Acute Kidney Injury from Intravitreal Anti-vascular Endothelial Growth Factor Drugs: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Yu Chien Tsao, Ting Ying Chen, Li An Wang, Chia Chun Lee, Wan Ju Annabelle Lee, Sheng Min Hsu, Chi Chun Lai, Shih Chieh Shao, Jia Horung Hung, Edward Chia Cheng Lai

Research output: Contribution to journalReview articlepeer-review


Background: Several observational studies have reported acute kidney injury from intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs for retinal diseases. However, systematic reviews and meta-analyses of randomized controlled trials on this critical topic are scant. Objective: To evaluate acute kidney injury risk associated with intravitreal anti-VEGF drugs in patients with retinal diseases. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials on 12 July, 2023, and included randomized controlled trials reporting acute kidney injury between anti-VEGF drugs (e.g., aflibercept, bevacizumab, brolucizumab, and ranibizumab) and controls for retinal diseases (e.g., age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy/diabetic macular edema, retinal vein occlusion, and myopic choroidal neovascularization). Data were synthesized by a fixed-effects model for pooling odds ratios (ORs) using the Peto method. Results: We included 13 randomized controlled trials (four and nine trials for aflibercept and ranibizumab, respectively) with a total of 4282 participants. The meta-analysis indicated intravitreal anti-VEGF drugs did not increase the acute kidney injury risk, compared with controls (odds ratio [OR]: 1.00, 95% confidence interval [CI] 0.49–2.04, I 2: 0%), and no differences in the acute kidney injury risk were observed between different anti-VEGF drugs (OR: 1.10, 95% CI 0.27–4.43, I 2: 0% for aflibercept; OR: 0.97, 95% CI 0.42–2.22, I 2: 0% for ranibizumab) and between different retinal diseases (OR: 4.61, 95% CI 0.07–284.13, I 2: not applicable for age-related macular degeneration; OR: 0.90, 95% CI 0.42–1.93, I 2: 0% for diabetic retinopathy/diabetic macular edema; OR: 1.57, 95% CI 0.16–15.88, I 2: 0% for retinal vein occlusion). Conclusions: Intravitreal anti-VEGF drugs were not associated with an acute kidney injury risk, regardless of which anti-VEGF drugs (aflibercept or ranibizumab) or retinal diseases (age-related macular degeneration, diabetic retinopathy/diabetic macular edema, or retinal vein occlusion) were involved. Systematic Review Protocol Registration: PROSPERO CRD42021267854.

Original languageEnglish
Pages (from-to)843-854
Number of pages12
Issue number6
Publication statusPublished - 2023 Nov

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Pharmacology
  • Pharmacology (medical)


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