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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Hypertension and nephrology

[Blood pressures of adolescents at screening program in Budapest]


[The Aim of the screening program was to investigate the blood pressure and the association with obesity, hypercholesterinaemia and increased body fluid in adolescents. Methods: A screening program was conducted during the period from April 2010 to May 2011.The screenings consisted of: blood pressure, heart rate, body composition determination, cholesterol, blood glucose, weight, height and BMI. Results: 2226 children fullfied all of the outlined criteria. Their range of age was between 14–18 years. The average systolic blood pressure was 126.34±12.55 Hgmm volt. At boys were higher 131.87±13.59 then at girls 117.49±5.69 Hgmm. The average diastolic blood pressure was 71.86±8.74 Hgmm. There were also higher at boys 72.61±9.17 then at girls 66.69±5.04 Hgmm. High systolic blood pressure (95%<) were 307/1326 cases at girls, and 403/876 cases at boys. High diastolic blood pressure were together with high systolic blood pressure, but less frequency. High diastolic blood pressure occurred at 85 girls and at 90 boys. Overweight and obes were 18.994% of girls and 15.26% of boys. The percentage of pathological high blood pressure was most frequent among boys and girls who are in the overweight group. The pathologically high level of body fat percentage appeared to be 12.98% among girls and 5.9% among boys. In elevated BMI groups the frequency of high body fat was 66% among girls and 81% among boys. The mean cholesterol was significantly higher in the overweight and obese group. Conclusions: Rates of hypertension and overweight and obesity are high in school children in Budapest, and increased bodyweight is a significant risk factor for hypertension. The results of the study will help to design preventive programmers.]

Hypertension and nephrology

[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).]

Hypertension and nephrology

[Rilmenidin - a versatile combination partner in the treatment of high blood pressure]


[The rilmenidin as an imidazoline agonist drug strongly decreases the central sympathetic activity, release of renine and the RAS activity. Because of these advantageous properties the peripheral vascular resistance falls and the blood pressure is decreased. Today it is excellent tool for combination therapy. Useful especially in stress induced hypertension. The antihypertensive effects of ACE inhibitors sor calcium antagonists are increased by rilmenidine. This drug decreases the insuline resistance, it has a positive effect on the carbohydrate and fat metabolism, because it is useful as a complementary therapy in metabolic syndrome and diabetes mellitus of type II. It is useful in stress induced hypertension, and in menopause as well.]

Hypertension and nephrology

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Background - The aim of this study was to compare ischemic stroke subtypes with the effects of risk factors, the relationship between grades of kidney disease and the severity of stroke subtypes. Methods - The current study was designed retrospectively and performed with data of patients who were hospitalised due to ischemic stroke. We included 198 subjects who were diagnosed with ischemic stroke of Grade 3 and above with chronic kidney disease. Results - In our study were reported advanced age, coronary artery disease, moderate kidney disease as the most frequent risk factors for cardioembolic etiology. Hypertension, hyperlipidemia, smoking and alcohol consumption were the most frequent risk factors for large-artery disease. Female sex and anaemia were the most frequent risk factors for small-vessel disease. Dialysis and severe kidney disease were the most frequent risk factors in unknown etiologies, while male sex, diabetes mellitus, prior stroke and mild kidney disease were the most frequent risk factors for other etiologies. National Institute of Health Stroke Scale (NIHSS) scores were lower for small-vessel disease compared with other etiologies. This relation was statistically significant (p=0.002). Conclusion - In order to improve the prognosis in ischemic stroke with chronic kidney disease, the risk factors have to be recognised and the treatment options must be modified according to those risk factors.

Hypertension and nephrology

[Case report of supine hypertension and extreme reverse dipping phenomenon decades after kidney transplantation]

BATTA Dóra, KŐRÖSI Zita Beáta, NEMCSIK János

[Supine hypertension, a consequence of autonomic neuropathy, is a rarely recognized pathological condition. Reported diseases in the background are pure autonomic failure, multiple system atrophy, Parkinson’s disease, diabetes and different autoimmune disorders. In our case report we present a case of supine hypertension which developed in a patient decades after kidney transplantation. The patient was followed for 25 months and we demonstrate the effect of the modification of antihypertensive medications. At the time of the diagnosis supine hypertension appeared immediately after laying down (office sitting blood pressure (BP): 143/101 mmHg; office supine BP: 171/113 mmHg) and on ambulatory blood pressure monitoring (ABPM) extreme reverse dipping was registered (daytime BP: 130/86 mmHg, nighttime BP: 175/114 mmHg). After the modification of the antihypertensive medications in multiple times, both office supine BP (office sitting BP: 127/92 mmHg; office supine BP: 138/100 mmHg) and on ABPM nighttime BP improved markedly (daytime BP: 135/92 mmHg, nighttime BP: 134/90 mmHg). In conclusions, our case report points out that autonomic neuropathy-caused supine hypertension and extreme reverse dipping can develop in chronic kidney disease, after kidney transplantation. The modification of the antihypertensive medications can slowly restore this pathological condition.]

