Angiogenesis inhibitor therapies: focus on kidney toxicity and hypertension

Area of Science:

• Oncology
• Nephrology
• Pharmacology

Background:

• Angiogenesis inhibitors targeting epidermal growth factor (EGF) receptor (EGFR) and vascular endothelial growth factor (VEGF) are vital in metastatic cancer treatment.
• Both EGFR and VEGF are expressed in the kidneys, leading to potential renal side effects with these targeted therapies.
• EGFR is found in renal tubules and epithelial cells, while VEGF is crucial for glomerular filtration and is expressed in podocytes.

Purpose of the Study:

• To review the renal side effects, specifically hypertension and proteinuria, associated with EGFR and VEGF inhibitors used in cancer therapy.
• To discuss the mechanisms and management of these common renal class effects.

Main Methods:

• Review of existing data on renal side effects of EGFR and VEGF inhibitors.
• Analysis of reported cases of renal complications, including acute renal failure, glomerulonephritis, and thrombotic microangiopathy.
• Discussion of the proposed mechanisms for hypertension and proteinuria.

Main Results:

• The most frequent renal side effects of VEGF antagonists are hypertension and proteinuria, which are typically manageable and reversible upon drug withdrawal.
• A dose-dependent increase in the risk of proteinuria and hypertension was observed in cancer patients receiving targeted therapies.
• While rare, cases of glomerulonephritis or thrombotic microangiopathy secondary to treatment have been reported.

Conclusions:

• Hypertension associated with these therapies is thought to be nitric oxide-dependent.
• Proteinuria appears linked to the downregulation of podocyte tight junction proteins.
• Understanding and monitoring these renal effects is crucial for managing patients undergoing targeted cancer therapy.