Biopsy-proven kidney-limited thrombotic microangiopathy associated with bevacizumab and pegylated liposomal doxorubicin: a case with a biphasic clinical course.

Drug-induced thrombotic microangiopathy (TMA) is an important cause of kidney injury in patients receiving anticancer therapy, although kidney-limited forms without systemic manifestations are often difficult to recognize. Pegylated liposomal doxorubicin (PLD)-associated TMA remains under-recognized, particularly in patients receiving concomitant vascular endothelial growth factor (VEGF) inhibitors. We report a case of biopsy-proven kidney-limited TMA associated with bevacizumab and PLD in a 52-year-old woman with metastatic ovarian serous adenocarcinoma, characterized by a biphasic clinical course. She developed progressive kidney dysfunction and proteinuria during treatment with bevacizumab followed by PLD. Despite discontinuation of bevacizumab, kidney dysfunction persisted. Kidney biopsy demonstrated findings consistent with TMA, including mesangiolysis, glomerular basement membrane duplication, and focal PAS-positive pseudothrombi suggestive of VEGF inhibitor-associated endothelial injury. Electron microscopy further revealed endothelial detachment, accompanied by a substance containing liposome-like particles, suggestive of the characteristic ultrastructural findings previously reported in PLD-associated TMA. The patient had no evidence of microangiopathic hemolytic anemia or thrombocytopenia, and no alternative cause of TMA was identified. Following discontinuation of PLD, kidney function improved markedly with complete resolution of proteinuria. This case highlights the importance of kidney biopsy and careful clinicopathological correlation in diagnosing drug-induced kidney-limited TMA.
Cancer
Care/Management

Authors

Chigusa Chigusa, Azegami Azegami, Nakayama Nakayama, Yoshimoto Yoshimoto, Hishikawa Hishikawa, Hagiwara Hagiwara, Hashiguchi Hashiguchi, Hayashi Hayashi
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