Hypertension and nephrology

[Goals, doubts and confidences in treatment of renal anemia]

KISS István, SZEGEDI János, KULCSÁR Imre, DEÁK György, KISS Zoltán, REMPORT Ádám, AMBRUS Csaba

JULY 20, 2013

Hypertension and nephrology - 2013;17(02)

[The authors sum up the physiology of erythropoiesis, the history of the erythropoietin’s discovery and the steps through which it became applicable to clinical adaptation. The biologically similar erythropoietin medicines and their application are reviewed. The setting of the target hemoglobin value and the weekly amount of erythropoietin needed for successful therapy are briefly surveyed. The authors draw attention to the fact that by increasing the dose the risk of mortality rises. Considering the other side effects they conclude based on international data and studies that “less is more” in this case namely the lower target value and erythropoietin dose can mean bigger therapeutic success. The erythropoietin treatment’s practice in Hungary is expressly efficient in the authors’ view.]



Further articles in this publication

Hypertension and nephrology

[Hypertension and diabetes mellitus]

SZEGEDI János, KISS István

[Hypertension and diabetes mellitus are endemics which affect large crowds; they play an important role in the morbidity and mortality of the population. Both diseases are cardiovascular risk factors, their co-occurrence increases the coronary risk. According to forecasts, there will be 60% increase in the number of hypertensive patients by 2025; it will affect 29% of the world’s adult population, 1.56 billion people. The number of patients with diabetes increases in all countries; 552 million diabetic patients should be expected by 2030. The simultaneous occurrence of both diseases may be a coincidence, but there is also causal relationship between the two diseases (diabetic nephropathy, metabolic syndrome). The two diseases often occur in endocrine diseases, and in connection with medicinal therapy (steroids, etc.). The simultaneous occurrence of these two diseases determines the therapeutic strategy. During the prevention and treatment of both diseases, the change in lifestyle has an important role (obesity, salt intake, physical activity).]

Hypertension and nephrology

[Practical aspects of therapy by erythropoiesis stimulating agents in renal anaemia]

DEÁK György, HERSZÉNYI Eszter, AMBRUS Csaba, KISS István

[Prevalence of renal anaemia due to insufficient production of erythropoietin increases progressively in the course of renal function deterioration. Renal anaemia is treated by erythropoesis stimulating agents (ESA). Outcomes of randomized clinical trials have taught us to avoid the strategy of normalization of hemoglobin (HGB) levels by ESA therapy as it may increase the risk of cardiovascular events and mortality. The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Anaemia published in 2012 recommends to start ESA therapy in the 90-100 g/l HGB range and suggests to keep HGB concentrations below 115 g/l. It is an inappropriate strategy to aim at normalizing hemoglobin (HGB) levels by ESA therapy because it may lead to progressive escalation of ESA doses even in the presence of diminished ESA responsiveness. High ESA doses and diseases causing ESA hyporesponsiveness eg. infections, chronic inflammation, malnutrition, insufficient dose of dialysis, severe hyperparathyroidism, iron deficiency are related to increased risk of mortality. KDIGO Clinical Practice Guideline for Anaemia emphasizes the importance of assessing and treating causes of ESA hyporesponsiveness, limits ESA dose escalation and recommends gradually changing ESA doses to avoid high amplitude HGB oscillation.]

Hypertension and nephrology

[Monitoring of the blood pressure lowering effectiveness of ramipril-amlodipine fix combination – a non-interventional trial (RAMONA study)]


[Purpose: Monitoring the effectiveness and safety of the fix combination formulation Egiramlon® therapy containing ramipril and amlodipin in patients, suffering from mild or moderate hypertension despite antihypertensive treatment. Patients and methods: Open, prospective, phase IV clinical observational study, which involved 9169 patients (age >18) with mild or moderate hypertension [TUKEB No: 16927- 1/2012/EKU (294/PI/12.)]. Ramipril/Amlodipin 5/5, 5/10, 10/5, 10/10 mg combinations were administered/ titrated in three visits, during the four months period according to the physician’s decision Blood pressure was measured by validated blood pressure sphygmomanometry and ABPM (Meditech, Hungary). The dosis of the fix combination formulation was determined individually during the visits by the 923 doctors involved in the study. The target blood pressure value was 140/90 mmHg, but in case of high risk patients population (diagnosed cardiovascular disease, diabetes), 130/90 mmHg target value was determined. Results: In 70.1% of the patients had no protocoll deviation. Patients data and examination results were processed according to this 6423 patient population. The average age of the patients were 60.2 year, in 50-50% sex distribution. The average duration of the treated hypertension was 9.8 years and the average blood pressure value was 157/91 mmHg. Till the end of the study, systolic blood pressure has decreased with 26.4 mmHg and diastolic pressure with 11.8 mmHg. An average 5.5 bpm heart rate frequency decreasing was observed at the end of the study. As a result of the treatment 52.4% of the patient population has reached the target blood pressure value.]

