Abstract P431: Renal Artery Stenosis Caused by a Bcr-Abl Tyrosine Kinase Inhibitor: Blood Pressure Response to Revascularization

Abstract

Introduction: Bcr-Abl tyrosine kinase inhibitors (TKI) are first line agents for management of chronic myelogenous leukemia (CML). Amongst the second generation TKIs, which have less resistance and improved side effect profile, nilotinib and ponatinib have also been reported to be associated with vascular adverse events (VAEs), including systemic and peripheral arterial stenosis. We report on a patient with CML treated with ponatinib, who developed bilateral renal artery stenoses, difficult to control hypertension, and responded to revascularization. Case: A 55 year old man, with CML due to a Bcr-Abl truncating mutation diagnosed in 2007, was treated with ponatinib 45 mg daily starting in 2011, which induced a complete remission. He subsequently developed hypertension. Hypertension appeared angiotensin II-dependent as BP normalized on combination of candesartan 32 mg once daily and hydrochlorothiazide 25 mg once daily. This treatment was however associated with an increase in serum creatinine from 1.4 to 2.6 mg/dL. Consistent with our clinical suspicion, a computed tomography angiogram revealed bilateral renal artery stenosis. He eventually required bilateral renal artery angioplasty and stenting as the BP could not be controlled without renin-angiotensin system blockers despite using up 5 classes of BP lowering drugs. Furthermore, follow up imaging of renal arteries showed progressive renal artery stenosis bilaterally. He underwent angioplasty and stenting in the left renal artery and angioplasty of both the branches of the right main renal artery, which could not be stented because of the early branching. After 6 months, BP is within target with 8 mg candesartan, amlodipine 10 mg and bisoprolol 2.5 mg daily, and the renal function is stable (creatinine 1.1 mg/dL). Overall, in this case, renal artery angioplasty and stenting stabilized renal function and improved control of hypertension. Discussion: Second generation TKIs are associated with VAEs, including renal artery stenosis. Renal artery angioplasty and stenting stabilized renal function and improved control of hypertension in this case. Future research should clarify the mechanisms of VAEs with TKIs, natural history, and long term response to revascularization in this setting.