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Hypertension and nephrology

APRIL 10, 2016

[Plasma ortho-tyrosine/para-tyrosine ratio predicts hyporesponsiveness to erythropoiesis-stimulating agents in dialyzed patients]

KUN Szilárd, MIKOLÁS Esztella, MOLNÁR Gergő Attila, SÉLLEY Eszter, LACZY Boglárka, CSIKY Botond, KOVÁCS Tibor, WITTMANN István

[Objectives: Patients suffering from end-stage renal failure (ESRF) are mostly treated with erythropoiesis-stimulating agents (ESAs). They often show hyporesponsiveness to ESA, which condition is associated with elevated production of free radicals. Phenylalnine (Phe) is converted into para- and ortho-tyrosine (p- and o- Tyr) by hydroxyl free radical. o-Tyr is produced exclusively in this way. However, physiological isomer p-Tyr is formed in significantly higher amounts by phenylalaninehydroxylase, mainly in the kidney. It has been shown that p-Tyr production is decreased in ESRF. As a result, p-Tyr can be replaced by o-Tyr in proteins, e.g. in proteins playing part in signal transduction of erythropoietin. We aimed to study the association of different Tyr isoforms with 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 p-, o-Tyr and Phe levels were detected using a high performance liquid chromatography (HPLC)-method, with fluorescence detection. ESA-demand was expressed as ESA-dose, ESAdose/ body weight and erythropoietin resistance index1 (ERI1, weekly ESA-dose/body weight/hemoglobin). Multivariate regression models were used to examine predictors of ESA-demand. In these models, most of the known predictors of ESA-hyporesponsiveness were included. Results: Lower p-Tyr levels were found in dialyzed patients compared with control subjects. In contrast, o-Tyr levels and o-Tyr/p-Tyr ratios were higher in dialyzed patients. Regarding dialyzed patients, o-Tyr level and o-Tyr/p-Tyr ratio were higher in ESA-HD than in non-ESA-HD and CAPD groups. Weekly ESA-dose/body weight and ERI1 correlated with o-Tyr/p-Tyr ratio (r=0.441, p=0.001; r=0.434, p=0.001, respectively). Finally, o-Tyr/p-Tyr ratio proved to be an independent predictor of ERI1 (β=0.330, p=0.016). Discussion: Our results suggest that elevation of o-Tyr/p-Tyr ratio could be responsible for ESA-hyporesponsiveness in dialyzed patients.]

Lege Artis Medicinae

NOVEMBER 20, 2007



[INTRODUCTION - Anaemia is a common complication among patients with malignant tumours, and is due to the disease itself or to the oncologic treatment. Anaemia worsens the patient’s quality of life and hampers anti-cancer treatment in the appropriate intervals and doses. Erythropoiesis stimulating protein therapy in the anaemia of oncologic patients raises the haemoglobin level, reduces the need for red blood cell transfusion and improves quality of life. This drug has recently become accessible in Hungary for the treatment of chemotherapy-induced anaemia in patients with small cell lung cancer. CASE REPORT - In this paper the case of a 64- year-old woman with small cell lung cancer who survived for more than 2 years is presented. Two-line chemotherapy was administered together with irradiation and darbepoetin alpha supportation. The successful treatment of anaemia with darbepoetin alpha permitted the administration of chemotherapy in the necessary intervals and doses. CONCLUSIONS - The adequate use of erythropoiesis stimulating protein facilitates the management of patients with small cell lung cancer, and improves their quality of life.]

Lege Artis Medicinae

OCTOBER 21, 2007



[Recombinant human erythropoietin has been used for more than 20 years for the treatment of renal anaemia, with epoetin-alfa and -beta representing the common traditional preparations. By the modification of the molecule’s carbohydrate moiety or structure a longer duration of erythropoietin receptor stimulation was achieved. The administration of these new molecules (darbepoetin, C.E.R.A.) once or twice a month is also sufficient to achieve serum haemoglobin target levels, making the treatment safer and more comfortable both for the patients and the personnel. These recently developed synthetic erythropoietin receptor stimulating molecules, along with recombinant human erythropoietin, are together called “Erythropoiesis Stimulating Agents”. In haemodialysed patients the intravenous route is preferred, but the subcutaneous administration can substantially reduce dose requirements. In praedialysed, transplanted or peritoneally dialysed patients, erythropoiesis stimulating agents should preferably be given subcutaneously both for economic and practical reasons. There are ongoing clinical trials with erythropoiesis stimulating molecules that can be administered by inhalation or per os. Current evidence suggests that the serum haemoglobin level should preferably not exceed 12 g/dl with the use of erythropoiesis stimulating agents. No cardiovascular protective effect of higher serum haemoglobin levels was demonstrated in two large clinical trials. Further well-designed studies are necessary to set evidence-based haemoglobin targets for erythropoiesis stimulating treatment. Arguments for a more widespread use of agents with extended duration include medical, financial and patient satisfaction reasons. The release of new erythropoiesis stimulating agents may further simplify the treatment of renal anaemia.]

AUGUST 15, 2011