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Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis
Evangelos Memmos1, Pantelis Sarafidis2, Panagiotis Pateinakis3
1Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Konstantinoupoleos 49, GR54642, Thessaloniki, Greece.
Insights
Low plasma Klotho levels are linked to increased cardiovascular events in dialysis patients. This association persists independently of traditional risk factors and markers of arterial stiffness, highlighting Klotho
Area of Science:
- Nephrology
- Cardiology
- Endocrinology
Background:
- Klotho, a transmembrane protein and FGF-23 co-receptor, influences mineral metabolism.
- The role of secreted Klotho in predicting outcomes for chronic kidney disease (CKD) patients remains incompletely understood.
- This study investigates the relationship between plasma Klotho levels and cardiovascular events in patients undergoing dialysis.
Purpose of the Study:
- To examine the association between plasma Klotho levels and cardiovascular events in hemodialysis patients.
- To determine if this association is independent of common risk factors, CKD-mineral bone disease (CKD-MBD) related factors, arterial stiffness, and atherosclerotic burden.
Main Methods:
- Seventy-nine chronic hemodialysis patients were monitored for a median of 5.5 years.
- Baseline measurements included plasma Klotho levels, carotid-femoral pulse wave velocity (cfPWV), and common carotid intima-media thickness (ccIMT).
- The primary endpoint was the first occurrence of all-cause death, non-fatal myocardial infarction, or non-fatal stroke.
Main Results:
- Patients with low Klotho levels (≤745 pg/ml) had significantly lower freedom from the primary endpoint compared to those with high Klotho levels (31% vs. 53%, p = 0.017).
- Low Klotho was associated with significantly lower cumulative cardiovascular survival (63% vs. 88%, p = 0.029) and freedom from a cardiovascular composite outcome (18% vs. 45%, p = 0.009).
- In Cox regression analysis, low Klotho remained a significant independent predictor of the primary endpoint after adjusting for multiple confounders, including cfPWV and ccIMT (HR: 2.759, p = 0.014).
Conclusions:
- Low plasma Klotho levels are significantly associated with an increased risk of cardiovascular events in hemodialysis patients.
- This association is independent of mineral-bone disease factors, common cardiovascular risk factors, and measures of arterial stiffness and atherosclerosis.
- Plasma Klotho may serve as an independent prognostic biomarker for cardiovascular risk in dialysis patients.
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.
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