title: Renal cortical albumin gene induction and urinary albumin excretion in response to acute kidney injury.
abstract: This study evaluated the potential utility of albuminuria as a "biomarker" of acute kidney injury (AKI) and tested whether AKI induces renal expression of the normally silent albumin gene. Urine albumin concentrations were measured in mice with five different AKI models (maleate, ischemia-reperfusion, rhabdomyolysis, endotoxemia, ureteral obstruction). Albumin gene induction in renal cortex, and in antimycin A-injured cultured proximal tubular cells, was assessed (mRNA levels; RNA polymerase II binding to the albumin gene). Albumin's clinical performance as an AKI biomarker was also tested (29 APACHE II-matched intensive care unit patients with and without AKI). Results were contrasted to those obtained for neutrophil gelatinase-associated lipocalin (NGAL), an established "AKI biomarker" gene. The experimental and clinical assessments indicated albumin's equivalence to NGAL as an AKI biomarker (greater specificity in experimental AKI; slightly better receiver-operating curve in humans). Furthermore, experimental AKI markedly induced the albumin gene (mRNA/RNA polymerase II binding increases; comparable to those seen for NGAL). Albumin gene activation in patients with AKI was suggested by fivefold increases in RNA polymerase II binding to urinary fragments of the albumin gene (vs. AKI controls). Experimental AKI also increased renal cortical mRNA levels for α-fetoprotein (albumin's embryonic equivalent). A correlate in patients was increased urinary α-fetoprotein excretion. We conclude that AKI can unmask, in the kidney, the normally silent renal albumin and α-fetoprotein genes. In addition, the urinary protein data independently indicate that albuminuria, and perhaps α-fetoprotein, have substantial utility as biomarkers of acute tubular injury.
authors.affiliation: Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Ware
authors.forename: Ali C M
authors.initials: AC
authors.lastname: Johnson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Zager
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000209:etiology / Q000652:urine*; D000328:Adult; D000368:Aged; D000418:Albumins / Q000235:genetics* / Q000378:metabolism*; D000419:Albuminuria / Q000652:urine*; D000818:Animals; D015415:Biomarkers / Q000652:urine; D002478:Cells, Cultured; D019446:Endotoxemia / Q000150:complications; D005260:Female; D005990:Glycerol / Q000009:adverse effects; D006801:Humans; D007672:Kidney Cortex / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000009:adverse effects; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D023421:Models, Animal; D015427:Reperfusion Injury / Q000150:complications; D012206:Rhabdomyolysis / Q000150:complications; D012720:Severity of Illness Index; D014517:Ureteral Obstruction / Q000150:complications
chemical_list: D000418:Albumins; D015415:Biomarkers; D008298:Maleates; C030272:maleic acid; D005990:Glycerol