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. 

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