title: Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation.
abstract: Delayed graft function (DGF) due to tubule cell injury frequently complicates deceased donor kidney transplants. We tested whether urinary neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) represent early biomarkers for DGF (defined as dialysis requirement within the first week after transplantation). Urine samples collected on day 0 from recipients of living donor kidneys (n = 23), deceased donor kidneys with prompt graft function (n = 20) and deceased donor kidneys with DGF (n = 10) were analyzed in a double blind fashion by ELISA for NGAL and IL-18. In patients with DGF, peak postoperative serum creatinine requiring dialysis typically occurred 2-4 days after transplant. Urine NGAL and IL-18 values were significantly different in the three groups on day 0, with maximally elevated levels noted in the DGF group (p < 0.0001). The receiver-operating characteristic curve for prediction of DGF based on urine NGAL or IL-18 at day 0 showed an area under the curve of 0.9 for both biomarkers. By multivariate analysis, both urine NGAL and IL-18 on day 0 predicted the trend in serum creatinine in the posttransplant period after adjusting for effects of age, gender, race, urine output and cold ischemia time (p < 0.01). Our results indicate that urine NGAL and IL-18 represent early, predictive biomarkers of DGF.
authors.affiliation: Nephrology, Yale University, New Haven, Connecticut, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Parikh
authors.forename: A
authors.initials: A
authors.lastname: Jani
authors.forename: J
authors.initials: J
authors.lastname: Mishra
authors.forename: Q
authors.initials: Q
authors.lastname: Ma
authors.forename: C
authors.initials: C
authors.lastname: Kelly
authors.forename: J
authors.initials: J
authors.lastname: Barasch
authors.forename: C L
authors.initials: CL
authors.lastname: Edelstein
authors.forename: P
authors.initials: P
authors.lastname: Devarajan
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine*; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D051799:Delayed Graft Function / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000652:urine*; D016030:Kidney Transplantation / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000652:urine*
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D020382:Interleukin-18; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins