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

BioDrugs. 2023 Nov;37(6):843-854. doi: 10.1007/s40259-023-00621-6. Epub 2023 Sep 7.

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.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / complications
  • Acute Kidney Injury* / drug therapy
  • Angiogenesis Inhibitors / adverse effects
  • Bevacizumab / adverse effects
  • Diabetic Retinopathy* / chemically induced
  • Diabetic Retinopathy* / complications
  • Diabetic Retinopathy* / drug therapy
  • Endothelial Growth Factors / therapeutic use
  • Humans
  • Intravitreal Injections
  • Macular Degeneration* / chemically induced
  • Macular Degeneration* / complications
  • Macular Degeneration* / drug therapy
  • Macular Edema* / chemically induced
  • Macular Edema* / complications
  • Macular Edema* / drug therapy
  • Randomized Controlled Trials as Topic
  • Ranibizumab / adverse effects
  • Recombinant Fusion Proteins / adverse effects
  • Retinal Diseases* / chemically induced
  • Retinal Diseases* / complications
  • Retinal Diseases* / drug therapy
  • Retinal Vein Occlusion* / chemically induced
  • Retinal Vein Occlusion* / complications
  • Retinal Vein Occlusion* / drug therapy
  • Systematic Reviews as Topic
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Bevacizumab
  • Endothelial Growth Factors
  • Ranibizumab
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors