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Cystatin C and Cardiac Measures in Children and Adolescents With CKD
Tammy M Brady1, Kelly Townsend2, Michael F Schneider2
1Division of Pediatric Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD.
Insights
In children with chronic kidney disease (CKD), higher cystatin C levels are linked to poorer cardiac structure and diastolic function. Cystatin C may independently predict cardiovascular disease risk in this population.
Area of Science:
- Pediatric Nephrology
- Cardiovascular Research
- Biomarker Discovery
Background:
- Cardiovascular disease (CVD) is a significant concern in pediatric chronic kidney disease (CKD).
- Cystatin C is a known marker for kidney function and an emerging biomarker for CVD events.
Purpose of the Study:
- To investigate the association between cystatin C levels and cardiac structure and function over time in children with CKD.
- To determine if cystatin C predicts diastolic dysfunction independently of kidney function.
Main Methods:
- Prospective cohort study of 678 children and adolescents with mild to moderate CKD.
- Annual measurement of serum cystatin C and biennial assessment of cardiac structure and function via echocardiography.
- Analysis included demographics, measured glomerular filtration rate (mGFR), and other clinical factors.
Main Results:
- Each 1-mg/L increase in cystatin C was associated with increased left ventricular mass index and altered diastolic function ratios (E/A, E'/A', E/E').
- While mGFR was associated with E'/A' ratio, cystatin C remained significantly associated with E'/A' even after adjusting for mGFR.
- These associations were independent of time.
Conclusions:
- Cystatin C levels are independently associated with cardiac structure and diastolic function in pediatric CKD.
- Cystatin C may serve as an independent predictor of CVD risk in children and adolescents with CKD, beyond its role as a kidney function marker.
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/m2.7]) 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.
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