Assessment of Endothelial and Microvascular Function in CKD: Older and Newer Techniques, Associated Risk Factors, and Relations with Outcomes

Abstract

<b><i>Background:</i></b> Endothelium is the inner cellular lining of the vessels that modulates multiple biological processes including vasomotor tone, permeability, inflammatory responses, hemostasis, and angiogenesis. Endothelial dysfunction, the basis of atherosclerosis, is characterized by an imbalance between endothelium-derived relaxing factors and endothelium-derived contracting factors. <b><i>Summary:</i></b> Starting from the semi-invasive venous occlusion plethysmography, several functional techniques have been developed to evaluate microvascular function and subsequently used in patients with CKD. Flow-mediated dilatation of the forearm is considered to be the “gold standard,” while in the last years, novel, noninvasive methods such as laser speckle contrast imaging and near-infrared spectroscopy are scarcely used. Moreover, several circulating biomarkers of endothelial function have been used in studies in CKD patients. This review summarizes available functional methods and biochemical markers for the assessment of endothelial and microvascular function in CKD and discusses existing evidence on their associations with comorbid conditions and outcomes in this population. <b><i>Key Messages:</i></b> Accumulated evidence suggests that endothelial dysfunction occurs early in CKD and is associated with target organ damage, progression of renal injury, cardiovascular events, and mortality. Novel methods evaluating microvascular function can offer a detailed, real-time assessment of underlying phenomena and should be increasingly used to shed more light on the role of endothelial dysfunction on cardiovascular and renal disease progression in CKD.

Endothelial dysfunction in COPD: a systematic review and meta-analysis of studies using different functional assessment methods

“…), whereas increased sympathetic tone (which is common among patients with COPD) has been suggested to impact the PAT signal [ 59 ]. More recent technologies evaluating skin or sublingual microcirculation are promising, as they are noninvasive and can be combined with several reactivity tests or exercise; however, only a few studies examined their correlations with coronary endothelial function and adverse outcomes [ 14 ]. In addition, it should be noted that all the aforementioned techniques require patient preparation (abstinence from smoking, caffeine, etc .)…”

“…Endothelial dysfunction, defined as a state of imbalance between endothelium-derived relaxing and contracting factors, is the earliest stage of atherosclerosis [ 14 ]. Starting from the very invasive method of the epicardial coronary angiography after intracoronary infusion of vasoactive drugs, several less invasive functional techniques ( i.e.…”

“…asymmetric dimethylarginine, endothelial microparticles, inflammation markers, etc .) have been used to evaluate peripheral endothelial function in individuals with high cardiovascular risk [ 14 ]. Despite the fact that all these techniques have boosted the research in this field, none of them has been established as a diagnostic tool for cardiovascular events prediction in daily clinical practice so far [ 15 ].…”

Is renal impairment predictor of future diabetic peripheral neuropathy? A 6-year follow-up cohort study

“…To date, the mechanisms of neurotoxicity in T2DM patients with renal impairment remains unclear, but they have been demonstrated in some studies [24,25]. Experimental evidence indicates that alterations in membrane excitability is induced by inhibition of the axonal Na + /K + pump, which abolishes the direct contribution of the hyperpolarizing pump current to the membrane potential, leading to an accumulation of extracellular K + that causes depolarization [26].…”

“…In addition, it is clear from previous research that impaired renal function results in microvascular endothelial dysfunction, even in the early stages of chronic kidney disease. Endothelial injury is caused by various factors, including in ammation, hypertension, diabetes-associated factors, and a uremic milieu [25,28]. Eventually, it leads to neuropathy due to impaired nerve blood ow, epineurial arteriovenous shunting, and reduced nerve oxygen tension [29].…”