Peritubular Capillary Rarefaction: An Underappreciated Regulator of CKD Progression

Abstract

Peritubular capillary (PTC) rarefaction is commonly detected in chronic kidney disease (CKD) such as hypertensive nephrosclerosis and diabetic nephropathy. Moreover, PTC rarefaction prominently correlates with impaired kidney function and predicts the future development of end-stage renal disease in patients with CKD. However, it is still underappreciated that PTC rarefaction is a pivotal regulator of CKD progression, primarily because the molecular mechanisms of PTC rarefaction have not been well-elucidated. In addition to the established mechanisms (reduced proangiogenic factors and increased anti-angiogenic factors), recent studies discovered significant contribution of the following elements to PTC loss: (1) prompt susceptibility of PTC to injury, (2) impaired proliferation of PTC, (3) apoptosis/senescence of PTC, and (4) pericyte detachment from PTC. Mainly based on the recent and novel findings in basic research and clinical study, this review describes the roles of the above-mentioned elements in PTC loss and focuses on the major factors regulating PTC angiogenesis, the assessment of PTC rarefaction and its surrogate markers, and an overview of the possible therapeutic agents to mitigate PTC rarefaction during CKD progression. PTC rarefaction is not only a prominent histological characteristic of CKD but also a central driving force of CKD progression.

Evaluation of renal fibrosis in patients with chronic kidney disease by shear wave elastography: a comparative analysis with pathological findings

“…Our results showed a trend of reduction in SWE values across the elevated grade of vessel wall thickening, which meant the more severe the arteriole stenosis in cases, the less stiff the kidney. The change in renal microvascular perfusion is the principal process underlying CKD progression, as well as renal fibrosis [26]. During the pathological process of renal fibrosis, renal microvascular changes such as intimal proliferation and medial thickening result in the reduction of luminal diameter, which in turn causes an increased resistance to flow and a decline in renal perfusion [27].…”

Acute kidney injury leading to CKD is associated with a persistence of metabolic dysfunction and hypertriglyceridemia

“…Alongside this, the pericytes that normally maintain vascular integrity migrate into the renal interstitium and become myofibroblasts, contributing to the progression of the fibrotic process. Migration of pericytes away from the vasculature results in vascular rarefaction, which is a hallmark of progressive CKD ( Kida, 2020 ).…”

Genetic Kidney Diseases (GKDs) Modeling Using Genome Editing Technologies

“…This filtration takes place in the glomerulus (specifically in the glomerular filtration membrane-GFM) of each nephron [166]. Blood, via the afferent arteriole, reaches the glomerulus, where molecules with a weight greater than 50 kDa and a size greater than 10 nm are excluded [166][167][168]. Blood is drained from the glomerulus through the efferent arteriole that branches forming the peritubular capillaries (PTCs), which extend along the PT and DCT, producing the exchange of substances.…”

“…Blood is drained from the glomerulus through the efferent arteriole that branches forming the peritubular capillaries (PTCs), which extend along the PT and DCT, producing the exchange of substances. Finally, the PTCs flow into arcuate vein and the blood leaves the kidney through the renal vein [167].…”