Nephrotoxicity induced by vascular endothelial growth factor inhibitors

Shirinsadat Badri,Azadeh Moghaddas,Sara Ataei,Rasool Soltani,Lillian Siberian,Mahnaz Momenzadeh

doi:10.34172/npj.2022.04

Abstract

Vascular endothelial growth factor (VEGF) is a special mitogen for vascular endothelial cells, an essential endogenous angiogenic cytokine, and the principal controller of vascular growth that plays a fundamental role in therapeutic angiogenesis pathways. VEGF-targeted therapy is categorized into the group of angiogenesis inhibitors that inhibit the expression or the activity of VEGF. It comprises counteracting VEGF antibodies, VEGF receptors, VEGF-trap, and tyrosine kinase inhibitor (TKIs) with selectivity for VEGF receptors. The kidney is both a target and a source of VEGF. VEGF may be a vital mediator to restore some types of renal diseases (e.g., non-diabetic renal diseases) and harmful in some other diseases (e.g., diabetes and diabetes complications). Due to their ability to prevent angiogenesis, VEGF inhibitors have been found as a powerful tool to treat angiogenesis-dependent diseases, including cancer and diabetic retinopathy. VEGF preserves the renal structure and function in normal physiologic conditions. Therefore, all treatments that inhibit the VEGF pathway may lead to renal disorders, especially renovascular diseases such as hypertension, proteinuria, nephrotic syndrome, decreased glomerular filtration rate (GFR), and thrombotic microangiopathy (TMA). In the present study, we reviewed some related reports and associated mechanisms, especially for hypertension and proteinuria.

Highlights

Vascular endothelial growth factor Vascular endothelial growth factor (VEGF) is a special mitogen for vascular endothelial cells, an essential endogenous angiogenic cytokine, and the primary controller of vascular growth that plays a fundamental role in therapeutic angiogenesis pathways
Recent studies have shown the pathological role of VEGF in developing severe microvascular and morphologic variations in different renal diseases, including chronic kidney disease (CKD), acute kidney injury (AKI), diabetic nephropathy, atherosclerosis, and metabolic syndrome [1]
Anti-angiogenic treatment is an original and efficient pathway for the treatment of angiogenesis-dependent diseases. Due to their ability to prevent angiogenesis, VEGF inhibitors have advanced as powerful tools to treat angiogenesis-dependent diseases, such as cancer and diabetic retinopathy

Summary

Introduction

Vascular endothelial growth factor Vascular endothelial growth factor (VEGF) is a special mitogen for vascular endothelial cells, an essential endogenous angiogenic cytokine, and the primary controller of vascular growth that plays a fundamental role in therapeutic angiogenesis pathways. It promotes endothelial cell proliferation, differentiation, and survival. VEGF-targeted therapy is categorized into the group of angiogenesis inhibitors that inhibit VEGF activity It comprises anti-VEGF antibodies (e.g., bevacizumab), VEGF receptor antagonist (ramucirumab), VEGF soluble receptor (e.g., aflibercept), Badri S et al and tyrosine kinase inhibitors (TKIs) with selectivity for VEGF receptors (e.g., sunitinib and sorafenib) [3]. Pegaptanib is the first ribonucleic acid aptamer, another class of VEGFbinding molecules [4]

Methods

Findings

Conclusion