Hypertension and nephrology

[Sevelamer: an old-new phosphate binder in chronic kidney disease]


JUNE 20, 2010

Hypertension and nephrology - 2010;14(03)

[Sevelamer HCl is a non-metal and non-calcium based phosphate binder, ion exchange resin, which not selectively binds the phosphate ions in the gastrointestinal tract. In Hungary since 2005, on the basis of strict professional guidelines, sevelamer is available therapy for chronic kidney disease patients with severe hyperphosphatemia on dialysis. On the basis of 17 prospective and retrospective studies, sevelamer HCl is an at least as effective phosphate binder as other calcium based binders, in reducing the serum phosphate level. The advantage of sevelamer compared to the other widely used calcium based phosphate binders is the significantly lower serum calcium level and less hypercalcemic episodes. Sevelamer therapy in chronic kidney disease patients reduces the progression of cardiovascular calcification and it has also a positive effect on cholesterol and LDL-cholesterol levels. The side effects of sevelamer therapy may be acidosis, and gastrointestinal complaints. This year the improved form, sevelamer carbonate, becomes available in Hungary. Sevelamer carbonate has similar phosphate and cholesterol binding capacity as that of sevelamer HCl, but it has several advantages: it has a positive effect on acid-base parameters, and may be administered in powder form, which is beneficial for children and for patients with swallowing disorders. The primary analysis of the DCOR study has not revealed any significant difference in the survival and cardiovascular mortality between patient groups treated with calcium based binder or sevelamer. The RIND trial data showed improved survival of new dialysis patients, who were initially treated with sevelamer. Further clinical studies are needed to kaverify the benefits of sevelamer therapy (mortality, cardiovascular calcification) in chronic kidney disease patients. The management of hyperphosphatemia in chronic renal failure is a major challenge even in the first decade of the 21th century. This is the fact, despite that recently three different groups of phosphate binders are available in the clinical practice: the calcium based binders (calcium carbonate, calcium acetate), sevelamer and lanthanum. Which is the best binder? A calcium based or a non-calcium based one? Over the past decade, these issues are in the mainstream of clinical research of nephrology.]



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Hypertension and nephrology

[Changes in endothelial cells caused by cigarette smoke]

WAGNER László, LACZY Boglárka, CSEH Judit, TAMASKÓ Mónika, MAZÁK István, MARKÓ Lajos, MOLNÁR Gergő Attila, WAGNER Zoltán, MOHÁS Márton, FEKETE Andrea, WITTMANN István

[Endothelial nitric oxide synthase enzyme is regulated through the phosphorylation of the Ser(1177) and the Thr(495) sites, which influence the biological availabilaty of nitric oxide. We examined the acute effect of cigarette smoke, which decreases nitric oxide production. Endothelial cells were treated with different concentrations and for different times with cigarette smoke buffer, then with reduced glutathione or different protein kinase inhibitors. We determined the total and the phosphorylated nitric oxide synthase levels with Western blot. Cigarette smoke increased phosphorylation in a concentration- and time dependent manner at the Ser(1177) site and more pronounced at the Thr(495) site. Besides, it also led to the dissociation of the active dimer form of the enzyme. Reduced glutathione inhibited these phosphorylations and prevented the dissociation of endothelial nitric oxide synthase enzyme. The inhibition of protein kinase A or B did not influence the effect of cigarette smoke. However, protein kinase C inhibitors increased the phosphorylation caused by cigarette smoke at Ser(1177), but decreased it at Thr(495) sites. Summarized, cigarette smoke shifts the phosphorylation of the enzyme towards an inhibitory state, further on, it leads to the dissociation of the enzymatically active form. This results in the decreased biological availabilaty of nitric oxide, in which protein kinase C may play an important role.]

Hypertension and nephrology

[News of the Hungarian Society of Nephrology]

Hypertension and nephrology

[Cardiovascular prevention in hypertensive patients - use an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker?]

