Vascular access success—building a foundation

Abstract

F patients on chronic hemodialysis and their caretakers, vascular access failure is the current norm.1 Vascular access dysfunction continues to be the Achilles’ heel of the hemodialysis procedure, and the magnitude of this problem is increasing over time. Thus, recent estimates suggest that for the United States hemodialysis population, the maintenance of functioning vascular access costs over 1 billion dollars per year. Although vascular access dysfunction has long been known to contribute to considerable morbidity, recent studies strongly suggest that the type of vascular access also contributes to patient mortality. Thus, in a review of data from the USRDS, the presence of a functional arteriovenous fistula is associated with a considerable lowered mortality than a PTFE graft or tunneled catheter, even when adjusting for multiple patient comorbidities.2 In response to these and similar data, there has been a concerted effort in the United States to shift to native arteriovenous fistulae and the dialysis access of choice.3 However, most patients in the United States continue to be dialyzed through the use of an ePTFE graft. Unfortunately, graft failure is almost inevitable, with at least 70% of patients experiencing at least 1 episode of graft failure over the first 2 years after graft placement.4 Graft failure often leads to the requirement for either temporary or even permanent use of tunneled catheters, which are associated with a tremendous septicemia rate and a further incremental increase in overall patient mortality.2 If there is a silver lining in this dark cloud, it is that considerable scientific resources are now being brought to bear on this previously intractable problem. A review of citations in Index Medicus indicates a dramatic increase in publications related to hemodialysis vascular access. These articles have spanned the gamut from basic science investigations all the way to the development of randomized clinical trials. The article by Roy-Chaudhury et al in this issue of Advances in Renal Replacement Therapy brings us up to date on recent advances in our understanding of ePTFE graft dysfunction as we move from the bench to the bedside. A logical approach to solving any biologically complex clinical problem is to proceed from clinical observation of the nature of the problem to basic experimentation to determine the biologic factors contributing to the problem. In the case of ePTFE graft dysfunction, this involves an understanding of the biophysics, cell biology, and biochemistry associated with the development of pseudointimal hyperplasia and intimal hyperplasia. In theory, this should then lead to basic experimental approaches designed to prevent or inhibit this biologic process. Taking what is learned from bench to bedside will then lead to clinical trails, which (if efficacy is demonstrated) will lead to changes in clinical practice (Table 1). In the real world of basic and clinical investigation, however, progress is rarely stepwise and logical. Parallel pathways of basic and clinical investigation are simultaneously pursued, and there is cross-talk between clinical observation, basic experimentation, and the results of clinical trials. Thus, it is timely to review where we stand in terms of advances and where progress must be made in dealing with ePTFE graft dysfunction. As shown in Table 2, considerable recent progress has been made on both a clinical and experimental level in defining the nature of the problems that contribute to vascular access dysfunction. Perhaps the key clinical discovery of the past decade has been the recognition that ePTFE graft thrombosis in hemodialysis patients is due to the development of venous stenotic lesions at or distal to the venous anastamosis. This recognition only took place after the routine use of angiography occurred after the development of graft