title: Hsp72 is an early and sensitive biomarker to detect acute kidney injury.
abstract: This study was designed to assess whether heat shock protein Hsp72 is an early and sensitive biomarker of acute kidney injury (AKI) as well as to monitor a renoprotective strategy. Seventy-two Wistar rats were divided into six groups: sham-operated and rats subjected to 10, 20, 30, 45 and 60 min of bilateral ischemia (I) and 24 h of reperfusion (R). Different times of reperfusion (3, 6, 9, 12, 18, 24, 48, 72, 96 and 120 h) were also evaluated in 30 other rats subjected to 30 min of ischemia. Hsp72 messenger RNA (mRNA) and protein levels were determined in both kidney and urine. Hsp72-specificity as a biomarker to assess the success of a renoprotective intervention was evaluated in rats treated with different doses of spironolactone before I/R. Renal Hsp72 mRNA and protein, as well as urinary Hsp72 levels, gradually increased relative to the extent of renal injury induced by different periods of ischemia quantified by histomorphometry as a benchmark of kidney damage. Urinary Hsp72 increased significantly after 3 h and continued rising until 18 h, followed by restoration after 120 h of reperfusion in accord with histopathological findings. Spironolactone renoprotection was associated with normalization of urinary Hsp72 levels. Accordingly, urinary Hsp72 was significantly increased in patients with clinical AKI before serum creatinine elevation. Our results show that urinary Hsp72 is a useful biomarker for early detection and stratification of AKI. In addition, urinary Hsp72 levels are sensitive enough to monitor therapeutic interventions and the degree of tubular recovery following an I/R insult.
authors.affiliation: Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Barrera-Chimal
authors.forename: Rosalba
authors.initials: R
authors.lastname: Pérez-Villalva
authors.forename: Cesar
authors.initials: C
authors.lastname: Cortés-González
authors.forename: Marcos
authors.initials: M
authors.lastname: Ojeda-Cervantes
authors.forename: Gerardo
authors.initials: G
authors.lastname: Gamba
authors.forename: Luis E
authors.initials: LE
authors.lastname: Morales-Buenrostro
authors.forename: Norma A
authors.initials: NA
authors.lastname: Bobadilla
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000378:metabolism; D000209:Acute-Phase Proteins / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D003401:Creatine / Q000097:blood; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D020382:Interleukin-18 / Q000652:urine; D007511:Ischemia / Q000378:metabolism / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008562:Membrane Glycoproteins / Q000652:urine; D011518:Proto-Oncogene Proteins / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D011991:Receptors, Virus; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D013148:Spironolactone / Q000633:toxicity; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C491143:HAVCR1 protein, human; D050884:HSP72 Heat-Shock Proteins; D000072596:Hepatitis A Virus Cellular Receptor 1; D020382:Interleukin-18; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D013148:Spironolactone; D003401:Creatine