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

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Abstract

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, I2: 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, I2: 0% for aflibercept; OR: 0.97, 95% CI 0.42–2.22, I2: 0% for ranibizumab) and between different retinal diseases (OR: 4.61, 95% CI 0.07–284.13, I2: not applicable for age-related macular degeneration; OR: 0.90, 95% CI 0.42–1.93, I2: 0% for diabetic retinopathy/diabetic macular edema; OR: 1.57, 95% CI 0.16–15.88, I2: 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.

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Author notes

  1. Yu-Chien Tsao, Ting-Ying Chen, Li-An Wang have contributed equally to this article.

Authors and Affiliations

  1. College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Yu-Chien Tsao, Ting-Ying Chen & Li-An Wang

  2. Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Chia-Chun Lee

  3. School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Wan-Ju Annabelle Lee, Shih-Chieh Shao & Edward Chia-Cheng Lai

  4. Department of Ophthalmology, Chi Mei Medical Center, Tainan, Taiwan

    Wan-Ju Annabelle Lee

  5. Department of Optometry, Chung Hwa University of Medical Technology, Tainan, Taiwan

    Wan-Ju Annabelle Lee

  6. Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 1 University Road, Tainan, 701, Taiwan

    Sheng-Min Hsu & Jia-Horung Hung

  7. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Sheng-Min Hsu & Jia-Horung Hung

  8. College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Chi-Chun Lai

  9. Department of Ophthalmology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan

    Chi-Chun Lai

  10. Department of Pharmacy, Keelung Chang Gung Memorial Hospital, No. 222 Maijin Road, Keelung, 204, Taiwan

    Shih-Chieh Shao

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  1. Yu-Chien Tsao
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Funding

National Cheng Kung University Hospital (NCKUH-11006018) and the Taiwan Ministry of Science and Technology (MOST 110-2314-B-006-086-MY3) provided funding for the preparation of this article. The funders had no specific roles in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the article.

Conflicts of Interest/Competing Interests

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, and Edward Chia-Cheng Lai have no conflicts of interest that are directly relevant to the content of this article.

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The data used and/or analyzed during the current study are available from the two corresponding authors on reasonable request.

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The codes used during the current study are available from the two corresponding authors on reasonable request.

Authors’ Contributions

SCS and JHH conceptualized this study. SCS and JHH led the literature review with contributions from YCT, TYC, and LAW. YCT, TYC, and LAW extracted, cleaned, analyzed, and interpreted the data. SCS and JHH wrote the manuscript, with contributions from ECCL. All authors approved the final manuscript for publication.

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Tsao, YC., Chen, TY., Wang, LA. et al. Acute Kidney Injury from Intravitreal Anti-vascular Endothelial Growth Factor Drugs: A Systematic Review and Meta-analysis of Randomized Controlled Trials. BioDrugs 37, 843–854 (2023). https://doi.org/10.1007/s40259-023-00621-6

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