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Association Between Serum Klotho and All-Cause Mortality in Chronic Kidney Disease: Evidence From a Prospective Cohort Study.

INTRODUCTION: This study aimed to investigate the relationship between circulating soluble Klotho concentration and all-cause mortality in individuals with chronic kidney disease (CKD).

METHODS: We conducted a prospective cohort study involving 2,456 participants with CKD from the National Health and Nutrition Examination Survey (NHANES) cycles spanning from 2007 to 2016. Complex sampling-weighted multivariate Cox proportional hazards models were used to estimate the association between serum Klotho level and all-cause mortality, presenting hazard ratios (HR) and 95% confidence intervals (CI). Additionally, a restricted cubic spline analysis was performed to explore potential non-linear associations.

RESULTS: During a median of 82 months of follow-up, 550 (22.40%) all-cause deaths were recorded. The median serum Klotho concentration was 760 pg/ml (interquartile ranges, 624, 958). After adjusting for potential covariates, the risk of all-cause mortality decreased by 4% for every 100 pg/ml increase in Klotho (HR = 0.96, 95% CI, 0.92, 0.99). The HR for the fourth quartile of Klotho compared to the first quartile was 0.73 (95% CI, 0.56, 0.96). The restricted cubic spline model revealed a distinctive "L"-shaped association between serum Klotho and all-cause mortality among patients with CKD, with a Klotho concentration of 760 pg/ml at the inflection point. When Klotho concentration was less than 760 pg/ml, a significant negative correlation between Klotho and all-cause mortality was observed (HR per 100 pg/ml increase in Klotho = 0.86, 95% CI, 0.78, 0.95).

CONCLUSION: This study documented a distinctive "L"-shaped association between serum Klotho levels and all-cause mortality among individuals with CKD. Further research is needed to validate these findings.

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