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Background and Hypothesis: Carfilzomib, a new proteasome inhibitor indicated for patients with relapsed/refractory myeloma, has been associated with cases of thrombotic microangiopathy (CFZ-TMA). The role of variants in the complement alternative pathway and therapeutic potential of complement blockade with eculizumab remain to be determined., Methods: We report 37 cases of CFZ-TMA recorded in the French reference center for TMA with their clinical characteristics, genetic analysis and outcome according to treatments., Results: A trigger was identified in more than half of cases, including 8 influenza and 5 SARS-CoV-2 cases. All patients presented with acute kidney injury (AKI) (KDIGO stage 3 in 31 (84%) patients) while neurological (n=13, 36%) and cardiac damage (n=7, 19%) were less frequent. ADAMTS13 and complement activity were normal (n= 28 and 18 patients tested) and no pathogenic variant in the alternative complement pathway was found in 7 patients tested.TMA resolved in most (n=34, 94%) patients but 12 (44%) still displayed stage 3 AKI at discharge. Nineteen (51%) patients were treated with therapeutic plasma exchange, 14 (38%) patients received corticosteroids and 18 (50%) were treated with eculizumab. However none of these treatments demonstrated a significant impact on outcomes., Conclusion: This study is the largest case series of CFZ-TMA since its approval in 2012. Patients present with severe AKI and experience frequent sequelae. Complement variants and blockade therapy do not seem to play a role in the pathophysiology and prognosis of the disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Deferasirox is the first oral iron chelator and, as such, is widely used for the treatment of chronic iron overload. However, recent data from large studies confirmed the renal toxicity of deferasirox. We report a case of Fanconi syndrome associated with acute renal failure in a patient receiving deferasirox. In particular, new insights regarding the pathophysiology of the renal disease due to this treatment are discussed. This case highlights the importance of a careful monitoring of kidney function, markers of proximal tubulopathy and ferritinaemia in patients receiving deferasirox.