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HSP72 is an early biomarker to detect cisplatin and acetaminophen nephrotoxicity
Rosalba Pérez-Villalva1,2, Jonatan Barrera-Chimal1,2, Juan Carlos Aguilar-Carrasco1,2
1a Molecular Physiology Unit , Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Mexico City , Mexico.
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.
Materials And 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.