title: HSP72 is an early biomarker to detect cisplatin and acetaminophen nephrotoxicity.
abstract: OBJECTIVE
  To evaluate whether the urinary HSP72 levels (uHSP72) are a useful biomarker for early diagnosis of acute kidney injury (AKI) induced by two widely used drugs: cisplatin and acetaminophen.
  
  
  METHODS
  To analyze the time-course of nephrotoxic injury and uHSP72 levels, male Wistar rats were administered a single high dose of cisplatin (7 mg/kg) or acetaminophen (750 mg/kg) and were assessed at 6, 12, 24, 48, 72, 96 and 120 h.
  
  
  RESULTS
  AKI induced by cisplatin was characterized by tubular injury that started at 6 h and was enhanced after 48 h. Plasma creatinine was increased only after 72 h. In contrast, uHSP72 levels were augmented after 6 h and were enhanced after 48 h of cisplatin administration, which was consistent with the tubular injury. In acetaminophen-induced AKI, the tubular lesions were less severe and predominantly characterized by tubular cell detachment. Interestingly, uHSP72 levels were increased after 6 h of acetaminophen injection and remained elevated at the following time points, reflecting the tubular injury, even in the absence of major functional changes.
  
  
  CONCLUSIONS
  In two models of renal injury induced by nephrotoxic drugs, we showed that uHSP72 could be used as an early biomarker to detect subtle to severe tubular injury.
authors.affiliation: a Molecular Physiology Unit , Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Mexico City , Mexico.|b Department of Nephrology , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan , Mexico City , Mexico.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Pérez-Villalva
authors.affiliation: a Molecular Physiology Unit , Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Mexico City , Mexico.|b Department of Nephrology , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan , Mexico City , Mexico.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Barrera-Chimal
authors.affiliation: a Molecular Physiology Unit , Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Mexico City , Mexico.|b Department of Nephrology , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan , Mexico City , Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Aguilar-Carrasco
authors.affiliation: a Molecular Physiology Unit , Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Mexico City , Mexico.|b Department of Nephrology , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan , Mexico City , Mexico.
authors.forename: Ixchel
authors.initials: I
authors.lastname: Lima-Posada
authors.affiliation: b Department of Nephrology , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan , Mexico City , Mexico.
authors.forename: Cristino
authors.initials: C
authors.lastname: Cruz
authors.affiliation: a Molecular Physiology Unit , Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Mexico City , Mexico.|b Department of Nephrology , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan , Mexico City , Mexico.
authors.forename: Victoria
authors.initials: V
authors.lastname: Ramírez
authors.affiliation: a Molecular Physiology Unit , Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Mexico City , Mexico.|c Instituto Nacional de Pediatría , Coyoacan , Mexico.
authors.forename: Yvett
authors.initials: Y
authors.lastname: González-Bobadilla
authors.affiliation: d Department of Pathology , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan , Mexico City , Mexico.
authors.forename: Norma
authors.initials: N
authors.lastname: Uribe
authors.affiliation: e Facultad de Ciencias Bioquímicas y Farmacéuticas , Universidad Nacional de Rosario , Rosario , Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Trumper
authors.affiliation: a Molecular Physiology Unit , Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Mexico City , Mexico.|b Department of Nephrology , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan , Mexico City , Mexico.
authors.forename: Norma A
authors.initials: NA
authors.lastname: Bobadilla
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects* / Q000633:toxicity; D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000175:diagnosis*; D000818:Animals; D015415:Biomarkers / Q000652:urine; D002945:Cisplatin / Q000009:adverse effects* / Q000633:toxicity; D042241:Early Diagnosis; D050884:HSP72 Heat-Shock Proteins / Q000652:urine*; D007684:Kidney Tubules / Q000293:injuries; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D015415:Biomarkers; D050884:HSP72 Heat-Shock Proteins; D000082:Acetaminophen; D002945:Cisplatin
keywords: Drug-induced AKI; tubular injury; urine biomarkers