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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.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.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%.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.

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.

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.

The end-stage renal disease (ESRD) population treated by dialysis has grown remorselessly over the last five decades, in all continents. This growth is already a major burden to the healthcare economies of wealthy countries, and is thus a challenge for policy makers, health care providers and financial planners [1]. Fortunately, recent data (just published in NDT) suggest a stabilization/decline in the incidence of ESRD in some developed countries, possibly related to the successful implementation of renoprotective strategies in pre-dialysis chronic kidney disease (CKD) [2,3]. Dialysis patients have an impressive and worrying mortality, comparable to or worse than that seen in many cancers, e.g. 20–25% annualized mortality in some systems [4]. Around 50% of this increased mortality is due to cardiovascular (CV) disease. This is explicable, as at the start of dialysis, up to 80% of subjects already have at least subclinical CV disease. Despite significant progress in many branches of medicine over the last decades—for example, significant reductions in myocardial infarction and stroke rates in the general population [5,6]—mortality rates for dialysis patients remain practically unchanged [4,7] over the same time period. This is first explained by more liberal criteria for inclusion in renal replacement therapy (RRT) programmes, with more elderly, diabetic and CV-diseased patients treated by dialysis in recent years. Second, CV disease in ESRD is often underinvestigated and undertreated, compared to CV disease in non-renal cohorts [8]. Third, therapeutic interventions in dialysis patients aimed at reducing CV morbidity and mortality may be either ‘too little, too late’ or inadequate, as most traditional and uraemia-specific [9] risk

Both chronic kidney disease (CKD) and type II diabetes mellitus (DM) are increasing in frequency among Western populations and both are potent risk factors for the development of anaemia. The presence of CKD and diabetes together represent the most important aetiopathogenic combination for the development of anaemia. New evidence has highlighted some of the underlying mechanisms which make diabetic patients more susceptible to dyserythropoiesis, particularly once they have developed concomitant CKD. In addition, recent publications from large-scale epidemiological studies have highlighted the impact of anaemia on diabetic patients. The purpose of this review was to focus on the pathophysiology and impact of anaemia in DM.

Leptospirosis is a re-emerging infectious disease, which may lead to multiple organ failure (MOF)and death.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.Albumin dialysis may confer a significant survival benefit on patients with leptospirosis-induced acute liver failure (ALF).

Due to the wide use of radiocontrast agents (RCA) in modern radiology and interventional cardiology, the incidence of radiocontrast-induced nephropathy (RCIN) is increasing. The risk factors for RCIN are primarily pre-existing (even mild) renal dysfunction, diabetes mellitus, absolute or relative hypovolemia, nephrotoxic drugs, etc., particularly in elderly patients. The presence of these risk factors seems to be more important than the type of contrast agent used. To date, there are several certainties and controversies in the prevention of RCIN. Hydration with normal saline and/or bicarbonate administration pre-and post-intervention is certainly useful. Though controversial, N-Acetylcysteine administration may be still advisable. Recent investigations showed the benefits of aminophylline/theophylline administration in RCA-induced renal tubular toxicity. Conventional hemodialysis cannot prevent RCIN, but may potentially aggravate renal dysfunction through hemodynamic instability. “High-flux” hemodialysis and hemodiafiltration may contribute efficiently to RCIN prevention, but systematic use of these modern dialysis techniques is limited by high costs and availability. The authors review — in a systematic manner, and in the perspective of evidence-based medicine — the most important data from literature concerning the prevention of RCIN.

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.

data from large well-conducted trials and the perception that what is true in the general population may not be equally efficient in renal patients. Particularly in the case of aldosterone antagonism, the fear of life-threatening hyperkalaemia (and of endocrine side effects) with spironolactone in dialysis patients may severely limit the large-scale clinical usage of this antialdosteronic drug. However, the same fears arise with angiotensin-converting enzyme (ACE) inhibition and angiotensin-receptor blockade years ago, whereas ACE inhibitors (ACEI) and angiotensin-receptor blockers (ARB) are nowadays well accepted in routine clinical practice in chronic uraemia subjects. Nevertheless, combining aldosterone with ACEI may further increase the hazard of life-threatening hyperkalaemia in patients of older age, with diabetes, prone to dehydration and with worsening heart failure [9]. We will discuss later the issue of safety of spironolactone in dialysis populations.

