Cystatin C and Cardiac Measures in Children and Adolescents With CKD

Background Cardiovascular disease (CVD) is highly prevalent among children with chronic kidney disease (CKD). Cystatin C is an established marker of kidney function and an emerging biomarker for CVD events. We quantified the relationship between cystatin C level and cardiac structure and function over time among children with CKD and assessed whether cystatin C level and diastolic function retained an association after accounting for kidney function. Study Design Prospective cohort study. Setting & Participants 678 children and adolescents with mild to moderate CKD enrolled in the CKD in Children (CKiD) Study with 1,228 echocardiographically obtained cardiac structure and function measurements. Predictor Serum cystatin C (mg/L) measured annually. Outcomes Cardiac structure (left ventricular mass index [g/m^2.7]) and cardiac function (shortening fraction; E/A, E′/A′, E/E′ ratios) measured every other year. Measurements Demographics and anthropometrics, measured glomerular filtration rate (mGFR), heart rate, blood pressure, hemoglobin z score, serum albumin level, and calcium-phosphorus product. Results Independent of time, each 1-mg/L increase in cystatin C level was independently associated with a concurrent 7.7% (95% CI, 5.3%-10.0%) increase in left ventricular mass index, a −4.7% (95% CI, −7.0% to −2.4%) change in E/A ratio, a −6.6% (95% CI, −9.0% to −4.2%) change in E′/A′ ratio, and a 2.5% (95% CI, 0.3%-4.7%) increase in E/E′ ratio. mGFR was also independently associated with E′/A′ ratio. When cystatin C level and mGFR were included in the same model, cystatin C level remained independently associated with E′/A′ ratio, whereas mGFR was not. Limitations 24% of the cohort was missing data for outcomes of interest or measurements; study population includes only children and adolescents with mild to moderate CKD. Conclusions In this study of children and adolescents with mild to moderate CKD, cystatin C level was independently associated with cardiac structure and diastolic function. Cystatin C level remained able to predict diastolic function decline via E′/A′ ratio even after adjusting for mGFR, suggesting that cystatin C level may have an independent role in CVD risk stratification among children and adolescents with CKD.