Nintedanib-Induced Renal Thrombotic Microangiopathy

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.

Keywords: Drug-induced kidney injury; Idiopathic pulmonary fibrosis; Nephrotic syndrome; Nintedanib; Proteinuria; Thrombotic microangiopathy; Tyrosine kinase inhibitor.

Fig. 1

Clinical course of the present case regarding urine protein, serum Cr, and serum albumin levels. Cr, creatinine.

Fig. 2

The pathological features of nintedanib-induced glomerular thrombotic angiopathy. a Light microscopy with periodic acid-Schiff staining shows typical microaneurysms filled with pale material (black arrows), segmental double contours of glomerular basement membranes (white arrow), and intracapillary foam cells (asterisks) (original magnification ×400). b Electron microscopy shows microaneurysmal dilatation of a capillary loop with marked widening of the subendothelial spaces (arrows) (original magnification ×1,500).