Background. Epidemiological data of renal disease are available from large national renal biopsy registries from Central and Western European countries; in contrast, detailed epidemiological data from Eastern European countries are missing. This report is the first review of histological data, over a period of 10 years (1995–2004), covering a population of over 6 million inhabitants and two distinct regions from an East European country – Romania. Methods. 635 eco-guided kidney biopsies from the Moldova (North-Eastern Romania, 8 counties, 4 754 048 inhabitants) and Banat (Western Romania, 3 counties, 1 454 747 inhabitants) regions were analysed. Data on serum creatinine concentration (sCr), 24 h proteinuria, haematuria, clinical diagnosis, histological diagnosis and complications after renal biopsy were collected. Results. The number of biopsies performed varied between 10.9 p.m.p./year in 1995 and 11.3 p.m.p./year in 2004. The most common clinical syndromes – as indication for performing the renal biopsy – were: nephrotic syndrome (52.3%), followed by nephritic syndrome (21.9%), acute renal failure (ARF) (12.4%), chronic kidney disease (CKD) (10.2%) and asymptomatic urinary abnormalities (AUA) (3.3% of the cases). The major histological groups identified were: primary glomerulonephritis (GN) (66.2%), secondary GN (26.4%), vascular nephropathies (2.3%), and tubulointerstitial nephropathies (TIN) (1.5%) of the cases. Among primary GN’s, the most frequent diagnoses were: membranoproliferative GN (MPGN) (29.4%, incidence in 2004 – 9.3 p.m.p./year), mesangioproliferative GN (MesGN) (28.9%, incidence – 10 p.m.p./year), membranous GN (MGN) (11.2%, incidence – 5.3 p.m.p./year), minimal change disease (MCD) (8.5%, incidence – 7.3 p.m.p./year), focal and segmental glomerulosclerosis (FSGS) (11.5%, incidence – 3.3 p.m.p./year) and crescentic GN (CGN) (7.9%, incidence – 3.3 p.m.p./year). The prevalence of membranoproliferative GN significantly decreased from 1995 to 2004. The prevalence of different types of secondary GN was similar to Western and Central European countries, with the particular difference of higher infectious diseases associated GN. Conclusion. The present data are an important contribution to the epidemiology of renal diseases in Europe, highlighting not only numerous similarities but also significant epidemiological differences in Western and Central European countries, particularly a higher, albeit declining, incidence and prevalence of membranoproliferative GN. This report represents the basis for the future of Romanian Registry of Renal Biopsies and is intended to serve as a source of information for nephrologists concerned with East European renal pathology.

Background. Measures of aortic stiffness—aortic pulsewave velocity (PWV) and augmentation index (AIx)—have been shown to be powerful predictors of survivalin adult haemodialysis (HD) patients. Very few datahave been reported regarding arterial stiffness inpaediatric renal populations.Methods. PWV and aortic AIx were determined fromcontour analysis of arterial waveforms recorded byapplanation tonometry using a SphygmoCor device in14 children on HD (age¼14.1 years) and in 15 age,height matched children controls.Results. Pre-HD AIx (29.7±15.4%) and PWV(6.6±1.0m/s) were significantly higher compared withchildren controls (8.3±8.0% and 5.4±0.6m/s, respec-tively, P

According to recent data, arterial stiffness is a major independent risk factor for cardiovascular morbidity and mortality in both the general and renal populations. Because of several factors (vascular calcifications among them), large arteries are stiffer in patients with chronic kidney disease compared with the nonrenal population, contributing to the enormous cardiovascular mortality in renal patients. This review briefly analyzes methods for determination of arterial stiffness, focusing on 2 parameters, pulse wave velocity and the augmentation index, particularly useful in assessing arterial compliance in renal patients. Effects of different methods of renal replacement therapy on arterial wall properties also are discussed. Finally, the most promising novel and/or potential therapies regarding reduction of arterial stiffness in renal patients are reviewed.

