Kidney failure and associated uraemia have implications for the cardiovascular system, brain, and blood–brain barrier (BBB). We aim to examine BBB disruption, by assessing brain-derived neurotropic factor (BDNF), neuron-specific enolase (NSE) levels, and gut-blood barrier (GBB) disruption by trimethylamine N-oxide (TMAO), in chronic kidney disease (CKD) patients. Additionally, endothelial tight-junction protein expressions and modulation via TMAO were assessed. Serum from chronic kidney disease (CKD) female and male haemodialysis (HD) patients, and controls, were used to measure BDNF and NSE by enzyme-linked immunosorbent assays, and TMAO by mass spectrometry. Immunofluorescent staining of subcutaneous fat biopsies from kidney transplant recipients, and controls, were used to measure microvascular expression of tight-junction proteins (claudin-5, occludin, JAM-1), and control microvasculature for TMAO effects. HD patients versus controls, had significantly lower and higher serum levels of BDNF and NSE, respectively. In CKD biopsies versus controls, reduced expression of claudin-5, occludin, and JAM-1 were observed. Incubation with TMAO significantly decreased expression of all tight-junction proteins in the microvasculature. Uraemia affects BBB and GBB resulting in altered levels of circulating NSE, BDNF and TMAO, respectively, and it also reduces expression of tight-junction proteins that confer BBB maintenance. TMAO serves as a potential candidate to alter BBB integrity in CKD.

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Prevention of cardiovascular disease (CVD) remains one of the largest public health challenges of our time. Identifying individuals at increased cardiovascular risk at an asymptomatic, subclinical stage is of paramount importance for minimizing disease progression as well as the substantial health and economic burden associated with overt CVD. Vascular ageing (VA) involves the deterioration in vascular structure and function over time, and ultimately leads to damage in the heart, brain, kidney, and other organs. VA encompasses the cumulative effect of all cardiovascular risk factors on the arterial wall over the life course and thus may help identify those at elevated cardiovascular risk, early in disease development. Although the concept of VA is gaining interest clinically, it is seldom measured in routine clinical practice due to lack of consensus on how to characterise VA as physiological versus pathological and various practical issues. In this state-of-the-art review and as a network of scientists, clinicians, engineers and industry partners with expertise in VA, we address six questions related to VA in an attempt to increase knowledge among the broader medical community and move the routine measurement of VA a little closer from bench towards bedside.