Anti VEGF che moagents, such as bevacizumab and sorafenib, can cause TMA by direct microvascular toxicity initiated by endo thelial injury. Bortezomib can also inhibit IL 6 induced Ceritinib molecular weight proliferation and angiogenesis and enhance the release of pro inflammatory cytokines and generation of cell mediated immune response. In addition, it has been shown that VEGF, acting through VEGFR 2, activates endothelial nitric oxide syn thase activity, leading to increased vasodilatory nitric oxide production. Anti VEGF therapies might cause systemic deficiency of nitric oxide with consequent hypertension. Therefore, it has been speculated that the mechanism by which proteasome inhibitors may induce TMA also involve modulation of VEGF.

Notably, although bortezomib is being increasingly used to treat antibody mediated rejection in organ transplant ation, no reports of associated TMA have emerged to date. Therefore, the strength of the association requires further validation. Carfilzomib is a tetrapeptide epoxyketone proteasome inhibitor. In preclinical studies, carfilzomib showed greater selectivity than bortezomib for the proteasome and had anti proliferative activity in cells resistant to bortezomib. In view of the previously reported asso ciation of bortezomib with TMA, we speculate that carfilzomib could have been involved in the patho genesis of renal TMA in our case. In contrast to previ ous reports of proteasome inhibitor associated TMA, our case describes a patient who presented with overt proteinuria and worsening hypertension but with out extrarenal features of microangiopathic hemolytic anemia, i.

e, renal limited TMA. Undoubtedly, it could be argued that the long standing history of essential hypertension could be responsible of some of the histo logical findings in the kidney biopsy specimen knowing that the renal TMA lesion in our patient is similar to that of malignant hypertension. Nonetheless, we hypothesize that the abruptness of the clinical presentation may reflect the onset of a mechanism of injury induced by carfilzo mib, triggering malignant hypertension in a patient who was perhaps at high risk of developing it due to his under lying essential hypertension. Conclusions In summary, we suggest that clinicians should be aware of the possibility of an association between exposure to carfilzomib and the development of a clinical syndrome characterized by worsening proteinuria and uncontrolled HTN and pathological evidence of renal TMA.

Discon tinuation of the drug should be considered only after careful evaluation of risks and benefits of the chemo therapy and the prognosis of the existing malignancy. Consent Informed consent was obtained from the next of kin for publication of this case. Background Intrahepatic selleck chemicals Pazopanib Cholangiocarcinoma is the second most common subtype of primary hepatobiliary cancer.