title: Netrin-1 and semaphorin 3A predict the development of acute kidney injury in liver transplant patients.
abstract: Acute kidney injury (AKI) is a serious complication after liver transplantation. Currently there are no validated biomarkers available for early diagnosis of AKI. The current study was carried out to determine the usefulness of the recently identified biomarkers netrin-1 and semaphorin 3A in predicting AKI in liver transplant patients. A total of 63 patients' samples were collected and analyzed. AKI was detected at 48 hours after liver transplantation using serum creatinine as a marker. In contrast, urine netrin-1 (897.8 ± 112.4 pg/mg creatinine), semaphorin 3A (847.9 ± 93.3 pg/mg creatinine) and NGAL (2172.2 ± 378.1 ng/mg creatinine) levels were increased significantly and peaked at 2 hours after liver transplantation but were no longer significantly elevated at 6 hours after transplantation. The predictive power of netrin-1, as demonstrated by the area under the receiver-operating characteristic curve for diagnosis of AKI at 2, 6, and 24 hours after liver transplantation was 0.66, 0.57 and 0.59, respectively. The area under the curve for diagnosis of AKI was 0.63 and 0.65 for semaphorin 3A and NGAL at 2 hr respectively. Combined analysis of two or more biomarkers for simultaneous occurrence in urine did not improve the AUC for the prediction of AKI whereas the AUC was improved significantly (0.732) only when at least 1 of the 3 biomarkers in urine was positive for predicting AKI. Adjusting for BMI, all three biomarkers at 2 hours remained independent predictors of AKI with an odds ratio of 1.003 (95% confidence interval: 1.000 to 1.006; P = 0.0364). These studies demonstrate that semaphorin 3A and netrin-1 can be useful early diagnostic biomarkers of AKI after liver transplantation.
authors.affiliation: Department of Nephrology, Dialysis & Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Lewandowska
authors.affiliation: Department of Nephrology, Dialysis & Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Matuszkiewicz-Rowińska
authors.affiliation: Vascular Biology Center, Georgia Regents University, Augusta, GA, United States of America.
authors.forename: Calpurnia
authors.initials: C
authors.lastname: Jayakumar
authors.affiliation: Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Oldakowska-Jedynak
authors.affiliation: Department of Biostatistics and Epidemiology, Georgia Regents University, Augusta, GA, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Looney
authors.affiliation: Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Michalina
authors.initials: M
authors.lastname: Galas
authors.affiliation: Department of General and Nutritional Biochemistry, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Dutkiewicz
authors.affiliation: Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Krawczyk
authors.affiliation: Vascular Biology Center, Georgia Regents University, Augusta, GA, United States of America.
authors.forename: Ganesan
authors.initials: G
authors.lastname: Ramesh
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D000328:Adult; D015415:Biomarkers; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000652:urine; D000075388:Netrin-1; D011379:Prognosis; D012372:ROC Curve; D040121:Semaphorin-3A / Q000378:metabolism* / Q000652:urine; D025521:Tumor Suppressor Proteins / Q000378:metabolism* / Q000652:urine; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D040121:Semaphorin-3A; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1