Nintedanib-Induced Renal Thrombotic Microangiopathy

• Published in: Case reports in nephrology and dialysis Vol. 11; no. 2; pp. 227 - 232
• Main Authors: Fujita, Takeshi, Nakagawa, Hideyuki, Yokota, Takashi, Umetani, Jun, Nagawa, Daiki, Nakata, Masamichi, Narita-Kinjo, Ikuyo, Murakami, Reiichi, Shimada, Michiko, Nakamura, Norio, Tomita, Hirofumi
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 22.07.2021; Karger Publishers
• Subjects: Anorexia; Antibodies; Blood pressure; Cancer therapies; Case reports; Creatinine; Diarrhea; Drug dosages; drug-induced kidney injury; Fibroblasts; Hypertension; idiopathic pulmonary fibrosis; Kidney diseases; Laboratories; Microscopy; nephrotic syndrome; nintedanib; Patients; Proteins; proteinuria; Pulmonary fibrosis; Single Case; Supervision; thrombotic microangiopathy; tyrosine kinase inhibitor; Urine; Vascular endothelial growth factor; Thrombotic microangiopathy; Tyrosine kinase inhibitor; Idiopathic pulmonary fibrosis; Drug-induced kidney injury; Nintedanib; Nephrotic syndrome; Proteinuria
• ISSN: 2296-9705; 2296-9705
• DOI: 10.1159/000517692

Abstract Nintedanib is a unique tyrosine kinase inhibitor used to suppress fibrosis in patients with idiopathic pulmonary fibrosis (IPF). Nintedanib has been shown to suppress multiple processes of fibrosis, thereby reducing the rate of lung function decline in patients with IPF. Since vascular endothelial growth factor is one of this agent’s targets, nephrotoxicity, including renal thrombotic microangiopathy (TMA), is a possible major adverse effect. However, only 2 previous cases of nintedanib-induced renal TMA have been published. Our patient was an 83-year-old man with IPF. As adverse effects including liver enzyme level elevation, diarrhoea, anorexia, and nephrotoxicity developed, the nintedanib dosage was reduced after 9 months. The digestive symptoms resolved promptly, but the proteinuria and reduced kidney function remained. Although the kidney injury had improved to some extent, we performed a percutaneous renal biopsy. The biopsy revealed typical TMA findings such as microaneurysms filled with pale material, segmental double contours of glomerular basement membranes, and intracapillary foam cells. After discontinuation of nintedanib, the patient’s nephrotoxicity improved. Nintedanib-induced renal TMA is reversible and is possibly dose-dependent. Here, we report the clinical course of our case and review the characteristics of nintedanib-induced renal TMA.