Pathologic Correlation with Renal Dysfunction after Intravitreal Injections of Vascular Endothelial Growth Factor Antagonists

Ann Clin Lab Sci. 2021 Nov;51(6):875-882.

Abstract

Objective: Vascular endothelial growth factor (VEGF) antagonists have been used for treating metastatic neoplasms. It has also been known that one of its side effects is to cause proteinuria and renal failure in the setting of thrombotic microangiopathy (TMA). The underlying mechanism is likely due to the inhibition of VEGF production in podocytes, resulting in diffuse fusion of foot processes and impaired glomerular endothelial fenestrations, and leading to massive proteinuria and subsequent glomerular endothelium injury. Intravitreal injection of VEGF antagonists (IIVA) has been also used to treat macular degeneration and diabetic retinal neo-vascular proliferation. The majority of patients tolerate the treatment well. However, IIVA can lead to renal dysfunction including proteinuria and gradual renal failure as a rare side effect. The goal of this study was to report two cases related to the nephrotoxicity of IIVA and review the literature associated with this topic.

Case report: The first diabetic patient had elevated serum creatinine at 3.25 mg/dl and proteinuria/creatinine ratio at 6.1 after 48-month treatment of IIVA. The first renal biopsy revealed thrombotic microangiopathy that was correlated with his increased serum creatinine and nephrotic range of proteinuria. The second diabetic patient had increased serum creatinine up to 1.89 mg/dl but low proteinuria. The second biopsy showed acute tubular necrosis that was correlated with his elevated serum creatinine.

Conclusion: Intravitreal injection of VEGF antagonist can be associated with thrombotic microangiopathy and acute tubular necrosis, leading to renal dysfunction.

Keywords: Acute Kidney Injury; Renal Biopsy; VEGF; intravitreal injection; monoclonal antibody.

Publication types

  • Case Reports

MeSH terms

  • Acute Kidney Injury* / blood
  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / diagnosis
  • Acute Kidney Injury* / therapy
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects
  • Bevacizumab* / administration & dosage
  • Bevacizumab* / adverse effects
  • Biopsy / methods
  • Creatinine / blood
  • Diabetic Retinopathy* / complications
  • Diabetic Retinopathy* / diagnosis
  • Diabetic Retinopathy* / drug therapy
  • Humans
  • Intravitreal Injections / methods
  • Kidney Cortex Necrosis* / etiology
  • Kidney Cortex Necrosis* / pathology
  • Kidney Function Tests / methods
  • Male
  • Middle Aged
  • Proteinuria / diagnosis
  • Proteinuria / etiology
  • Retinal Neovascularization* / diagnostic imaging
  • Retinal Neovascularization* / etiology
  • Thrombotic Microangiopathies* / diagnostic imaging
  • Thrombotic Microangiopathies* / etiology
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*

Substances

  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Creatinine