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Understanding the pathophysiology of hemodialysis access problems as a prelude to developing innovative therapies

Nature Clinical Practice Nephrology volume 4, pages 628–638 (2008)Cite this article

Abstract

Maintenance of a functioning vascular access for hemodialysis is a major challenge for nephrologists, vascular surgeons and—most importantly—the patients themselves. Greater insight into the pathophysiology of access thrombosis, stenosis, aneurysm formation, fistula maturation failure and catheter infection will aid the development of innovative ways to prevent and treat these complications. According to the results of observational studies, agents that decrease the release of inflammatory mediators, improve endothelial function, and inhibit the migration and proliferation of vascular smooth-muscle cells might improve the maturation and survival of native hemodialysis fistulas and synthetic hemodialysis grafts by reducing the risks of thrombosis and stenosis. Currently available drugs that interfere with metalloproteinases could prevent the formation of aneurysms, and bacterial quorum sensing offers a promising target for the prevention of biofilm infection in hemodialysis catheters.

Key Points

  • No effective treatments currently exist for the many problems associated with hemodialysis vascular accesses; however, an improved understanding of the basic pathophysiology of these complications has generated innovative ideas for future solutions

  • Observational studies support some of the pathophysiologic insights, but randomized prospective clinical studies are needed for confirmation

  • Drugs that interfere with angiotensin production, improve endothelial function, promote nitric oxide release (including calcium channel blockers), or interfere with inflammatory mediators are the most promising approaches to the prevention of intimal hyperplasia, which is the main cause of thrombosis and stenosis

  • Drugs that interfere with matrix metalloproteinases might reduce the risk of aneurysm formation; however, these agents could also theoretically inhibit access maturation

  • Biofilms are a major problem in the pharmacologic treatment of catheter-related sepsis; two potential future treatment strategies are locking the bacteria in the planktonic phase and inhibiting quorum sensing

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Figure 1: Early understanding of the pathogenesis of vascular thrombosis.
Figure 2: The pathogenesis of intimal hyperplasia following vascular access creation.
Figure 3: Putative role of adventitial cells in the pathogenesis of intimal hyperplasia.

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Authors and Affiliations

  1. CJ Diskin is a Clinical Associate Professor, TJ Stokes is a Clinical Associate Professor, and LM Dansby, L Radcliff and TB Carter are Nephrologists in the Hypertension, Nephrology, Dialysis and Transplantation Clinic, Auburn University, Opelika, AL, USA.,

    Charles J Diskin, Thomas J Stokes, Linda M Dansby, Lautrec Radcliff & Thomas B Carter

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  1. Charles J Diskin
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  2. Thomas J Stokes
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  3. Linda M Dansby
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  4. Lautrec Radcliff
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Correspondence to Charles J Diskin.

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Diskin, C., Stokes, T., Dansby, L. et al. Understanding the pathophysiology of hemodialysis access problems as a prelude to developing innovative therapies. Nat Rev Nephrol 4, 628–638 (2008). https://doi.org/10.1038/ncpneph0947

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