Perspectives on hypertension's prevalence, treatment and control in a high cardiovascular risk East European country: data from the SEPHAR III survey.

OBJECTIVES: To estimate the trend in arterial hypertension's prevalence, awareness, treatment, and control in Romania, starting from the latest national survey Study for the Evaluation of Prevalence of Hypertension and Cardiovascular Risk in Romania III that has a crucial importance for the development of prevention strategies at national level. METHODS: A representative sample of 1970 Romanian adults (mean age 48.38 years, age range 18-80 years, 52.5% women, 72.58% response rate), was enrolled. During the two study visits, three blood pressure (BP) measurements were performed at 1-min interval. Hypertension was defined as study SBP at least 140 mmHg and/or study DBP at least 90 mmHg at both study visits or previously diagnosed hypertension, regardless of BP values. BP control was defined as SBP less than 140 mmHg and DBP less than 90 mmHg in hypertensive patients. RESULTS: General hypertension prevalence is 45.1% (19.1% newly diagnosed hypertension, 80.9% awareness of hypertension), increasing with age, regardless of sex and area of residence. Although the majority (72.2%) of hypertensive patients were treated (51.9% with two or more drugs), only 30.8% of them had controlled BP values. Following the evolution from the last 11 years, it is expected that in 2020 the prevalence of hypertension to be up to 44%, the awareness up to 96.2%, treatment of hypertension up to 83.7%, and BP control up to 36.6%. CONCLUSION: Hypertension's prevalence in Romania is on the rise despite the increase in awareness, treatment, and control. Possible explanations of this trend might be the increasing incidence of unhealthy lifestyle and diet, including high salt intake, and a general increase in the prevalence of obesity, diabetes mellitus, and dyslipidemia.

Arterial stiffness in dialysis patients: where are we now?

Patients with end-stage renal disease treated by chronic dialysis have an impressive mortality, which more than half of this mortality is attributable to cardiovascular disease. Despite stratification for sex, race, and the presence of diabetes, cardiovascular disease mortality is 10-30 times higher in dialysis patients compared to general population. In dialysis patients, both atherosclerosis (mainly affecting the intima of the arteries) and arteriosclerosis (affecting predominantly the media of large- and middle-sized arteries diffusely) are highly prominent. Arteriosclerosis characterized by reduced arterial compliance (i.e., reduced elasticity of the arteries) is due to increased fibrosis, loss of elastic fibers, and extensive vessel wall calcification. Arteriosclerosis is closely related to arterial stiffness. A generally accepted mechanistic view is that an increase in arterial stiffness causes a premature return of reflected waves in late systole, increasing central pulse pressure, thus systolic. An increased arterial stiffness can increase the risk of stroke through several mechanisms, including an increase in central pulse pressure, influencing arterial remodeling both at the site of the extracranial and intracranial arteries, increasing carotid wall thickness, and the development of stenosis and plaques, and the likelihood of plaque rupture. Very importantly, it was also suggested that arterial stiffness itself independently plays a role in exacerbating chronic kidney disease progression. This review deals briefly with the definition of arterial stiffness, methods of measuring arterial stiffness and pathophysiology of arterial stiffness, and factors related with arterial stiffness.

The role of the renin-angiotensin-aldosterone system in renal artery stenosis, renovascular hypertension, and ischemic nephropathy: diagnostic implications.

The renin-angiotensin-aldosterone system (RAAS) has an impressive pathophysiology and numerous systemic correlations, as it is a major regulatory system of vascular and renal function. RAAS represents an important player in the pathogenesis of renal artery stenosis (RAS) and ischemic nephropathy. The activation of the RAAS and sympathetic overactivity are highly responsible for the cardiovascular and renal morbidity in RAS patients. The evaluation of the RAAS activity remains an unsolved issue in the clinical assessment of RAS/ischemic nephropathy with important therapeutic consequences. Selection of patients with RAS for revascularization procedures is based on the benefit in terms of renal function improvement/stabilization and improvement of BP control. Unfortunately, this issue still remains a major challenge for nephrologists.

Trace elements in end-stage renal disease--unfamiliar territory to be revealed.