Background Measurements of aortic stiffness [aortic pulse wave velocity (PWV) and augmentation index (AIx)] have been established as powerful predictors of survival on hemodialysis (HD). Abnormal endothelial-dependent and endothelial-independent vascular reactivity and increased arterial stiffness are commonly described in HD patients. There is, however, a lack of information on the comparative impact of different renal replacement therapies (RRTs) on PWV and AIx, and how these different methods might influence endothelial-dependent abnormal vasodilatation. Objective To describe in a cross-sectional design arterial compliance and distensibility in continuous ambulatory peritoneal dialysis (CAPD) versus HD versus renal transplant (RTx) patients, compared with age- and blood pressure-matched essential hypertensive controls. The PWV and aortic AIx were determined from contour analysis of arterial waveforms recorded by applanation tonometry in 40 CAPD, 41 HD, 20 RTx patients (with normal serum creatinine), and 20 controls with essential hypertension (all normotensive under treatment). Endothelial-dependent and endothelial-independent vascular reactivities were assessed by changes in AIx following challenges with inhaled salbutamol and sublingual nitroglycerin respectively. Results CAPD patients had significantly stiffer arteries than all other categories. The PWV was 8.29 ± 1.09 m/second in CAPD patients, significantly higher ( p < 0.05) compared to HD subjects (7.19 ± 1.87 m/s). Both dialysis subgroups had significantly higher PWV values compared to RTx patients (6.59 ± 1.62 m/s) and essential hypertensive controls (6.34 ± 1.32 m/s), p < 0.05. The AIx had a profile similar to PWV in different RRTs. All groups with the exception of CAPD subjects had a significant decrease in AIx following salbutamol. Moreover, the vasodilatation induced by either nitroglycerin or salbutamol was significantly blunted compared to HD. Overall, both dialysis categories had more abnormal responses compared to RTx patients and essential hypertensive controls. Conclusion CAPD is associated with stiffer arteries and more profoundly abnormal endothelial-dependent vasomotor function, compared to matched HD subjects. These differences in arterial physical properties might explain differences seen in cardiac structure and function between the RRTs.

BACKGROUND Patients with end-stage renal disease on dialysis have among the highest cardiovascular event rates documented. Abnormal nitric oxide (NO)-dependent endothelial reactivity and increased arterial stiffness are commonly described in hemodialysis (HD) patients. Measures of aortic stiffness--aortic pulse wave velocity (PWV) and augmentation index (AGI)--have been shown to be powerful predictors of survival on hemodialysis. It is not known how these parameters interfere with successful renal transplantation. METHODS PWV and aortic AGI (difference between the first and second systolic peak on the aortic pressure waveform divided by the pulse wave height) were determined from contour analysis of arterial waveforms recorded by applanation tonometry using a SphygmoCor device in 41 HD patients (20 men; age, 41.8 years) and in a control group of 20 patients with essential hypertension (HTA) (10 men; age, 43.6 years). Twenty of the HD patients (10 men; age, 39.7 years) received live-related renal transplants (RTx) and were restudied (3 months after RTx, normal serum creatinine). NO-dependent and NO-independent vascular reactivity were assessed by changes in AGI after challenges with inhaled salbutamol (SAL) and sublingual nitroglycerin (NTG), respectively. RESULTS AGI values were significantly lower in RTx patients compared with subjects on hemodialysis (15.9 +/- 13.9% vs. 27.9 +/- 11.9%, P

