SuO038
SERUM KLOTHO IS CORRELATED TO CARDIOVASCULAR COMPLICATIONS OF CHRONIC KIDNEY DISEASE IN CHILDREN

INTRODUCTION AND AIMS: Serum Klotho (sKlotho) protein is an anti-aging agent known to prevent blood vessels from calcification and cardiomyocytes from hypertrophy and fibrosis. Relation between sKlotho levels and early cardiovascular damage in children with CKD is not clear yet. Aim of the study was to investigate whether sKlotho levels are decreased in children with CKD and if they correlate with cardiovascular complications of the disease.

METHODS: In this prospective, single-center, observational study children with CKD stages G2-5 were compared to healthy controls in terms of: serum levels of sKlotho (ELISA, Immuno-Biological Laboratories), peripheral blood pressure, central blood pressure and arterial stiffness parameters [measured by pulse wave analysis and velocity (PWV)] and left ventricular hypertrophy (LVH) and diastolic function parameters (echocardiography [ECHO]). Correlations between sKoltho and cardiovascular parameters in both groups were investigated.

RESULTS: The study involved 38 children (21 boys, 17 girls) aged 12.23 ±4.19 (mean eGFR 43.73±27.3 mL/min/1.73m²) and 38 healthy controls. There were no differences in age, gender and body mass index between groups. CKD subjects had significantly lower sKlotho levels than healthy controls (1507.8±835.6 vs. 2636.8±1650.7 [pg/mL], p=0.01). sKlotho levels did not correlate with eGFR in CKD patients. In CKD group both peripheral and central blood pressure was significantly elevated comparing to control group. Arterial stiffness parameters: augmentation index normalized to heart rate 75 beats per minute (AIx75HR) and PWV Z-score were markedly higher in children with CKD than in healthy controls (12.35±18.9 vs. 3.5±11.71 [%], p=0.03 and -0.37±1.27 vs. -1.1±0.99, p=0.02, respectively).Left ventricular mass index (LVMI) was higher in CKD children than in healthy children (30.47 ±8.68 vs. 25.57±6.7 [g/m²], p=0.02).The A wave was significantly increased,the E/A ratio decreased and the E deceleration time (Edt) prolonged in children in CKD group compared to control group. The E’med and E’lat waves were lower in children with CKD than in healthy subjects. In CKD group sKlotho was negatively correlated with peripheral blood pressure: systolic blood pressure (SBP) (r=-0.54, p=0.003), diastolic blood pressure (DBP) (r=-0.52, p=0.005), DBP Z-score (r=-0.5, p=0.007), mean arterial pressure (MAP) (r=-0.46, p=0.016) and central blood pressure: aortic SBP (AoSBP) (r=-0.42, p=0.029), aortic DBP (AoDBP) (r=-0.52, p=0.005) and aortic MAP(AoMAP) (r=-0.46, p=0.016). Moreover, sKlotho correlated with PWV (r=-0.45, p=0.02). Following correlations of sKlotho with ECHO parameters were found: left ventricular posterior wall thickness at end-diastole (LVPWd) (r=-0.38, p=0.03), LVMI (r=-0.54, p=0.0009) and LVMI Z-score (r=-0.56, p=0.0006). No such correlations were found in healthy children.

CONCLUSIONS: 1. In children with CKD sKlotho levels are significantly decreased, independently of GFR. 2. In children with CKD sKlotho correlates negatively with both peripheral and central blood pressure and with left ventricular mass. 3. sKlotho may serve as a useful biochemical marker of early cardiovascular damage in the course of CKD in children.