BACKGROUND:Anaemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are the most used treatment option. In observational studies, higher haemoglobin (Hb) levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to Hb levels around 9-10 g/dL. Randomized studies found that targeting higher Hb levels with ESA causes an increased risk of death, mainly due to adverse cardiovascular outcomes. It is possible that this is mediated by ESA dose rather than haemoglobin concentration, although this hypothesis has never been formally tested.METHODS:We present the protocol of the Clinical Evaluation of the Dose of Erythropoietins (C.E. DOSE) trial, which will assess the benefits and harms of a high versus a low ESA dose therapeutic strategy for the management of anaemia of end stage kidney disease (ESKD). This is a randomized, prospective open label blinded end-point (PROBE) design trial due to enroll 900 haemodialysis patients. Patients will be randomized 1:1 to 4000 UI/week i. v. versus 18000 UI/week i. v. of epoetin alfa, beta or any other epoetin in equivalent doses. The primary outcome of the trial is a composite of cardiovascular events. In addition, quality of life and costs of these two strategies will be assessed. The study has been approved and funded by the Italian Agency of Drugs (Agenzia Italiana del Farmaco (AIFA)) within the 2006 funding plan for independent research on drugs (registered at www.clinicaltrials.gov (NCT00827021)).

In this study we assessed the seroprevalence of hepatitis E virus (HEV) infection in both the Italian population and immigrants from developing countries in Foggia (Apulia, Southern Italy). The seroprevalence of HEV was determined in 1217 subjects [412 (34%) immigrants and 805 Italian subjects (blood donors, general population, HIV-positive, haemodialysis patients)]. Serum samples were tested for anti-HEV and confirmed by Western blot assay; in positive patients HEV RNA and genotype were also determined. There were 8·8% of patients that were positive to anti-HEV, confirmed by Western blot. The prevalence in immigrants was 19·7%, and in Italians 3·9% (blood donors 1·3%, general population 2·7%, HIV-positive patients 2·0%, haemodialysis patients 9·6%). Anti-HEV IgM was found in 38/107 (35·5%) of the anti-HEV-positive serum samples (34 immigrants, four Italians). This study indicates a higher circulation of HEV in immigrants and Italian haemodialysis patients, whereas a low prevalence of HEV antibodies was seen in the remaining Italian population.

Background: Hepatitis E virus is the etiologic agent of an enterically transmitted viral hepatitis associated with inadequate hygienic conditions.HEV is endemic in developing countries where it occurs in sporadic and endemic form, but autochthonous sporadic cases of hepatitis E have been reported in North America and in Europe, including Italy.The aim of the present study is to assess the seroprevalence of antibodies to HEV in autochthonous Italian population and in immigrants from developing countries in the province of Foggia.Methods: The seroprevalence of HEV was determined in a cohort of 1217 subjects, 412 (34%) were asymptomatic immigrants (mostly from countries in Sub-Saharan Africa) who had recently arrived in Italy and 805 were four different Italian populations (volunteer blood donors, normal healthy individuals, HIV-positive patients, hemodialysis patients).Serum samples were tested for anti-HEV by a commercial enzyme immunoassay (EIA) based on recombinant proteins; repeatedly positive obtained results were confirmed with a Western Blot assay (Recomblot HEV).Results: A total of 107 (8.8%) of the 1217 serum samples examined were reactive to anti-HEV IgG and confirmed by Western Blot.The prevalence in immigrants was 19.6%, in Italians was 4.0% (blood donors 1.3%, normal healthy individuals 3.3%, HIV-positive patients 3.0%, hemodialysis patients 11.5%) Anti-HEV IgM was found in 20/107 subjects (18.7%) of the anti-HEV IgG positive serum samples, 17 in immigrants and 3 in Italians.All anti-HEV positive subjects were asymptomatic and alanine transferase values were elevated only in 8/20 patients with anti-HEV IgM-positive. Conclusions:The results of this study indicate a high circulation of HEV in immigrant population and hemodialysis patients, whereas the prevalence of HEV antibodies was low in the other Italian population, compared to that of other European countries.

