The systemic microcirculation in dialysis populations

Abstract

In a rapidly expanding population of patients with chronic kidney disease, including 2 million people requiring renal replacement therapy, cardiovascular mortality is 15 times greater than the general population. In addition to traditional cardiovascular risk factors, more poorly defined risks related to uremia and its treatments appear to contribute to this exaggerated risk. In this context, the microcirculation may play an important early role in cardiovascular disease associated with chronic kidney disease. Experimentally, the uremic environment and dialysis have been linked to multiple pathways causing microvascular dysfunction. Coronary microvascular dysfunction is reflected in remote and more easily studied vascular beds such as the skin. There is increasing evidence for a correlation between systemic microvascular dysfunction and adverse cardiovascular outcomes. Systemic microcirculatory changes have not been extensively investigated across the spectrum of chronic kidney disease. Recent advances in non‐invasive techniques studying the microcirculation in vivo in man are increasing the data available particularly in patients on hemodialysis. Here, we review current knowledge of the systemic microcirculation in dialysis populations, explore whether non‐invasive techniques to study its function could be used to detect early stage cardiovascular disease, address challenges faced in studying this patient cohort and identify potential future avenues for research.

Unravelling the pathophysiology of chronic kidney disease-associated pruritus

“…Of note, generally the barrier function is still intact [ 18–20 ]. Additionally, microangiopathy is one of the characteristic findings in chronic kidney disease (CKD) [ 21 , 22 ]. It was first described in the skin in 1980 as thickening of the basement membrane, endothelial activation and chronic inflammatory cell infiltrates in cutaneous capillaries [ 23 ].…”

“…Today microangiopathy in CKD is perceived as a spectrum of structural remodelling of small vessels (diameter <100–300 μm) and multifactorial endothelial dysfunction caused by hypertension, metabolic [ 24–27 ], endocrine {e.g. in the calcium phosphate balance [ 28 , 29 ] and parathyroid hormone (PTH) [ 30 ]} and immune alterations in a uremic environment [ 21 , 22 ]. These lead to hypoxia, oxidative stress, apoptosis, a decrease in endothelial progenitor cells and disturbed angiogenesis [ 21 ].…”

New Insights to the Crosstalk between Vascular and Bone Tissue in Chronic Kidney Disease–Mineral and Bone Disorder

“…The luminal membrane is directly exposed for uremic toxins and other disturbances caused by CKD. Changes in the glycocalyx (the protective layer of glycoproteins and proteoglycan, which reduces the endothelium's contact with blood cells and macromolecules) has been reported in CKD patients [83]. The damage to the endothelium in CKD is most likely caused by hypertension, the state of low chronic inflammation, uremic toxin retention, dyslipidemia, and the disturbances in the mineral balance.…”

An exploratory study of the relationship between systemic microcirculatory function and small solute transport in incident peritoneal dialysis patients

“…11,12 Recent years have seen the development of several techniques to noninvasively study, in vivo, the structure and function of the microcirculation. 13,14 In kidney cohorts, these techniques have been used to demonstrate reduced capillary density in the skin and under the tongue, [15][16][17] reductions in the vasodilatory response of the skin microcirculation to physical and chemical stimuli 18,19 and impairment of glycocalyx barrier properties. 20 The relationship between the systemic and peritoneal microcirculations is likely to be complex, wherein both are influenced by demographic and biochemical factors including age, sex, co-morbidity and inflammation.…”

“…Figure 1.Techniques used to study the cutaneous and sublingual microcirculations (modified from Williams et al14 , with permission). (A) Schematic representation of iontophoretic delivery of vasoactive substances.…”