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Ultrasound examination was performed in 80 hemodialysis (HD) patients with chronic hepatitis C in order to determine the ultrasound predictors of compensated liver cirrhosis. The ultrasound score (US) was calculated from the morphological parameters (liver size, morphology, surface, echogenicity and spleen volume) and the hemodynamic parameters (portal vein diameter and portal vein mean flow velocity). The US ranged from 0 to 200, with a cut-off value of 66, for discrimination between absence and presence of liver cirrhosis. A logistic regression model with stepwise variable selection was used to determine predictors of the progression of liver disease. According to the calculated US, patients were divided into two groups. The first group consisted of 37 (46.3%) patients with US greater than 66, indicating the presence of compensated liver cirrhosis. The second group included 43 (53.7%) patients without liver cirrhosis, with US equal to or less than 66. The value of liver morphology was significantly higher, but the portal vein flow velocity was significantly lower in patients with compensated liver cirrhosis compared with those without cirrhosis. Furthermore, rounded liver surfaces and increased liver echogenicity were significantly more frequent in patients with compensated liver cirrhosis compared with the non-compensated group. Logistic regression model with stepwise discriminant analysis identified liver morphology, liver echogenicity and portal vein mean flow velocity as independent ultrasound predictors of compensated liver cirrhosis in HD patients with chronic hepatitis C. Ultrasound examination could be used for non-invasive diagnosis of compensated liver cirrhosis, with accurate estimation of the disease severity in HD patients with chronic hepatitis C.

Late nephrology referral of patients with chronic kidney disease (CKD) has been suggested as increasing mortality alter the initiation of dialysis. The aim of this study was to assess the impact of nephrology referral on the initiation of haemodyalisis (HD) and mortality during HD treatment in end-stage renal disease (ESRD) patients who have died in our institution over a five-year period. We studied data from all 117 patients on HD treatment in our institution who died (after 90 days of HD treatment) in the period between 01.01. 2002 and 31.12. 2006. Early (ER) and late referral (LR) were defined by the time of follow-up by a nephrologist greater than or less than 6 months, respectively, before the initiation of haemodialysis. Out of a total of 117 patients, 37.6% (44 patients) started HD in the ER group and 62.4% (73 patients) in the LR group. At the start of HD, LR patients were older, had a higher proportion of temporary catheters and had a significantly lower levels of haemoglobin and diuresis. Creatinine clearance was less in the LR (7.67 ± 3.86 ml/min/1.73 m²) vs. the ER group (8.70 ± 3.62 ml/min/1.73 m²), but not significantly different. Cardiovascular disease (CVD), defined by a history of myocardial infarction, cerebral vascular disease, peripheral arteriopathy, and/or heart failure, was also significantly more common among LR patients compared to ER (56%; 27%, p = 0.002). During the haemodyalisis treatment, the LR group had significantly lower levels of haemoglobin and haematocrit. CVD accounted for about 64% of deaths observed in the LR group. According to echocardiography data, there were no significant differences in the left ventricular mass index (LVMI) between the LR and ER groups at the time of dialysis initiation, but during haemodialysis treatment the LR group had significantly greater LVMI than the ER group (232,96 ± 92,48 g/m² vs. 184,09 ± 51,74 g/m²; p = 0,031). The time until death in months during dialysis treatment was significantly different between the LR and ER group, (69.51 ± 64.03 vs. 113.27 ± 89.03, p = 0.0025). LR patients experienced a greater degree of anaemia and a high prevalence of CVD at the time of dialysis initiation. Our data suggest that the anaemia, CV damage and progression of left ventricular hypertrophy (LVH) in the LR patients during haemodialysis treatment are associated with poor survival on haemodialysis. [ABSTRACT FROM AUTHOR]

Patient survival is a key index of the overall adequacy of treatment in most chronic diseases. Analyses of survival of patients undergoing haemodialysis is very important, as it may offer clues and ideas for prolonging survival of patients with end-stage renal disease (ESRD). The aims of this study were to describe the characteristics of the patients on maintenance haemodialysis therapy over a period of 20 years, to determine the survival rate of these patients according to ages at the onset of haemodialysis, the primary renal diseases, and the cause of death, and to determine the survival rate at five, ten, fifteen and twenty years of haemodialysis treatment at our centre. The charts of 518 unselected patients, 282 male and 236 female, treated with maintenance haemodialysis therapy in a period of 20 years (1985-2005) were reviewed. At the time of evaluation, 164 patients were currently being treated, and 354 patients overall had been diseased. Statistical analysis was performed to evaluate the relationship between survival and patient characteristics such as age, gender, primary renal disease, and age at dialysis onset. Actual survival rates were determined by the Kaplan-Meier method. The survival rate of our patients treated with maintenance haemodialysis was 60%, at 5 years, 37% at 10 years, 25% at 15 years and 9% at 20 years. Female patient survival was superior to male. Patients aged under 40 at the start of dialysis had a better survival probability compared to older patients. Patients with diabetes mellitus and nephroangiosclerosis, had a lower survival rate compared to patients with glomerulonephritis and with adult dominant polycystic kidney disease. Cardiac death was the most common cause of death in patients involved in the study. About 52% of the patients died from cardiovascular disease. Death is the most severe consequence of inadequate dialysis and can be used as an index of the adequacy of the dialysis therapy. Treatment factors that may improve outcomes include an early start of dialysis therapy, a high dose of dialysis (Kt/V over 1.2), correction of anemia, adequate protein and caloric intake, control of calcium and phosphate metabolism, and the use of biocompatible dialyzers. [ABSTRACT FROM AUTHOR]

