Clinicopathological Study on Endothelial Injury in Severe Glomerular Microangiopathy Induced by Ramucirumab

A patient with advanced colon cancer treated with ramucirumab, an anti-vascular endothelial growth factor receptor-2 agent developed nephrotic-range proteinuria and hypertension. A renal biopsy revealed hyaline occlusive glomerular microangiopathy with macrophage infiltration and focal podocyte swelling with hyperplasia. Furthermore, a circular fibrocellular crescent formation was observed. Anti-CD34 immunostaining indicated severe endothelial injury. Circulating syndecan-1, which is derived from the glycocalyx covering the endothelium, was moderately increased, similar to the plasma D-dimer level, but not as high as that in systemic endotheliopathy. This case suggests that severe kidney-specific endothelial injury may be responsible for the development of a unique extracapillary glomerulopathy as a side effect of ramucirumab.