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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: 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.

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.

Although anaemia management has improved in haemodialysis (HD) patients in recent years, many of them still have haemoglobin (Hb) levels below the current recommendations. The consequent anaemia could be one of the links between malnutrition and inflammation, and higher mortality in HD patients. The study objective was to determine the relationship between Hb levels and outcome in patients undergoing HD, accounting for inflammation and malnutrition. We retrospectively analysed a total of 236 patients on HD between January 2003 and December 2005, classified by absence or presence of inflammation and malnutrition (defined as serum albumin levels < 40 g/L and CRP > 8mg/l). Serum levels of Hb, ferritin, creatinine, cholesterol, triglycerides, HDL (high-density lipoprotein cholesterol), LDL (low-density lipoprotein cholesterol), albumin and CRP were measured monthly, fibrinogen was measured every third month. Over the period of three years, 73 out of 236 patients (30%) had died, most from cardiovascular diseases (62%). Presence of inflammation and malnutrition (in 44% of patients) was associated with older age (60.69 -/+ 12.46 vs. 54.52 -/+ 12.37, p = 0.0002), lower levels of Hb (99.53 -/+ 14.97 vs. 111.86 -/+ 10.38 g/l, p = 0.0000), creatinine (835.88 -/+ 179.84 vs. 1069.98 -/+ 821.23-/+mol/l, p = 0.0047), albumin (36.58 -/+ 3.41 vs.40.32 -/+ 2.82 g/l, p = 0.0000), cholesterol (4.32 -/+ 1.04 vs. 4.75 -/+ 1.09 mmol/l, p = 0.0025) and higher levels of fibrinogen (4.94 -/+ 1.18 vs. 4.29-/+0.91g/l, p=0.0000) and CRP (30.42-/+29.47 vs. 5.24-/+4.89 mg/l, p=0.0000). The Kaplan-Meier analysis showed that, irrespective of the absence or presence of inflammation and malnutrition, the all-cause mortality was higher in patients with Hb <110g/l (Log-Rank, p=0.00147; p=0.00222). On the other hand, Kaplan-Meier showed that, irrespective of the absence or presence of anaemia (Hb > 110g/l and Hb < 110g/l), the all-cause mortality was higher in patients with the presence of inflammation and malnutrition (Log-Rank, p=0.00222; p=0.00263). The Cox proportional hazard analysis, adjusting for age, showed that only lower serum levels of Hb and higher CRP were associated with all-cause mortality (chi-square=110,306, p=0.0000). Our findings confirm the association of Hb levels < 110g/L with higher mortality among maintenance HD patients, especially in patients with the presence of inflammation and malnutrition. Further investigation of the relationships among anaemia, inflammation and malnutrition and survival is warranted.

Background: The high prevalence of hepatitis C virus (HCV) infection in hemodialysis patients is of great concern because they have a higher rate of mortality than HCV-negative hemodialysis patients. The aim of the study was to evaluate the efficacy and safety of pegylated interferon alpha-2a monotherapy in hemodialysis patients with chronic HCV infection., Methods: Fourteen dialysis patients with chronic HCV infection were scheduled to receive 135 mug pegylated interferon alpha-2a subcutaneously, once a week, after dialysis session for a period of 48 weeks. Efficacy and safety were assessed by end of treatment viral response, sustained viral response, biochemical response, and adverse events. Serum HCV RNA levels were assessed using reverse transcriptase polymerase chain reaction (RT-PCR), while HCV genotype was analyzed by RT-PCR followed by hybridization of amplified products., Results: Of the 14 patients enrolled in the study, 9 completed treatment. Eight patients (57%) had undetectable levels of HCV RNA at the end of treatment, while one patient remained positive. Two (14.3%) patients were discontinued because of insufficient therapeutic response. Three patients (21.34%) did not finish treatment because serious adverse events occurred: one patient with bronchopneumonia and one with pericarditis were discontinued from treatment, while one patient died due to cerebral hemorrhage. Sustained viral response was present in 36% of the patients (5/8 patients) at the end of the follow up period. Biochemical response with normalization of serum ALT levels during treatment was observed in all treated patients (83 +/- 20.1 U/L at baseline vs. 23.4 +/- 4.6 U/L at week 48). The most common adverse events were flu-like syndrome, myalgia, arthralgia, and pancytopenia. Most of the adverse events were manageable. The serious adverse events were believed to be unrelated to the therapy, but rather to the co-morbidities of the hemodialysis patients., Conclusions: Pegylated interferon alpha-2a treatment was effective in a considerable proportion of the treated hemodialysis patients with hepatitis C, and it was reasonably safe to use.

The hepatitis C virus is a highly prevalent infection among chronic dialysis patients and represents one of the major problems of hemodialysis units. Hepatitis C virus transmission occurs either by blood transfusion or nosocomially. One of the proposed pathways of nosocomial transmission of the hepatitis C virus is cross-contamination through the dialysis procedure. In an effort to elucidate whether the hepatitis C virus may pass across the hemodialysis membrane, we have performed analyses of ultrafiltrates collected in different stages of hemodialysis treatments, using different types of hemodialysis membranes and different types of dialysis machines. Samples collected from the dialysis compartment during the rinsing of the blood compartment at the end of the hemodialysis treatment were also analyzed. The hepatitis C virus was found in 17 out of 58 ultrafiltrate samples taken at different times of the hemodialysis treatment. Moreover, the hepatitis C virus was present in 15 out of 17 samples collected from the dialysate compartment during the saline solution rinsing step of the blood compartment. The presence of the hepatitis C virus had no strict correlation with the type of dialysis membrane or with the type of dialysis machine. Although the results suggest that the passage of the hepatitis C virus during the hemodialysis treatment is multi-factorial and case- specific, the most critical point is when the blood is flushed out with physiological saline.

Patient survival from our hemodialysis (HD) center over the past 11 years was analyzed. Four hundred four patients, 212 female and 192 male, were treated by chronic intermittent HD. Patients were offered standard acetate-cellulosic membranes of 1.0-1.3 m2. During this period 181 patients died. One hundred three patients were transferred to other HD centers, and some were transplanted. One hundred twenty patients are still on HD treatment. The 5 year survival rate of patients treated in our center was 58%. Women lived longer than men, and age correlated significantly with survival rate. Patients with chronic glomerulonephritis and adult polycystic kidney disease had the best survival rates while diabetic patients and those with post hypertensive nephropathy had the poorest survival rates. Forty-four percent of patients had a cardiac related cause of death, cerebrovascular accident was the cause in 15%, and 11% died due to septic condition (infection) while 8% died due to liver disease.