Mechanistic Representation of Clusterin, a Damage Biomarker for Early Detection of Drug-induced AKI

Authors: Hamzavi N, Woodhead JL
Conference: American Society of Nephrology (ASN) Kidney Week
Keywords: Acute kidney injury (AKI), biomarker, Clusterin (CLU), RENAsym
Software: RENAsym®
Division: Quantitative Systems Pharmacology (QSP)

Background

Novel biomarkers have the potential to address early diagnosis and timely intervention of acute kidney injury (AKI). To fully leverage the clinical potential of these biomarkers, a mechanistic understanding of the biological processes that lead to biomarker release is essential.

Methods

We developed a mechanistic model of clusterin (CLU) within the framework of RENAsym, a QST model of drug-induced AKI that incorporates key cellular injury mechanism and renal hemodynamics. After cellular injury, clusterin gene is known to be upregulated. The clusterin model was used to predict urinary clusterin following cisplatin administration to rats in connection with necrosis and/or dedifferentiation of proximal tubular cells (PTC).

Conclusion

  • This modeling informes that signals from necrotic tubular cells can predict the change of absolute magnitude of urinary clusterin.
  • QST modeling enables prediction of behavior of novel kidney injury biomarkers following acute kidney injury.

By Nader Hamzavi and Jeffrey L. Woodhead

Kidney Week 2024, October 23-27, 2024, San Diego, CA