ANTIFUNGAL-ASSOCIATED ACUTE KIDNEY INJURY: A DISPROPORTIONALITY ANALYSIS AND SYSTEMATIC REVIEW
Author(s)
MALAVIKA SURESH, PhD Research Scholar1, Mohammed Salim Karattuthodi, PharmD, PhD2, Gouri Nair, M pharm, PhD3, Sonal Sekhar, M pharm, PhD4.
1Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India, 2Department of Pharmacy Practice, College of Pharmacy, Gulf Medical University, Ajman, Ajman, United Arab Emirates, 3Department of Pharmacology, M S Ramaiah University Of Applied Sciences, Bengalore, India, 4Manipal College of Pharmaceutical Sciences, Manipal, India.
1Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India, 2Department of Pharmacy Practice, College of Pharmacy, Gulf Medical University, Ajman, Ajman, United Arab Emirates, 3Department of Pharmacology, M S Ramaiah University Of Applied Sciences, Bengalore, India, 4Manipal College of Pharmaceutical Sciences, Manipal, India.
OBJECTIVES: The study aimed to identify and characterize antifungal-associated AKI signals using the FDA Adverse Event Reporting System (FAERS) and a systematic review of published case reports.
METHODS: A retrospective case/non-case study was conducted using FAERS data from Q4 2005 to Q2 2025, accessed and analyzed via the OpenVigil 2.1 platform. Disproportionality analysis was performed using the reporting odds ratio (ROR), with 95% confidence intervals. A signal is considered as an increased risk, when the lower limit of the 95% confidence interval of ROR exceeds 1. Additionally, a systematic review was conducted across PubMed, Embase, and Scopus to identify case reports of AKI associated with antifungal agents that corresponded to the confirmed signals identified in the disproportionality analysis.
RESULTS: 23 antifungals with confirmed AKI signals were found. In general, the highest ROR was observed for olorofim 12.57 (3.81-41.45), but with limited reports reflecting extreme uncertainty. Among the agents with high ROR and substantial event volume, amphotericin B 5.37 (4.97-5.81), ambisome 5.82 (4.84-6.99), and fluconazole 4.20 (3.98-4.43) are clinically worth finding. Triazole accounted for the highest proportion (53.44%) of AKI events. Along with this higher frequency, AKI associated with triazoles and polyenes was characterized by a greater burden of adverse outcomes. For triazoles, the proportions of outcomes were death (55.76%), hospitalization (57.69%), disability (80%), and life-threatening event (63.16%), whereas for polyenes, they were 23.33%, 19.69%, 20%, and 21.05%, respectively. A total of 31 case reports/series were included in the systematic review, of which the liposomal amphotericin B was the most highly reported antifungal (n=18).
CONCLUSIONS: Collectively, the disproportionality analysis and systematic review indicate that AKI is disproportionately reported across multiple antifungal classes, generating safety signals. Liposomal amphotericin B was the most frequently implicated agent for AKI. The findings underscore the need for careful renal monitoring and further confirmatory studies.
METHODS: A retrospective case/non-case study was conducted using FAERS data from Q4 2005 to Q2 2025, accessed and analyzed via the OpenVigil 2.1 platform. Disproportionality analysis was performed using the reporting odds ratio (ROR), with 95% confidence intervals. A signal is considered as an increased risk, when the lower limit of the 95% confidence interval of ROR exceeds 1. Additionally, a systematic review was conducted across PubMed, Embase, and Scopus to identify case reports of AKI associated with antifungal agents that corresponded to the confirmed signals identified in the disproportionality analysis.
RESULTS: 23 antifungals with confirmed AKI signals were found. In general, the highest ROR was observed for olorofim 12.57 (3.81-41.45), but with limited reports reflecting extreme uncertainty. Among the agents with high ROR and substantial event volume, amphotericin B 5.37 (4.97-5.81), ambisome 5.82 (4.84-6.99), and fluconazole 4.20 (3.98-4.43) are clinically worth finding. Triazole accounted for the highest proportion (53.44%) of AKI events. Along with this higher frequency, AKI associated with triazoles and polyenes was characterized by a greater burden of adverse outcomes. For triazoles, the proportions of outcomes were death (55.76%), hospitalization (57.69%), disability (80%), and life-threatening event (63.16%), whereas for polyenes, they were 23.33%, 19.69%, 20%, and 21.05%, respectively. A total of 31 case reports/series were included in the systematic review, of which the liposomal amphotericin B was the most highly reported antifungal (n=18).
CONCLUSIONS: Collectively, the disproportionality analysis and systematic review indicate that AKI is disproportionately reported across multiple antifungal classes, generating safety signals. Liposomal amphotericin B was the most frequently implicated agent for AKI. The findings underscore the need for careful renal monitoring and further confirmatory studies.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
EPH257
Topic
Epidemiology & Public Health, Health Policy & Regulatory, Real World Data & Information Systems
Topic Subcategory
Safety & Pharmacoepidemiology
Disease
Infectious Disease (non-vaccine), No Additional Disease & Conditions/Specialized Treatment Areas, Urinary/Kidney Disorders