ArticleJournal of the American Society of Nephrology : JASN2015
Klotho and phosphate are modulators of pathologic uremic cardiac remodeling.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03234361 (Preventing Hypertension and Sympathetic Overactivation by Targeting Phosphate), which is not on this map. Cited by 174 papers, 3 of them syntheses that pooled it.
What it found
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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.
Preventing Hypertension and Sympathetic Overactivation by Targeting Phosphate
Who cites it
174 citing papers in PubMed, 3 syntheses or guidelines pooled it, 268 citations in OpenAlex.
- Relationship between serum growth differentiation factor 15, fibroblast growth factor-23 and risk of atrial fibrillation: A systematic review and meta-analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- Fibroblast growth factor-23 and the risk of cardiovascular diseases and mortality in the general population: A systematic review and dose-response meta-analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- Meta-Analysis of the Association between Fibroblast Growth Factor 23 and Mortality and Cardiovascular Events in Hemodialysis Patients.Blood purification · 2019Pooled it
- Klotho, fibroblast growth factor-23, and the renin-angiotensin system - an analysis from the PEACE trial.European journal of heart failure · 2019Trial
- Effects of Potassium Magnesium Citrate Supplementation on 24-Hour Ambulatory Blood Pressure and Oxidative Stress Marker in Prehypertensive and Hypertensive Subjects.The American journal of cardiology · 2016Trial
- Therapeutic Lithium Enhances Klotho Expression and Mitochondrial Size and Branching in Human Cardiac Fibroblasts Involving Nuclear Factor-kappa B Inhibition.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Article
- Klotho revisited: tubular heterogeneity reshapes mineral metabolism, aging, and CKD.Pflugers Archiv : European journal of physiology · 2026Review
- In vitro modeling of renal injury-induced cardiac effects using human iPSC-derived organoids.Cell communication and signaling : CCS · 2026Article
- A Western Diet High in Phosphate Primes the Development of the CKD-Mineral Bone Disorder in an Alport Syndrome Model.Kidney360 · 2026Article
- Klotho in the kidney distal convolution regulates urinary Klotho excretion and kidney calcium reabsorption, but not phosphate homeostasis.Kidney international · 2026Article
- Sustained and reversible effects of a dietary phosphate intake on bone and mineral metabolism during aging.GeroScience · 2026Article
- High-Phosphate-Induced Hypertension: The Pathogenic Role of Fibroblast Growth Factor 23 (FGF23) Signaling in Sympathetic Nervous System Activation.International journal of molecular sciences · 2026Review
- Klotho G-395A Polymorphism as a Risk Factor for Atrial Fibrillation in Patients on Maintenance Hemodialysis.Advances in urology · 2026Article
- Ten Hot Topics in Cardiovascular Risk Management for Chronic Kidney Disease.Cardiorenal medicine · 2026Review
- Adipokines and Vascular Modulators in CKM: Emerging Biomarkers as Diagnostic and Therapeutic Targets.International journal of molecular sciences · 2025Review
- High dietary phosphate intake induces anxiety in normal male mice.Brain, behavior, & immunity - health · 2025Article
- Recharging the Powerhouse: Mitochondrial Dysfunction and Therapy in Cardiorenal Syndrome Type 4.Current heart failure reports · 2025Review
- Genetic deletion of the sodium phosphate cotransporter NaPi2a ameliorates heart failure in mice.Scientific reports · 2025Article
- Maintaining kidney health in aging societies: a JSN and ERA call to action.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Elevated phosphate levels in CKD - a direct threat for the heart.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
114 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Cardiac dysfunction in CKD is characterized by aberrant cardiac remodeling with hypertrophy and fibrosis. CKD is a state of severe systemic Klotho deficiency, and restoration of Klotho attenuates vascular calcification associated with CKD. We examined the role of Klotho in cardiac remodeling in models of Klotho deficiency-genetic Klotho hypomorphism, high dietary phosphate intake, aging, and CKD. Klotho-deficient mice exhibited cardiac dysfunction and hypertrophy before 12 weeks of age followed by fibrosis. In wild-type mice, the induction of CKD led to severe cardiovascular changes not observed in control mice. Notably, non-CKD mice fed a high-phosphate diet had lower Klotho levels and greatly accelerated cardiac remodeling associated with normal aging compared with those on a normal diet. Chronic elevation of circulating Klotho because of global overexpression alleviated the cardiac remodeling induced by either high-phosphate diet or CKD. Regardless of the cause of Klotho deficiency, the extent of cardiac hypertrophy and fibrosis correlated tightly with plasma phosphate concentration and inversely with plasma Klotho concentration, even when adjusted for all other covariables. High-fibroblast growth factor-23 concentration positively correlated with cardiac remodeling in a Klotho-deficient state but not a Klotho-replete state. In vitro, Klotho inhibited TGF-β1-, angiotensin II-, or high phosphate-induced fibrosis and abolished TGF-β1- or angiotensin II-induced hypertrophy of cardiomyocytes. In conclusion, Klotho deficiency is a novel intermediate mediator of pathologic cardiac remodeling, and fibroblast growth factor-23 may contribute to cardiac remodeling in concert with Klotho deficiency in CKD, phosphotoxicity, and aging.
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Registered trials
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.