Role of Monocytes Adhesion and Vascular Lesions in Vascular Access Success or Failure in Uremic Patients

Research Project Objectives

For patients with progressive chronic kidney disease the definitive treatment is a renal replacement therapy. One of the methods is hemodialysis, which is frequently chosen in patients above 65y. of age. Several clinical practice guidelines recommend an arteriovenous fistula (AVF), rather than a central venous catheter or arteriovenous graft, as the preferred access for maintenance hemodialysis (HD) therapy. Despite efforts to improve placement of AVF in both the hemodialysis incident and prevalent population, many patients continue dialysis through a central venous catheter, exposing them to higher risks of infection, co-morbidity and mortality in comparison to use an AVF for HD. Furthermore, AVF primary failure rates are reportedly as high in 20-50% in published series confirming that ultrasound cannot sufficiently inform the clinician to accurately predict success or failure. Because of higher risk of early AVF failure offering this type of access is questionable in diabetics, unfavorable artery/vein diameter and elderly people. To perform hemodialysis vascular access ensuring adequate blood flow is required. Such access is most commonly obtained by the creation of the vascular connection between an artery and a vein on the upper limb. Recent data from European and National registries clearly indicate huge increase of incident dialysis patients above 65y. In older patients with many co-morbidities and limited predictive survival decision whether to start dialysis, when and how should be cautious. When choosing vascular access fistula non-maturation problem must be taken into account. The successful creation of a permanent vascular access depends on vessel health, patient characteristics and possibly genetic factors. In patients with end stage renal disease circulating monocytes are activated and proinflammatory monocytes are expanded. Recent data indicates that uremic conditions drive monocytes to differentiate and interact with artery wall promoting atherosclerosis. This interaction can be studied in the laboratory by testing inflammatory activity of THP-1 monocytes and by checking proatherosclerotic and calcification markers in the artery specimen (taken during AVF creation).

Research hypothesis: monocytes activation and advancement of vascular lesions affect the process of remodeling (maturation) of arteriovenous fistula, determines its usability (functionality). The investigators also hypothesize that an increase in the collagen content of the vascular media (medial fibrosis) preoperatively would impair vascular dilation and thereby, limit the postoperative increase in arteriovenous fistula diameter, blood flow and finally AVF maturation.

Working second hypothesis: the metrical age of patient with mild to moderate vascular lesions is not limiting factor in AVF success rate and maturation.

The main aim of the study is assessment of changes in the vessels and monocyte activation and its impact on the ability to create AVF and its usability for hemodialysis. Secondary objective of this study is to perform enhanced assessments of arterial health preoperatively and correlate these measurements with vascular lesions. The investigators intend to perform preoperative vascular mapping, flow mediated dilatation (FMD) and assess endothelial function. These non invasive measurements will provide a more accurate picture of overall vascular health prior to AVF formation with the ultimate intention of informing the clinician as to the likelihood of success or failure.