Background: A consensus about the optimal timing of dialysis initiation is still controversial. Thus, the goal of this analysis was to compare outcomes in patients with early and late referral with early and late initiation of hemodialysis (HD)., Methods: We studied 190 patients (mean age 52.03±14.22) who were initiated on HD between 1994 and 2004. Patients who received regular nephrology care during 12 months before HD initiation were categorized as early referrals (ER) and those without nephrology care were late referrals (LR). The early start (E-start) was defined by the estimated GFR (eGFR) at start of HD≥7.5 mL/min/1.73 m2, and the late start (L-start) by eGFR of <7.5 mL/min/1.73 m2. The four groups of patients (ER with E-start and L-start; LR with E-start and L-start) were prospectively followed in the next 60 months after HD initiation., Results: During the follow-up, 43.3% of E-start and 43.2% of L-start patients died, without significant difference in survival between the groups [HR for L-start vs. E-start=1.06 (95% CI 0.69-1.62); p=0.797]. When survival between ER and LR groups was compared (28.1% patients in the ER and 53.2% in the LR died), there was significant difference in survival [HR for LR vs. ER=2.16 (95% CI 1.28-3.65); p=0.004]. Compared with patients with ER and L-start, higher mortality was observed among those with LR and L-start [HR 3.51 (95% CI 1.48-8.35); p=0.004] and LR with E-start [HR 2.79 (95% CI 1.16-6.7); p=0.022]. There was no significant difference between patients in ER with L-start and ER with E-start., Conclusions: Our study showed that ER above 12 months before HD initiation and L-start of dialysis was associated with a reduced mortality risk in HD patients.

Ultrasound examination was performed in 80 hemodialysis (HD) patients with chronic hepatitis C in order to determine the ultrasound predictors of compensated liver cirrhosis. The ultrasound score (US) was calculated from the morphological parameters (liver size, morphology, surface, echogenicity and spleen volume) and the hemodynamic parameters (portal vein diameter and portal vein mean flow velocity). The US ranged from 0 to 200, with a cut-off value of 66, for discrimination between absence and presence of liver cirrhosis. A logistic regression model with stepwise variable selection was used to determine predictors of the progression of liver disease. According to the calculated US, patients were divided into two groups. The first group consisted of 37 (46.3%) patients with US greater than 66, indicating the presence of compensated liver cirrhosis. The second group included 43 (53.7%) patients without liver cirrhosis, with US equal to or less than 66. The value of liver morphology was significantly higher, but the portal vein flow velocity was significantly lower in patients with compensated liver cirrhosis compared with those without cirrhosis. Furthermore, rounded liver surfaces and increased liver echogenicity were significantly more frequent in patients with compensated liver cirrhosis compared with the non-compensated group. Logistic regression model with stepwise discriminant analysis identified liver morphology, liver echogenicity and portal vein mean flow velocity as independent ultrasound predictors of compensated liver cirrhosis in HD patients with chronic hepatitis C. Ultrasound examination could be used for non-invasive diagnosis of compensated liver cirrhosis, with accurate estimation of the disease severity in HD patients with chronic hepatitis C.

Background: Guidelines should help the practicing nephrologists to reduce the variability in diagnostic and treatment strategies, and achieve the best possible patients' outcomes. The aim of our study was to look at the treatment strategies and the shortcomings in the implementation of the chronic kidney disease mineral and bone disorder (CKD-MBD) KDOQI guidelines in dialysis units across the Republic of Macedonia in 2009, and to analyze trends with regard to our previous analysis from 2005., Methods: A questionnaire was sent in 2009 to all dialysis units in our country for data concerning CKD-MBD in dialysis patients. This study included 742 patients, comparable with the reply we got on the same our 2005 survey, with a total of 588 patients. We collected the last 6 months mean values of biochemical parameters [calcium (Ca), phosphate (P), and intact parathyroid hormone (iPTH)], as well as treatment data including dialysate Ca concentration, phosphate binding agents, and vitamin D doses., Results: The majority of patients in both surveys had values within the target ranges for all parameters, except for iPTH, which was <150 pg/ml in most patients, in both reports. Compared to the 2005 study, in 2009 we found a significantly improved control of all four biochemical parameters, but a greater proportion of patients within guidelines targets was found only for serum Ca (79 vs. 67.4%, P<0.05). Treatment with low Ca dialysate concentration of 1.25 mmol/L continued to be an underused option (3.7 vs. 6.1%), while the 1.75 mmol/L was still the standard dialysate in the majority of patients (57.7 vs. 64.2%). The dose of calcium carbonate was significantly reduced (2.77±1.71 vs. 3.06±1.54, P<0.01) in 2009 compared to 2005. The mean of the achieved targets increased significantly in 2009 (2.33±1.05 vs. 2.13±1.03, P<0.01)., Conclusion: There was an improved control of all bone and mineral parameters in our dialysis units, following the publication of the CKD-MBD KDOQI guidelines. In order to improve the iPTH values, a more frequent use of low Ca dialysate (1.25 mmol/L) and of non-calcium-based phosphate binders in this small subset of patients should be implemented, as recommended by the guidelines. Individualization of the CKD-MBD management may be successful, even when newer treatment options are not available. Finally, the guidelines implementation process should be a continuous and self-monitored process, with the help of periodic surveys.