Health-related quality of life in patients with chronic kidney disease Assessment of quality of life in patients with different degrees of chronic kid- ney disease is an important issue because of its impact on clinical decisions and financial resource management in the health-care system. The aim of this study was to assess whether a generic instrument like the SF-36 questionnaire is able to discriminate three different populations of patients with different degrees of renal disease (pre-ESRD, ESRD, TxR). Five hundred sixty-three patients from 12 Italian nephrology units completed the SF-36 scales by themselves. The results from these samples were compared with those from the general population. Univariate analysis and multivariate regression were used. The generic SF-36 questionnaire proved to be a powerful instrument to discriminate populations with different degrees of chronic renal failure. The quality of life of patients on dialysis is significantly worse than that of the nor- mal population and other patients with less severe renal function impairment. (G Ital Nefrol 2008; 25: 694-701) Conflict of interest: None

Assessment of quality of life in patients with different degrees of chronic kidney disease is an important issue because of its impact on clinical decisions and financial resource management in the health-care system. The aim of this study was to assess whether a generic instrument like the SF-36 questionnaire is able to discriminate three different populations of patients with different degrees of renal disease (pre-ESRD, ESRD, TxR). Five hundred sixty-three patients from 12 Italian nephrology units completed the SF-36 scales by themselves. The results from these samples were compared with those from the general population. Univariate analysis and multivariate regression were used. The generic SF-36 questionnaire proved to be a powerful instrument to discriminate populations with different degrees of chronic renal failure. The quality of life of patients on dialysis is significantly worse than that of the normal population and other patients with less severe renal function impairment.

The interest of investigators in intensified dialysis regimens has been growing in recent years, especially since the HEMO Study Group showed that a higher dose of thrice-weekly hemodialysis fails to reduce mortality and morbidity but improves clinical outcomes. Alternative hemodialysis strategies including short daily hemodialysis (SDHD), long hemodialysis (LHD) and nocturnal daily hemodialysis (NDHD) have been developed in the hope to improve patients' outcomes. A growing number of investigators are studying patients on alternative dialysis regimens and most publications in this field have reported significant improvements in clinical outcomes including left ventricular hypertrophy, blood pressure control, anemia, calcium-phosphate metabolism, and fluid and electrolyte balance; all of these parameters can be considered as indirect signs of improvement in quality of life. However, the strength of these results is often limited by shortcomings in study design. Indeed, in most of these studies an adequate control group is missing, the patient groups are not properly matched, and the number of patients enrolled is small. Similarly, most studies have evaluated the effects of NDHD and/or nocturnal LHD on health-related quality of life (HRQoL) by questionnaire administration. Even though better results might be achieved with nocturnal hemodialysis, no conclusive data exist to prove statistically significant differences in HRQoL between conventional and intensive hemodialysis. In conclusion, all of these novel dialysis strategies offer reliable opportunities for uremic patients, but further trials are needed to determine whether alternative hemodialysis can reduce morbidity and mortality in this high-risk population of patients.

PURPOSE:In order to reduce the hemodialysis (HD)-induced pro-inflammatory activity we need to use a biocompatible dialysis membrane, avoid backfiltration and possibly use adsorbents. Hemodiafiltration reinfusion (HFR) is a new on-line hemodiafiltration (HDF) technique combining these aspects. This study aimed to evaluate the biocompatibility of the single dialysis session comparing standard HD and HFR.METHODS:Eighteen patients on chronic HD were enrolled in five Centers. Patients underwent one standard and two HFR study sessions; in each session we evaluated leukocyte activation at 0, 5, 15, 60 and 240 min; and interleukin-6 (IL-6), C-reactive protein (CRP) and IL-1 receptor antagonist (IL-1Ra) levels at 0, 60 and 240 min.RESULTS:Leukocyte activation was similar in HD and HFR, while the post-dialysis IL-6 increase was lower with HFR; CRP levels were stable during HFR, but increased after HD, and IL-1Ra did not demonstrate any difference.CONCLUSIONS:These preliminary data show that HFR still has a better biocompatibility in the single dialysis session.

BACKGROUND:Calorie-protein malnutrition is associated with increased morbidity and mortality in hemodialysis patients. The aim of this study was to evaluate the prevalence of malnutrition in uremic patients treated with hemodialysis in two areas of Southern Italy.METHODS:A questionnaire was sent out to all Dialysis Centers in the two regions to select and enrol eligible patients by considering these parameters: Body Mass Index (BMI), serum albumin, serum creatinine, urea, calcium, phosphate, triglycerides, cholesterol, body weight. Enrolment criteria were patients on dialysis for at least six months and BMI less than 21 kg/m2. The dialytic dose was evaluated by reporting the hours of dialysis and filter surfaces. The number of weekly sessions (n. 3) remained unchanged over time.RESULTS:Twenty-three Dialysis Centers in the two Regions replied to our questionnaire and 149 patients were enrolled in the study out of the 1546 patients examined. The overall prevalence of calorie-protein malnutrition was observed in 9.6% of the patients. The prevalence of malnutrition was found to be higher in males and in patients on dialysis for longer time. We observed no correlation with the hypoproteic diet administered in the pre-dialysis phase. Malnourished patients showing progressive weight loss were older and had undergone dialysis for a longer time.CONCLUSIONS:This retrospective study indicates low prevalence of malnutrition in the two regions examined. The lack of correlation between the hypoproteic diet and dialytic dose suggests the need for further studies to evaluate if increased dialytic dose or early start of dialysis could improve the nutritional status and quality of life in elderly patients.

