Serum adiponectin complexes and cardiovascular risk in children with chronic kidney disease

Abstract

In contrast to the general population, patients with chronic kidney disease (CKD) experience increased total adiponectin levels despite an increased prevalence of cardiovascular disease. Adiponectin circulates as trimer, low molecular weight (LMW), and high molecular weight (HMW) complexes. The distribution and role of each subfraction in CKD is unknown. This cross-sectional analysis examined the association of serum adiponectin and its subfractions with known cardiovascular risk factors in 105 children (median age 12 years; 56% male) enrolled into the Chronic Kidney Disease in Children (CKiD) study, an observational cohort study of children with CKD stage 2-4.HMW accounted for 46% of total adiponectin, followed by LMW (34%) and trimer (20%). In multivariable analysis, LMW was independently associated with iohexol glomerular filtration rate (GFR) (p = 0.004) and was higher in pubertal versus prepubertal children (p = 0.005). HMW/LMW ratio was independently associated with age and iohexol GFR (all p < 0.001). Unexpectedly, systolic blood pressure was positively correlated with HMW (p = 0.01), and HMW/LMW ratio (p = 0.007) and inversely correlated with LMW (p = 0.009). Among subfractions, only LMW was significantly correlated with left ventricular mass (LVM) index (p = 0.05). In multivariable analysis, decreased LMW was independently associated with higher LVM index [β= -0.25, 95% confidence interval (CI) -0.50, -0.03, p=0.04) after adjustment for body mass index (BMI), age, and blood pressure.The higher total adiponectin levels in children with CKD are associated with higher HMW and lower LMW. This imbalance may be an important biomarker for increased cardiovascular risk despite higher levels of total adiponectin in children with CKD.

Fig. 1

Adiponectin complex distribution in serum of a child with chronic kidney disease (CKD). The relative intensity of adiponectin is plotted against the retention volume of each fraction. Three peaks are clearly separated, representing the high (HMW) and low LMW molecular weight and trimer complexes. The bottom panel shows the Western blot using adiponectin antibodies to filtration column fractions, separating out adiponectin complexes by molecular weight [19]

Fig. 2

Distribution of adiponectin complexes according to gender, race, pubertal status and obesity. Data presented as median (IQR)

Fig. 3

Distribution of HMW/LMW by iohexol GFR (n=105), overall p=0.049. Data presented as median (IQR)