Lower circulating soluble Klotho level is associated with increased risk of all-cause mortality in chronic kidney disease patients: a systematic review and meta-analysis

Charoenngam, Nipith; Ponvilawan, Ben; Ungprasert, Patompong

doi:10.1007/s11255-020-02510-1

Cited by 14 publications

(17 citation statements)

References 28 publications

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“…Interestingly, in our study population, klotho concentration had a U-shaped relationship with all-cause, CVD and cancer mortality. Previous epidemiological studies in the old or chronic kidney disease population revealed that klotho concentration was negatively associated with death 23 24. Indeed, overexpression of soluble klotho upregulated fibroblast growth factors-23 levels, which may lead to hypovitaminosis D 25.…”

Section: Discussionmentioning

confidence: 99%

Biological ageing and the risks of all-cause and cause-specific mortality among people with diabetes: a prospective cohort study

Chen

Yin

Zhao

et al. 2022

J Epidemiol Community Health

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BackgroundThe aetiology of diabetes is complex with limited treatment strategies. Growing animal studies have shown that targeted antiageing can improve the outcomes of diabetes. However, population evidence is limited. This study aims to evaluate the associations of biological ageing with all-cause and cause-specific mortality among people with diabetes.MethodsA total of 5278 people with diabetes from the National Health and Nutrition Examination Survey 1999–2014 were included. Biological ageing was measured from different perspectives, including phenotypic age, biological age, telomere length and klotho concentration. Phenotypic/biological age acceleration was the residual resulting from a linear model when regressing phenotypic/biological age on chronological age. Cox proportional hazards models were used to examine the relationships between ageing and all-cause, cardiovascular disease (CVD), and cancer mortality.ResultsOver median follow-up for 7.3 years, 1355 diabetics died. There was a positive and linear association of mortality with phenotypic age acceleration (HRall-cause 1.04; HRCVD 1.04; HRcancer 1.04, p<0.001) and biological age acceleration (HRall-cause 1.03; HRCVD 1.04; HRcancer 1.03, p<0.001). Telomere length was inversely associated with all-cause mortality (tertile (T)3 vs T1: HR 0.67, p<0.05). The concentration of klotho had a U-shaped relationship with mortality (T2 vs T1: HRall-cause 0.62; HRCVD 0.48; HRcancer 0.47, p<0.05). Further, stratified analysis by age and sex found that the associations of ageing-related markers with mortality were more significant in the aged and female subgroup.ConclusionsBiological ageing was positively associated with mortality among people with diabetes, indicating therapies targeting antiageing could be encouraged to halt the progression of diabetes.

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Section: Discussionmentioning

confidence: 99%

Biological ageing and the risks of all-cause and cause-specific mortality among people with diabetes: a prospective cohort study

Chen

Yin

Zhao

et al. 2022

J Epidemiol Community Health

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“…A decreased sKlotho level has been observed in the early stages of CKD, preceding the elevation of serum creatine (Scr) level; the sKlotho level gradually decreases with CKD progression ( Shimamura et al, 2012 ; Liu et al, 2017 ; Neyra et al, 2020b ). More importantly, reduced sKlotho was associated with increased adverse clinical outcomes in CKD patients, including Scr doubling, CKD progression, all-cause mortality, and CKD-mineral bone disorders (CKD-MBD) ( Kuro, 2017 ; Charoenngam et al, 2020 ; Yang et al, 2020 ). Therefore, sKlotho is postulated as a promising biomarker in early CKD diagnosis and prognosis.…”

Section: Introductionmentioning

confidence: 99%

The controversy of klotho as a potential biomarker in chronic kidney disease

Liu

Sha

et al. 2022

Front. Pharmacol.