Although associated with unfavorable outcomes in the general population, abnormal blood levels of various trace elements have not been consistently studied in the end-stage renal disease population (with the notable exception of aluminum). This is surprising, as the uremic patient treated by chronic dialysis loses one major route of trace element excretion and is exposed systematically to a foreign environment (the dialysis fluid) possibly contaminated with significant amounts of potential deleterious trace elements. Moreover, some biological important trace elements may be lost through the dialysis membrane. Most studies to date demonstrated significantly altered blood levels of trace elements in ESRD patients compared to healthy controls. However, the biological impact of these abnormalities in renal disease is largely unknown and should be clarified by future studies. A further step would be the design of well-controlled randomized interventional studies, examining the potential therapeutic benefit of supplementing one or more trace elements in ESRD patients, a population characterized by an impressive mortality due to cardiovascular, infectious and neoplasic disease.

Direct renin inhibitors: ONTARGET for success?

Direct renin inhibitors are the first new class of antihypertensive to emerge since angiotensin II receptor blockers. We discuss their reno- and cardioprotective potential, based on extrapolation from animal models and phase three trials that are currently ongoing. This paper reviews the potential benefits of direct renin inhibitors (DRIs), the only new anti-hypertensive class developed in the last decade, as compared to pre-existing classes of drug inhibiting more downstream, such as Angiotensin Converting Enzyme inhibitors (ACEI), Angiotensin 2 Receptor Blockers (ARBS).

Factors affecting the quality of life of haemodialysis patients from Romania: a multicentric study.

BACKGROUND: The quality of life (QoL) is an important predictor of outcome in end-stage renal disease (ESRD) patients. Therefore, QoL needs to be regularly assessed in this setting. Our study describes QoL, as well as demographic and clinical variables associated with QoL in chronic haemodialysis (HD) patients in Romania. METHODS: All prevalent chronic HD patients (N = 709; mean age 51.7 +/- 12.6 years) in 12 dialysis centres from the three main regions of Romania were included in the study. Six hundred and six of these completed the Short-Form Health Survey (SF-36) and the Kidney Disease Quality of Life Questionnaire-Short Form (KDQOL-SF). RESULTS: The mean physical component summary (PCS) score was 46.3 +/- 19.2, and the mean mental component summary (MCS) score was 55.1 +/- 19.3. These figures were lower than those previously described in non-dialysis age-matched Romanian individuals. The mean kidney disease summary component (KDSC) score was 68.3 +/- 11.3, similar to other studies. The worst dimension of QoL was work, whereas the best ones were cognitive function and quality of social interaction. We found older age, female gender, lower socio-economic status and higher educational level to be associated with lower QoL scores. CONCLUSIONS: The QoL of HD patients in Romania is lower than that in the general population. Our results suggest that at least one-third of these patients might be considered for rehabilitation therapy, in order to try and prevent complications and mortality.

Balkan endemic nephropathy: a still unsolved puzzle.

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial renal disease, occurring in certain regions in 5 countries of the Balkan peninsula. Its etiology is largely unknown, though several hypotheses have been formulated and are discussed in this review. In several cases, etiological hypotheses (e.g., viral, ochratoxin or trace element involvement) are verified only in local endemic areas and can not be confirmed when tested elsewhere. Only certain families in the endemic areas are affected. An exposure of at least 20 years to the unknown factors in the endemic areas seems to be mandatory for the development of the disease, but a genetic predisposition to this disease also seems to be mandatory. Prominent clinical features are severely shrunken kidneys, a more severe anemia relative to the level of renal function, and a slow progression to end-stage renal failure. An international approach to solving the etiological and pathogenetic enigma of BEN is needed in the coming years. It is also time to reevaluate other chronic, slowly progressive tubulointerstitial nephropathies diagnosed elsewhere in the world and to search for possible etiological similarities with BEN.

Sleep disorders: a systematic review of an emerging major clinical issue in renal patients.

