[Nephrotoxicity--proteinuria and hypertension--]

Gan To Kagaku Ryoho. 2008 Oct;35(10):1649-53.
[Article in Japanese]

Abstract

Targeted and biological therapies have been investigated as methods of improving anticancer therapy. One approach to targeted therapy is to inhibit tumor angiogenesis, which has a critical role in the development of cancer. However, the potential for further improvement in outcomes is likely to be limited by its nephrotoxic side effects such as urinary protein and hypertension. Among the anti-angiogenesis inhibitors, the humanized monoclonal antibody, bevacizumab, directed against VEGF(vascular endothelial growth factor), is the first anti-angiogenic agent to be approved for cancer therapy, but it has a high frequency of these side effects. Hypertension could be due to a reduction of eNOS activity and rarefaction of microvessels in various tissues and organs induced by VEGF inhibition. Bevacizumab also induces proteinuria, glomerular endothelial cell detachment and suppression of nephrin, an important protein for the maintenance of the glomerular slit diaphragm, sometimes leading to nephritic syndrome and/or thrombotic microangiopathy in the glomeruli. Periodic monitoring of blood pressure and urinary protein should be necessary in patients on anti- VEGF agents. Patients showing nephrotoxicities need special referral to nephrologists and to be treated using proper anti-hypertension drugs.

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Humans
  • Hypertension / chemically induced*
  • Hypertension / physiopathology*
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / urine*
  • Neoplasms / drug therapy
  • Proteinuria / chemically induced*
  • Proteinuria / urine*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antineoplastic Agents
  • Vascular Endothelial Growth Factor A
  • ErbB Receptors