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What are the commonly reported kidney toxicities associated with targeted therapies?
In the past decade, advances in cell biology have led to the development of anti-cancer agents that target specific molecular pathways.
The National Cancer Institute defines targeted therapies as “drugs or substances that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression.”
Targeted therapies are now commonly used in cancer treatment, and it is vital that their kidney toxicities be recognized and investigated.
Kidney adverse effects of targeted therapies occur through several complex mechanisms.
Early reports suggested that targeted therapies were associated with a range of toxicities from hypertension to AKI.
The below table summarizes the kidney effects of targeted therapies.
Kidney Known Side Effects of Various Targeted Therapies
NAME OF AGENT | MECHANISM OF ACTION OF THE TARGETED THERAPY | REPORTED NEPHROTOXICITIES |
---|---|---|
Bevacizumab | VEGF inhibitor | HTN, proteinuria, nephrotic syndrome, pre-eclampsia like syndrome, kidney limited TMA |
Aflibercept | VEGF inhibitor | HTN, proteinuria |
Sunitinib | Multi-kinase TKI | HTN, proteinuria, MCD/FSGS, AIN, Chronic interstitial nephritis |
Pazopanib | Multi-kinase TKI | HTN, proteinuria |
Axitinib | Multi-kinase TKI | HTN, proteinuria |
Sorafenib | Multi-kinase TKI | HTN, proteinuria, MCD/FSGS, AIN, chronic interstitial nephritis, hypophosphatemia |
Imatinib | Cellular TKI(BCR-ABL) | ATN, HTN, hypocalcemia, hypophosphatemia |
Dasatinib | Multi-kinase TKI | Proteinuria |
Nilotinib | Multi-kinase TKI | HTN |
Ponatinib | Multi-kinase TKI | HTN |
Cetuximab | EGFR inhibitor | Hypomagnesaemia, Hypokalemia, AKI, Hyponatremia, glomerulonephritis |
Panitumumab | EGFR inhibitor | Hypomagnesaemia, AKI, Hypokalemia |
Erlotinib | EGFR inhibitor | AKI, Hypomagnesaemia |
Afatinib | EGFR inhibitor | AKI, Hyponatremia |
Gefitinib | EGFR inhibitor | AKI, hypokalemia, fluid retention, minimal change disease, proteinuria |
Vemurafenib | B-RAF inhibitor | AIN, ATN, hypophosphatemia, Fanconi syndrome |
Dabrafenib | B-RAF Inhibitor | AIN, ATN, hypophosphatemia |
Crizotinib | ALK inhibitor | ATN, kidney cysts |
Ipilumumab | CTLA-4 inhibitor | AIN, MN, MCD, hyponatremia, TMA |
Nivolumab | PD-1 Inhibitor | AIN |
Pembrolizumab | PD-1 Inhibitor | AIN |
Temsirolimus | mTOR inhibitor | ATN, FSGS |
Carfilzomib | Proteasome inhibitor | Prerenal, ATN, TMA |
Bortezomib | Proteasome inhibitor | TMA |
Lenalidomide | Immunomodulators | Fanconi syndrome, AIN, MCD |
Trametinib | MEK inhibitor | AKI |
AIN , Acute interstitial nephritis; AKI , acute kidney injury; ALK , Anaplastic lymphoma kinase; ATN , acute tubular necrosis; BCR-ABL , breakpoint cluster region-abelson; BRAF , B-Raf proto-oncogene serine/threonine-protein kinase; CTLA-4 , cytotoxic T lymphocyte antigen-4; EGFR , epidermal growth factor receptor; FSGS , focal segmental glomerulosclerosis; HTN , hypertension; MCD , minimal change disease; MEK , mitogen-activated protein kinase; MN , membranous nephropathy; mTOR , mechanistic target of rapamycin (also known as the mammalian target of rapamycin); PD , programmed cell death; TKI , tyrosine kinase inhibitor; TMA , thrombotic microangiopathy; VEGF , vascular endothelial growth factor.