortality risk among middle-aged and older adults taking prescription opioids.Preventive medicine reports · 2025Article
- Klotho Suppresses Indoxyl Sulfate-Mediated Apoptosis in Human Kidney Proximal Tubular (HK-2) Cells through Modulating the AKT/Nrf2 Mechanism.ACS omega · 2025Article
- Bidirectional upregulation of Klotho by triiodothyronine and baicalein: mitigating chronic kidney disease and associated complications in aged BALB/c mice.Biogerontology · 2025Article
231 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Klotho has profound effects on phosphate metabolism, but the mechanisms of how Klotho affects phosphate homeostasis is unknown. We detected Klotho in the proximal tubule cell, brush border, and urinary lumen, where phosphate homeostasis resides. Increasing Klotho in the kidney and urine chronically by transgenic overexpression or acutely by intravenous infusion caused hypophosphatemia, phosphaturia from decreased proximal phosphate reabsorption, and decreased activity and protein of the principal renal phosphate transporter NaPi-2a. The phosphaturic effect was present in FGF23-null mice, indicating a direct action distinct from Klotho's known role as a coreceptor for FGF23. Direct inhibition of NaPi-2a by Klotho was confirmed in cultured cells and in cell-free membrane vesicles characterized by acute inhibition of transport activity followed by decreased cell surface protein. Transport inhibition can be mimicked by recombinant beta-glucuronidase and is associated with proteolytic degradation and reduced surface NaPi-2a. The inhibitory effect of Klotho on NaPi-2a was blocked by beta-glucuronidase inhibitor but not by protease inhibitor. Klotho is a novel phosphaturic substance that acts as an enzyme in the proximal tubule urinary lumen by modifying glycans, which cause decreased transporter activity, followed by proteolytic degradation and possibly internalization of NaPi-2a from the apical membrane.
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