Lower aminotransferase activity in dialysis patients makes the assessment of the natural history of hepatitis C virus (HCV) infection difficult. The aim of the study was to determine the risk factors associated with the aminotransferase activity in dialysis patients with chronic hepatitis C. According to the serum levels of alanine aminotransferase (ALT) during the follow-up, the patients were divided in the two groups. The first group consisted of 34 chronically HCV infected patients with persistently normal levels of ALT. The second group included 46 chronically HCV infected patients with elevated levels of ALT. Genotype 1 was the dominant genotype in both groups (78 patients, 97.5%). Patients with the elevated ALT levels were characterized with a significantly shorter dialysis duration (p = 0.048) and a significantly shorter duration of HCV infection (p = 0.005) compared to the patients with persistently normal levels of ALT. The values of measured ultrasound parameters were not significantly different between the two groups. The univariate analysis identified a higher serum level of direct bilirubin (p = 0.044), shorter duration of dialysis (p=0.048), and shorter duration of HCV infection (p = 0.005) as potential predictors of elevated serum ALT levels in dialysis patients. After a stepwise logistic regression, none of the potential predictors was independently associated with the elevated ALT levels. Serum aminotransferase levels are poor predictors of liver disease progression in dialysis patients with chronic hepatitis C. Further studies should be conducted in order to identify non-invasive indicators of the disease progression in uremic patients with hepatitis C (Tab. 3, Ref. 22).

Background: The ability of brain natriuretic peptide (BNP) together with other traditional and nontraditional risk factors to predict cardiovascular (CV) mortality in hemodialysis (HD) patients has not been well established. The aim of this prospective study was to determine the predictive cutoff values of baseline measurement of BNP along with the known CV disease risk factors to predict all-cause and CV mortality in HD patients., Methods: BNP concentration before HD was measured in 125 prevalent HD patients (age 53.0 ± 13.5 years, HD vintage 75.2 ± 61.0 months). In addition, several traditional CV risk factors (blood pressure, dyslipidemia, diabetes mellitus, body mass index, left ventricular hypertrophy) and uremia/dialysis-related CV risk factors (anemia, calcium and phosphate impairment, malnutrition, inflammation, ultrafiltration, HD duration, Kt/V) were examined., Results: During the 2-year follow-up, we lost 28 out of 125 patients (22.5%), with CV disease (65.7%) being the main cause of mortality. The cutoff point for BNP, as predictor of the clinical outcome, according to the ROC curve was 1,194 pg/ml for CV mortality with sensitivity and specificity of 63 and 65%, respectively (AUC 0.61 and confidence interval (CI) 95% 0.47-0.75). Kaplan-Meier analysis showed that all-cause (log-rank, p = 0.002) and CV mortality (log-rank, p = 0.001) were the cause of a significantly lower survival in patients with a mean BNP >1,200 pg/ml. The univariate Cox regression analysis found the following factors to be predictors of all-cause mortality: hemoglobin (<110 g/l), phosphorus (>1.78 mmol/l), albumin (<40 g/l), C-reactive protein (CRP ≥ 10 mg/l), BNP (>1,200 pg/ml) and cardiac ejection fraction (≤ 55%). The multivariate Cox regression analyses demonstrated that only CRP ≥ 10 mg/l with a hazard ratio (HR) 6.82 (CI 95% 1.86-24.9, p = 0.004) and BNP >1,200 pg/ml with HR 5.79 (CI 95% 1.58-21.3, p = 0.004) were predictors of all-cause mortality. BNP >1,200 pg/ml with HR 13.52 (CI 95% 1.68-108.9, p = 0.014) was found to be an even stronger predictor of CV mortality than CRP ≥ 10 mg/l with HR 6.53 (CI 95% 1.35-31.6, p = 0.020)., Conclusions: Our study pointed out that BNP >1,200 pg/ml as a marker of cardiac dysfunction and CRP ≥ 10 mg/l as a marker of inflammation identify HD patients at increased risk of CV mortality., (2011 S. Karger AG, Basel.)

