title: Novel marker for the detection of sickle cell nephropathy: soluble FMS-like tyrosine kinase-1 (sFLT-1).
abstract: BACKGROUND
  Given the burden and poor outcome of end-stage renal disease in sickle cell disease (SCD), early markers of sickle cell nephropathy (SN) are desirable. Disordered angiogenesis underlies many complications of SCD. We aimed to determine the relationship between serum FMS-like tyrosine kinase-1 (sFLT-1) and other biomarkers of renal damage for the early diagnosis of SN.
  
  
  METHODS
  Forty-seven SCD patients and 49 healthy controls were enrolled. Microalbuminuria was determined in patient urine samples. Blood samples were tested for sFLT-1, serum creatinine, and various hemolysis and inflammation markers. Peripheral blood monocyte expression of sFLT-1 was measured using real-time polymerase chain reaction (PCR).
  
  
  RESULTS
  The serum level of sFLT-1 (pg/ml) in SCD patients was higher than controls (median/range/IQR = 142/ 60-1300/61 pg/ml vs. 125/ 110-187/52 pg/ml, respectively) (p = 0.006). Median (range) of sFLT-1 level was higher in SCD patients with microalbuminuria compared to SCD patients with normoalbuminuria, 185 (140-1300) vs. 125 (60-189) mg/g, respectively) (p = 0.004). There was a significant positive correlation between serum sFLT-1 and microalbuminuria, lactate dehydrogenase (LDH), and indirect bilirubin (r = 0.59, 0.39, 0.30, and p = <0.001, 0.007, 0.041, respectively). sFLT-1 sensitivity in early detection of renal affection in SCD was 93.6%, while specificity was 68.6%. Finally, peripheral blood monocytes (PBM) sFLT-1 expression was significantly higher in SCD patients compared to controls (p = 0.05).
  
  
  CONCLUSIONS
  sFLT-1 may contribute to pathogenesis of albuminuria in SCD patients and constitute a novel renal biomarker of SN.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt. ilhamyoussry@yahoo.com.|Pediatric Hematology & BMT Unit, Department of Pediatrics, Faculty of Medicine, Cairo University, 1 Ben Kutiba Street, Section Seven, Nasr City, 11487, Cairo, Egypt. ilhamyoussry@yahoo.com.
authors.forename: Ilham
authors.initials: I
authors.lastname: Youssry
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Samuel
authors.initials: S
authors.lastname: Makar
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Rania
authors.initials: R
authors.lastname: Fawzy
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Manal
authors.initials: M
authors.lastname: Wilson
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Ghada
authors.initials: G
authors.lastname: AbdAllah
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Eman
authors.initials: E
authors.lastname: Fathy
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Happy
authors.initials: H
authors.lastname: Sawires
mesh_terms: D000293:Adolescent; D000419:Albuminuria / Q000209:etiology; D000755:Anemia, Sickle Cell / Q000097:blood / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000175:diagnosis*; D008297:Male; D009000:Monocytes / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Microalbuminuria; Sickle cell disease; Sickle cell nephropathy; Soluble FMS-like tyrosine kinase