Hypertension and nephrology

[Monitoring of effectiveness of ramipril-amlodipine fixed combination, a non-interventional trial (Ramona study). Subgroup analysis of patients with chronic kidney disease]


[Hypertension and chronic kidney disease are independent cardiovascular risk factors. The 5th Cardiovascular Consensus Conference has recommended chronic kidney disease in high-risk category. In chronic kidney disease hypertension is observed in most cases. In patients with chronic kidney disease blood pressure targets are as 140/90 mmHg blood pressure below must be achieved without overt proteinuria. In chronic kidney disease combined antihypertensive therapy treatment should be initiated according the Hungarian Society of Hypertension recommendations. Aims: Monitoring the effectiveness and safety of the fix combination of ramipril/amlodipine Egiramlon® therapy in chronic kidney disease suffering from mild or moderate hypertension despite antihypertensive treatment. Patients and methods: Open, prospective, phase IV clinical observational study, which involved known chronic kidney disease (age over 18 years) with mild or moderate hypertension. Ramipril/amlodipine fixed combination (5/5, 5/10, 10/5 or, 10/10 mg) were administered or titrated in three visits, during the 4 months of trial period. The doses of the fixed combination drugs were determined individually during the visits by the 923 physicians involved in the study. The target blood pressure value was <140/90 mmHg according the new guidelines of ESH/ESC. Results: 70.1% of total patient (9169) was fulfilled the protocol during the four month of trial (6423 patients). In this population 194 patients suffered from chronic kidney disease. The age of patients was 68.52±1.84 (mean±SD) years, 85 (43.8) women and 109 (56.2%) men. 74.74% of total patients with chronic kidney disease has reached target blood pressure at the end of 4th month (primary endpoint). The blood pressure has decreased significantly (all p<0.0001) from 158.04/90.46±9.97/8.30 mmHg (1. visit) to 138.77/82.12±10.68/7.21 mmHg 2. visit and to 130.40/78.59±7.56/5.75 at the and of trial (3. visit), it means -27.64/- 11.87 mmHg decrease from the beginning of the 4th Month (3. visit). eGFR level increased significantly from 46.3±16.49 ml/min/1,73m2 to 49.0±19.58 ml/min/1,73m2. Patients suffered from chronic kidney disease have tolerated well the various doses of fixed combination of ramipril/amlodipine, and adverse events have no occurred correlation of treatment.]

Hypertension and nephrology

[Risk estimates of advanced chronic kidney disease and predicting mortality in dialyzed patients]


[In mostly the second part of the last decade lots of epidemiological study have been released about the progression of the chronic kidney disease (CKD) and theirs connection with the risk of death. The fact that lots of nephrologist from all over the world (from Canada to New-Zealand) are pretty much interested in this topic is absolutely proved by national (REIN Study – French Registry) and international (KDIGO Controversies Conference, DOPPS 1-5, or the European AROII Study) researchers with these epidemiological questions in their focus. The risk estimation facts that are able to show the life expectancy of patients with CKD 3-5 (expected time to dialysis or mortality risk before renal replacement therapy – RRT) and the early or hopefully longer survival odds of the dialyzed ones could be very useful not only for the medical stuff but also for the patients. In case of the predialyzed patients the focus has to be on the Bansal score and also on the Kidney Failure Risk Equation (KFRE) scores (with 4 and 8 variable); on the other hand in dialyzed patients the REIN score that prognose a short-term survival and the Cohen model (both are easy calculated with webcalculators) are in the highlight of importance. There is not a big difference (2- 7%) in validated researches between the prognosed and the real survival dates. Despite of this prediction has to always be evaluated individually in favour of the best decision we can make for the patients and in order to choose the right treatment: conservative therapy, dialysis or transplantation.]