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

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.

Hearing loss and its association with the proteome of perilymph, cerebrospinal fluid, and tumor tissue in patients with vestibular schwannoma

“…Increases in CFHR1-CFHR5 gene copy numbers or dimerization have been linked to the pathogenesis of the kidney diseases C3 glomerulopathy and atypical hemolytic uremic syndrome (32). Additionally, CFHR2 and CFHR3 are reported to be associated with a risk of cardiovascular disease in children with chronic kidney disease (33) and kidney function decrease in IgA nephritis (34). High-activity, low-frequency variants of the CFHR2 allele are reported to be associated with a sensory de cit, namely age-related macular degeneration (35).…”

Specific patterns and potential risk factors to predict 3-year risk of death among non-cancer patients with advanced chronic kidney disease by machine learning

“…The sample size of the complete cohort data may be very small, but it will be significant and meaningful. [76] Last, more information about treatment can make the prediction better and classification of ESRD mortality in detail. But it is difficult to collect the same treatments, including medication and dialysis from different hospitals using EMR datasets.…”

Cardiovascular Risks of Hypertension: Lessons from Children with Chronic Kidney Disease

“…Additionally, ApoC-II was correlated with LVH and an abnormal ABPM profile [ 114 ]. In a consequent study, another proteomic biomarker complement factor H (CFH) and related proteins were studied in 102 children with CKD stages 1–4 [ 115 ]. Plasma CFH-related protein-2 (CFHR2) level was higher in children with CKD and ambulatory hypertension.…”

“…Plasma CFH-related protein-2 (CFHR2) level was higher in children with CKD and ambulatory hypertension. Moreover, CFH-related protein-3 (CFHR3) was negatively correlated with LVH [ 115 ]. These findings suggest that early assessment of above-mentioned proteomic biomarkers may have clinical utility in discriminating CV risk in children with pre-dialysis CKD.…”