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.

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.

Keywords:

• Drug-induced AKI
• urine biomarkers
• tubular injury

Acknowledgements

We are grateful to Martha Carrasco for her technical assistance. The results presented in this paper have not been published previously.

Disclosure statement

N. A. B. and J. B. C. are inventors of HSP72 patents. The rest of the authors have no conflicts of interest to disclose.

Additional information

Funding

This project was supported through grants from the Mexican Council of Science and Technology [CONACyT 235855, 235964 and 272390 to N. A. B.] and the National Autonomous University of Mexico [IN223915 to N. A. B.].