Background: Acute liver failure (ALF) because of mushroom poisoning is associated with a high mortality (particularly in children), despite optimal medical therapy (OMT), including charcoal haemoperfusion and haemodiafiltration. MARS is a new, cell-free, extracorporeal liver assistance method utilizing an albumin dialysate for the removal of albumin-bound toxins. Methods: We describe the first series in the literature (also first MARS treatments in Romania) with ALF because of mushroom poisoning in children (M/F ¼2/4, age ¼ 7-16 years). Liver function was evaluated pre-MARS and 15-min post-MARS, 24 h following each treatment and 30 days post-MARS. Findings: All patients had severe hepatic dysfunction: hepatic encephalopathy (HE; four grade II, one grade III, one grade IV), ALT ¼ 4082 (3400-5600) IU/L, bilirubin ¼ 6.3 (2-10) mg/dL, prothrombin time (PT) ¼ 52.5 (23-141) s. MARS was uneventful and well-tolerated. Two 6-h sessions per patient were performed with a similar immediate impact on liver tests: mean drop in ALT of � 33 and � 35%, respectively, and in bilirubin of � 39 and � 36%, respectively. ALT levels 24 h following MARS-1, remained unchanged but continued to drop by a further � 28% following MARS-2. By contrast, all patients had a significant rebound in bilirubin (þ39%) 24 h following MARS-1; however, following MARS-2 a rebound was seen only in two cases (þ220%). PT improved by 37% after MARS-1 and normalized in four patients after MARS-2. Outcome: Four patients survived and completely recovered the hepatic function. Negative prognostic markers: lack of complete correction of PT, continuous rebound and increase in bilirubin, and lack of improvement in HEpost-MARS-1. Survival in six well-matched cases, treated by OMT ¼ 0/6 (P < 0.05). Conclusions: MARS is a safe and highly effective depurative therapy in children with ALF. Survival is predicted only by the impact/results of the initial MARS sessions and not by any of the baseline parameters.

Background. Renal involvement [as acute renal failure (ARF)] is a prominent feature of both mild and severe leptospirosis—a re-emerging infectious disease. Few large series describe in detail clinical and laboratory features of cases with ARF and their outcome. Methods. We performed a retrospective analysis (1997–2001) of all consecutive, serological confirmed leptospirosis cases with ARF (ns58, 53 male, age 44" 13 years, rural residentss31%, animal contacts88%. Results. Clinical manifestations ()50% prevalence): oliguria 95%, fever and jaundice 93%, nausea and vomiting 83%, haemorrhagic diathesis 80%, headache, hepatomegaly 76%, myalgias, abdominal pain 70%, hypotension 62%, disturbed consciousness 50%. A pattern of multiple organ failure (MOF) was frequent: ARF together with hepatic failure in 72%, respiratory failure in 38%, circulatory failure in 33%, pancreatitis in 25% and rhabdomyolysis in 5% of cases. Renal dysfunction: 35% of cases had a renal K q -wasting defect and 43% a FENa )1% and low-osmolarity urine despite volume depletion. Haematuria was encountered in 12 and mild proteinuria in 10 subjects. Outcome: 26% deaths, 64% normal hepatic and renal function at 90 days from presentation (however 29% maintained the initial tubular defect), 10% persistent mild renal failure. All deceased patients had, beside ARF, at least two other organ failures, affected consciousness, and haemorrhagic diathesis vs a prevalence for the above features of only 34, 33, and 72%, respectively, in the survivors group (P-0.05). Conclusions. Leptospirosis presenting with ARF is a severe disease, frequently leading to MOF and to death in one-third of the patients. In particular, the haemorrhagic diathesis and cerebral involvement are markers for unfavourable patient and renal outcomes.

