Observational studyAmerican journal of kidney diseases : the official journal of the National Kidney Foundation2024
Klotho and Clinical Outcomes in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.
Observational study in American journal of kidney diseases : the official journal of the National Kidney Foundation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 12 citations in OpenAlex.
- A Western Diet High in Phosphate Primes the Development of the CKD-Mineral Bone Disorder in an Alport Syndrome Model.Kidney360 · 2026Article
- Toxicological Effects and Health Impacts of Per- and Polyfluoroalkyl Substances (PFAS) in Humans.Toxics · 2026Review
- Chronic Kidney Disease and Cellular Senescence.International journal of molecular sciences · 2026Review
- Article
- Antiaging Properties of the Klotho Protein.Cells · 2026Review
- [Potential of early diagnosis and targeted therapy for Klotho protein in chronic kidney disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Klotho's Impact on Cardiovascular Disease, Fractures, and Mortality in Hemodialysis.Kidney international reports · 2025Article
- Hyperphosphatemia in Kidney Failure: Pathophysiology, Challenges, and Critical Role of Phosphorus Management.Nutrients · 2025Review
- Pathophysiology of chronic kidney disease-mineral bone disorder (CKD-MBD): from adaptive to maladaptive mineral homeostasis.Clinical kidney journal · 2025Article
- Baseline fibroblast growth factor 23 predicts incident heart failure and cardiovascular mortality in patients with chronic kidney disease: A 3-year follow-up study.International journal of cardiology. Heart & vasculature · 2025Article
- Inflammation-Induced Klotho Deficiency: A Possible Key Driver of Chronic Kidney Disease Progression.International journal of general medicine · 2025Review
- 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
- Anemia and Mineral Bone Disorder in Kidney Disease Patients: The Role of FGF-23 and Other Related Factors.International journal of molecular sciences · 2024Review
- The association between klotho and kidney and cardiovascular outcomes: a comprehensive systematic review and meta-analysis.Clinical kidney journal · 2024Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
RATIONALE &
objectiveKlotho deficiency may affect clinical outcomes in chronic kidney disease (CKD) through fibroblast growth factor-23 (FGF23)-dependent and -independent pathways. However, the association between circulating Klotho and clinical outcomes in CKD remains unresolved and was the focus of this study. STUDY
designProspective observational study. SETTING &
participants1,088 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study with an estimated glomerular filtration rate (eGFR) of 20-70mL/min/1.73m EXPOSURE: Plasma Klotho level at the year-1 study visit. OUTCOMES: 5-year risks of all-cause mortality, heart failure hospitalization, atherosclerotic cardiovascular events, and a composite kidney end point that comprised a sustained 50% decrease in eGFR, dialysis, kidney transplant, or eGFR<15mL/min/1.73m ANALYTICAL APPROACH: We divided Klotho into 6 groups to account for its nonnormal distribution. We used Cox proportional hazards regression and subdistribution hazards models to compare survival and clinical outcomes, respectively, between Klotho groups. We sequentially adjusted for demographic characteristics, kidney function, cardiovascular risk factors, sample age, and FGF23.
resultsMean eGFR was 42mL/min/1.73m LIMITATIONS: Despite adjustments, we cannot exclude the potential influence of residual confounding or sample storage on the results. A single measurement of plasma Klotho concentration may not capture Klotho patterns over time.
conclusionsIn a large, diverse, well-characterized CKD cohort, Klotho was not associated with clinical outcomes, and Klotho deficiency did not confound the association of FGF23 with mortality or heart failure hospitalization. PLAIN-LANGUAGE SUMMARY: Klotho is a protein that is vital to mineral metabolism and aging and may protect against cardiovascular disease. Klotho levels decrease in chronic kidney disease (CKD), but the association between Klotho and clinical outcomes in CKD remains uncertain. In a prospective cohort study of more than 1,000 people with CKD, circulating Klotho levels were not associated with kidney disease progression, cardiovascular outcomes, or mortality. These results suggest that the decrease in circulating Klotho levels in CKD does not play a prominent role in the development of poor clinical outcomes.
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