An Integrated Approach for Representing Knowledge on the Potential of Drugs to Cause Acute Kidney Injury

Daniel Fernández-Llaneza (), Romy M. P. Vos, Joris E. Lieverse, Helen R. Gosselt, Sandra L. Kane-Gill, Teun Gelder and Joanna E. Klopotowska
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Daniel Fernández-Llaneza: University of Amsterdam
Romy M. P. Vos: Vrije Universiteit Amsterdam
Joris E. Lieverse: University of Amsterdam
Helen R. Gosselt: Netherlands Pharmacovigilance Centre Lareb
Sandra L. Kane-Gill: University of Pittsburgh
Teun Gelder: Leiden University Medical Centre
Joanna E. Klopotowska: University of Amsterdam

Drug Safety, 2025, vol. 48, issue 1, No 4, 43-58

Abstract: Abstract Introduction and Objective The recent rise in acute kidney injury (AKI) incidence, with approximately 30% attributed to potentially preventable adverse drug events (ADEs), poses challenges in evaluating drug-induced AKI due to polypharmacy and other risk factors. This study seeks to consolidate knowledge on the drugs with AKI potential from four distinct sources: (i) bio(medical) peer-reviewed journals; (ii) spontaneous reporting systems (SRS); (iii) drug information databases (DIDs); and (iv) NephroTox website. By harnessing the potential of these underutilised sources, our objective is to bridge gaps and enhance the understanding of drug-induced AKI. Methods By searching Medline, studies with lists of drugs with AKI potential established through consensus amongst medical experts were selected. A final list of 63 drugs was generated aggregating the original studies. For these 63 drugs, the AKI reporting odds ratios (RORs) using three SRS databases, the average frequency of ADEs from four different DIDs and the number of published studies identified via NephroTox was reported. Results Drugs belonging to the antivirals, antibacterials, and non-steroidal anti-inflammatory pharmacological classes exhibit substantial consensus on AKI potential, which was also reflected in strong ROR signals, frequent to very frequent AKI-related ADEs and a high number of published studies reporting adverse kidney events as identified via NephroTox. Renin-angiotensin aldosterone system inhibitors and diuretics also display comparable signal strengths, but this can be attributed to expected haemodynamic changes. More variability is noted for proton-pump inhibitors. Conclusions By integrating four disjointed sources of knowledge, we have created a novel, comprehensive resource on drugs with AKI potential, contributing to kidney safety improvement efforts.

Date: 2025
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DOI: 10.1007/s40264-024-01474-w

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