The renal microcirculation in chronic kidney disease: novel diagnostic methods and therapeutic perspectives

Abstract

Chronic kidney disease (CKD) affects 8–16% of the population worldwide and is characterized by fibrotic processes. Understanding the cellular and molecular mechanisms underpinning renal fibrosis is critical to the development of new therapeutics. Microvascular injury is considered an important contributor to renal progressive diseases. Vascular endothelium plays a significant role in responding to physical and chemical signals by generating factors that help maintain normal vascular tone, inhibit leukocyte adhesion and platelet aggregation, and suppress smooth muscle cell proliferation. Loss of the rich capillary network results in endothelial dysfunction, hypoxia, and inflammatory and oxidative effects and further leads to the imbalance of pro- and antiangiogenic factors, endothelial cell apoptosis and endothelial-mesenchymal transition. New techniques, including both invasive and noninvasive techniques, offer multiple methods to observe and monitor renal microcirculation and guide targeted therapeutic strategies. A better understanding of the role of endothelium in CKD will help in the development of effective interventions for renal microcirculation improvement. This review focuses on the role of microvascular injury in CKD, the methods to detect microvessels and the novel treatments to ameliorate renal fibrosis.

Applications and Mechanisms of Tripterygium Wilfordii Hook. F. and its Preparations in Kidney Diseases

“…Oxidative stress is an important factor in inducing the progression of kidney diseases ( Coppolino et al, 2018 ). It has been proven that oxidative stress can damage kidneys via increasing the synthesis of NADPH oxidases ( Nlandu Khodo et al, 2012 ), regulating kelch-like ECH-associated protein1- (KEAP1-) nuclear factor erythroid 2-related factor 2 (NRF2) ( Nezu et al, 2017 ), promoting endothelial mesenchymal (EnMT) ( Li S. et al, 2021 ) and disrupting the balance with autophagy ( Sureshbabu et al, 2015 ). Podocyte injury ( Nagata, 2016 ), renal tubular fibrosis ( Duni et al, 2019 ), CKD ( Coppolino et al, 2018 ) and acute kidney injury ( Sureshbabu et al, 2015 ) are all related to oxidative stress.…”

Augmented Renal Clearance: What Have We Known and What Will We Do?

“…Considering the mechanism of ARC is unclear till now, animal models based on the risk factors of ARC, including sepsissubarachnoid hemorrhage, burns, and high RFR or modeled by injection of amino acids to stimulate the disease state and augmented GFR ( Ge et al, 2019 ; Lagier et al, 2019 ; Hu et al, 2020 ) may be better research method to explore ARC mechanism. Moreover, in the following research, in vivo and in vitro models such as isolated kidney perfusion, transporter knockout mice for transport system studies on drugs with different excretion mechanisms ( Higgins et al, 2012 ; Ma et al, 2018 ) and invasive or noninvasive techniques such as synchrotron radiation, fluorescence microangiography methods, and intravital multiphoton microscopy for renal micro-circulation assessment ( Li et al, 2021 ), will help us explore the mechanism and deeply understand the occurrence and development process of ARC.…”

Assessment of microcirculatory function during hemodialysis

“…Hemodialysis adds additional insult, perpetuating the degradation of the vasculature [2 ▪ ,4 ▪▪ ,6,7], with further reductions to microcirculatory blood flow and oxygenation, largely (but not exclusively) because of ultrafiltration and blood volume changes [13]. The repetitive insults of intermitted hemodialysis results in cumulative damage and ischemic–reperfusion injury heightening mortality for this vulnerable population [9,11,14–19].…”