増田 貴博

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.

The primary treatment goal of chronic kidney disease (CKD) is preserving renal function and preventing its progression to end-stage renal disease. Glomerular hypertension and tubular hypoxia are critical risk factors in CKD progression. However, the renal hemodynamics make it difficult to avoid both factors due to the existence of peritubular capillaries that supply oxygen to the renal tubules downstream from the glomerulus through the efferent arteriole. In the treatment strategies for balancing glomerular pressure and tubular oxygen supply, afferent and efferent arterioles of the glomerulus determine glomerular filtration rate and blood flow to the peritubular capillaries. Therefore, sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors as well as classical renin-angiotensin system inhibitors, which can change the diameter of afferent and/or efferent arterioles, are promising options for balancing this dual target and achieving renal protection. This review focuses on the clinical importance of glomerular pressure and tubular oxygen supply and proposes an effective treatment modality for this dual target.