Soluble Klotho is not independently associated with cardiovascular disease in a population of dialysis patients

BACKGROUND Dialysis patients suffer from a high burden of cardiovascular disease (CVD). Partly this is due to progressive deterioration of calcium-phosphate homeostasis. Previous studies suggested that besides FGF-23, low levels of Klotho, a protein linked to aging, might constitute a key factor in this detrimental relationship. The purpose of the present study was to determine the relationship between serum Klotho (sKlotho) and the presence of CVD in dialysis patients. METHODS Plasma levels of sKlotho were measured in a cohort of dialysis patients and related to left ventricular (LV) dysfunction (defined as a LV ejection fraction<45%) and LV mass using echocardiography. Coronary artery disease (CAD) and calcification score were assessed using computed tomography angiography. Abdominal aortic calcification score (AACscore) was measured by abdominal X-ray. RESULTS We included 127 dialysis patients, 67±7 years old, 76% male, 67% on hemodialysis, median sKlotho 460 pg/mL (25th-75th percentile 350-620 pg/mL). Patients with a low sKlotho (<460 pg/mL) showed significantly more CAD (81% versus 61%; p=0.02) and LV dysfunction (19% versus 3%; p<0.01). However, after adjusting for confounders, sKlotho was not independently associated with the presence of CVD or the AACscore. CONCLUSIONS In the present cohort of dialysis patients, sKlotho was not independently associated with CVD. However, patients with a low sKlotho level (<460 pg/mL) did show CAD and LV dysfunction more frequently. Therefore, while sKlotho might be a marker for CVD in dialysis patients, the current data does not support a direct cardioprotective effect of sKlotho.