Background: Incidence increase of diabetes mellitus (DM) has taken epidemic proportions in the world. Diabetic nephropathy (DN) is a most serious complication, taking a leading place as a factor in the progression of chronic kidney disease (CKD). Dialysis treatment of these patients is complex, expensive, and exerts an excessive burden on the health budgets of the affected countries., Methods: We performed a nationwide precise observational study with the aim of analysing diabetics on dialysis in dialysis centres throughout the Republic of Macedonia (RM) in 2002 and in 2006; to compare the results from patients records; and to gather data on the epidemiology, clinical characteristics and complications of diabetes type 1 (DM1) and diabetes type 2 (DM2)., Results: The prevalence of HD patients in RM was 1114 vs 1074 in 2002 and 2006, respectively. Of these, 109 (9.78%) vs. 115 (10.71%) had DM in 2002 and 2006, respectively. The percentage of diabetics on dialysis between different centers varied between 3% to 21% vs. 2.4% to 22.07% in 2002 and 2006, respectively. The mean age of the patients was 58+/-10.29 vs. 56.5+/-10.71 in 2002 and 2006, respectively. Patients with DM1 were 19 (17.43%) vs. 15 (13.04%) and with DM2 were 90 (82.57%) vs. 100 (86.96%) in 2002 and 2006, respectively. 28 (25.68%) vs. 31 (26.96%) patients were on oral anti-diabetic drugs and 62 (57.21%) vs. 69 (60%) patients were on insulin in 2002 and 2006, respectively. Mean age of DM1 patients was 47+/-11.6 y. vs. 45+/-7.32 y. respectively and of DM2 was 60.37+/-8.33 y. vs. 61.14+/-10.23 y., in 2002 and 2006, respectively. Mean time of insulin treatment was 9.5+/-6.63 y. vs. 10.85+/-9.29 y. in 2002 and 2006. Mean Body Mass Index (BMI) was 26.4 vs. 23.49+/-4.74 kg/m2 in DM1 and 25.5 vs. 24.77+/-3.70 kg/m2 in DM2 patients in 2002 and 2006, respectively. Thrombosis of first arteriovenous fistulae (AVF) occurred in 41% vs. 25.22% in 2002 and 2006, respecttitvely. Hepatitis C virus (HCV) infection was confirmed in 57% vs. 44% of DM patients in 2002 and 2006, respectively. Most common co-morbidity in patients was hypertension, 91% vs. 80.87% in 2002 and 2006, respectively., Conclusion: The number of diabetics on dialysis in the Republic of Macedonia did not increase in the period from 2002 to 2006. In DM2 diabetics on dialysis the frequency of complications is higher and time on dialysis is shorter than in DM1 patients. Early detection of diabetic nephropathy by primary care physicians as well as collaborative treatment by diabetologists, nephrologists, cardiologists and ophthalmologists before and during dialysis are important for improvement of treatment and survival of diabetic patients on dialysis.

Purpose: The aim of this study was to evaluate the persistence of sustained viral response after treatment of hepatitis C with pegylated interferon alpha-2a in hemodialysis patients., Methods: 14 hemodialysis patients with chronic hepatitis C were treated with pegylated interferon alpha-2a for a period of 48 weeks. Achieved sustained viral response rate was 35.7% (5/14 patients) at week 72, i.e. 24 weeks after the treatment ended. All treated patients were then prospectively followed until week 144. Follow-up viral data, such as HCV antibodies, serum HCV RNA, and HCV RNA genotype, were determined at week 96 and week 144. HCV antibodies were determined by a 3rd-generation ELISA assay. The presence of HCV RNA was determined using reverse transcriptase polymerase chain reaction (AMPLICOR Hepatitis C Virus Test). HCV genotype was analyzed by reverse transcriptase polymerase chain reaction followed by hybridization of amplified products. The biochemical data were recorded every 24 weeks during the follow-up period., Results: The 5 patients (35.7%), who achieved sustained viral response (SVR), remained HCV RNA negative at week 96. At week 144, 4 hemodialysis patients (28.6%) remained HCV RNA negative. There was a relapse of HCV infection in 1 patient after week 96 of the study. The patients who remained HCV RNA negative also maintained the achieved biochemical response throughout the follow-up period., Conclusion: Long-term follow-up of treated hemodialysis patients with pegylated interferon alpha-2a showed persistence of the sustained viral and biochemical response.

