BCR-ABL tyrosine kinase inhibitors associated acute kidney injury: a pharmacovigilance study based on the FAERS database with a case report.

backgroundAlthough tyrosine kinase inhibitors (TKIs) are the standard first-line treatment for chronic myeloid leukemia (CML), their renal safety profiles need investigation. Herein, we report a case of flumatinib-associated acute kidney injury (AKI). We also conducted a disproportionality analysis to evaluate TKI-related renal risks using pharmacovigilance data.

methodsThis report described the case of a patient with CML who developed AKI during flumatinib treatment. A meta-analysis was subsequently performed to assess the incidence of flumatinib-associated renal adverse events. Adverse event reports for TKIs (imatinib, dasatinib, nilotinib, flumatinib, radotinib, bosutinib, and ponatinib) from 2004 to 2024 were retrieved from the FDA Adverse Event Reporting System (FAERS). Reporting odds ratios (RORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the reporting associations of TKIs with AKI or renal-related adverse events.

resultsA 54-year-old woman developed severe AKI requiring dialysis after 5 months of flumatinib treatment, with a kidney biopsy confirming acute tubulointerstitial injury. Her kidney function completely recovered after flumatinib was discontinued and glucocorticoid therapy was initiated and remained stable after the therapeutic transition to imatinib during the 14-month follow-up period. A meta-analysis of 11 cohort studies showed a pooled incidence of flumatinib-related renal adverse events of 7% (95% CI, 4%-10%; I² = 71.0%). Analysis of the FAERS data revealed 117,520 reports of TKI-related adverse events, including 381 cases of AKI (0.32%) and 1,336 renal adverse events (1.14%). Compared with non-TKIs, TKIs were not associated with increased disproportionality signals for AKI (ROR = 0.31; 95% CI 0.28-0.34) or renal adverse events (ROR = 0.48; 95% CI 0.45-0.50). Among TKIs, dasatinib (ROR = 0.55; 95% CI 0.42-0.72) and nilotinib (ROR = 0.46; 95% CI 0.34-0.62) were associated with lower disproportionality signals for AKI, whereas bosutinib and ponatinib did not significantly increase disproportionality compared with imatinib.

conclusionsTKIs, including flumatinib, may cause AKI; however, FAERS-based disproportionality analysis does not indicate an increased renal safety signal compared to non-TKIs. Among TKIs, dasatinib and nilotinib have lower reporting disproportionality than imatinib does, suggesting a potential therapeutic advantage of their use for patients with kidney diseases. CLINICAL TRIAL NUMBER: Not applicable.