Nephrotoxicity induced by intravitreal vascular endothelial growth factor inhibitors: emerging evidence

Kidney Int. 2019 Sep;96(3):572-580. doi: 10.1016/j.kint.2019.02.042. Epub 2019 Apr 9.

Abstract

Vascular endothelial growth factor (VEGF) inhibitors have emerged as powerful tools to treat malignant neoplasms and ocular diseases by virtue of their ability to inhibit angiogenesis. Recent data indicate that intravitreal injections of VEGF inhibitors can lead to significant systemic absorption as well as a measurable reduction of plasma VEGF activity. There is increasing evidence showing that vitreal absorption of these drugs is associated with cases of accelerated hypertension, worsening proteinuria, glomerular disease, thrombotic microangiopathy, and possible chronic renal function decline. In this review, the 3 most commonly used anti-VEGF agents-bevacizumab, ranibizumab, and aflibercept-are discussed, highlighting their intravitreal absorption and associated effects on the kidney as a target organ system. We provide clinical suggestions for clinicians to both better manage patients receiving anti-VEGF agents intravitreally and detect any putative systemic renal effects of these agents. While acknowledging the risks of aberrant retinal angiogenesis, it is important for clinicians to be aware of the potential for adverse renal risks with use of these agents.

Keywords: aflibercept; bevacizumab; diabetic nephropathy; podocyte; proteinuria; ranibizumab; thrombotic microangiopathy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects*
  • Angiogenesis Inhibitors / pharmacokinetics
  • Bevacizumab / administration & dosage
  • Bevacizumab / adverse effects
  • Bevacizumab / pharmacokinetics
  • Diabetic Retinopathy / drug therapy*
  • Humans
  • Intravitreal Injections
  • Kidney / drug effects*
  • Kidney / pathology
  • Ocular Absorption
  • Proteinuria / chemically induced*
  • Proteinuria / pathology
  • Ranibizumab / administration & dosage
  • Ranibizumab / adverse effects
  • Ranibizumab / pharmacokinetics
  • Receptors, Vascular Endothelial Growth Factor / administration & dosage
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / pharmacokinetics
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Recombinant Fusion Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • aflibercept
  • Bevacizumab
  • Receptors, Vascular Endothelial Growth Factor
  • Ranibizumab