Patients with renal disease are at increased risk of acquiring hepatitis C virus (HCV) infection because of their frequent exposure to blood from transfusions or exposure to HCV-contaminated medical equipment during hemodialysis. The prevalence of anti-HCV antibodies among hemodialysis patients varies between 5-10% in the developed world, and 10-70% in developing countries. Acute hepatitis C is often mild and associated with few, if any symptoms. The major complication of acute HCV infection is chronic hepatitis, which occurs in up to 80% of the cases, the long-term outcome being cirrhosis, portal hypertension, hepatic failure, and hepatocellular carcinoma. Interferon alpha (IFN-alpha) has shown activity against HCV. Twenty four to 48 week course of therapy with interferon could lead to a sustained loss of HCV RNA, normalization of alanine aminotrasferase (ALT) levels, and resolution of the liver disease. Sustained viral response was achieved in approximately half of the treated patients. Therapy with interferon was associated with a number of adverse events such as: "flu-like" symptoms, neurological, gastrointestinal symptoms, anemia, fatigue, thrombocytopenia, leucopenia. A major advance in therapy came with the addition of ribavirin to interferon therapy. Peginterferon-alpha-2a (40KD) is a new 'pegylated' subcutaneous formulation of interferon-alpha-2a, that was developed to improve the pharmacokinetic profile and therapeutic efficacy of interferon-alpha-2a. In our study, fourteen hemodialysis patients with chronic hepatitis C received 135 microg PEG-IFN alpha-2a subcutaneously, once a week, after dialysis session for a period of 48 weeks. In the intention-to-treat analysis, sustained viral response was present in 36% of the patients (five out of fourteen patients) at the end of the follow up period. The biochemical response with normalization of serum ALT levels during the treatment was observed in all treated patients (83 +/- 20.1 U/L at base line vs. 23.4 +/- 4.6 U/L after the 48 weeks; p < 0.01). At present, therapy for hepatitis C should be considered in hemodialysis patients with significant liver disease, minimal other co morbidities, and a reasonable likelihood of prolonged survival or if renal transplantation is planned.

Clinical features, aminotransferases levels, and antibody to HCV have only limited correlation with the activity of liver disease and cannot accurately predict persistence versus eradication of the virus in haemodialysis patients. Although permanent loss of serum HCV RNA appears to correlate with resolution of the disease, little is known about the predictive value of a single HCV RNA value. The aim of the study was to evaluate the viraemia in the serum of HCV antibody positive haemodialysis patients during a period of 3 years. The study group consisted of 65 HCV antibody positive patients from our dialysis unit. HCV antibodies were measured every 6 months by ELISA third-generation assay. The presence of serum HCV RNA was assessed by reverse-transcriptase polymerase chain reaction (RT-PCR) once a year during the period of 3 years. Serum levels of aminotransferases were measured monthly with standard automated analyzers. There were three different patterns of viraemia after the third assessment of the serum HCV RNA in HCV antibody positive patients: 47% (30/65) were persistently HCV RNA positive, 38% (25/65) were intermittently HCV RNA positive, and 15% (10/65) were persistently HCV RNA negative. The dominant genotype was 1a, detected in 97% of the patients positive for HCV RNA. The HCV RNA persistently positive patients had significantly higher levels of ALT compared to HCV RNA persistently negative patients (50.07 +/- 30.0 vs. 28.5 +/- 10.0 U/L, p < 0.027). There was no significant difference between the three groups of patients according to age, haemodialysis duration, and serum levels of AST. This pattern of intermittent viraemia clearly showed that a single negative result of the presence of serum HCV RNA in an HCV antibody positive patient should not be taken as a proof of a persistent resolution of HCV. Thus, repeated testing for HCV RNA is necessary to assess viraemia accurately in HCV antibody positive patients. HCV antibody positive patients who were persistently serum HCV RNA negative could be potentially infectious because of the possibility of the persistence of occult hepatitis C.

Background: Haemodialysis (HD) patients are at increased risk of the development of arterial intimal (AIC) and medial calcification (AMC). The aim of our study was to analyze the association between the pre-defined potential risk factors and the status of various arterial calcifications in our HD patients., Methods: In a cross-sectional study of 150 patients (91 male, mean age 54.55 +/- 12.46 yrs, HD duration 104.77 +/- 68.02 mths) we first determined the presence of AIC and AMC using plain radiography of the pelvis. We then compared the percentages of different radiogram findings in patients stratified according to various cut-off levels or the codes of each clinical and biochemical parameter (mean value of one year laboratory data recorded in the files)., Results: We determined arterial calcifications in 77.3% of our patients (AIC in 45.3%, AMC in 32%). The significantly higher frequencies of arterial calcifications of both groups (AIC and/or AMC) and isolated AIC presence were found in patients older than 55 at inclusion and 45 at the start of treatment with HD, with a serum C-reactive protein (CRP) > 4.5 mg/L, predominantly of male gender with diabetes. The patients with a significantly higher occurrence of arterial calcifications had lower percentages of total serum calcium (Ca) levels but within the K/DOQI guideline recommendations. Also, we found a significantly higher proportion of isolated AIC presence in the group of patients with corrected total serum Ca levels > 2.35 mmol/L and serum intact parathyroid hormone (iPTH) levels out of the range proposed by K/DOQI guidelines. In parallel, a significantly higher percentage of absence of arterial calcifications (ACA) was obtained in the patients with corrected total serum Ca levels < 2.35 mmol/L, body mass index (BMI) < 23 kg/m(2), mean pulse pressure < 60 mmHg, blood leucocytes < 6.5 x 10(9)L and serum triglycerides < 1.8 mmol/L. Finally, we found a significantly higher presence of isolated AMC in patients with mean Kt/V < 1.3 (poor dialysis adequacy), serum triglycerides > 1.8 mmol/L and outside K/DOQI guideline achievements for corrected total serum Ca. In the 12 month period data analyzed, there were no significant differences in other risk factors such as the dose of prescribed calcium carbonate and vitamin D3, serum levels of albumin, cholesterol, phosphate (P) and Ca x P product., Conclusions: AIC and AMC were frequently present in our HD population. Age, gender, BMI, diabetes, pulse pressure, dialysis adequacy, serum CRP, triglycerides, Ca and iPTH, as well as blood leucocyte levels were associated with the occurrence of arterial calcifications in our HD patients.

