Axitinib
Tyrosine kinase inhibitors
MECHANISM OF ACTION
Second generation TKI blocking VEGF receptor (VEGF receptor TKI)
MECHANISM OF KIDNEY INJURY
AIN (Acute interstitial nephritis), TMA (thrombotic microangiopathy) (systemic/kidney limited). HTN; vascular endothelial growth factor (VEGF) signaling pathway inhibition . Reduction of vasodilator production such as NO and enhance production of vasoconstriction such as endothelin 1
CLINICAL KIDNEY SYNDROME
AKI, Proteinuria/Albuminuria, Nephrotic syndrome, Hematuria, Hypertension, BLE edema, Anasarca.
HTN; variable; up to 81% of patients with all grade HTN and up to36% of patients experienced severe (grade 3) hypertension
CARDIOVASCULAR ADVERSE EFFECTS
Hypertension, CHF, possible increase in MACE
LYTE ABNORMALITIES
Hypoalbuminemia
RISK FACTORS
MITIGATION STRATEGIES
n/a
SUGGESTIONS
Hold offending drug and rechallenge after AKI/proteinuria resolves, Discontinue offending drug, Add ACEi/ARB, Check GN work up (ANA, ANCA, DsDNA, SPEP with FLC, Hep B sero, Hep C sero, HIV, C3, C4, anti-GBM, cryoglobulins), Check TMA work up (send haptoglobin, peripheral smear, LDH), If nephrotic proteinuria or TMA, discontinue.
NOTES/COMMENTS
PHARMACOKINETICS
Molecular Weight
Volume of Distribution
Plasma Protein Binding
Metabolism
Bioavailability
Half-life elimination
Time to peak
Excretion
Dialyzable?
No
REF:
https://doi.org/10.1053/j.ajkd.2015.02.340
PMID: 29318210
PATHOLOGY SLIDES:
ENTRY UPDATES:
Raad Chowdhury
MN/USA
Sep 25, 2022