Association of plasma ortho-tyrosine/ para-tyrosine ratio with responsiveness of erythropoiesis-stimulating agent in dialyzed patients

Szilárd Kun, Esztella Mikolás, Gergo A. Molnár, Eszter Sélley, Boglárka Laczy, Botond Csiky, Tibor Kovács, I. Wittmann

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objectives: Patients with end-stage renal failure (ESRF) treated with erythropoiesis-stimulating agents (ESAs) are often ESA-hyporesponsive associated with free radical production. Hydroxyl free radical converts phenylalanine into ortho-tyrosine, while physiological isomer para-tyrosine is formed enzymatically, mainly in the kidney. Production of 'para-tyrosine' is decreased in ESRF and it can be replaced by ortho-tyrosine in proteins. Our aim was to study the role of tyrosines in ESA-responsiveness. Methods: Four groups of volunteers were involved in our cross-sectional study: healthy volunteers (CONTR; n = 16), patients on hemodialysis without ESA-treatment (non-ESA-HD; n = 8), hemodialyzed patients with ESA-treatment (ESA-HD; n = 40), and patients on continuous peritoneal dialysis (CAPD; n = 21). Plasma ortho-, para-tyrosine, and phenylalanine levels were detected using a high performance liquid chromatography (HPLC)-method. ESA-demand was expressed by ESA-dose, ESA-dose/body weight, and erythropoietin resistance index1 (ERI1, weekly ESA-dose/body weight/hemoglobin). Results: We found significantly lower para-tyrosine levels in all groups of dialyzed patients when compared with control subjects, while in contrast ortho-tyrosine levels and ortho-tyrosine/para-tyrosine ratio were comparatively significantly higher in dialyzed patients. Among groups of dialyzed patients the ortho-tyrosine level and ortho-tyrosine/para-tyrosine ratio were significantly higher in ESA-HD than in the non-ESA-HD and CAPD groups. There was a correlation between weekly ESA-dose/body weight, ERI1, and ortho-tyrosine/para-tyrosine ratio (r = 0.441, P = 0.001; r = 0.434, P = 0.001, respectively). Our most important finding was that the ortho-tyrosine/para-tyrosine ratio proved to be an independent predictor of ERI1 (β = 0.330, P = 0.016). In these multivariate regression models most of the known predictors of ESA-hyporesponsiveness were included. Discussion: Our findings may suggest that elevation of the ratio of ortho-tyrosine/para-tyrosine could be responsible for decreased ESA-responsiveness in dialyzed patients.

Original languageEnglish
Pages (from-to)190-198
Number of pages9
JournalRedox Report
Volume19
Issue number5
DOIs
Publication statusPublished - 2014

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Hematinics
Tyrosine
Plasmas
Continuous Ambulatory Peritoneal Dialysis
Body Weight
2-tyrosine
Phenylalanine
Chronic Kidney Failure
Free Radicals
Dialysis
High performance liquid chromatography
Peritoneal Dialysis
Erythropoietin

Keywords

  • Chronic
  • Darbepoetin alfa
  • Hydroxyl radical
  • Kidney failure
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Clinical Biochemistry
  • Biochemistry, medical
  • Physiology
  • Medicine(all)

Cite this

Association of plasma ortho-tyrosine/ para-tyrosine ratio with responsiveness of erythropoiesis-stimulating agent in dialyzed patients. / Kun, Szilárd; Mikolás, Esztella; Molnár, Gergo A.; Sélley, Eszter; Laczy, Boglárka; Csiky, Botond; Kovács, Tibor; Wittmann, I.

In: Redox Report, Vol. 19, No. 5, 2014, p. 190-198.

Research output: Contribution to journalArticle

Kun, Szilárd ; Mikolás, Esztella ; Molnár, Gergo A. ; Sélley, Eszter ; Laczy, Boglárka ; Csiky, Botond ; Kovács, Tibor ; Wittmann, I. / Association of plasma ortho-tyrosine/ para-tyrosine ratio with responsiveness of erythropoiesis-stimulating agent in dialyzed patients. In: Redox Report. 2014 ; Vol. 19, No. 5. pp. 190-198.
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AU - Kun, Szilárd

AU - Mikolás, Esztella

AU - Molnár, Gergo A.

AU - Sélley, Eszter

AU - Laczy, Boglárka

AU - Csiky, Botond

AU - Kovács, Tibor

AU - Wittmann, I.

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KW - Chronic

KW - Darbepoetin alfa

KW - Hydroxyl radical

KW - Kidney failure

KW - Oxidative stress

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