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Background:   Patients with sickle cell disease (SCD) are at high risk of renal dysfunction and cardiovascular morbidity. The association between cystatin C and renal function is well known, however, cystatin C has recently emerged as a strong predictor of cardiovascular events and adverse outcomes in patients with and without kidney disease, mostly related to both inflammation and atherosclerosis.Aim:   To determine cystatin C levels in 53 children and adolescents with SCD compared to 40 age- and sex-matched healthy controls and assess its relation to markers of hemolysis, iron overload, sickle vasculopathy, and carotid intima–media thickness (CIMT).Methods:   Patients with SCD in steady state were studied, focusing on hydroxyurea therapy, hematological profile, serum ferritin, high-sensitivity C-reactive protein (hs-CRP), urinary albumin–creatinine ratio (UACR), and serum cystatin C. Echocardiography and CIMT were assessed using high-resolution ultrasound. Heart disease was defined by systolic left ventricle dysfunction (shortening fraction &lt;30% or ejection fraction &lt;55%).Results:   Carotid IMT was significantly higher in patients with SCD compared to controls ( P &lt; .001). Patients with SCD having nephropathy, heart disease, or history of frequent sickling crisis (≥3 attacks/y) had significantly higher cystatin C levels than those without ( P &lt; .05). Patients with SCD treated with hydroxyurea had lower cystatin C levels than untreated patients ( P = .039). High-sensitivity C-reactive protein, UACR, ejection fraction, and CIMT were independently related to cystatin C in multiple regression analysis. The cutoff values of cystatin C for detection of renal or cardiovascular complications were determined.Conclusion:   Cystatin C may be considered a biological marker for vascular dysfunction and subclinical atherosclerosis in SCD.

Clinical Predictive Value of Cystatin C in Pediatric Sickle Cell Disease: A Marker of Disease Severity and Subclinical Cardiovascular Dysfunction