title: Kidney NGAL is a novel early marker of acute injury following transplantation.
abstract: Acute kidney injury secondary to ischemia-reperfusion in renal allografts often results in delayed graft function. We tested the hypothesis that expression of neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of acute kidney injury following transplantation. Sections from paraffin-embedded protocol biopsy specimens obtained at approximately one hour of reperfusion after transplantation of 13 cadaveric (CAD) and 12 living-related (LRD) renal allografts were examined by immunohistochemistry for expression of NGAL. The staining intensity was correlated with cold ischemia time, peak post-operative serum creatinine, and dialysis requirement. There were no differences between the LRD and CAD groups in age, gender or preoperative serum creatinine. Using a scoring system of 0 (no staining) to 3 (most intense staining), NGAL expression was significantly increased in CAD specimens (2.3+/-0.8 versus 0.8+/-0.7 in LRD, p<0.001). There was a strong correlation between NGAL staining intensity and cold ischemia time (R=0.87, p<0.001). Importantly, NGAL staining in these early CAD biopsies was strongly correlated with peak postoperative serum creatinine, which occurred days later (R=0.86, p<0.001). Four patients developed delayed graft function requiring dialysis during the first week posttransplantation; all of these patients displayed the most intense NGAL staining in their first protocol biopsies. We conclude that NGAL staining intensity in early protocol biopsies represents a novel predictive biomarker of acute kidney injury following transplantation.
authors.affiliation: Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Mishra
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.forename: Caitlin
authors.initials: C
authors.lastname: Kelly
authors.forename: Mark
authors.initials: M
authors.lastname: Mitsnefes
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Mori
authors.forename: Jonathan
authors.initials: J
authors.lastname: Barasch
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000473:pathology; D000209:Acute-Phase Proteins / Q000032:analysis*; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002102:Cadaver; D002648:Child; D051799:Delayed Graft Function / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006801:Humans; D007668:Kidney / Q000737:chemistry* / Q000473:pathology; D016030:Kidney Transplantation; D000071068:Lipocalin-2; D054834:Lipocalins; D019520:Living Donors; D008297:Male; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D015427:Reperfusion Injury / Q000175:diagnosis* / Q000473:pathology; D014019:Tissue Donors
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins