Thrombotic microangiopathy associated with proteasome inhibitors

The ubiquitin proteasome pathway plays a key role in cell cycle, function and survival. Bortezomib (BTZ) and Carfilzomib (CFZ) are the first two inhibitors of the proteasome pathway, indicated in treatment of patients with multiple myeloma. In the past few years, there have been few case reports that have highlighted the association between proteasome inhibitors (BTZ and CFZ) with acute kidney injury (AKI). In most of these case reports and initial trials, the underlying mechanism of AKI has been unclear. In this article, we discuss the association and pathogenesis of proteasome inhibitors-associated AKI. We also report the first case of CFZ-associated AKI with kidney biopsy evidence of thrombotic microangiopathy and the presence of microangiopathic hemolytic anemia.