Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients - PubMed (original) (raw)

Clinical Trial

Albina Nowak et al. PLoS One. 2014.

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.

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Conflict of interest statement

Competing Interests: The authors declare that TECOmedical AG, Switzerland measured the soluble Klotho and FGF23 levels in their hemodialysis cohort for this study. The authors of this manuscript have no commercial or professional association with TECOmedical AG. They have nothing to declare concerning employment, consultancy, patents, products in development, marketed products, etc. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1

Figure 1. Cumulative survival by tertiles of secreted Klotho.

Patients were stratified by their baseline Klotho levels according to the tertiles. Kaplan-Meier analysis with long-rank test did not reveal a significant difference between groups (P = 0.42).

Figure 2

Figure 2. Cumulative survival by tertiles of Fibroblast growth factor 23 (FGF23).

Patients were stratified by their FGF23 levels according to the tertiles. Kaplan-Meier analysis with long-rank test approached a significant difference between groups (P = 0.05).

Figure 3

Figure 3. Klotho and FGF23 levels in patients with and without atrial fibrillation.

Figure 4

Figure 4. Klotho (A) and FGF23 (B) levels in controls versus hemodialysis patients.

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Grants and funding

The authors thank TECOmedical AG, Switzerland for measurements of soluble Klotho and FGF23 levels. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. In addition to the above, there was no other funding for this study. The authors’ organisations had no other external or internal funding.

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