Commonly reported kidney toxicities associated with targeted therapies

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 AGENTMECHANISM OF ACTION OF THE TARGETED THERAPYREPORTED NEPHROTOXICITIES
BevacizumabVEGF inhibitorHTN, proteinuria, nephrotic syndrome, pre-eclampsia like syndrome, kidney limited TMA
AfliberceptVEGF inhibitorHTN, proteinuria
SunitinibMulti-kinase TKIHTN, proteinuria, MCD/FSGS, AIN, Chronic interstitial nephritis
PazopanibMulti-kinase TKIHTN, proteinuria
AxitinibMulti-kinase TKIHTN, proteinuria
SorafenibMulti-kinase TKIHTN, proteinuria, MCD/FSGS, AIN, chronic interstitial nephritis, hypophosphatemia
ImatinibCellular TKI(BCR-ABL)ATN, HTN, hypocalcemia, hypophosphatemia
DasatinibMulti-kinase TKIProteinuria
NilotinibMulti-kinase TKIHTN
PonatinibMulti-kinase TKIHTN
CetuximabEGFR inhibitorHypomagnesaemia, Hypokalemia, AKI, Hyponatremia, glomerulonephritis
PanitumumabEGFR inhibitorHypomagnesaemia, AKI, Hypokalemia
ErlotinibEGFR inhibitorAKI, Hypomagnesaemia
AfatinibEGFR inhibitorAKI, Hyponatremia
GefitinibEGFR inhibitorAKI, hypokalemia, fluid retention, minimal change disease, proteinuria
VemurafenibB-RAF inhibitorAIN, ATN, hypophosphatemia, Fanconi syndrome
DabrafenibB-RAF InhibitorAIN, ATN, hypophosphatemia
CrizotinibALK inhibitorATN, kidney cysts
IpilumumabCTLA-4 inhibitorAIN, MN, MCD, hyponatremia, TMA
NivolumabPD-1 InhibitorAIN
PembrolizumabPD-1 InhibitorAIN
TemsirolimusmTOR inhibitorATN, FSGS
CarfilzomibProteasome inhibitorPrerenal, ATN, TMA
BortezomibProteasome inhibitorTMA
LenalidomideImmunomodulatorsFanconi syndrome, AIN, MCD
TrametinibMEK inhibitorAKI

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.

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