BARNA István

[The primary aim of cardiovascular prevention is to reach adequate blood pressure control. To prevent the development of target organ lesion it is essential to use long-acting, well tolerable drugs without significant side effects. Angiotensin-converting enzyme (ACE) inhibitors are popular and excellent preparations but their side effects reduce life long patient compliance. Angiotensin II receptor blockers (ARBs) are effective drugs having unique tolerability and a capability to reduce cardiovascular morbidity and mortality to the same extent as the ACE inhibitors. Especially high risk patients benefit from their combination with thiazide diuretics or with calcium channel blockers. Clinical trials proved that telmisartan can be safely given and well tolerable alone or in combination to high risk cardiovascular patients, in heart and renal, peripheral vascular and cerebrovascular diseases combined or not with diabetes.]

Hypertension and nephrology

[Recognition of subclinical atherosclerosis: new results of the ÉRV Programme and the ÉRV Registry]

FARKAS Katalin, KOLOSSVÁRY Endre, JÁRAI Zoltán, KISS István

[In the ÉRV Programme of the Hungarian Society of Hypertension hypertensive patients were screened for the presence of peripheral arterial disease (PAD). Ankle/brachial index (ABI) and major cardiovascular risk factors were recorded before the five years long prospective phase of the program. A total of 21 892 hypertensive men and women (9162 males; mean age: 61.45 years) who were attended at 55 hypertension outpatient clinics in Hungary during a 17 month period, were included in the study. The prevalence of PAD defined by low ABI (≤0.9) was 14.0%. In the two blood pressure target groups (140/90 mmHg and 130/80 mmHg) the ratio of patients with controlled blood pressure was 45% and 33%, respectively. The prevalence of PAD (ABI≤0.9) was 10.9% in the controlled and 16.1% in the uncontrolled group (p<0.0001). During the control visits a significant decrease of blood pressure was observed. ÉRV Registry was initiated for ABI screening in subjects at risk for PAD in the general practice. The prevalence of PAD was 18.3%. The prevalence of PAD (low ABI value) is high in hypertensive patients. Uncontrolled hypertension increases the risk of PAD. The results indicate, that ABI screening is a simple and cost-effective method for the diagnosis of preclinical atherosclerosis, which may improve cardiovascular risk prediction.]

Hypertension and nephrology

[News of the Hungarian Society of Hypertension]

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Risk factors for ischemic stroke and stroke subtypes in patients with chronic kidney disease

GÜLER Siber, NAKUS Engin, UTKU Ufuk

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

[Importance, prevalence and therapy of vitamin D deficiency]

SZABÓ András

[Annual citations in the PubMed database on vitamin D were approximately 5000, this represents a doubling in the last decade and a 20% increase in the last year. There is renewed interest in vitamin D synthesis, metabolism and action. The two principal reasons for increased interest can be: 1. new knowledge regarding the nonhormonal, autocrine, and paracrine actions of 1,25-dihydroxylated vitamin D metabolites in man, 2. the worsening, worldwide trend to vitamin D insufficiency. Clinical vitamin D research in last years has confirmed the presence of a worldwide problem of vitamin D depletion, a problem that appears to be worsening. Largescale population based studies bear out long-held concerns that low serum 25(OH)D levels are associated with a number of adverse outcomes in the human musculoskeletal, innate immune, and cardiovascular systems. In fact, low vitamin D levels are significantly associated with all-cause mortality in the U.S. population and Hungary respectively. It is hypothesized that the global rise in incidence of obesity contributes to the worsening of the problem of vitamin D deficiency, amplifying adverse impacts on the host skeleton, immunoreactivity to microbes, and metabolic status. Finally, it should be remembered that treatment of vitamin D deficiency has two phases: restoration of 25(OH)D levels up to more than 30 ng/ml; and maintenance of the serum 25(OH)D level in that range. The present upper level (UL) of vitamin D intake that is deemed to be safe (2000 IU/day) must be re-evaluated considering data acquired over the past 15 years.]

Hypertension and nephrology

[Non-invasive evaluation of cardiovascular risk in pediatric chronic kidney disease patients]

BÁRCZI Adrienn, DÉGI Arianna Amália, KIS Éva, REUSZ György

[Cardiovascular diseases are the leading cause of mortality and morbidity in children with chronic kidney disease (CKD). Similar to adults, children with CKD experience a high burden of traditional and uremia-associated risk factors. Recent years, several studies were published in connection with cardiovascular risk factors, patomechanism, and early markers of cardiovascular diseases. Early signs of cardiomyopathy, such as left ventricular hypertrophy or dysfunction, and markers of atherosclerosis, such as increased intima-media thickness of the carotid artery or increased wall stiffness of the aorta are frequently present in early stages of CKD in children. As prevention is important in pediatrics, the evaluation of subtle changes of the cardiovascular system provide opportunity for early treatment and that enables children to develop normally and have a better long-term quality of life. Recently, newer non-invasive cardiovascular imaging modalities have been emerged to diagnose subclinical alterations of the heart and vessels in this specific population with kidney disease. In this review, we provide an overwiev of the emerging imaging techniques used to detect early subclinical organ damage in pediatric chronic kidney disease patients.]