The prevalence of sleep disorders is significantly higher (up to 80%) in patients with chronic uremia compared to the general population. Sleep disorders appear even in the early stages of chronic kidney disease. These disturbances are complex, including difficulties in falling asleep and awakening, interrupted sleep, nightmares, restless legs syndrome, sleep apnea syndrome, etc. There are still disagreements on the major etiological factors of sleep disorders in the uremic patient. Older age, long dialysis vintage, alcohol and tobacco abuse and, particularly, the presence of significant comorbidities are major determinants of sleep disorders in dialysis patients. Proper assessment of sleep disorders in the renal population is still under investigation; recent studies have mostly addressed patients' perception based on questionnaires. More precise polysomnographic assessments are less studied in renal patients. Sleep disorders significantly affect quality of life in dialysis patients. An accurate and early identification of such disturbances would lead to a significant improvement in quality of life, and probably also in outcome, in uremic patients. Sleep apnea syndrome is extremely frequent in dialysis patients, with obvious consequences for cardiovascular morbidity and mortality. Proper diagnosis and therapy of sleep apnea syndrome could significantly reduce cardiovascular risk. Although sleep quality improves after renal transplantation, allograft recipients still have significantly more sleep disorders than healthy individuals. Here, we review recent data on sleep disturbances in renal patients, focusing on the end-stage renal disease patient treated by dialysis.

Current dilemmas in inhibiting the renin-angiotensin system: do not forget real life.

For a long time, the inhibition of the renin-angiotensin-aldosterone (RAA) axis has been considered a must in almost all patients with progressive chronic kidney disease (CKD), with the aim of reducing the rate of progression to end-stage renal disease (ESRD). However, recent data from a meta-analysis, including the ALLHAT study, and a study in Canadian diabetic patients questioned the usefulness of angiotensin converting enzyme (ACE) inhibition in delaying the onset of dialysis. Publication of these data led to an intensive recent debate among reputed nephrologists, with numerous pros and cons regarding the pharmacological influence of CKD progression. The authors of the present review critically discuss the arguments and counterarguments of this challenging debate. Finally, a cautious view for the practicing nephrologist is expressed, highlighting the difference between study patients and real-life patients, and the possible overlooked aspects of recent renal protection studies (the importance of central blood pressure, of ambulatory blood pressure monitoring and possible, the impact of angiotensin converting inhibitors on stroke), are presented.

Causes and consequences of increased arterial stiffness in chronic kidney disease patients.

Cardiovascular (CV) morbidity and mortality is greatly enhanced in patients with chronic kidney disease, compared to the non-renal population. One key element of this high CV burden appears to be arterial stiffness, as an expression of premature vascular aging. Increased arterial stiffness in renal patients may be a consequence of vascular calcification, chronic volume overload, inflammation, endothelial dysfunction, oxidative stress and several other factors. The authors review briefly the main pathophysiological mechanisms leading to reduced arterial compliance. Increased arterial stiffness has significant clinical consequences: isolated systolic hypertension, left ventricular hypertrophy (and failure), and reduced myocardial perfusion. Better knowledge of the mechanisms of arterial functional and morphologic alteration may help in developing more refined therapeutic strategies aimed to reduce the high CV burden in chronic kidney disease. The potential therapeutic interventions - mainly the use of certain antihypertensive drugs and reduction of vascular calcification - are finally discussed.

Acute liver failure due to leptospirosis successfully treated with MARS (molecular adsorbent recirculating system) dialysis.

BACKGROUND: Leptospirosis is a re-emerging infectious disease, which may lead to multiple organ failure (MOF)and death. CASE PRESENTATION: We report the first case of severe leptospirosis complicated with acute renal and liver failure, successfully treated with albumin dialysis--molecular adsorbent recirculating system (MARS). Despite antibiotic therapy, optimum medical supportive treatment and timely initiated haemodialysis, the outcome was complicated by severe liver failure: hepatic encephalopathy grade III, hypoglycemia, prominent hyperbilirubinemia (TBIL 31.3 mg/dl, DBIL 28.6 mg/dl)and hepatic cytolysis (ALT 535 IU/l, AST 179 IU/l) and prolongation of the prothrombine time (68.4 sec). The patient underwent two sesions of albumin dialysis with the MARS procedure with complete recovery of hepatic and renal function. CONCLUSION: Albumin dialysis may confer a significant survival benefit on patients with leptospirosis-induced acute liver failure (ALF).

Serial echocardiographic changes in patients on hemodialysis: an evaluation of guideline implementation.

