NDT Advance Access originally published online on January 9, 2006
Nephrology Dialysis Transplantation 2006 21(3):823; doi:10.1093/ndt/gfi346
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Letters and Replies
Notes on angiotensin inhibition and vascular access survival: time for randomized controlled trials
HNDT Auburn University Opelika AL, USA
Email: Hndt512{at}bellsouth.net
Sir,
I would like to extend our congratulations to Dr Garrancho [1] for his work on the beneficial effects of the use of angiotensin-converting enzyme inhibitors (ACEIs) in the prevention of vascular access failure. When we first published the beneficial effects of ACEIs on graft survival 8 years ago [2], we had previously hypothesized, as Dr Garrancho correctly notes, a benefit due to an antiproliferative effect on smooth muscle [3], since angiotensin II had been shown previously to promote the synthesis of platelet-derived growth factor in smooth muscle cells in rats and that effect could be inhibited by cilazapril [4]. However, as I noted at the time, the very discovery of ACEIs was related to the finding that pit viper venom contained a family of peptides that inhibited the enzyme that caused the degradation of bradykinins. That enzyme, of course, later became known as angiotensin-converting enzyme and that family of peptides became the ACEIs. Bradykinins are known to activate endothelial cells into arachidonic acid mobilization and prostacyclin (PGI2) production [5]. Of course, PGI2 is a powerful vasodilator that inhibits platelet activation and promotes the release of nitric oxide. Therefore, the beneficial effect of ACEIs may be due as much to a beneficial effect on endothelial function as to its effect as an antiproliferative agent. We still do not know the precise mechanism of this benefit. That is why I am somewhat disappointed that Dr Garrancho did not control for other drugs that could potentially affect access survival. We had found a beneficial effect of pentoxyfylline in addition to ACEIs [2]. More recently, Dr Saran [6] found a beneficial effect of calcium-channel blockers (which is also noted to have a beneficial effect on endothelial cells [3]) in addition to ACEIs, whilst we both found a deleterious effect of warfarin on access survival. In summary, while several of us have found a benefit to ACEIs on vascular access survival, we have not identified the precise mechanism, nor have we determined an appropriate pharmacological regime in the promotion of access survival. The benefits of observational studies such as ours, Dr Saran's and Dr Garrancho's are quite limited and unless the investigators have controlled for the effect of other drugs that have also been shown to be of benefit in addition to the ACEIs, we cannot be sure that all confounding effects have been eliminated. Therefore, recommendations for pharmacological treatment for the prevention of vascular access failure should be given with caution. The time for observational studies is past and the time for an appropriate randomized controlled prospective study is overdue.
Conflict of interest statement. None declared.
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 Top References |
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- Garrancho JM, Kirchgessner J, Arranz M et al. Haemoglobin level and vascular access survival in haemodialysis patients. Nephrol Dial Transplant 2005; 20: 2453–2457
[Abstract/Free Full Text] - Diskin CJ, Stokes TJ, Thomas SG et al. An analysis of the effect of routine medications on hemodialysis vascular access survival. Nephron 1998; 78: 365–368[CrossRef][Web of Science][Medline]
- Diskin CJ, Stokes TJ, Pennell AT. Pharmacologic intervention to prevent vascular access thrombosis. Nephron 1993; 64: 1–26[Medline]
- Powell JS, Rouge M, Muller RK, Baumgartner HR. Cilazapril suppresses myointimal proliferation after vascular injury: effects on growth factor induction in vascular smooth muscle cells. Basic Res Cardiol 1991; 86 [Suppl 1]: 65–74
- Crutchley DJ, Ryan JW, Ryan US, Fisher GH. Bradykinin-induced release of prostacyclin and thromboxanes from bovine pulmonary artery endothelial cells. Studies with lower homologs and calcium antagonists. Biochim Biophys Acta 1983; 751: 99–107[Medline]
- Saran R, Dykstra DM, Wolfe RA et al. Association between vascular access failure and the use of specific drugs: the dialysis outcomes and practice patterns study. Am J Kidney Dis 2002; 40: 1255–1263[CrossRef][Web of Science][Medline]
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