Age-related renal microvascular changes: Evaluation by three-dimensional digital imaging of the human renal microcirculation using virtual microscopy

Abstract

The renal microvasculature is targeted during aging, sometimes producing chronic kidney disease (CKD). Overdiagnosis of CKD in older persons is concerning. To prevent it, a new concept of “healthy aging” is arising from a healthy renal donor study. We investigated the renal microcirculatory changes of three older persons and compared them with that of one patient with nephrosclerosis using a three-dimensional (3D) reconstruction technique that we previously developed. This method uses a virtual slide system and paraffin-embedded serial sections of surgical material that was double-immunostained by anti-CD34 and anti-α smooth muscle actin (SMA) antibodies for detecting endothelial cells and medial smooth muscle cells, respectively. In all cases, the 3D images proved that arteriosclerotic changes in large proximal interlobular arteries did not directly induce distal arterial change or glomerulosclerosis. The nephrosclerotic patient showed severe hyalinosis with luminal narrowing of small arteries directly inducing glomerulosclerosis. We also visualized an atubular glomerulus and intraglomerular dilatation of an afferent arteriole during healthy aging on the 3D image and showed that microcirculatory changes were responsible for them. Thus, we successfully visualized healthy aged kidneys on 3D images and confirmed the underlying pathology. This method has the ability to investigate renal microcirculatory damage during healthy aging.