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NDT Advance Access originally published online on July 2, 2008
Nephrology Dialysis Transplantation 2008 23(9):3036-3037; doi:10.1093/ndt/gfn316
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Reply

E-mail: desai{at}med.umich.edu

Sir,

The letter by Calò and Davis highlights some very interesting issues regarding the complex effects that exogenous erythropoietin (EPO) therapy may have on various cell types, tissues and organs and emphasizes the urgent need to define the effects of chronic EPO administration to patients with chronic kidney disease who are in a state of nitric oxide deficiency and heightened oxidative stress [1,2]. Based on their observations in mononuclear cells of hemodialysis patients, Calò and Davis suggest that EPO induces heme oxygenase-1 (HO-1) expression which may in turn upregulate expression of ecNOS, thus producing the compensatory increase in NO observed in EPO-treated Balb/c mice in our study. At this time, we do not have any data in support of the proposed mechanism but intend to fully explore the potential link between HO-1 and EPO in future experiments. Moreover, our current results do not allow us to unequivocally conclude that EPO-mediated upregulation of renal NOS is responsible for the elevated urinary nitrite concentrations. It is also unclear whether the EPO-mediated rise in ADMA concentrations has any effect on NOS inhibition and, to our knowledge, no published study to date has addressed the effect of EPO on HO-1 activity in mice. The interaction between HO-1 and NOS in the rat has been investigated by several laboratories [3–5] and in vitro and in vivo studies support the idea that EPO induces the expression of HO-1 [6,7]. Hence, in summary, the hypothesis proposed by Calò and Davis is very reasonable and its validity needs to be investigated in our mouse model. We thank Calò and Davis for their comments.

Conflict of interest statement. None declared.

Anjali Desai1 and Jeffrey S. Warren2

1 Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA 2 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA

References

  1. Schmidt RJ, Baylis C. Total nitric oxide production is low in patients with chronic renal disease. Kidney Int (2000) 58:1261–1266.[CrossRef][Web of Science][Medline]
  2. Agarwal R. Chronic kidney disease is associated with oxidative stress independent of hypertension. Clin Nephrol (2004) 377–383. 61.
  3. Li Volti G, Sorrenti V, Murabito P, et al. Pharmacological induction of heme oxygenase-1 inhibits iNOS and oxidative stress in renal ischemia-reperfusion injury. Transplant Proc (2007) 39:2986–2991.[CrossRef][Web of Science][Medline]
  4. Datta PK, Koukouritaki SB, Hopp KA, et al. Heme oxygenase-1 induction attenuates inducible nitric oxide synthase expression and proteinuria in glomerulonephritis. J Am Soc Nephrol (1999) 10:2540–2550.[Abstract/Free Full Text]
  5. Ahmad M, Turkseven S, Mingone CJ, et al. Heme oxygenase-1 gene expression increases vascular relaxation and deceases inducible nitric oxide synthase in diabetic rats. Cell Mol Biol (2005) 51:371–376.[Web of Science][Medline]
  6. Katavetin P, Inagi R, Miyata T, et al. Erythropoietin induces heme-oxygenase-1 expression and attenuates oxidative stress. Biochem Biophys Res Commun (2006) 359:928–934.[Web of Science]
  7. Calò LA, Stanic L, Davis PA, et al. Effect of epoetin on HO-1 mRNA level and plasma antioxidants in hemodialysis patients. Int J Clin Pharmacol Ther (2003) 41:187–192.[Web of Science][Medline]

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This Article
Right arrow Extract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
23/9/3036    most recent
gfn316v1
Right arrow Alert me when this article is cited
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Right arrow Articles by Desai, A.
Right arrow Articles by Warren, J. S.
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