Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis - PubMed (original) (raw)

Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis

Evangelos Memmos et al. BMC Nephrol. 2019.

Abstract

Background: Klotho is a transmembrane protein acting as a co-receptor for FGF-23 and thus exerts clinical actions on mineral metabolism. The association of secreted Klotho with outcomes in CKD patients is unclear. This study examined the relation between plasma Klotho and cardiovascular events in dialysis patients, accounting for common and CKD-MBD related risk factors, arterial stiffness and atherosclerotic burden.

Methods: Seventy-nine chronic hemodialysis patients were observed for a median follow-up of 5.5 years. Klotho levels as well as carotid-femoral pulse wave velocity (cfPWV) and common carotid intima-media thickness (ccIMT) measurements were performed at baseline. The primary end-point was first occurrence of all-cause death, non-fatal myocardial infarction or non-fatal stroke. Secondary end-points were: (i) all-cause mortality; (ii) cardiovascular mortality; (iii) a combination of cardiovascular death, non-fatal MI, non-fatal stroke, resuscitation after cardiac arrest, coronary revascularization, heart failure hospitalization and atrial fibrillation.

Results: Cumulative freedom from the primary endpoint was 31% for the low-Klotho group (≤745 pg/ml) and 53% for the high-Klotho group (logrank p = 0.017); HR: 2.137, 95%CI 1.124-4.065. Cumulative survival was insignificantly lower (44% vs 56%, p = 0.107), but cumulative cardiovascular survival (63% vs 88%, p = 0.029) and cumulative freedom from the cardiovascular composite outcome (18% vs 45%, p = 0.009) were significantly lower in the low-Klotho group. In modelled Cox-regression analysis the association of low Klotho with the primary endpoint remained significant after stepwise adjustment for cFGF3, PTH, Ca x P product, established risk factors (age, dialysis vintage, diabetes, hypertension, smoking, history of cardiovascular disease) as well as cfPWV and ccIMT [Model 6: HR:2.759, 95%CI 1.223-6.224, p = 0.014].

Conclusions: Low Klotho is associated with cardiovascular events in hemodialysis patients, independently from factors associated with mineral-bone disease, common risk factors and intermediate outcomes, such as cfPWV and ccIMT.

Keywords: Arteriosclerosis; Cardiovascular events; Hemodialysis; Klotho; Mortality.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1

Fig. 1

Kaplan Meier survival curves and life tables for occurrence of the primary endpoint (all-cause death or myocardial infarction or stroke)

Fig. 2

Fig. 2

Kaplan Meier survival curves and life tables for occurrence of the secondary endpoints: a) all-cause mortality, b) cardiovascular mortality and c) the composite endpoint (All cause death, or non-fatal MI or non-fatal stroke or coronary revascularization or hospitalization for heart failure or resuscitation after cardiac arrest, or AF)

Fig. 3

Fig. 3

Hazard ratios for all study endpoints in the low-Klotho and the high-Klotho groups

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