BACKGROUND: Few studies have addressed the description of serial changes in left ventricular mass (LVM) and relevant risk factors. All these studies were initiated before the implementation of EBPG or K/DOQI guidelines. The aims of our study were to prospectively describe trends in left ventricular (LV) structure and function, evaluate risk factors for progression of LVM derived from serial echocardiographic measurements starting January 2003, 6 months after full implementation of EBPG in our unit. METHODS: One hundred seventy-six patients were enrolled at baseline, between 1 January 2003 and 1 October 2004; 33 patients were excluded from analysis due to poor echocardiographic window, 14 patients died and 26 were transplanted or transferred during the follow-up period of minimum 12 months. One hundred and three patients were included in the final analysis (mean age 51 years, mean follow-up 24.1 +/- 14.4 months). Echocardiography was performed at inclusion and at the end of study. Biochemical, blood pressure (BP) and medication data were collected and the means of monthly values were used. RESULTS: At baseline, 86.4% of the patients had left ventricular hypertrophy (LVH) (56.3% concentric hypertrophy, 30.1% eccentric hypertrophy, 6.8% concentric remodeling and only 6.8% normal LV geometry), 25.6% had systolic dy-sfunction and 50.5% had abnormal LV volume index (LVVI). Similar data were recorded at follow-up (82.5%, 44.7%, 37.9%, 7.7%, 9.7%, and 19.5%, respectively). Baseline left ventricular mass index (LVMI) significantly correlated with hemoglobin (Hb) and total protein level. LVMI at follow-up correlated to Hb, SBP, PP, mean level of serum phosphate, calcium x phosphate product and cholesterol. Independent predictors for LVMI (multiple regressions) were anemia and mineral metabolism markers. In our population, 62.1% of the patients had a regression of LVMI, with a mean decrease in LVMI of 12 g/m 2 (1.7 +/- 11.7 g/m 2 /month) over more than 12 months of guideline implementation. Regressors had a significant improvement of anemia, serum phosphate level and calcium x phosphate product (p<0.05). CONCLUSION: Our study suggests that a holistic interventional approach, targeting various pathogenic mechanisms, as per guidelines, can elicit at least a partial regression in LV structural and functional abnormalities in hemodialysis patients.

Analysis of safety and efficacy of pegylated-interferon alpha-2a in hepatitis C virus positive hemodialysis patients: results from a large, multicenter audit.

BACKGROUND: Hepatitis C virus (HCV) infection rates are still high in hemodialysis (HD) centers in developing countries. Standard interferon (IFN) monotherapy is associated with good results in HCV-positive patients (more than 30% rate of sustained virological response) but with poor tolerance. Pegylated interferon (PEG-IFN) is better tolerated and has a more sustained antiviral effect in the general population. There have been no large trials to date with PEG-IFN in hemodialysis populations. METHODS: We report the largest series to date of HCV+ HD patients (n=78) treated with PEG-IFN alfa -2a 135 microg s.c. weekly monotherapy. The primary outcomes were (a) efficacy - assessed by the viral response at 12, 48 weeks and 6 months after completion of therapy, and (b) rate of serious adverse events. RESULTS: In 48/78 (61.5%) patients an early (12 weeks) viral response was obtained. Viral end-of-treatment response (ETR) was evaluated in the 21 patients (26.9%) who reached week 48 on therapy: only 15 subjects (19.2% of the initial population) had undetectable HCV-RNA levels. In these 15 patients, a sustained viral response (SVR) was recorded in 11 - i.e. 14.1% of the initial intention-to-treat (ITT) population. A high prevalence of noncompliance (32%) and of adverse events (83%) was recorded; minor adverse effects (flu-like syndrome, mild-to-moderate thrombocytopenia, leukopenia and anemia) responded to symptomatic therapy or dose reduction, but often caused lack of compliance. The incidence rate of serious adverse events was 0.19/patient-year (median time to event 20.5 weeks), and incidence of deaths was 0.11/patient-year. CONCLUSIONS: In dialysis patients, PEG-IFN alfa -2a is poorly tolerated and associated with a high number of serious adverse events, causing a significant lack of compliance/discontinuation of therapy. In this largest HCV-positive hemodialysis population survey, we report a low sustained viral response in an ITT analysis, compared with previously published historical data using non-PEG-IFN, a low compliance rate and an unsatisfactory overall safety profile, not supporting the superiority of PEG-IFN monotherapy.

