Nephrotoxicity Associated with Novel Anticancer Agents (Aflibercept, Dasatinib, Nivolumab): Case Series and Nephrological Considerations

Abstract

<jats:p>Cancer patients have an incidence of about 60% kidney disease development and are at elevated risk of acute renal damage. Kidney disease in these patients is frequently associated with nephrotoxicity from the ongoing oncological treatment. New anticancer therapeutic strategies, such as targeted therapies and immunotherapies, offer substantial benefits in the treatment of many neoplasms. However, their use is associated with significant nephrotoxicity, which qualitatively differs from that seen with traditional cytotoxic chemotherapy, while the underlying mechanisms are complex and still to be clearly defined. Nephrologists need to be knowledgeable about the array of such renal toxicities for effective collaboration with the oncologist in the prevention and management of kidney involvement. Renal adverse effects may range from asymptomatic proteinuria to renal failure, and their prompt identification and timely treatment is essential for optimal and safe care of the patient. In this article, after presenting clinical cases we discuss the differing renal toxicity of three novel anticancer agents (aflibercept, dasatinib, and nivolumab) and possible measures to counter it.</jats:p>

Exploiting senescence for the treatment of cancer

“…This study also showed that dasatinib, a multityrosine kinase inhibitor that targets, amongst others, the SRC kinase and PI3K-AKT signalling nodes, can kill senescent cells. Quercetin, a natural flavonoid, also has senolytic activity 183,200,201 . It is not clear how exactly quercetin induces senolysis, but it has been reported that it interferes with the anti apoptotic protein BCL XL through inhibition of upstream pathways including PI3K.…”

Nephrotoxicity of Anti-Angiogenic Therapies

“…To date, there is no predictive biomarker of kidney dysfunction for patients receiving these treatments. Creating a database registry for anti-angiogenic therapies and their renal adverse effects could be very helpful [ 169 ]. In the KDIGO (Kidney Disease Improving Global Outcomes) Controversies Conference on onco-nephrology, for patients with CKD, TKIs may be used at a lower-than-standard dose and increased secondarily according to individual tolerability and response [ 160 ].…”

Nephrotoxicity induced by vascular endothelial growth factor inhibitors

“…In addition, the VEGF pathway's inhibition can result in hypertension by microvascular rarefaction, and consequently, cause an increase in peripheral resistance, fibrosis, and deficit of podocytes (21). Increased oxidative stress can cause endothelial damage and hypertension, while VEGF prevents the endothelial damage induced by oxidative stress (22).…”