Hypertension and nephrology

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

KUN Szilárd1, MIKOLÁS Esztella1, MOLNÁR Gergő Attila1, SÉLLEY Eszter1, LACZY Boglárka1, CSIKY Botond1, KOVÁCS Tibor1, WITTMANN István1

APRIL 10, 2016

Hypertension and nephrology - 2016;20(02)

[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.]


  1. Pécsi Tudományegyetem, Általános Orvostudományi Kar, II. Sz. Belgyógyászati Klinika és Nephrológiai Centrum, Pécs



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[Initiation of antihipertensive therapy with fix combinations, focusing on perindopril, amlodipine and indapamide]


[Early clinical studies proved that most hypertensive patients (>70%) need drug combinations to reach the target blood pressure. We should combine two or three - sometimes more - drugs from different antihypertensive classes for quicker normalisation of blood pressure and to reduce incidence and severity of hypertensive complications. Several international and Hungarian (MHT 2015) guidelines emphasize the advantages of fix combinations against free combinations. Most frequently used combinations contain ACEi + calcium antagonist, or ACEi + diuretic. From them I will focus on the perindopril + amlodipine or perindopril + indapamide combinations. If we do not reach target blood pressure, triple fix combinations (e.g. perindopril + amlodipine + indapamide) can also be used. Now there are fix combinations of different strengths, therefore we may start the therapy with these fix combinations according to patients’ characteristics (e.g. age, complications, concomitant diseases).]

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