Background: Hemodialysis (HD) patients are at increased risk for arterial intimal (AIC) and medial calcification (AMC)., Methods: In a cross-sectional study on 153 HD patients we evaluated the presence of AIC and AMC using plain radiography of the pelvis and the presence of atherosclerotic lesions using high-resolution B-mode ultrasonography of the common carotid arteries (CCA)., Results: The radiography of the pelvis confirmed the frequent presence of AIC (35.3%) and AMC (35.9%) in our HD patients. Arterial calcification was absent (non calcified-NC) in a minority of patients (28.8%). Patients with AIC had significantly higher prevalence of atherosclerotic plaques on CCA (78.6%) compared with both other groups and a higher number of documented atherosclerotic complications, such as cardiovascular (85.2%), cerebrovascular (33.3%) and peripheral arterial disease (38.9%) in comparison with the NC patients. According to the 1-year calculated data from patient records, there were no significant differences in the specific HD risks, such as the dose of prescribed calcium carbonate and vitamin D3, serum levels of calcium, phosphate, calcium-phosphate product and intact parathyroid hormone. All four bone metabolism markers within the range proposed by K/DOQI guidelines were achieved in 9.3%, 14.5% and 20.4% in the AIC, AMC and NC group, respectively., Conclusions: Patients with AIC and AMC are frequently found in the HD population. Screening for arterial calcifications in chronic kidney disease patients is suggested even in the early pre-dialysis period. The highest proportion of patients within the guidelines proposed range for bone and mineral metabolism markers was observed in the NC group. A longer period of data analysis is required in order to evaluate the possible role of some traditional and HD-specific risk factors for the development of arterial calcifications. The achievement of the K/DOQI guidelines is an important issue in the prevention of those conditions.

Patient survival is a key index of the overall adequacy of treatment in most chronic diseases. Analyses of survival of patients undergoing haemodialysis is very important, as it may offer clues and ideas for prolonging survival of patients with end-stage renal disease (ESRD). The aims of this study were to describe the characteristics of the patients on maintenance haemodialysis therapy over a period of 20 years, to determine the survival rate of these patients according to ages at the onset of haemodialysis, the primary renal diseases, and the cause of death, and to determine the survival rate at five, ten, fifteen and twenty years of haemodialysis treatment at our centre. The charts of 518 unselected patients, 282 male and 236 female, treated with maintenance haemodialysis therapy in a period of 20 years (1985-2005) were reviewed. At the time of evaluation, 164 patients were currently being treated, and 354 patients overall had been diseased. Statistical analysis was performed to evaluate the relationship between survival and patient characteristics such as age, gender, primary renal disease, and age at dialysis onset. Actual survival rates were determined by the Kaplan-Meier method. The survival rate of our patients treated with maintenance haemodialysis was 60% at 5 years, 37% at 10 years, 25% at 15 years and 9% at 20 years. Female patient survival was superior to male. Patients aged under 40 at the start of dialysis had a better survival probability compared to older patients. Patients with diabetes mellitus and nephroangiosclerosis, had a lower survival rate compared to patients with glomerulonephritis and with adult dominant polycystic kidney disease. Cardiac death was the most common cause of death in patients involved in the study. About 52% of the patients died from cardiovascular disease. Death is the most severe consequence of inadequate dialysis and can be used as an index of the adequacy of the dialysis therapy. Treatment factors that may improve outcomes include an early start of dialysis therapy, a high dose of dialysis (Kt/V over 1.2), correction of anemia, adequate protein and caloric intake, control of calcium and phosphate metabolism, and the use of biocompatible dialyzers.