BACKGROUND HD has been reported to determine an increase in QTc interval and QTc dispersion (QT(max)-QT(min))-risk factors that predispose to severe ventricular arrhythmias and sudden death. However, most studies have included end-stage renal disease (ESRD) patients with significant heart pathology. We therefore aimed to study the impact of a single HD session in subjects without manifest cardiac disease. METHODS Sixty-eight stable, non-diabetic HD patients (47.1% males, age 40.2+/-12.7 years, HD duration 57+/-36 months and 37% hypertensive), with normal maximal ECG stress test and sub-endocardiac viability index and without ECG left ventricular hypertrophy were included. QT interval was calculated 10 min pre- and post-HD, as an average of three consecutive complexes, and corrected for heart rate using Bazett's formula (QTc=QT/(R-R)(1/2)). Na(+), K(+), Ca(2+), PO(4), pH and BP levels were also determined pre- and post-HD. RESULTS The QTc interval increased significantly post-HD to 434+/-29 from 421+/-26 ms pre-HD (P=0.005); an abnormally prolonged QTc (>440 ms) was recorded in 34% cases pre-HD and in 46% post-HD, i.e. 1.5-2.3 times higher than in the high risk EURODIAB IDDM population. However, this effect was not homogeneous. Only 47 subjects had an increase in QTc duration after a dialysis session, while in 21 a decrease in QTc duration was recorded. The increase in QTc post-HD correlated with Ca(2+) homeostasis. Patients with greater increases in QTc after dialysis had higher baseline plasma calcium levels (r=0.47, P

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.

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 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).

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.

Nephrology societies and dialysis registries are reporting a dramatic increase in the number of elderly patients who require dialysis. During the last decade the number of patients starting renal replacement therapy (RRT) has increased for all ages but the increase for patients over the age of 75 years has been particularly dramatic, with a 4.3-fold rise in the USA [1]. In view of this development, it is necessary to examine more closely the quality of the results (survival, selected technique, and morbidity) of kidney replacement therapy in this age group. Despite the fact that very old patients raise the most difficult problems with respect to indication and dialysis therapy management because of their multiple comorbidities and presumed short life expectancy, there are few studies devoted to very old end-stage renal disease (ESRD) patients and their conclusions are rather discordant. Some studies report very poor survival of very old patients on dialysis, whereas others report more favorable outcomes. Moreover, specific predictive factors that could help in deciding whether dialysis would offer pre-ESRD old patients substantial prolongation of life expectancy with an acceptable quality of life are lacking [2]. Below we discuss in more depth the reasons why, in general, dialysis should not be withheld from patients above 75 years of age. Let us first consider the title of this controversy: ‘‘The dilemma of renal replacement therapy in patients over 75 years.’’ Is this actually a dilemma? Basically, a dilemma is characterized by the need to choose between two evils, or in the present case between two possibilities. If the question is posed ‘‘should 75-year-old patients be started on dialysis: yes or no?’’ it is sensible to ask the question the other way round. What could be the reasons for not providing them with dialysis? Is the survival time too short? Is the quality of life that can be achieved unsatisfactory? Are there so many old people above 75 years of age and dialysis facilities are insufficient? Do financial constraints make age a matter of rationing? Good survival on dialysis for the very old is currently well documented. Shaefer and Rohrich showed that survival in very old patients after 12 months from the start of dialysis treatment was 70.5%, and after 24 months 50.3%, and after 60 months 18.5%. These results provide no rationale for withholding dialysis treatment, even when life expectancy of over 75-year-old dialysis patients is compared with that of younger dialysis patients. In fact 75-year-old dialysis patients have a life expectancy of only 36% of age-matched healthy controlled individuals. Therefore, the remaining life time is, M. Busuioc P. Gusbeth-Tatomir A. Covic (&) Nephrology Clinic and Dialysis Center, Parhon University Hospital, ‘‘Gr.T. Popa’’ University of Medicine and Pharmacy, Carol 1st Blvd. Nr. 50, Iasi 700503, Romania e-mail: acovic@xnet.ro

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.

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.

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.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.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.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.

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.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.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 (p0.05).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.

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.

