Prognostic Value and Link to Atrial Fibrillation of Soluble Klotho and FGF23 in Hemodialysis Patients

Abstract

Deranged calcium-phosphate metabolism contributes to the burden of morbidity and mortality in dialysis patients. This study aimed to assess the association of the phosphaturic hormone fibroblast growth factor 23 (FGF23) and soluble Klotho with all-cause mortality. We measured soluble Klotho and FGF23 levels at enrolment and two weeks later in 239 prevalent hemodialysis patients. The primary hypothesis was that low Klotho and high FGF23 are associated with increased mortality. The association between Klotho and atrial fibrillation (AF) at baseline was explored as secondary outcome. AF was defined as presence of paroxysmal, persistent or permanent AF. During a median follow-up of 924 days, 59 (25%) patients died from any cause. Lower Klotho levels were not associated with mortality in a multivariable adjusted analysis when examined either on a continuous scale (HR 1.25 per SD increase, 95% CI 0.84–1.86) or in tertiles, with tertile 1 as the reference category (HR for tertile two 0.65, 95% CI 0.26–1.64; HR for tertile three 2.18, 95% CI 0.91–2.23). Higher Klotho levels were associated with the absence of AF in a muItivariable logistic regression analysis (OR 0.66 per SD increase, 95% CI 0.41–1.00). Higher FGF23 levels were associated with mortality risk in a multivariable adjusted analysis when examined either on a continuous scale (HR 1.45 per SD increase, 95% CI 1.05–1.99) or in tertiles, with the tertile 1 as the reference category (HR for tertile two 1.63, 95% CI 0.64–4.14; HR for tertile three 3.91, 95% CI 1.28–12.20). FGF23 but not Klotho levels are associated with mortality in hemodialysis patients. Klotho may be protective against AF.

Is chronic kidney disease-mineral and bone disorder associated with the presence of endothelial progenitor cells with a calcifying phenotype?

“…Epidemiological data have supported a causal role of the impairment of FGF23-klotho axis in the onset and progression of vascular calcification, although this issue is still under debate [35]. In contrast to previous studies, klotho levels were higher in dialysis patients, but perhaps this discrepancy may be due to differences in the protocols used for klotho assay [36]. …”

Mortality Prediction Using Modern Peptide Biomarkers in Hemodialysis Patients - A Comparative Analysis

“…MR-pro-ANP, copeptin, MR-pro-ADM and CT-pro-ET1 were measured using an automated immunoluminometric assay on a Kryptor system (B.R.A.H.M.S AG, Henningsdorf, Germany) as previously described in [22,23,24]. Plasma FGF23 and alpha-Klotho concentration were manually measured using ELISA methods (Immuno-Biologic Laboratories Co., Ltd. Japan; and Immutopics, San Clemente, CA, USA, respectively) [21]. Plasma beta-2-microglobulin concentrations were measured using a turbidimetric assay (Randox Laboratories, Antrim, United Kingdom).…”

“…These studies included high sensitive troponins T and I, natriuretic peptides (MR-pro-ANP, BNP, NT-pro-BNP), vasoactive peptides (copeptin, MR-pro-adrenomedullin, CT-pro-endothelin), FGF23 and alpha-Klotho [18,19,20,21]. With the current study, we wanted to find out, which of these biomarkers could qualify for risk prediction on a routine basis in asymptomatic hemodialysis patients.…”

Impact of Phosphorus Restriction and Vitamin D-Substitution on Secondary Hyperparathyroidism in a Proteinuric Mouse Model

“…These data suggest that klotho expression might be reduced early in kidney disease, resulting in FGF23 resistance and a high inverse correlation of FGF23 and klotho expression across all groups (r=-0.66). In hemodialysis patients, the plasma concentration of soluble α-klotho, which is thought to represent renal klotho expression, was reduced, while FGF23 levels were increased [29].…”