BACKGROUND:Obesity is a well-known cause of increased morbidity and mortality in the general population, while its influence on the hemodialysis population is yet to be defined. Obesity probably has a protective effect on survival in hemodialysis. In this study, we evaluated the prevalence of obesity in the hemodialysis population of Puglia and Lucania, two regions of Southern Italy, by using simple and easily accessible parameters collected by the participating centres.METHODS:One thousand five hundred and forty-six patients on stable hemodialysis for at least 6 months from 23 Centres were studied. One hundred and sixty patients had a body mass index (BMI) more than 25 kg/m2; "preobesity" was defined as a BMI ranging between 25 and 30 kg/mq, while "obesity" as a BMI > 30. All data regarding the underlying renal disease, the use of low-protein diet before beginning hemodialysis, weight and height at the beginning of treatment and the different kinds of treatment were collected. A careful analysis of the last dialysis treatment by means of biochemical data was carried out.RESULTS:The prevalence of preobesity and obesity was 3.1 and 7.3%, respectively. Eighty-three percent of patients in the preobesity group and seventy-two percent in the obesity group were female (p<0.001). The prevalence of diabetes was 19 and 24% in the preobesity and obesity groups, respectively, while it was 8% in patient with normal BMI (p<0.0001). Age and duration of low-protein diet were similar to those observed in the general population, while dialytic age was greater in preobesity group (p<0.01). Conclusions. Our study has shown that the prevalence of obese people undergoing hemodialysis is increasing. It is therefore necessary to introduce new measures to obtain a good nutritional status in end stage renal disease patients; in particular fat free mass is to be increased, since an improvement in the patient's nutritional status acts as a protecting factor against morbidity and mortality.

We studied 212 patients from 13 Italian dialysis centers to evaluate the clinical aspects of dialysis-related amyloidosis in continuous ambulatory peritoneal dialysis (CAPD). The mean age was 64.2 +/- 12.3 years and mean time on dialysis was 36.9 +/- 25.1 months. Residual diuresis was 615.7 +/- 554.0 mL/day and plasma beta 2-microglobulin (beta 2M) level was 27.0 +/- 12.8 mg/L. Radiological skeletal examination, neurological problems related to beta 2M, and urinary and dialytic balance of beta 2M were evaluated. Correlations between age, time on dialysis, residual diuresis, beta 2M plasma levels, beta 2M peritoneal and renal removal, carpal tunnel syndrome, and bone disease were studied. Only the number of bone lesions had a significant positive correlation with patient age and negative correlation with residual diuresis. The latter had an inverse relation with beta 2M plasma levels. Dialytic age did not correlate with any of the parameters. No other correlation was observed. Hand lesions were found in 85% of patients with bone dialysis-related amyloidosis. In conclusion, residual diuresis in our patients played a positive role in the number of bone localizations. Only age, but not time on dialysis, had a positive impact on the bone lesions. The high percentage of hand lesions suggests that the observation of this skeletal segment is a simple, safe, and effective modality of bone follow-up for dialysis-related amyloidosis.

An increasing number of elderly patients with uraemia are treated by dialysis therapy. Virtually every published study on nutritional status of patients undergoing maintenance haemodialysis treatment or continuous ambulatory peritoneal dialysis (CAPD) has indicated that a substantial proportion of patients undergoing regular dialysis treatment have protein calorie malnutrition. Problems of undernutrition increase significantly with age; a combination of socioeconomic, psychological, and biochemical problems interfering with acquiring and assimilating a balanced diet are responsible for nutritional deficiencies in older people. We assessed the prevalence of protein calorie malnutrition in 183 regular dialysis patients aged 65 years or older treated with haemodialysis or CAPD. This group of patients was compared to two other groups aged 18-40 years (62 patients) and 41-64 years (239 patients). Presence of malnutrition was assessed by selected serum chemistries, anthropometry and Subjective Global Nutritional Assessment. Adequacy of dialysis, protein nitrogen appearance, as an index of protein intake, and residual renal function were measured. The results indicate that protein calorie malnutrition occurs commonly in regular dialysis patients, with a higher prevalence of malnutrition in the elderly; 51% of patients of the elderly group were classified as malnourished, and no difference was found with the two dialytic modalities.

