ArticleKidney international2017
Recombinant α-Klotho may be prophylactic and therapeutic for acute to chronic kidney disease progression and uremic cardiomyopathy.
Article in Kidney international, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 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.
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Who cites it
142 citing papers in PubMed, 2 syntheses or guidelines pooled it, 268 citations in OpenAlex.
- 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
- Circulating α-Klotho Levels in Relation to Cardiovascular Diseases: A Mendelian Randomization Study.Frontiers in endocrinology · 2022Pooled it
- Pharmaceutical Strategies for Translating Klotho-Based Therapeutics: From Biologic Developability to Advanced Delivery Systems.Pharmaceutics · 2026Review
- 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
- Hyperbranched poly(β-amino ester)s-mediated delivery of engineered Klotho mRNA rescues senescence and restores cellular homeostasis in aged and Klotho deficient iMSCs.Drug delivery and translational research · 2026Article
- Klotho in the kidney distal convolution regulates urinary Klotho excretion and kidney calcium reabsorption, but not phosphate homeostasis.Kidney international · 2026Article
- A Western Diet High in Phosphate Primes the Development of the CKD-Mineral Bone Disorder in an Alport Syndrome Model.Kidney360 · 2026Article
- Extracellular Vesicles as Mediators of Endothelial and Tubular Injury in Cardiac Surgery-Associated Acute Kidney Injury.Biomedicines · 2026Review
- Heterogeneous regulation of fibroblast growth factor 23 in acute kidney injury, chronic kidney disease, and polycystic kidney disease: mechanisms, diagnostic utility, and clinical implications.Frontiers in molecular biosciences · 2026Review
- Klotho: A multifaceted protector in sepsis-induced organ damage and a potential therapeutic target.World journal of critical care medicine · 2025Review
- Klotho Suppresses Indoxyl Sulfate-Mediated Apoptosis in Human Kidney Proximal Tubular (HK-2) Cells through Modulating the AKT/Nrf2 Mechanism.ACS omega · 2025Article
- The effects of Klotho delivering mesenchymal stem cell-derived small extracellular vesicles on acute kidney injury.Journal of nanobiotechnology · 2025Article
- Renal-Cardiac Crosstalk in the Pathogenesis and Progression of Heart Failure.Circulation research · 2025Review
- MiR-556-3p mediated repression of klotho under oxidative stress promotes fibrosis of renal tubular epithelial cells.Scientific reports · 2025Article
- The association between low-concentration heavy metal exposure and chronic kidney disease risk through α-klotho.Scientific reports · 2025Article
- Klotho in age-related cardiovascular diseases: Insights into mitochondrial dysfunction and cell death.International journal of cardiology. Heart & vasculature · 2025Review
- Soluble average Klotho level as a prognostic marker for acute kidney injury outcomes: a 90-day follow-up study.Biomarkers in medicine · 2025Article
- Calcium-sensing receptor- and ADAM10-mediated klotho shedding is regulated by tetraspanin 5.FEBS letters · 2025Article
- Molecular pathophysiology of chronic kidney disease-mineral and bone disorder: Focus on the fibroblast growth factor 23-Klotho axis and bone turnover dynamics.Experimental physiology · 2025Review
- Unveiling the Emerging Role of Klotho: A Comprehensive Narrative Review of an Anti-aging Factor in Human Fertility.Current protein & peptide science · 2025Review
82 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
7 authors at 3 institutions in 2 countries.
Funding
Abstract
α-Klotho is highly expressed in the kidney, and its extracellular domain is cleaved and released into the circulation. Chronic kidney disease (CKD) is a state of α-Klotho deficiency, which exerts multiple negative systemic effects on numerous organs including the cardiovascular system. Since acute kidney injury (AKI) greatly escalates the risk of CKD development, we explored the effect of α-Klotho on prevention and treatment on post-AKI to CKD progression and cardiovascular disease. Therein, ischemia reperfusion injury-induced AKI was followed by early administration of recombinant α-Klotho or vehicle starting one day and continued for four days after kidney injury (CKD prevention protocol). A CKD model was generated by unilateral nephrectomy plus contralateral ischemia reperfusion injury. Late administration of α-Klotho in this model was started four weeks after injury and sustained for 12 weeks (CKD treatment protocol). The prevention protocol precluded AKI to CKD progression and protected the heart from cardiac remodeling in the post-AKI model. One important effect of exogenous α-Klotho therapy was the restoration of endogenous α-Klotho levels long after the cessation of exogenous α-Klotho therapy. The treatment protocol still effectively improved renal function and attenuated cardiac remodeling in CKD, although these parameters did not completely return to normal. In addition, α-Klotho administration also attenuated high phosphate diet-induced renal and cardiac fibrosis, and improved renal and cardiac function in the absence of pre-existing renal disease. Thus, recombinant α-Klotho protein is safe and efficacious, and might be a promising prophylactic or therapeutic option for prevention or retardation of AKI-to-CKD progression and uremic cardiomyopathy.
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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.