The association between creatinine versus cystatin C-based eGFR and cardiovascular risk in children with chronic kidney disease using a modified PDAY risk score

Background: Children with chronic kidney disease (CKD) have a high prevalence of cardiovascular disease (CVD) risk factors which may contribute to the development of cardiovascular events in adulthood. Among adults with CKD, cystatin C-based estimates of glomerular filtration rate (eGFR) demonstrate a stronger predictive value for cardiovascular events than creatinine-based eGFR. The PDAY (Pathobiological Determinants of Atherosclerosis in Youth) risk score is a validated tool used to estimate the probability of advanced coronary atherosclerotic lesions in young adults. Objective: To assess the association between cystatin C-based versus creatinine-based eGFR (eGFR cystatin C and eGFR creatinine, respectively) and cardiovascular risk using a modified PDAY risk score as a proxy for CVD in children and young adults. Methods: We performed a cross-sectional study of 71 participants with CKD [median age 15.5 years; inter-quartile range (IQR) 13, 17], and 33 healthy controls (median age 15.1 years; IQR 13, 17). eGFR was calculated using age-appropriate creatinine- and cystatin C-based formulas. Median eGFR creatinine and eGFR cystatin C for CKD participants were 50 (IQR 30, 75) and 53 (32, 74) mL/min/1.73 m², respectively. For the healthy controls, median eGFR creatinine and eGFR cystatin were 112 (IQR 85, 128) and 106 mL/min/1.73m² (95, 123) mL/min/1.73 m², respectively. A modified PDAY risk score was calculated based on sex, age, serum lipoprotein concentrations, obesity, smoking status, hypertension, and hyperglycemia. Results: Modified PDAY scores ranged from −2 to 20. The Spearman’s correlations of eGFR creatinine and eGFR cystatin C with coronary artery PDAY scores were −0.23 (p = 0.02) and −0.28 (p = 0.004), respectively. Ordinal logistic regression also showed a similar association of higher eGFR creatinine and higher eGFR cystatin C with lower PDAY scores. When stratified by age <18 or ≥18 years, the correlations of eGFR creatinine and eGFR cystatin C with PDAY score were modest and similar in children [−0.29 (p = 0.008) vs. −0.32 (p = 0.004), respectively]. Despite a smaller sample size, the correlation in adults was stronger for eGFR cystatin C (−0.57; p = 0.006) than for eGFR creatinine (−0.40; p = 0.07). Conclusions: Overall, the correlation between cystatin C- or creatinine-based eGFR with PDAY risk score was similar in children. Further studies in children with CKD should explore the association between cystatin C and cardiovascular risk.