Influence of Tyrosine Kinase Inhibitors on Hypertension and Nephrotoxicity in Metastatic Renal Cell Cancer Patients

Abstract

Renal cell carcinoma (RCC) is one of the most common kidney malignancies. An upgraded comprehension of the molecular biology implicated in the development of cancer has stimulated an increase in research and development of innovative antitumor therapies. The aim of the study was to analyze the medical literature for hypertension and renal toxicities as the adverse events of the vascular endothelial growth factor (VEGF) signaling pathway inhibitor (anti-VEGF) therapy. Relevant studies were identified in PubMed and ClinicalTrials.gov databases. Eligible studies were phase III and IV prospective clinical trials, meta-analyses and retrospective studies that had described events of hypertension or nephrotoxicity for patients who received anti-VEGF therapy. A total of 48 studies were included in the systematic review. The incidence of any grade hypertension ranged from 17% to 49.6%. Proteinuria and increased creatinine levels were ascertained in 8% to 73% and 5% to 65.6% of patients, respectively. These adverse events are most often mild in severity but may sometimes lead to treatment discontinuation. Nephrotoxicity and hypertension are related to multiple mechanisms; however, one of the main disturbances in those patients is VEGF inhibition. There is a significant risk of developing hypertension and renal dysfunction among patients receiving anti-VEGF treatment; however, there is also some evidence that these side effects may be used as biomarkers of response to antiangiogenic agents.

Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo

“…Most of the current developments in this field are still solely focused on kidney (proximal) tubular epithelial cells. However, renal toxicity can also primarily occur in the glomerulus ( Barri et al., 2004 , Musu et al., 2011 , Naesens et al., 2009 , Semeniuk-Wojtas et al., 2016 ). Nephrotoxic drugs such as bisphosphonates, cyclosporine, NSAIDs, antihypertensive drugs, and anti-angiogenesis inhibitors have been shown to predominantly lead to glomerulopathies by compromising endothelial-podocyte crosstalk or podocyte integrity ( Radhakrishnan and Perazella, 2015 ).…”

Evaluation of renal function change during first-line tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma

“…The loss of VEGF function through pharmacologic inhibition is associated with damage to glomerular endothelial cells and podocytes. Additionally, anti-VEGF treatment leads to vasoconstriction via decreased nitrogen monoxide and prostaglandin I2 production, resulting in decreased blood flow in the glomeruli ( 7 , 21 ). SU and SO target a number of kinases, such as VEGFRs or platelet-derived growth factor receptors; they are not selective.…”

Renal Soluble Guanylate Cyclase Is Downregulated in Sunitinib‐Induced Hypertension

“…The rationale for using antiangiogenic RTKIs in tumor treatment is to inhibit tumor growth and metastatic spread by interfering with tumor vascularization 1. A frequently occurring adverse effect common to antiangiogenic RTKIs is rapidly developing arterial hypertension that needs adequate management to preserve the therapeutic usability of these drugs 7, 8, 9, 10. Understanding of the pathogenesis of this form of hypertension is required to provide effective antihypertensive treatment that does not counteract the tumor growth and metastatic spread‐inhibiting activity of antiangiogenic RTKIs 2, 3…”