Cystatin C and Cardiac Measures in Children and Adolescents With CKD

Abstract

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.

Keywords: Biomarker; adolescents; cardiac function; cardiac structure; cardiovascular disease (CVD); children; chronic kidney disease (CKD); cystatin C; echocardiograph; left ventricular hypertrophy (LVH); left ventricular mass (LVM); pediatrics; renal function; systolic function.