Peritubular capillary rarefaction: a new therapeutic target in chronic kidney disease

Chronic kidney disease (CKD) has reached worldwide epidemic proportions and desperately needs new therapies. Peritubular capillary (PTC) rarefaction, together with interstitial fibrosis and tubular atrophy, is one of the major hallmarks of CKD and predicts renal outcome in patients with CKD. PTC endothelial cells (ECs) undergo apoptosis during CKD, leading to capillary loss, tissue hypoxia, and oxidative stress. Although the mechanisms of PTC rarefaction are not well understood, the process of PTC rarefaction depends on multiple events that occur during CKD. These events, which lead to an antiangiogenic environment, include deprivation of EC survival factors, increased production of vascular growth inhibitors, malfunction of ECs, dysfunction of endothelial progenitor cells, and loss of EC integrity via pericyte detachment from the vasculature. In this review, we focus on major factors regulating angiogenesis and EC survival and describe the roles of these factors in PTC rarefaction during CKD and possible therapeutic applications.