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 ≤2.5 g/dL [≤25 g/L]) and optimal iron status for at least 8 weeks before inclusion were enrolled and randomly assigned to subcutaneous administration of the same total dose of epoetin beta either once every 2 weeks (group 2w; n=104) or once weekly (group 1w; n=103) for 24 weeks. Results: Per-protocol analyses (group 1w=102 versus group 2w=101) showed similar hemoglobin levels throughout the assessment period (weeks 13 to 24): mean, 11.38 g/dL; 95% confidence interval (CI), 11.23 to 11.54 versus 11.41 g/dL; 95% CI, 11.22 to 11.58. Mean difference was 0.028 g/dL (95% CI, −0.208 to 0.264) in the prespecified range (±0.5 g/dL). Epoetin dose ratio of group 2w to group 1w was 0.94 (95% CI, 0.813 to 1.076), also in the prespecified range of equivalence (0.80 to 1.25). Hemoglobin levels and epoetin doses were stable during the study irrespective of treatment schedule, with no differences between groups at any time. Both schedules were well tolerated. Conclusion: Once-every-2-weeks and once-weekly subcutaneous epoetin beta regimens are equivalent in the maintenance phase of anemia treatment in long-term stable hemodialysis patients without diabetes, with similar safety profiles.

Background. Abnormalities of diurnal blood pressure (BP) rhythm (nondipping) are well-described in dialysis patients, and have prognostic importance. It is controversial whether successful renal transplantation (RTx) improves diurnal BP rhythm. To date, no study has attempted to define and model the evolution of diurnal BP rhythm profiles from dialysis to engraftment, focusing on the immediate (4-6 weeks) and medium-term (>1 year) postengraftment periods. Methods. To test if kidney transplantation normalizes the BP profile, ambulatory blood pressure monitoring (ABPM) was performed in 20 living related transplants (age, 30.3 + 5, years; 11 males, on dialysis for 25.6 months) 1 month preRTx and repeated 1 month and >1 year (ABPM 3 ) after successful RTx. Dipping was defined as a sleep-to-awake ratio >0.92 (for systolic BP) and >0.90 (for diastolic BP). Results. PreRTx only 15% patients were dippers. At 1 month postRTx (creatinine clearance, 65.8 ml/min), all patients were complete nondippers. However, after >1 year postRTx (creatinine clearance, 70.4 ml/min), 40% were now dippers. Most importantly, overall, 30% of the patients improved significantly their circadian rhythm (35.3% of the initial preRTx nondippers). Despite successful renal transplantation, 55% patients maintained unchanged their nondipping profile throughout all three ABPM recordings. The only determinants of long-term postRTx circadian rhythm are the contemporary level of the renal function and the baseline, dialysis dipping profile: SBP 3 sleep-to-awake ratio is related with serum creatinine 3 (r=0.58, P=0.001), creatinine clearance (r = -0.41, P=0.036) and SBP, sleep-to-awake ratio (r=0.48, P=0.034); similarly DBP 3 sleep-to-awake ratio is related with serum creatinine 3 (r=0.63, P=0.001), creatinine clearance (r = -0.471, P=0.036) and SBP 1 sleep-to-awake ratio (r=0.53, P=0.016). In all, 57% of the variance in dipping status can be attributed and explained by the contribution of renal function and initial circadian variability. Conclusions. Half of the nondipper dialysis patients maintain a permanently abnormal circadian rhythm, despite successful RTx. In the short term, RTx is associated with a highly abnormal diurnal profile, exclusively related to ciclosporin dose and levels. However, in the longer term, renal transplantation leads to a significant improvement of the circadian blood pressure profile, influenced by the renal function level and by the pretransplantation dipping profile.

Increased aortic stiffness-measured as aortic augmentation index (AIx), a global stiffness marker-has emerged as a powerful predictor of survival in hemodialysis (HD). A single HD session is known to produce considerable improvement in aortic stiffness. We set out, for the first time, to examine the relative contributions to the post-HD drastic improvement in aortic stiffness of ultrafiltration rate and volume, or blood pressure (BP) changes. Aortic AIx (difference between the first and the second systolic peak of the aortic pressure waveform divided by pulse wave height) was determined hourly and recorded by applanation tonometry using a SphygmoCor device in 20 chronic HD patients (9 males, age 55.1 years). The other parameters recorded were: weight pre- and post-HD, ultrafiltration volume (UFV), hemoglobin, albumin, creatinine, urea reduction rate (URR), calcium and PTH, and BP. The dialysis significantly decreased AIx from 24.2+/-11.27% to 15.57+/-12.58% (p

