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New research · Nephrology
Biological & pharmaceutical bulletin · 23h
Animal / preclinicalBiological & pharmaceutical bulletin · 2026

Population Toxicodynamic Modeling of the Acute Kidney Injury-to-Chronic Kidney Disease Transition Following Repeated Cisplatin Administration in Rats.

Takumi Hotta, Hirohito Muroi, Haruno Oku … Nobuyuki Sugioka
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NephrologyAnimal / preclinical

Cisplatin's kidney toxicity signal decays slowly, with a half-life of 79 days.

Population Toxicodynamic Modeling of the Acute Kidney Injury-to-Chronic Kidney Disease Transition Following Repeated Cisplatin Administration in Rats.

Takumi Hotta et al. · Biological & pharmaceutical bulletin · 2026
Background

Cisplatin (cis-diammineplatinum (II) dichloride [CDDP]) induces acute kidney injury (AKI), and repeated dosing may lead to incomplete recovery and progression to chronic kidney disease (CKD).

Purpose

This study aimed to develop a mathematical model to characterize the CDDP-induced AKI-to-CKD transition during repeated administration.

79
Results
d
The toxic signal from cisplatin in the kidney takes 79 days to halve.
More results

However, the quantitative dynamics underlying the AKI-to-CKD transition remain unclear.

Rats received three cycles of CDDP at 21-d intervals under different dosing regimens, but with an identical cumulative dose (9 mg/kg).

A toxicodynamic model based on Cr mass balance was developed.

More results

Renal function progressively decreased in a dose-dependent manner across cycles.

“
Conclusion

The proposed modeling approach may facilitate prediction of the AKI-to-CKD transition and support the optimization of safer CDDP treatment strategies.

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