Hypertension and nephrology

[Health Protective Screening Program of Hungary 2010-2020. Metabolic syndrome - Results in 2010-2012]

KÉKES Ede, BARNA István, DAIKI Tenno, DANKOVICS Gergely, KISS István

[1 597 163 health assessments were performed on 65267 persons as a part of screening program. 132 964 participants were participated in our lifestyle advice program. The number of questionnaire responses for health statue were 3 717 480 during three years. This publication presents the results of metabolic disorders explored by screening. The metabolic syndrome was characterized by visceral obesity, abnormal glucose level and elevated blood pressure. Reasonable suspicion of metabolic syndrome was occured in 33-38% of subjects. Where the positive criteria was present, there were higher values of investigated parameters (waist, glucose, cholesterol, systolic blood pressure, uric acide level) compared with those of negative criteria.]

Hypertension and nephrology

[Managing hypertension using a fixed combination of an angiotensin converting enzyme inhibitor and a calcium channel blocker]

E. Chazova, G. Ratova, V. Nedogoda, M. Lopatin, B. Perepech, V. Tsoma

[The objective of the study was to compare the efficacy of a low-dose combination of an angiotensin-converting enzyme (lisinopril 10 mg) and a dihydropyridine calcium channel blocker (amlodipine 5 mg) (Ekvator, Gedeon Richter) (Group 1) and enalapril with or without hydrochlorothiazide (Group 2) in hypertension. Materials and methods: The study included 93 patients with hypertension (36% of men and 64% of women). The mean age was 52.6±12 years and the mean duration of hypertension was 7.5±6.1 years. The initial office blood pressure (BP) was 149.2±13.8/91.4±81 mmHg. Patients were randomized into two groups (Group 1, n=51 and Group 2, n=36). Results: The fixed-dose combination of amlodipine/lisinopril offered the potential to reduce the office BP by -28.9±11.3/-16.0±8.7 mmHg; p<0.0001. In Group 2 the office BP dropped by -22.9±17.9/-11.5±10.7 mmHg; p<0.0001. Patients in Group 1 achieved goal blood pressure more frequently than patients in Group 2 (94.1% versus 72.2% patients respectively; p=0.008). There were no significant changes in the heart rate in either group. The reduction of microalbuminuria (the reduction in urinary albumin excretion (UAE)) by -13.8±24.4 mg/24h (p<0.001) was observed only in patients from Group 1. The quality of life of patients from Group 2 improved. However, the quality of life improvements were more significant in Group 1 than in Group 2 (p=0.002). Conclusion: The fixed-dose combination of amlodipine/lisinopril offers the potential to achieve a target blood pressure in 94% of patients with hypertension, produces a nephroprotective effect and improves patients’ quality of life.]

All articles in the issue

Related contents

Hypertension and nephrology

[Biosimilar erythropoietins in nephrology - benedictio seu maledictio?]

KISS István

[Biological medicines of protein or polypeptide origin produced with biotechnology are far more complex in structure than the low molecular weight chemical ones. In conjunction with chemical drugs generic copies are completely the same, while in the field of biological medicines only similarity can be stated, as identical molecules cannot be produced. Spatial structure, isomers and side chains cause difference and for this reason these are called biosimilar drugs. Immunogenity of biosimilar drugs is very different and the risk of antibody production against them is diverse. Pure red cell aplasia, a rare side effect of erythropoietins is a life-threatening condition so every effort must be done for its prevention. Biosimilar drugs are not to be replaced with each other, and even the reference drugs should not be substituted in order to identify easily the side effects of each drug. Importantly financing should support these clinical principles namely a cheaper drug could be started as a new treatment but a former treatment should not be replaced because of cost sensitivity. It is important to provide the availability of the very expensive biologically active drugs to each patient but it is acceptable that the treatment should be as cost-effective as possible. Similarly to the generic copy program of chemical drugs biosimilar drugs are also important for the clinical practice, however their use needs appropriate regulation and farmacovigilance.]