Late nephrology referral of patients with chronic kidney disease (CKD) has been suggested as increasing mortality after the initiation of dialysis. The aim of this study was to assess the impact of nephrology referral on the initiation of haemodyalisis (HD) and mortality during HD treatment in end-stage renal disease (ESRD) patients who have died in our institution over a five-year period. We studied data from all 117 patients on HD treatment in our institution who died (after 90 days of HD treatment) in the period between 01.01. 2002 and 31.12. 2006. Early (ER) and late referral (LR) were defined by the time of follow-up by a nephrologist greater than or less than 6 months, respectively, before the initiation of haemodialysis. Out of a total of 117 patients, 37.6% (44 patients) started HD in the ER group and 62.4% (73 patients) in the LR group. At the start of HD, LR patients were older, had a higher proportion of temporary catheters and had a significantly lower levels of haemoglobin and diuresis. Creatinine clearance was less in the LR (7.67 +/- 3.86 ml/min/1.73 m2) vs. the ER group (8.70 +/- 3.62 ml/min/1.73 m2), but not significantly different. Cardiovascular disease (CVD), defined by a history of myocardial infarction, cerebral vascular disease, peripheral arteriopathy, and/or heart failure, was also significantly more common among LR patients compared to ER (56%; 27%, p = 0.002). During the haemodyalisis treatment, the LR group had significantly lower levels of haemoglobin and haematocrit. CVD accounted for about 64% of deaths observed in the LR group. According to echocardiography data, there were no significant differences in the left ventricular mass index (LVMI) between the LR and ER groups at the time of dialysis initiation, but during haemodialysis treatment the LR group had significantly greater LVMI than the ER group (232,96 +/- 92,48 g/m2 vs.184,09 +/- 51,74 g/m2; p = 0,031). The time until death in months during dialysis treatment was significantly different between the LR and ER group, (69.51 +/- 64.03 vs.113.27 +/- 89.03, p = 0.0025). LR patients experienced a greater degree of anaemia and a high prevalence of CVD at the time of dialysis initiation. Our data suggest that the anaemia, CV damage and progression of left ventricular hypertrophy (LVH) in the LR patients during haemodialysis treatment are associated with poor survival on haemodialysis.

Background: The existence of adynamic bone disease (ABD) as most prevalent form of renal osteodystrophy in recent years and its reduced ability to handle an exogenous calcium load has implied a higher risk for vascular and soft-tissue calcifications. The effect of low dialysate calcium (LCD) on parathyroid hormone (PTH) secretion in ABD patients has not yet sufficiently been clarified. This randomized, prospective study aimed to compare the effects of LCD and high calcium dialysate (HCD) on the evolution of bone and mineral parameters related to ABD in dialysis patients., Methods: 52 out of 60 patients with predialysis intact PTH<100 pg/ml completed this study and were equally distributed over LCD (1.25 mmol/l) or HCD (1.75 mmol/l) treatment. The duration of the study was 6 months and the only peroral phosphate binder administered was calcium carbonate. Total and ionised calcium were measured monthly in serum before and after dialysis while serum parameters relevant to bone were measured at the enrollment and at 3-month intervals., Results: There were no differences in predialysis mean phosphate or calcium x phosphorus product (Ca x P). The most common side effects of both treatments were comparable. Hypotension occurred in 16% and 17% and cramps in 6% and 8% of the dialysis sessions, in the HCD and LCD group, respectively. The groups did not differ in the mean tCa before dialysis, but this parameter was significantly higher in the HCD group vs. LCD at the end of dialysis (2.59+/-0.18 vs. 2.44+/-0.19 mmol/l; p<0.01). The patients of the HCD group also had a significantly higher mean iCa both before (1.08+/-0.05 vs. 1.04+/-0.06 mmol/l; p=0.02) and at the end of dialysis (1.18+/-0.04 vs. 1.48+/-0.04 mmol/l; p<0.01). There were no differences within the LCD group between baseline and end of dialysis treatment values of tCa and iCa. However, the mean tCa and iCa were markedly increased at the end of dialysis in the HDC group [2.40+/-0.21 vs. 2.59+/-0.18 mmol/l (p<0.01); 1.08+/-0.05 vs. 1.18+/-0.04 mmol/l (p<0.01)]. Mean serum levels of iPTH and total alkaline phosphatase in the LCD group were increased at 3 months and at the end of the study compared with the baseline levels [(38.6+/-22.9 vs. 63.3+/-46.0 vs. 78.6+/-44.7 pg/ml); (59.5+/-18.7 vs. 75.9+/-26.7 vs. 84.0+/-35.4 U/l)], respectively, and bone alkaline phosphatase increased also only after 6 months of treatment (23.4+/-7.3 U/l vs. 35.6+/-22.3). The bone markers in the HCD group did not change. At the end of the study all bone parameters in the LCD group were significantly higher than in the HCD group., Conclusion: There was an evolution towards parameters reflecting higher bone turnover in patients treated with dialysate calcium of 1.25 mmol/l, probably by prevention of a positive calcium balance and enabling sustained stimulation of PTH secretion. Hence, LCD might be considered a valuable therapeutic option for ABD patients.

Background: Lanthanum carbonate (LC) has been proposed as a new phosphate binder. Presented here are the results from one centre that participated in a multicentre trial to assess the effect of treatment with LC and calcium carbonate (CC) on the evolution of renal osteodystrophy in dialysis patients. Bone biopsies were performed at baseline, after 1 year of treatment and after a further 2-year follow-up period to assess the lanthanum concentration in bone and plasma., Methods: Twenty new dialysis patients were randomized to receive LC (median dose 1250 mg) for 1 year (n = 10), followed by 2 years of CC treatment or CC (n = 10) during the whole study period (3 years)., Results: After 36 weeks of treatment, steady state was reached with plasma lanthanum levels varying around 0.6 ng/ml. Six weeks after cessation of 1 year of treatment, the plasma lanthanum levels declined to a value of 0.17 +/- 0.12 ng/ml (P < 0.05) and after 2 years to 0.09 +/- 0.03 ng/ml. Plasma and bone lanthanum levels did not correlate with the average lanthanum dose at any time point. The mean bone concentration in patients receiving LC increased from 0.05 +/- 0.03 to 2.3 +/- 1.6 microg/g (P < 0.05) after 1 year and slightly decreased at the end of the study to 1.9 +/- 1.6 microg/g (P < 0.05)., Conclusions: Bone deposition after 1 year of treatment with LC is low (highest concentration: 5.5 microg/g). There is a slow release of lanthanum from its bone deposits 2 years after the discontinuation of the treatment and no association with aluminium-like bone toxicity.