Background. Health-related quality of life (QoL) in haemodialysis (HD) patients is a significant predictor of mortality and hospitalization. Patients’ adaptation to a chronic disease is determined by their beliefs about illness and treatment. In this cross-sectional study we examined the impact of illness representations on QoL of HD patients and the influence of HD duration on this relationship. Methods. Eighty-two clinically stable HD patients completed the Short Form-36 Health Survey (mean age 47.9±12.1, mean treatment duration 72±50.6, 53.6% males). Illness representations were assessed by a structured interview containing questions derived from The Revised Illness Perception Questionnaire. Results. Our results indicate a relatively low QoL of HD patients, with an important proportion of patients scoring less than 43 for the physical component summary (65.9%) and less than 51 for the mental component summary (58.5%). HD patients consider their illness as having a chronic course, which they understand and control quite well. A higher personal control is associated with a lower emotional response and a better understanding of the disease. However, the perceived negative consequences of the disease upon patients’ personal lives are considerable, as is their emotional response. Four of the six components of illness representations were strongly related to QoL parameters. On multiple regression analysis, between 15 and 31% in the variance of the physical and mental component of QoL was explained by three dimensions of illness representations: the perceived course of the disease, personal control and emotional response. Only the emotional response dimension of the illness representations is related to treatment duration (r ¼� 0.48, P

BACKGROUND Increased aortic stiffness markers--aortic pulse wave velocity (PWV) and augmentation index (AIx)--have emerged as powerful predictors of survival in haemodialysis (HD). Various and often contradictory abnormalities of endothelium-dependent (ED) and endothelium-independent (EID) vasomotor function, have been described in dialysis subjects, pre- and post-dialysis, using methods that are difficult to export to the clinical setting or to large prospective trials assessing their relevance. Therefore, we determined the influence of a HD session on PWV and the ED and EID vascular reactivity, employing pulse wave analysis (PWA) of the aortic waveforms, combined with provocative pharmacological stimuli known to reduce wave reflection. METHODS PWV and aortic AIx (difference between the first and second systolic peak on the aortic pressure waveform divided by the pulse wave height) were determined from PWA of arterial waveforms recorded by applanation tonometry using a SphygmoCor device in 41 HD (20 males, age 41.8 years) and in 20 controls with essential hypertension (10 males, age 43.6 years). ED and EID vascular reactivity were assessed by changes in AIx following inhaled salbutamol and sublingual nitroglycerin (GTN), respectively, pre- and post-dialysis session. Echocardiography was performed in all patients, pre-HD and before the PWV recordings. RESULTS Pre-HD AIx (27.9+/-11.9%) was significantly higher compared with hypertensive patients with normal renal function (16.5+/-17%, P

Due to the impressive cardiovascular (CV) morbidity and mortality in uremic patients, assessment of CV risk factors in the dialysis population is a crucial challenge in nephrology. Cardiovascular risk factors in dialysis patients may have a different significance in ESRD patients compared to the general population. The Framingham risk equation seems not to be valid in chronic uremia. Furthermore, new powerful outcome predictors have emerged in recent years: pulse pressure, dipping status, pulse wave velocity, augmentation index. The concept of "U"-shaped association between blood pressure (as well as cholesterolemia) and mortality are extensively discussed. The authors are focusing on the value of office and ambulatory blood pressure measurements in the uremic population. An extensive evaluation of blood pressure and vascular compliance in dialysis patients is proposed. Efficient dialysis, ACE-inhibitors and beta-blockers, statins, antiplatelet treatment and adequate control of calcium-phosphorus metabolism should be the mainstay of therapy in the ESRD patients with several CV risk factors.

