title: Semaphorin 3A is a new early diagnostic biomarker of experimental and pediatric acute kidney injury.
abstract: BACKGROUND
  Semaphorin 3A is a secreted protein that regulates cell motility and attachment in axon guidance, vascular growth, immune cell regulation and tumor progression. However, nothing is known about its role in kidney pathophysiology. Here, we determined whether semaphorin3A is induced after acute kidney injury (AKI) and whether urinary semaphorin 3A can predict AKI in humans undergoing cardiopulmonary bypass (CPB).
  
  
  RESULTS
  In animals, semaphorin 3A is localized in distal tubules of the kidney and excretion increased within 3 hr after reperfusion of the kidney whereas serum creatinine was significantly raised at 24 hr. In humans, using serum creatinine, AKI was detected on average only 48 hours after CPB. In contrast, urine semaphorin increased at 2 hours after CPB, peaked at 6 hours (2596±591 pg/mg creatinine), and was no longer significantly elevated 12 hours after CPB. The predictive power of semaphorin 3A as demonstrated by area under the receiver-operating characteristic curve for diagnosis of AKI at 2, 6, and 12 hours after CPB was 0.88, 0.81, and 0.74, respectively. The 2-hour urine semaphorin measurement strongly correlated with duration and severity of AKI, as well as length of hospital stay. Adjusting for CPB time and gender, the 2-hour semaphorin remained an independent predictor of AKI, with an odds ratio of 2.19.
  
  
  CONCLUSIONS
  Our results suggest that semaphorin 3A is an early, predictive biomarker in experimental and pediatric AKI, and may allow for the reliable early diagnosis and prognosis of AKI after CPB, much before the rise in serum creatinine.
authors.affiliation: Department of Medicine and Vascular Biology Center, Georgia Health Sciences University, Augusta, Georgia, United States of America.
authors.forename: Calpurnia
authors.initials: C
authors.lastname: Jayakumar
authors.forename: Punithavathi
authors.initials: P
authors.lastname: Ranganathan
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.forename: Catherine D
authors.initials: CD
authors.lastname: Krawczeski
authors.forename: Stephen
authors.initials: S
authors.lastname: Looney
authors.forename: Ganesan
authors.initials: G
authors.lastname: Ramesh
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology / Q000652:urine*; D000818:Animals; D015415:Biomarkers / Q000652:urine; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine*; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007686:Kidney Tubules, Distal / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011237:Predictive Value of Tests; D012372:ROC Curve; D040121:Semaphorin-3A / Q000097:blood / Q000652:urine*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C108639:SEMA3A protein, human; D040121:Semaphorin-3A; D003404:Creatinine