Hypertension and nephrology

[Hungarian virus research and NASA – nephrology aspects]

RADÓ János

APRIL 10, 2016

Hypertension and nephrology - 2016;20(02)

[After the occurrence of varicella viruses remain in a latent condition in the ganglions, but could be reactivated from here causing the disease of herpes zoster. In the years of 1960, we described a herpes zoster „house epidemic” where only the steroid treated patients were infected. Varicella zoster virus was identified by virological methods. Also in a steroid treated patient fatal meningoencephalitis was caused by the generalized herpes zoster. The VZ infection was obviously potentiated by the steroid. Our publications about the interaction between the VZ virus and steroid treatment was echoed – among others – by an editorial of four leading medical journals. Investigators of a NASA medical group also cited our articles. They found during and after spaceflight that in the astronauts symptomless reactivation of the VZ virus, EBV and CMV occurred which was contributed to the stress induced hypercortisolemia. Today we see more worries in the prognosis and outlook in certain cases of the herpes zoster than before. One reason of that is the high number of newly recognized complications. Recently also several new pathway of pathomechanisms has been explored, which led to serious risks. In addition, it turned out that in certain disorders as the artheritis temporalis, where today antivirus antibiotic is the first choice drug, instead of steroid administered alone in the past, inducing further progression in the basic disease and sometimes fatal complications when given too long. Nephrological patients are at special risk in the presence of chronic renal disease, high age and associated diabetes mellitus. The risk may even increase after an otherwise successful renal transplantation in response to the administration of steroids and other compounds. Fortunately in the meantime a vaccine was developed against the VZ virus, studied in large populations and found to be very effective. It probably will be a benediction to the old people with chronic renal disease, after transplantation as well as in others suffering from high risk diseases.]

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[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.]

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