Once-every-2-weeks and once-weekly epoetin beta regimens: equivalency in hemodialyzed patients.

BACKGROUND: Currently, less frequent than once-weekly subcutaneous epoetin administration regimens were shown to be equally effective and safe as once-weekly schedules in stable predialysis and peritoneal dialysis patients. Bioequivalency of once-every-2-weeks and once-weekly subcutaneous administration of the same total dose of epoetin beta for the maintenance phase of anemia treatment in stable iron-replete long-term hemodialysis patients therefore was investigated prospectively. METHODS: Two hundred seven stable selected hemodialysis patients without diabetes, acute illness, significant inflammation, malnutrition or hyperparathyroidism administered once-weekly subcutaneous epoetin beta and preserving stable hemoglobin levels between 10 and 12 g/dL (100 and 120 g/L; difference between maximum and minimum of 3 subsequent levels

The epidemics of cardiovascular disease in elderly patients with chronic kidney disease--two facets of the same problem.

There is increasing evidence that even mild renal dysfunction is a novel potent cardiovascular risk factor in the general elderly population. With more severe renal impairment, cardiovascular risk increases proportionately. This issue deserves attention, as chronic kidney disease (CKD) is predominantly a disease of the elderly, and the mean age of end-stage renal disease patients entering dialysis is growing constantly. In the dialysis population, when clinically significant cardiovascular disease (CVD) (particularly congestive heart failure) is present, survival is worse. Thus, every effort should be made to identify and treat cardiovascular risk factor in the early stages of CKD. However, elderly renal patients receive less proper cardiovascular therapy compared to non-renal subjects of the same age. This review deals briefly with the most significant data published in the last decade on CVD in elderly with CKD.

Arterial wave reflections and mortality in haemodialysis patients--only relevant in elderly, cardiovascularly compromised?

BACKGROUND: Chronic kidney disease (CKD) patients have a 3-30-fold increased risk of death compared with the general population. This mortality difference is even more pronounced in younger subjects. Two markers of aortic stiffness--aortic pulse wave velocity (PWV) and augmentation index (AIx)--have been prospectively related to all-cause and cardiovascular (CV) mortality in end-stage renal disease (ESRD) populations. The aims of our study were first, to confirm the important deleterious effect of arterial stiffness in uraemia and second, to assess the impact on survival of increased AIx in a relatively young non-diabetic dialysis population, with minimal CV disease. METHODS: Ninety-two patients (mean age 42.6 +/- 11.2 years) were included in the study and followed for a period of 61 +/- 25 months. None of the patients had diabetes mellitus, and only 3.3% had prior history of CV disease. AIx was determined by applantation tonometry using a SphygmoCor device (AtCor, PWV Inc., Westmead, Sydney, Australia). RESULTS: Mean AIx in our study population was 19.9 +/- 13.7%; other significant haemodynamic parameters were: systolic blood pressure (SBP) 129 +/- 24 mmHg, pulse pressure 35.3 +/- 17.5 mmHg with 27.2% of the study population receiving angiotensin-converting enzyme inhibitors (ACE-I). On univariate analysis, in our group AIx correlated with: body weight (P < 0.001), radial SBP (P < 0.001) and haemoglobin levels (P < 0.05). There was no correlation between AIx and any of the echocardiographic parameters. In the stepwise multiple regression analysis, the only independent predictors for AIx were weight (P < 0.001), SBP (P < 0.001) and haemoglobin (P < 0.05) with the model explaining 33% of the AIx variability (adjusted R(2) = 0.33). During the follow-up period, 15 deaths were recorded. In the Cox analysis (P = 0.014; chi square 20.7 for the model) the only independent predictors for all-cause mortality were age (P = 0.001), left ventricular mass index (P = 0.032) and ACE-I therapy (P = 0.039) while AIx did not reach statistical significance. There was no difference in patients' survival when divided by AIx tertiles, assessed by the log rank test (P = 0.78). CONCLUSION: Our results fail to support the notion that an increased effect of wave reflections on central arteries is a strong and independent predictor of mortality in all ESRD patients on haemodialysis. The effect of arterial wave reflections might be in fact dependent on patient age and concurrent comorbidity status.