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.

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).

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 <30% or ejection fraction <55%).

Carotid IMT was significantly higher in patients with SCD compared to controls (P < .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 < .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.

Cystatin C may be considered a biological marker for vascular dysfunction and subclinical atherosclerosis in SCD.