A case/non-case study of a national pharmacovigilance database to explore drug-induced acute kidney injury.

Background: Monitoring safety throughout a medicine's lifecycle is essential. Pharmacovigilance systems are rich sources contributing to this aim in a real world context.

Aim: To identify and estimate disproportionality rates associated with the drugs that are most frequently reported to induce acute kidney injury (AKI).

Method: A case/non-case study was conducted, using data extracted in 2022 from the Portuguese National Pharmacovigilance Database for the period between 01/01/2009 and 12/31/2020. Cases were identified using the 'Acute Renal Failure' standardized MedDRA query, all remaining reports were considered non-cases, and a random sample without replacement of 4 non-cases per case was extracted. Data were expressed as the reporting odds ratio (ROR) and the 95% confidence interval.

Results: During this 11-year period, 352 AKI cases were identified, representing 0.7% of the 53,505 reports received. A total of 559 different drugs were considered 'suspect' in these AKI cases. Three therapeutic subgroups (ATC2) showed a significant ROR: antithrombotic agents (ROR 6.72; 95% CI 2.23-20.22), antivirals for systemic use (ROR 4.02; 95% CI 2.76-5.87), and antineoplastic drugs (ROR 2.14; 95% CI 1.48-3.11). Additionally, we identified individual drugs with significant RORs where no class effect was observed, namely mycophenolic acid, ciclosporin, tacrolimus, simvastatin, prednisolone, vancomycin, and deferasirox. In total, eleven drugs were identified as potentially associated with the occurrence of AKI.

Conclusion: This study highlights the importance of clinical pharmacy activities in closely monitoring renal function of people with known risk factors or those prescribed medications known to increase the risk of AKI. Some of the medications identified require further investigation to validate their association with AKI.