Skip to main content

Mechanism of Inhibitory Effect of 3- Hydroxykynurenine on Erythropoiesis in Patients with Renal Insufficiency

  • Chapter
Developments in Tryptophan and Serotonin Metabolism

Abstract

Increase of 3-hydroxykynurenine (3-HKYN) concentration was observed in plasma patients with chronic renal insufficiency (CRI). These changes positively correlated with the concentration of creatinine, but negatively correlated with haematological parameters: haematocrit, haemoglobin and red blood cells count. The changes were accompanied by a slight decrease of the concentration of erythropoietin (EPO) in plasma of patients with CRI. The “in vitro” study in the conditions of hypoxia showed that 3-HKYN inhibited the release of EPO from HepG2 cells to the culture base. In conclusion, the erythropoiesis in CRI could be attributed to the influence of 3-HKYN on EPO synthesis. Thus, we propose that 3-HKYN can be an uraemic of toxin partially responsible for anaemia patients with CRI.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. K.U. Eckardt, Pathophysiology of renal anemiaClin. Nephrol. 53,S2–S8 (2000).

    PubMed  CAS  Google Scholar 

  2. I. Macdougall, Role of uremic toxins in exacerbating anemia in renal failureKidney lnt 59 S67–S72 (2001).

    Article  Google Scholar 

  3. W. Jelkman, T. Hellwing-Burgel, Biology of erythropoietinAdv. Exp. Med. Bio.l 502,169–87 (2001).

    Google Scholar 

  4. A.J. Erslev, A. Besarab, Erythropoietin in the pathogenesis and treatment of the anemia of chronic renal failureKidney /nt. 51,622–630 (1997).

    Article  CAS  Google Scholar 

  5. K. Saito, S. Fujigaki, M.P. Heyes, K. Shibata, M. Takemura, H. Fujii, H. Wada, A. Noma, M. Seishima, Mechanism of increases in L-kynurenine and quinolinic acid in renal insufficiencyAm. J. Physiol. 279,F565–F572 (2000).

    CAS  Google Scholar 

  6. E.W. Holmes, S.E. Kahan, Tryptophan distribution and metabolism in experimental chronic renal insufficiencyExp. Mol. Pathol. 46,89–101 (1987).

    Article  PubMed  CAS  Google Scholar 

  7. E.W. Holmes, P.M. Russell, G.J. Kinzler, C.R. Reckard, R.C. Flanigan, K.D. Thompson, E.W. Berme, Oxidative tryptophan metabolism in renal allograft recipients: increased kynurenine synthesis is associated with inflammation and OKT3 therapyCytokine 4,205–213 (1992).

    Article  PubMed  CAS  Google Scholar 

  8. D. Pawlak, A. Tankiewicz, P. Mysliwiec, W. Buczko, Tryptophan metabolism via kynurenine pathway in experimental chronic renal failureNephron 90,328–335 (2002).

    Article  PubMed  CAS  Google Scholar 

  9. D. Pawlak, A. Tankiewicz, W. Buczko, Kynurenine and its metabolites in the rat with experimental renal insufficiencyJ. Physiol. Phrarmncol. 52,755–766 (2001).

    CAS  Google Scholar 

  10. D. Pawlak, K. Pawlak, J. Malyszko, M. Mysliwiec, W. Buczko, Accumulation of toxic products degradation of kynurenine in hemodialyzed patientsInt. Urol. Nephrol. 33,399–404 (2001).

    Article  PubMed  CAS  Google Scholar 

  11. R. Buchi, D. Alberati-Gani, P. Malherbe, C. Kohler, C. Broger, A.M. Cesura, Cloning and functional expression of a soluble form of kynurenine/a-aminoadipate aminotransferase from rat kidneyJ. Biol. Chem. 270,29330–29335 (1995).

    Article  Google Scholar 

  12. M.P. Heyes, Quantification of 3-hydroxykynurenine in brain by high-performance liquid chromatography and electrochemical detectionJ. Chromatogr. 428,340–344 (1988).

    Article  PubMed  CAS  Google Scholar 

  13. A.G. Brox, F. Zhang, H. Guyda, RF. Gagnon, Subtherapeutic erythropoietin and insulin-like growth factor-I correct the anemia of chronic renal failure in the mouseKidney Int. 50,937–943 (1996).

    Article  PubMed  CAS  Google Scholar 

  14. W.C. Faquin, T.J. Schneider, M.A. Goldberg, Effect of inflammatory cytokines on hypoxia-induced erythropoietin productionBlood 79,1987–1994 (1992).

    PubMed  CAS  Google Scholar 

  15. A.M. Goldberg, A.G. Glass, M.i. Cunningham, F.H. Bunn, The regulated expression of erythropoietin by two human hepatoma cell lines/’roc. Nail. Acad. Sci. USA 84,7972–7976 (1987).

    Article  CAS  Google Scholar 

  16. J. Fandrey, S. Frede, W. Ehleben, T. Porwol, H. Acker, W. Jelkamann, Cobalt chloride and desfen-ioxamine antagonize the inhibition of erythropoietin production by reactive oxygen speciesKidney Int. 51,492–496 (1997).

    Article  PubMed  CAS  Google Scholar 

  17. J. Fandrey, S. Frede, W. Jelkmann, Role of hydrogen peroxide in hypoxia-induced erythropoietin productionBiochem. J. 303,507–510 (1994).

    PubMed  CAS  Google Scholar 

  18. G.L. Wang, G.L. Semenza, Purification and characterization of hypoxia-inducible factor IJ. Biol. Chem. 270,1230–1237 (1995).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Pawlak, D., Koda, M., Wołczyński, S., Mysliwiec, M., Buczko, W. (2003). Mechanism of Inhibitory Effect of 3- Hydroxykynurenine on Erythropoiesis in Patients with Renal Insufficiency. In: Allegri, G., Costa, C.V.L., Ragazzi, E., Steinhart, H., Varesio, L. (eds) Developments in Tryptophan and Serotonin Metabolism. Advances in Experimental Medicine and Biology, vol 527. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0135-0_43

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-0135-0_43

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4939-6

  • Online ISBN: 978-1-4615-0135-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics