title: Clinical Predictive Value of Cystatin C in Pediatric Sickle Cell Disease: A Marker of Disease Severity and Subclinical Cardiovascular Dysfunction.
abstract: 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.
  
  
  OBJECTIVE
  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 <30% or ejection fraction <55%).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Cystatin C may be considered a biological marker for vascular dysfunction and subclinical atherosclerosis in SCD.
authors: 1 Faculty of Medicine, Pediatric Department, Ain Shams University, Cairo, Egypt.
authors: Azza Abdel Gawad
authors: AAG
authors: Tantawy
authors: 1 Faculty of Medicine, Pediatric Department, Ain Shams University, Cairo, Egypt.
authors: Amira Abdel Moneam
authors: AAM
authors: Adly
authors: 2 Faculty of Medicine, Clinical Pathology Department, Ain Shams University, Cairo, Egypt.
authors: Eman Abdel Rahman
authors: EAR
authors: Ismail
authors: 1 Faculty of Medicine, Pediatric Department, Ain Shams University, Cairo, Egypt.
authors: Mai
authors: M
authors: Abdelazeem
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging; D050197:Atherosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D059168:Carotid Intima-Media Thickness; D002648:Child; D055316:Cystatin C / Q000097:blood*; D005260:Female; D005293:Ferritins / Q000378:metabolism; D006801:Humans; D008297:Male; D012720:Severity of Illness Index; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D002097:C-Reactive Protein; D005293:Ferritins
keywords: cardiovascular; carotid intima–media thickness; cystatin C; nephropathy; sickle cell disease; vascular complications