The role of PVAT in vascular ageing in chronic kidney disease and type 2 diabetes.

Chronic kidney disease (CKD) is associated with a strong increase in cardiovascular risk, which is a consequence of accelerated vascular ageing. This process is hallmarked by vascular remodeling, chronic low-grade inflammation, calcification, and increased vascular stiffness. Vascular ageing is more pronounced in CKD patients who are also suffering from diabetes. The majority of type 2 diabetes (T2D) patients are obese with visceral adipose tissue (VAT) playing a central role in causing insulin resistance and metabolic syndrome. VAT is distributed through the abdominal cavity and is present surrounding the abdominal organs and the vasculature, the latter also called perivascular adipose tissue (PVAT). PVAT may be protective at some sites but it may also promote vascular ageing at other vascular sites because of its pro-atherogenic effects. This deranged function of PVAT may serve as a link between accelerated vascular ageing in CKD and T2D. I hypothesize that CKD and/or T2D derange PVAT function results in aggravated vascular ageing including development of atherosclerosis and calcification. In the current proposal, I will assess the pro-atherogenic environment of PVAT in patients with CKD with or without T2D.

In this study we will assess the role of T2D and CKD (end stage renal disease and pre emptive) in PVAT dysfunction.

PVAT plays an important role in driving vascular ageing manifested by medial smooth muscle cell (SMC) dedifferentiation into an osteogenic phenotype that induces intimal and/or medial calcification. I furthermore hypothesize that this process of vascular inflammation and calcification is most severe in patients with both chronic kidney disease and Type 2 diabetes (diabetic nephropathy).

T0: informed consent

T1: venapuncture 1 day before transplantation

Not applicable.