Among non-traditional cardiovascular risk factors both malnutrition and inflammation appear to be strong predictors of mortality and morbidity in haemodialysis (HD) patients. Our study objective was to determine predictors of all-cause and cardiovascular mortality, considering the nutritional and immunologic parameters, in a cohort of HD patients treated in a single haemodialysis centre. 216 patients on HD were analyzed for clinical, nutritional-serum albumen and BMI, immunologic-serum CRP (C-reactive protein) and fibrinogen and dialysis parameters -- ultrafiltration, length of dialysis in hours, HD dose (using spKt/V and eKt/V). Mortality was monitored prospectively over a two-year period. Fifty-five of the 216 HD patients died during the follow-up period and the main cause of death was cardiovascular disease (CVD) -- 33 patients out of 55 (60%), followed by infection/sepsis (13 pts, 24%). The patients who died were significantly older, had a significantly shorter duration of HD in hours, ultrafiltration was significantly less, HD doses were significantly lower, as were serum levels of albumin (36.06 +/- 4.17 vs. 39.74 +/- 3.31; p=0.000) and Hg (93.14 +/- 15.43 vs. 109,16 +/- 12,08; p=0.000), but they had significantly higher serum levels of CRP (40.26 +/- 34.75 vs. 8.71 +/- 7.68, p=0.000) and fibrinogen (5.28 +/- 1.28 vs. 4.42 +/- 0.97, p=0.000). Kaplan-Meier survival estimates showed that the group with the lowest levels of albumin (< 3.5 g/L), and with the greatest levels of CRP (>20 mg/l) and fibrinogen (>5 g/L) had the lowest survival (log-rank test p=0.0008, p=0.00000, p=0.0000). However, in the Cox proportional hazards model, a high CRP and low Hg level (chi-square=96.467, p=0.0000) were predictors of all-cause mortality, whereas serum level of albumin did not show to be predictive. When only cardiovascular mortality is entered into the Cox model, CRP and Hg levels are still more important in predicting mortality (chi-square=70.055, p=0.0000) and only if CRP is not taken into account in the multivariate analysis, serum albumin level remains, after Hg, the strongest predictor for both overall and cardiovascular mortality (chi-square=76,564, p=0.0000; chi-square 50.619 p=0.0000). It can be concluded that inflammation predicted all-cause and cardiovascular mortality in our study group, because high CRP, as a marker of inflammation and low haemoglobin, as a result of inflammation, remained powerful predictors of both overall and cardiovascular death.

Acquired renal cystic disease (ARCD) is a well documented complication of end-stage renal disease, and it has been related to the duration of dialysis therapy. The association of this condition with renal cell adenoma or carcinoma has already been established. There have also been studies on the concentration of some tumor markers in hemodialysis (HD) patients, clinically free from neoplastic disease, where it was concluded that some tumor markers could be elevated, despite the absence of malignant disease, suggesting their altered metabolism i.e. clearance by the hemodialysis membrane. We compared the pre-dialysis serum concentration of several tumor markers in three groups of chronic HD patients, all of whom had been on maintenance HD treatment for more than 5 years. Group 1 consisted of 16 patients without ARCD with a mean HD treatment duration of 97.06 +/- 28.25 months. Group 2 consisted of 32 patients with a mean HD treatment of 105.62 +/- 24.4 months, who had ARCD with less than 10 renal cysts detected by ultrasonography. Group 3 consisted of 14 patients with a mean HD duration of 109.92 +/- 37.72 months, with ARCD and more than 10 renal cysts. Concentration of the following tumor markers was determined by EIA or ELISA methods: carcinoembryonic antigen (CEA), mucin-like carcinoma-associated antigen (MCA), neuron-specific enolase (NSE), carbohydrate antigen 19-9 (CA 19-9), prostatic specific antigen (PSA), carbohydrate antigen 125 (CA 125), alpha fetoprotein (AFP), cytokeratin 19-fragments 21-1 (CYFRA 21-1). The concentration of all the tumor markers was comparable in all three patient groups, with no statistically significant difference between groups. The mean concentrations of MCA, PSA, CA 125 and AFP were within the normal range. CEA and CYFRA 21-1 had mean values in the upper limit of their normal values, while NSE and CA 19-9 were increased by more than twofold in all three patient groups. We concluded that (i) tumor markers should be used with caution when diagnosing neoplastic diseases in chronic HD patients, because of their altered metabolism, and (ii) that in the follow up of ARCD with possible neoplastic alteration, imaging techniques remain dominant diagnostic tools.