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Wednesday, April 23, 2014

Carfilzomib induced renal injury: mechanism of action?

Multiple myeloma is the second most common type of hematologic malignancy. 

Carfilzomib is a second-generation epoxyketone proteasome inhibitor that is approved for treatment of relapsed and refractory multiple myeloma. Phase 2 trials have reported that 25% of treated patients have renal adverse effects. Pre-renal/vasoconstriction-related insult from this chemotherapy agent has been documented.

Recently, even a case of tumor lysis syndrome has been reported with this agent. According to the product labeling, the frequency of tumor lysis syndrome (TLS) is less than 1% in patients treated with carfilzomib. Is it possible then to prevent AKI via pre treatment with allopurinol and or rasburicase?

Also being presented at NKF 2014 e poster and a recent publication is the use of N-acetyl-l-cysteine to partially mitigated the renal injury upon re-challenge in case of carfilzomib related AKI. This case report hypothesizes that acute renal injury from carfilzomib is caused by vasoconstriction of the renal vessels, which may be prevented by N-acetyl-l-cysteine.


More can be learned about the mechanism of renal injury if biopsy proven cases are published. Thus far no biopsy proven AKI cases have been reported in the literature. 

image source: www.cancer.gov

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