Complement Factor H and Related Proteins as Markers of Cardiovascular Risk in Pediatric Chronic Kidney Disease

Biomedicines. 2022 Jun 13;10(6):1396. doi: 10.3390/biomedicines10061396.

Abstract

Cardiovascular disease (CVD) is the main cause of mortality among chronic kidney disease (CKD) patients, both in adults and in children. Hypertension is one of the risk factors of CVD. For early detection of subclinical CVD in pediatric CKD, 24 h ambulatory blood pressure monitoring (ABPM), cardiosonography, and arterial stiffness assessment were evaluated. CAKUT (congenital anomalies of the kidney and urinary tract) are the main etiologies of pediatric CKD. Previously, by a proteomic approach, we identified complement factor H (CFH) and related proteins differentially expressed between children with CAKUT and non-CAKUT CKD. In this study, we aimed to evaluate whether CFH, CFH-related protein-2 (CFHR2), and CFH-related protein-3 (CFHR3) were related to CVD risk in children with CKD. This study included 102 subjects aged 6 to 18 years old. The non-CAKUT group had higher plasma CFHR3 levels than the CAKUT group (p = 0.046). CFHR3 was negatively correlated with LV mass (p = 0.009). CFHR2 was higher in children with CKD with 24 h hypertension in the ABPM profile (p < 0.05). In addition, children with non-CAKUT CKD with day-time hypertension (p = 0.036) and increased BP load (p = 0.018) displayed a lower plasma CFHR3 level. Our results highlight that CFH and related proteins play a role for CVD in children with CKD. Early assessment of CFH, CFHR2, and CFHR3 may have clinical utility in discriminating CV risk in children with CKD with different etiologies.

Keywords: cardiovascular disease; children; chronic kidney disease; complement factor H; complement factor H-related protein; congenital anomalies of the kidney and urinary tract; hypertension.