Hypertension and nephrology

[Restless legs syndrome in patients with chronic kidney disease]

LINDNER Anett, FORNÁDI Katalin, MOLNÁR Miklós Zsolt

[The aging of the population, the high prevalence of chronic diseases and the consequent rapid increase of healthcare expenditures present a difficult challenge for the medical care system and for the society in the developed countries. Sleep disorders are increasingly recognized as very frequent chronic diseases with significant pathophysiological and psychosocial consequences. In the last 20 years an increasing number of studies reported high prevalence of sleep disorders, such as restless legs syndrome in patients with kidney disease. Chronic renal failure is the most common condition presenting with secondary restless legs syndrome. It is associated with insomnia, depressive symptoms and anxiety, impaired quality of life, as well as elevated cardiovascular risk. Compliance of the patients with restless legs syndrome is decreased, and it is more likely that they discontinue dialysis treatment. This may be related to higher mortality in kidney disease patients with restless legs syndrome.]

Hypertension and nephrology

[Cardiovascular risk assessment in chronic kidney disease, significance of left ventricular myocardial mass index]

SÁGI Balázs, KÉSŐI István, VAS Tibor, CSIKY Botond, NAGY Judit, KOVÁCS Tibor

[Introduction: Earlier studies have shown that cardiovascular (CV) mortality and morbidity in chronic kidney disease (CKD) often exceed their average population, and left ventricular hypertrophy (LVH) is an independent risk factor for CV disease. However, in CKD, the relationship between LVH, arterial stiffness (AS) and renal function has not yet been fully elucidated. Little data is available on their prognostic role. Aims of our study a) cross-sectional examination of the relationship between left ventricular mass index (LVMI), arterial vascular stiffness, and renal function, b) in our follow-up study, clarification of the LVMI, the prognostic role of AS in patients with CKD, IgA nephropathy (IgAN). Methods: In our cross-sectional study, 79 IgAN patients were examined in our clinic. The myocardial mass index (LVMI) was determined using an estimation formula after echocardiographic measurements. Arterial stiffness was measured using a photoplethizmography technique (PulseTrace) and characterized by the stiffness index (SI). The MDRD formula was used to estimate renal function (GFR) (eGFR, ml/min/1.73 m2). In the prognostic study the primary combined endpoint was total mortality, the most important CV events (stroke, myocardial infarction or cardiovascular interventions such as revascularization) and end stage renal disease. Secondary endpoints were CV and renal endpoints separately. Results: Of the 79 patients included in our cross-sectional study, 50 were men, with an average age of 46 ± 11 years. The mean value of LVMI was 106.66 ± 22.98 g/m2. Patients were divided into groups of 115 g/m2 for males considered to be abnormal and 95 g/m2 for women. LVMI is closely correlated with SI and inversely with eGFR (corr. coeff: 0.358; p <0.05 or -0.526; p <0.001). In case of LVH, SI was significantly higher in both sexes (p = 0.005 in males, p = 0.04 in females). In case of higher LVMI, renal function was significantly lower (p = 0.002 in males, p = 0.01 in females). Metabolic syndrome occurred in several cases in both sexes with LVH, but the difference was only significant in male patients (males 6 vs. 10, p = 0.008; females 2 vs. 4, p = 0.29). In our follow-up study, the presence of LVH in men significantly reduced survival in both primary and secondary endpoints, whereas in women there was no significant difference. Conclusion: In IgAN decreasing of renal function is closely related to left ventricular hypertrophy and vascular stiffness, as well as a close relationship was found between LVMI and AS. Reduced renal function is associated with an increase in LVMI and an increase in AS, which may result in a worse prognosis for both CV and renal outcomes. The underlying role of all these can be assumed to be a common vascular and myocardial pathological remodeling.]