Acute liver failure (ALF) as a result of mushroom poisoning is associated with a high mortality (particularly in children), despite optimal medical therapy (OMT), including charcoal haemoperfusion and haemodiafiltration. MARS is a new, cell-free, extracorporeal liver assistance method utilizing an albumin dialysate for the removal of albumin-bound toxins.We describe the first series in the literature (also first MARS treatments in Romania) with ALF because of mushroom poisoning in children (M/F=2/4, age=7-16 years). Liver function was evaluated pre-MARS and 15-min post-MARS, 24 h following each treatment and 30 days post-MARS.All patients had severe hepatic dysfunction: hepatic encephalopathy (HE; four grade II, one grade III, one grade IV), ALT=4082 (3400-5600) IU/L, bilirubin=6.3 (2-10) mg/dL, prothrombin time (PT)=52.5 (23-141) s. MARS was uneventful and well-tolerated. Two 6-h sessions per patient were performed with a similar immediate impact on liver tests: mean drop in ALT of -33 and -35%, respectively, and in bilirubin of -39 and -36%, respectively. ALT levels 24 h following MARS-1, remained unchanged but continued to drop by a further -28% following MARS-2. By contrast, all patients had a significant rebound in bilirubin (+39%) 24 h following MARS-1; however, following MARS-2 a rebound was seen only in two cases (+220%). PT improved by 37% after MARS-1 and normalized in four patients after MARS-2.Four patients survived and completely recovered the hepatic function. Negative prognostic markers: lack of complete correction of PT, continuous rebound and increase in bilirubin, and lack of improvement in HE post-MARS-1. Survival in six well-matched cases, treated by OMT=0/6 (P0.05).MARS is a safe and highly effective depurative therapy in children with ALF. Survival is predicted only by the impact/results of the initial MARS sessions and not by any of the baseline parameters.

Diurnal BP rhythm is known to be abnormal (reduced BP fall with sleep) in chronic renal failure, dialysis and renal transplantation patients. In subjects with primary hypertension and with reduced diurnal BP fall with sleep there is consistent evidence of increased target-organ damage. However, the few studies that have addressed the reproducibility of diurnal rhythm in normal or hypertensive subjects have concluded that the BP fall with sleep is poorly reproducible. It is not known whether the same is true for patients with renal disease.In 30 subjects with autosomal polycystic kidney disease (ADPKD), mild chronic renal failure and normal office BP levels on standardised anti-hypertensive treatment, ambulatory blood pressure monitoring (ABPM) was done three times over a twelve month period to assess the reproducibility of blood pressure fall with sleep.When comparing ABPM 2 with the ABPM 1 recording (3 months difference between measurements) only 43.3% of the patients maintained the initial dipping category (defined by quartiles of the ABPM 1 diurnal BP distribution). The same proportion of subjects had a similar dipping category, when ABPM 3 was compared to ABPM 1 (9 months difference between measurements), but a large (24%) subset of patients had dramatic shifts in their amplitude in nocturnal BP fall, significantly greater than those recorded after a shorter inter-measurement interval. Equally important, our study reveals the fact that, with time, there is no tendency to decrease circadian variation: a similar proportion (a quarter to one third) of patients increased or decreased their amplitude in nocturnal BP fall, at 3 and 9 months. When several ABPM measurements are repeated for the same patients, the repeatability is even worse, since only 36.6% of our study population maintained the initial dipping category across all three ABPM determinations (ABPM 1 and ABPM 2 and ABPM 3).There is a widespread abnormality in diurnal BP rhythm in ADPKD patients with renal impairment, but the extent of this abnormality varies considerably over time. It is too simplistic to assume that, having arbitrarily categorised subjects into "dippers" or "non-dippers", these labels will always be valid. Thus, it would be unwise to extrapolate the impact of a single baseline circadian BP profile on organ target end points.

Conclusion: 1) The AC was easy to use and instructions were readily explained to indigent pts in a busy clinical setting. 2) Baseline sway and artifact were considered trivial. 3) P-waves and overall quality were rated from acceptable to exceeding expectations, and tracings were easily interpreted by physicians with various levels of experience. 4) The AC provided quick, accurate assessment of cardiac rhythm in a remote area without land telecommunications. Disclosure of Interest: None Declared