Drug-induced nephrotoxicity remains a leading cause of kidney dysfunction, often with severe or even fatal outcomes. Computational approaches, in particular artificial intelligence (AI), offer a promising alternative by providing reliable, cost-effective, and ethically sound tools for assessing drug-induced nephrotoxicity. Thereby, potentially reducing reliance on animal testing. This study was driven by three core objectives: (i) to analyze the chemical space of compounds associated with drug-induced nephrotoxicity, (ii) to construct a robust supervised machine learning (ML) model for classification, followed by a quantitative Read-Across Structure-Activity Relationship (qRASAR) study, and (iii) to develop an open-access, eXplainable AI (XAI) platform named “KidneyToxᵥ1. 0” (https: //kidneytoxv1. streamlit. app/) for nephrotoxicity prediction. Beyond providing predictions, “KidneyToxᵥ1. 0” offers interpretability through interactive SHAP-based waterfall plots, enabling both domain experts and non-experts to understand the contribution of molecular descriptors to toxicity outcomes. These modelling analyses will assist chemists in designing less nephrotoxic molecules in the future.
Amin et al. (Tue,) studied this question.