title: Neutrophil gelatinase-associated lipocalin is a sensitive biomarker for the early diagnosis of acute rejection after living-donor kidney transplantation.
abstract: BACKGROUND
  Early diagnosis of kidney allograft dysfunction is crucial for the management and long-term survival of transplanted kidneys. We investigated whether neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) are capable of being used as novel biomarkers of acute kidney allograft dysfunction.
  
  
  METHODS
  We measured serum and urine NGAL, urine IL-18, and urine L-FABP levels on the first 3 days after transplantation. To assess the diagnostic sensitivity of these biomarkers, a receiver-operating characteristic curve (ROC) was plotted, and the area under the curve (AUC) was calculated to quantify the accuracy of the parameter. Sections from paraffin-embedded biopsy specimens were examined by immunohistochemistry for NGAL expression.
  
  
  RESULTS
  Twelve cases were clinically diagnosed as acute rejection (AR) by renal biopsy. Urine NGAL was the most sensitive of these markers for detection of acute kidney allograft dysfunction. The cutoff value of urine NGAL was 66.0 ng/ml, with an AUC of 0.79 (95 % CI 0.68-0.88). Sensitivity of serum NGAL was about the same as urine NGAL with an AUC of 0.75 (0.64-0.85). IL-18 and L-FABP were 0.584 (95 % CI 0.433-0.725) and 0.612 (95 % CI 0.460-0.749), respectively. NGAL was more useful than other biomarkers to detect AR of kidney allograft dysfunction. NGAL staining intensity was significantly increased in the proximal tubules of the transplants with AR than in transplants that were not acutely rejected.
  
  
  CONCLUSIONS
  Urine NGAL level was found to be the most sensitive biomarker of acute kidney allograft dysfunction after living-donor kidney transplantation.
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-city, 162-8666, Tokyo, Japan. knitta@kc.twmu.ac.jp
authors.forename: Junko
authors.initials: J
authors.lastname: Kohei
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishida
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanabe
authors.forename: Tanabe
authors.initials: T
authors.lastname: Kazunari
authors.forename: Ken
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Kosaku
authors.initials: K
authors.lastname: Nitta
mesh_terms: D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000652:urine*; D000328:Adult; D064591:Allografts; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine; D015331:Cohort Studies; D016001:Confidence Intervals; D042241:Early Diagnosis; D050556:Fatty Acid-Binding Proteins / Q000652:urine*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D006085:Graft Survival; D006801:Humans; D020382:Interleukin-18 / Q000652:urine; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000175:diagnosis / Q000453:epidemiology; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine*; D012372:ROC Curve; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D020382:Interleukin-18; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins