title: Mild elevation of urinary biomarkers in prerenal acute kidney injury.
abstract: Prerenal acute kidney injury (AKI) is thought to be a reversible loss of renal function without structural damage. Although prerenal and intrinsic AKI frequently coexist in clinical situations, serum creatinine and urine output provide no information to support their differentiation. Recently developed biomarkers reflect tubular epithelial injury; therefore, we evaluated urinary biomarker levels in an adult mixed intensive care unit (ICU) cohort of patients who had been clinically evaluated as having prerenal AKI. Urinary L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), N-acetyl-β-D-glucosaminidase (NAG), and albumin in patients with prerenal AKI showed modest but significantly higher concentrations than in patients with non-AKI. We also conducted a proof-of-concept experiment to measure urinary biomarker excretion in prerenal AKI caused by volume depletion. Compared with cisplatinum and ischemia-reperfusion models in mice, volume depletion in mice caused a modest secretion of L-FABP and NGAL into urine with more sensitive response of L-FABP than that of NGAL. Although no histological evidence of structural damage was identified by light microscopy, partial kidney hypoxia was found by pimonidazole incorporation in the volume depletion model. Thus, our study suggests that new AKI biomarkers can detect mild renal tubular damage in prerenal acute kidney injury.
authors.affiliation: Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan.
authors.forename: Kent
authors.initials: K
authors.lastname: Doi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Katagiri
authors.forename: Kousuke
authors.initials: K
authors.lastname: Negishi
authors.forename: Sho
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Hamasaki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
authors.forename: Takehiro
authors.initials: T
authors.lastname: Matsubara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishii
authors.forename: Naoki
authors.initials: N
authors.lastname: Yahagi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugaya
authors.forename: Eisei
authors.initials: E
authors.lastname: Noiri
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D058186:Acute Kidney Injury / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine; D000368:Aged; D000419:Albuminuria / Q000209:etiology / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D002945:Cisplatin; D004195:Disease Models, Animal; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000652:urine; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D020382:Interleukin-18 / Q000652:urine; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D008875:Middle Aged; D015513:Oncogene Proteins / Q000652:urine; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine; D015427:Reperfusion Injury / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000652:urine*; D015854:Up-Regulation
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; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C071332:Lcn2 protein, mouse; D000118:Acetylglucosaminidase; D002945:Cisplatin