title: Circulating AST, H-FABP, and NGAL are early and accurate biomarkers of graft injury and dysfunction in a preclinical model of kidney transplantation.
abstract: OBJECTIVE
  To investigate circulating biomarkers of initial graft injury in a porcine kidney autotransplant model.
  
  
  BACKGROUND
  Injury endured by kidney grafts early posttransplant determines their outcome. However, creatinine (clearance) is a poor surrogate of tissue injury and urinary biomarkers are limited by graft anuria or persistent native kidney diuresis. No validated circulating biomarkers quantifying initial graft injury exist.
  
  
  METHODS
  Minimally injured porcine kidney grafts (n = 6) were cold stored (18 hours) and autotransplanted. Moderately (n = 6) and severely injured grafts (n = 7) were exposed to 30 or 60 minutes warm ischemia before storage and autotransplantation. Four biomarkers [aspartate transaminase (AST), heart-type fatty acid-binding protein (H-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl-β-glucosaminidase (NAG)] were measured posttransplant and compared with creatinine (clearance) and histology.
  
  
  RESULTS
  Diuresis was delayed in moderately [2.5 days (2-3)] and severely [4 days (4-5)] versus minimally injured grafts (P < 0.001). Creatinine peaked later than AST, H-FABP, and NGAL [4 days (3-5) vs 3 hours (3-6), 6 hours (6-24), 2 days (1-3), respectively] and only differentiated minimally from severely injured grafts. Peak AST and H-FABP distinguished all injury grades. Neutrophil gelatinase-associated lipocalin discriminated initial graft injury 2 days posttransplant. Peak AST, H-FABP, and NGAL correlated with peak creatinine [Pearson coefficients: 0.70 (P = 0.001), 0.85 (P < 0.0001), 0.80 (P < 0.0001)]. N-acetyl-β-glucosaminidase was not different. Decreased clearance accounted for a small percentage of H-FABP and NGAL increase. Histology was not different among transplanted groups.
  
  
  CONCLUSIONS
  Plasma AST, H-FABP, and NGAL reflect the severity of initial kidney graft injury and predict graft dysfunction earlier and more accurately than creatinine (clearance) and histology. They represent promising tools to improve patient care after kidney transplantation.
authors: Department of Abdominal Transplant Surgery, University Hospitals Leuven, KULeuven, Belgium. ina.jochmans@med.kuleuven.be
authors: Ina
authors: I
authors: Jochmans
authors: Evelyne
authors: E
authors: Lerut
authors: Jos
authors: J
authors: van Pelt
authors: Diethard
authors: D
authors: Monbaliu
authors: Jacques
authors: J
authors: Pirenne
mesh_terms: D000118:Acetylglucosaminidase / Q000097:blood; D058186:Acute Kidney Injury / Q000097:blood / Q000175:diagnosis*; D000209:Acute-Phase Proteins / Q000032:analysis*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000097:blood*; D005260:Female; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D054834:Lipocalins / Q000097:blood*; D023421:Models, Animal; D055031:Primary Graft Dysfunction / Q000097:blood / Q000175:diagnosis*; D013552:Swine
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins; D054834:Lipocalins; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000118:Acetylglucosaminidase