Abstract
Chronic kidney disease (CKD) is a substantial global health problem with devastating impacts on patients' morbidity and mortality. Kidney fibrosis, specifically tubulointerstitial fibrosis, is considered the final common pathway in the progression of virtually all forms of CKD. Peritubular capillary rarefaction, which refers to a decrease in peritubular capillary density leading to hypoxic and ischemic conditions, has long been recognized as a hallmark pathologic feature of tubulointerstitial fibrosis and a pivotal biological alteration leading to CKD progression. Conversely, recent literature has challenged this paradigm by proposing that tubulointerstitial fibrosis and CKD progression are closely associated with the upregulation of proangiogenic pathways. As such, peritubular capillary rarefaction may be a consequence rather than a cause of tubulointerstitial fibrosis. Furthermore, a growing body of evidence suggests that the microenvironment of the kidney vasculature, which may be referred to as the vascular niche, is a dynamic entity that regulates vascular homeostasis, key molecular signaling pathways, and inflammation. In this review, we detail how the vascular niche may modify the course of various kidney diseases by influencing cell differentiation and the immune response. Understanding the complex interplay between the cellular and molecular components of the vascular niche may eventually lead to the identification of novel therapeutic targets to limit tubulointerstitial fibrosis and halt CKD progression. This could potentially involve modulating the secretion of angiocrine factors, regulating immune cell activity within the vascular niche, or interfering with the transformation of endothelial cells and pericytes into myofibroblasts, which are key players in kidney fibrogenesis.