ArticleJournal of the American Society of Nephrology : JASN2015
Soluble Klotho Protects against Uremic Cardiomyopathy Independently of Fibroblast Growth Factor 23 and Phosphate.
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. Cited by 150 papers, 2 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
150 citing papers in PubMed, 2 syntheses or guidelines pooled it, 262 citations in OpenAlex.
- Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD).The Cochrane database of systematic reviews · 2025Pooled it
- Beneficial effects of physical exercise on the osteo-renal Klotho-FGF-23 axis in Chronic Kidney Disease: A systematic review with meta-analysis.International journal of medical sciences · 2024Pooled it
- The effects of tenapanor on serum fibroblast growth factor 23 in patients receiving hemodialysis with hyperphosphatemia.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019Trial
- Trial
- The association between soluble klotho and cardiovascular parameters in chronic kidney disease: results from the KNOW-CKD study.BMC nephrology · 2018Trial
- Response of fibroblast growth factor 23 to volume interventions in arterial hypertension and diabetic nephropathy.Medicine · 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
- Cardiorenal and Metabolic Dimensions of Cardiomyopathies and Heart Failure: Focus on SGLT2i, GLP1-RA, and ns-MRA.Current cardiology reports · 2026Review
- Klotho G-395A Polymorphism as a Risk Factor for Atrial Fibrillation in Patients on Maintenance Hemodialysis.Advances in urology · 2026Article
- Assessment of Cardiovascular Risk and Examination of Blood Klotho Levels in Patients with Ankylosing Spondylitis.Journal of clinical medicine · 2025Article
- Klotho's Impact on Cardiovascular Disease, Fractures, and Mortality in Hemodialysis.Kidney international reports · 2025Article
- Growth hormone treatment associates with improved circulating anti-aging protein Klotho and reduced arterial stiffness in children with CKD.Clinical kidney journal · 2025Article
- Klotho Suppresses Indoxyl Sulfate-Mediated Apoptosis in Human Kidney Proximal Tubular (HK-2) Cells through Modulating the AKT/Nrf2 Mechanism.ACS omega · 2025Article
- Renal-Cardiac Crosstalk in the Pathogenesis and Progression of Heart Failure.Circulation research · 2025Review
- Klotho plasma levels are an independent predictorof mortality in women with acute coronary syndrome.Scientific reports · 2025Article
- Klotho Is Cardioprotective in the mdx Mouse Model of Duchenne Muscular Dystrophy.The American journal of pathology · 2025Article
- Non-Invasive Assessment of Vascular Damage Through Pulse Wave Velocity and Superb Microvascular Imaging in Pre-Dialysis Patients.Biomedicines · 2025Article
- Interaction Effect of Estimated Pulse Wave Velocity and Serum Klotho Level on Chronic Kidney Disease.Aging medicine (Milton (N.S.W)) · 2025Article
- Conformational landscape of soluble α-klotho revealed by cryogenic electron microscopy.Scientific reports · 2025Article
- α-Klotho is associated with cardiovascular and all-cause mortality in patients with stage 3b and 4 chronic kidney disease (CKD): a long-term prospective cohort study.Journal of nephrology · 2025Article
90 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Cardiac hypertrophy occurs in up to 95% of patients with CKD and increases their risk for cardiovascular death. In the kidney, full-length membranous Klotho forms the coreceptor for fibroblast growth factor 23 (FGF23) to regulate phosphate metabolism. The prevailing view is that the decreased level of Klotho in CKD causes cardiomyopathy through increases in serum FGF23 and/or phosphate levels. However, we reported recently that soluble Klotho protects against cardiac hypertrophy by inhibiting abnormal calcium signaling in the heart. Here, we tested whether this protective effect requires changes in FGF23 and/or phosphate levels. Heterozygous Klotho-deficient CKD mice exhibited aggravated cardiac hypertrophy compared with wild-type CKD mice. Cardiac magnetic resonance imaging studies revealed that Klotho-deficient CKD hearts had worse functional impairment than wild-type CKD hearts. Normalization of serum phosphate and FGF23 levels by dietary phosphate restriction did not abrogate the aggravated cardiac hypertrophy observed in Klotho-deficient CKD mice. Circulating levels of the cleaved soluble ectodomain of Klotho were lower in wild-type CKD mice than in control mice and even lower in Klotho-deficient CKD mice. Intravenous delivery of a transgene encoding soluble Klotho ameliorated cardiac hypertrophy in Klotho-deficient CKD mice. These results suggest that the decreased level of circulating soluble Klotho in CKD is an important cause of uremic cardiomyopathy independent of FGF23 and phosphate, opening new avenues for treatment of this disease.
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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.