Hypertension and nephrology

[Biosimilar erythropoesis stimulating agents - from registration to clinical practice]

KISS István

[The original patent drugs appear immediately on expiry of all rights in generic and biosimilar drugs in the pharmaceutical market, favorable supply option which helps in the rational management of medicines, mainly for generic drugs cheaper to allow more patient care. Of course, this is a well-organized legal and regulatory framework, thoughtful strategy can be successful in every respect. In another non-identical molecular structure biosimilar drugs in different immunogenicity of knowledge and risk is not defined in clinical practice and therefore the risk is still underestimated and not well regulated in the world, and increasing the number reported is the antibody formation case of a biosimilar erythropioetin also. The immunogenicity of original biological and of biosimilar drugs in identifying, defining a prominent role in the post-marketing surveillance, pharmacovigilance, and the special methods of control of immunogenicity. The original and the biosimilar medicines interchangeability, marketability of the assets relating to the regulations are not uniform in Europe or the European registration scheme is an important new biosimilar medicinal products, is that the medicinal product, the documentation is not expected to be accompanied by a risk management plan, as well as action to ensure the safety (pharmacovigilance) as part of the collection and reporting of adverse reactions to the official. It is important that the professional management of renal anemia guidelines - the practice of nephrology erythropoietin therapy - clearly define the biological medicines (originator and biosimilar erythropoietin) application requirements and suggestions. Consequently, this summary wants to draw attention to the therapeutic potential of biosimilar drugs, generic drugs to distinguish between explicit and the potential risks and the need to reduce the risks of professional and health policy decisions.]

Hypertension and nephrology

[Erythropoiesis-stimulating agents and oxidative stress in hemodialysis patients]

MONOSTORI Péter, S. VARGA Ilona, KISS József Zoltán, KISS István, HASZON Ibolya, PAPP Ferenc, SÜMEGI Viktória, BERECZKI Csaba, NÉMETH Ilona, TÚRI Sándor

[Oxidative stress plays an important role in the elevation of the cardiovascular risk of patients with chronic kidney insufficiency. The oxidative stress becomes more severe together with the deterioration of the renal function, and the hemodialysis sessions may also induce repetitive oxidative insults. Erythropoesis-stimulating agents (ESAs) may alter the level of oxidative stress via their effects on hematopoiesis, resulting in indirect effects on changes of iron metabolism and the levels of antioxidants. We review the current knowledge about the administration of ESAs as concerns effects on oxidative parameters in hemodialysis patients. We discuss the relationship between the characteristics of the ESA therapy (type, administration frequency and dosage of ESA, length of the therapy, administration withdrawal) and the oxidative stress in view of earlier and recent research.]

Lege Artis Medicinae


NAGY Judit, KISS István

[Erythropoietin produced by the foetal liver and the adult kidney is the major stimulator of erythropoiesis. Erythropoietin production is regulated by hypoxic activation of erythropoietin gene transcription. Recently, new sites of erythropoietin production have been found mainly in the central nervous system and in the cardiovascular system. These tissues have a paracrine and/or autocrine system of erythopoietin. The pleiotropic function of erythropoietin in these systems is tissue and cell protection by several mechanisms including inhibition of apoptosis, attenuation of ischaemic or reperfusion injury, anti-inflammatory and antioxidative effects. Furthermore, it promotes vascular recovery and enhances neoangiogenesis. In vivo and in vitro studies have proved that systemically administered human erythropoietin can also provide tissue protection. However, adverse effects of erythropoietin treatment such as hypertension, hyperviscosity and thrombosis may override the beneficial effect of systemic erythropoietin treatment. There are preliminary data that erythropoietin analogues, e.g., asyaloerythropoietin or carbamylated erythropoietin can provide tissue protection without stimulating erythropoiesis.]

Lege Artis Medicinae


REUSZ György, SZABÓ J. Attila

[Erythropoiesis stimulating agents are glycoproteins in which the oligosaccharide chains that terminate in sialic acid bind to the peptide with glycosidic bond. The lower the sialic acid content of the erythropoietin, the higher its receptor affinity, while its half-life in the circulation decreases. The biological effect depends on the balance of these factors. In the third-generation erythropoiesis stimulating molecule CERA (continuous erythropoietin receptor activator) a large polyethylene glycol molecule is substituted for sialic acid to ensure slow elimination and better biological efficiency. During treatment with erythropoiesis stimulating agents, haemoglobin levels show cyclic fluctuation. This cyclicity is undesirable, so its frequency and amplitude should be reduced as much as possible. The most recent results suggest that CERA may reduce haemoglobin cyclicity.]