Comparison of adverse renal events between ranibizumab and aflibercept in patients with diabetic macular oedema: A global network study

Purpose Patients with diabetic macular oedema (DMO) are susceptible to renal injury, raising the risks of acute kidney injury (AKI) and end-stage renal disease (ESRD) associated with anti-VEGF therapies. We aimed to compare the risks of AKI and ESRD between aflibercept and ranibizumab in DMO patients, focusing on AKI and ESRD in conjunction with all-cause mortality. Methods A target trial emulation using the TriNetX Global Collaborative Network included adult patients with DMO who initiated treatment with aflibercept or ranibizumab in routine clinical practice. Ranibizumab exposure reflected real-world use and included both approved dosages. Patients with pre-existing ESRD or chronic kidney disease stage 5 were excluded. Propensity score matching was applied to balance demographics, comorbidities, medication use, and laboratory parameters. Time-to-event analyses were performed for AKI, ESRD, and all-cause mortality. Sensitivity analyses included application of a minimum 7-day latency window after treatment initiation to address potential temporality bias. Results After matching, 3411 patients were included in each treatment group (mean age, 64.0 ± 12.4 years; 51.5% male). During follow-up, aflibercept was not associated with an increased risk of AKI (hazard ratio [HR]: 0.97, 95% confidence interval [CI]: 0.89-1.06), ESRD (HR: 0.95, 95% CI: 0.83–1.09), or all-cause mortality (HR: 0.99, 95% CI: 0.89–1.10), when compared with ranibizumab. Results were consistent across subgroup and sensitivity analyses, including analyses incorporating a 7-day latency window with an HR of 1.08 (95% CI: 0.94–1.24) for AKI, and 0.89 (95% CI: 0.76–1.04) for ESRD. Conclusions In this multinational, real-world study, aflibercept and ranibizumab demonstrated comparable risks of AKI, ESRD and mortality among patients with DMO after adjustment for measured confounders. Given the observational design, real-world dose heterogeneity, and limitations in detailed treatment-timing data, these findings should be interpreted with caution.