Biomarkers for drug-induced renal damage and nephrotoxicity-an overview for applied toxicology

Area of Science:

• Nephrology
• Toxicology
• Biomarker Discovery

Background:

• Kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), are increasing globally, particularly in aging populations and those with comorbidities like diabetes and heart failure.
• Drug-induced kidney injury is a significant cause of AKI, especially in intensive care settings, highlighting the need for better diagnostic tools.
• Traditional renal damage markers, such as serum creatinine, often indicate established injury and lack sensitivity for early detection.

Purpose of the Study:

• To review traditional and novel diagnostic tools for detecting renal damage.
• To highlight the importance of early AKI detection and monitoring of CKD.
• To discuss the development and potential of new urinary protein and transcriptional biomarkers in nephrotoxicity assessment.

Main Methods:

• Literature review of traditional and novel diagnostic methods for kidney injury.
• Discussion of molecular toxicology approaches for identifying nephrotoxicity biomarkers.
• Analysis of identified urinary protein biomarkers (e.g., Kim-1, clusterin, osteopontin, RPA-1) and transcriptional biomarkers.

Main Results:

• Novel urinary biomarkers enable earlier detection of AKI compared to established markers.
• These biomarkers provide insights into the location and mechanisms of nephron damage.
• While many biomarkers have been identified and qualified in preclinical models (e.g., rats), further validation in humans is ongoing.

Conclusions:

• Emerging urinary biomarkers represent a significant advancement in diagnosing and monitoring kidney diseases.
• These novel tools are essential for enhancing drug development and patient care by enabling timely intervention.
• Continued research and validation are necessary to fully integrate these biomarkers into clinical practice for AKI and CKD management.