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Klotho is an identified longevity gene with beneficial pleiotropic effects on the kidney. Evidence shows that a decline in serum Klotho level occurs in early chronic kidney disease (CKD) and continues as CKD progresses. Klotho deficiency is associated with poor clinical outcomes and CKD mineral bone disorders (CKD-MBD). Klotho has been postulated as a candidate biomarker in the evaluation of CKD. However, the evidence for the clinical significance of the relationship between Klotho and kidney function, CKD stage, adverse kidney and/or non-kidney outcomes, and CKD-MBD remains inconsistent and in some areas, contradictory. Therefore, there is uncertainty as to whether Klotho is a potential biomarker in CKD; a general consensus regarding the clinical significance of Klotho in CKD has not been reached, and there is limited evidence synthesis in this area. To address this, we have systematically assessed the areas of controversy, focusing on the inconsistencies in the evidence base. We used a PICOM strategy to search for relevant studies and the Newcastle–Ottawa Scale scoring to evaluate included publications. We reviewed the inconsistent clinical findings based on the relationship of Klotho with CKD stage, kidney and/or non-kidney adverse outcomes, and CKD-MBD in human studies. Subsequently, we assessed the underlying sources of the controversies and highlighted future directions to resolve these inconsistencies and clarify whether Klotho has a role as a biomarker in clinical practice in CKD.

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“…Furthermore, Evangelos et al indicated that Klotho deficiency was an independent predictor of cardiovascular and all-cause mortality in patients treated with chronic hemodialysis and the elderly population ( 29 ). According to a meta-analysis, low circulating soluble Klotho concentration was strongly related to increased all-cause mortality in patients with CKD ( 30 ). However, these studies have severe drawbacks, including the small size, inclusion of only populations with CKD or older age, and lack of a precise explanation for the actual relationship between Klotho concentration and mortality as well as the threshold value.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, soluble Klotho has been shown to reduce fibrosis and block the epithelial–mesenchymal transition associated with fibrosis ( 47 ). Moreover, serum Klotho promotes endothelial nitric oxide generation, while also exerting systemic pleiotropic antioxidative, antithrombotic, and anti-inflammatory activities ( 30 ). According to research, FGF23 is associated with end-stage renal disease and acute kidney damage, severe infections and inflammation, and even cancer progression, which is considered a possible cause of death in people with CKD ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

Association between serum Klotho concentration and all-cause and cardiovascular mortality among American individuals with hypertension

Yan

2022

Front. Cardiovasc. Med.

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Background and aimsEvidence indicates that serum Klotho concentration is associated with mortality in patients with chronic kidney disease (CKD). However, evidence on this association among people with hypertension is scarce. Therefore, we aimed to examine the association between serum Klotho concentration and all-cause and cardiovascular mortality in American patients with hypertension.Methods and resultsWe included 6,778 participants with hypertension from the National Health and Nutrition Examination Survey (NHANES) 2007–2014. A Cox proportional hazard model was used to compute the hazard ratios (HRs) and 95% confidence intervals (CIs). The correlation between serum Klotho concentration and mortality was determined using restricted cubic spline and piecewise linear regression analyses. During 36,714 person-years of follow-up, 575 deaths were documented. Lower serum Klotho concentration was associated with increased all-cause mortality, but not cardiovascular mortality after multivariate adjustment. According to spline analysis, the correlation between serum Klotho concentration and all-cause mortality was non-linear (P < 0.001), and the threshold value was 574 pg/mL. The HR below the threshold point was 0.79 (95% CI: 0.67–0.93); no significant difference was found above the threshold point.ConclusionHigher serum Klotho concentration was associated with lower all-cause mortality, but not cardiovascular mortality in patients with hypertension with or without chronic renal impairment.

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Lower circulating soluble Klotho level is associated with increased risk of all-cause mortality in chronic kidney disease patients: a systematic review and meta-analysis

Cited by 14 publications

References 28 publications

Biological ageing and the risks of all-cause and cause-specific mortality among people with diabetes: a prospective cohort study

Biological ageing and the risks of all-cause and cause-specific mortality among people with diabetes: a prospective cohort study

The controversy of klotho as a potential biomarker in chronic kidney disease

Association between serum Klotho concentration and all-cause and cardiovascular mortality among American individuals with hypertension

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