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.