Kidney NGAL is a novel early marker of acute injury following transplantation
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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.
KeywordsAcute renal failure Delayed graft function Biomarkers Lipocalins Protocol biopsy
Dr. Devarajan is supported by grants from the NIH/NIDDK (RO1-DK53289, P50-DK52612, R21-DK070163), a Grant-in-Aid from the American Heart Association Ohio Valley Affiliate, and a Translational Research Initiative Grant from Cincinnati Children’s Hospital Medical Center. Dr. Barasch is supported by grants from the NIH/NIDDK (RO1-DK55388, RO1 DK-58872) and a Research Grant from the March of Dimes Foundation.
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