CAPD outcomes were compared between a group of 301 diabetic patients (mean age +/- SD, 58.9 +/- 12.7 years, 55.8% males) and a group of 1689 non-diabetic patients (mean age +/- SD 57.8 +/- 14.8 years, 55.9% males) treated in 30 centres participating in the Italian Cooperative Peritoneal Dialysis Study Group from 1980 to 1989, with follow-up observation periods of 444 years (mean +/- SD, 1.48 +/- 1.24) and of 3502 years (mean +/- SD, 2.07 +/- 1.91) respectively. CAPD was the first modality for 87.2% of diabetics and 78.1% of non-diabetics (P < 0.001). The percentage of patients who needed a partner for CAPD was 45.9% in diabetics and 30.2% in non-diabetics (P < 0.001). In diabetics compared with non-diabetics, cardiovascular diseases and cachexia were nearly twice and infections other than peritonitis more than three times as frequent in causing death. In diabetics, survival was significantly worse (P < 0.0001) and the relative risk of death 2.13 times higher (P < 0.001). The technique survival and the relative risk of drop-out were not significantly different in the two groups. Clinical problems were the most important cause of drop-out among diabetics. The probability and relative risk of drop-out due to peritonitis, as well as of the first peritonitis episode, were not significantly different between the two groups and between diabetics using or not using intraperitoneal insulin. Days per patient year of hospitalization, excluding the first, were 18.4 in diabetics and 14.3 in non-diabetics. CAPD-related problems caused hospitalization in a similar way in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

A cohort retrospective study was used to analyze the effect of comorbidity on survival of end-stage renal disease (ESRD) patients undergoing dialysis. The authors analyzed the survival of 255 patients (144 men, 111 women; median age 54 years; range 8-81 years) followed at the District Hemodialysis Unit in Foggia, Italy, over a 15 year period (median follow-up 30 months; range 1-190 months). Two subscales assessing the overall severity of the identified coexistent diseases and overall physical impairment, and a composite four level index of coexistent diseases (ICED) were assembled using information recorded at the time of admission. The Cox proportional hazard model was applied to evaluate the association of various patient characteristics with the probability of death. Mortality risk was associated with patient age (RR = 3.4 for patients aged 42-61; RR = 4.8 for patients older than age 61 compared with patients younger than age 42), initial condition leading to renal failure (RR = 3.1 for diabetes compared with primary renal disease) and ICED (RR = 3.0 for patients with uncontrolled coexistent disease or severe impairment compared with patients with no coexistent disease and no or mild impairment). Gender and type of dialysis were not associated with mortality risk. It was concluded that, as is the case with other chronic conditions, co-morbidity is a powerful independent prognostic factor in determining the mortality of ESRD patients.

Fifteen patients (mean age 59.9 +/- 16.1 years) treated by CAPD for a mean of 21.6 +/- 14 months, underwent peritoneal clearances before and after 15 days of intraperitoneal phosphatidylcholine (PC) treatment (50 mg/L). No difference was observed in urea, creatinine, uric acid, and reverse dextrose clearances. A statistically significant increase in phosphate clearances (4 and 6 hr dwell times) (1.36%) and a reduction in drainage volume (2 hr dwell time) (1.36%) were observed after treatment. Urine output and percent dextrose reabsorption were unchanged. The ultrafiltration (UF) showed a tendency to increase, which lasted for 15 days after discontinuation of treatment. This tendency allowed the patients to reduce, during the same period, the amount of hypertonic solution (23.8 L vs. 21.3 L) required. The tendency to increase UF over time deserves further study.

Three hundred eighty-eight sequential reverse dextrose clearances (RDC) have been performed in 61 unselected patients (12 of whom were diabetics), whose mean age was 54 years (30-79). They were treated for a mean time of 23 +/- 12 months (0-60); the total observation time was 1,440 months. One hundred forty-two episodes of peritonitis were registered, producing a peritonitis incidence of 1 episode per 10.2 patient months. The RDC values are significantly inversely related to dwell-time and show a tendency to increase over time; they never, however, reach statistical significance. Age of patients, episodes of peritonitis and primary renal disease (diabetes) had no influence. It is important to underline the significant inverse relationship between ultrafiltration and residual diuresis. Unknown mechanisms regulate this relationship.

Catheter obstruction due to fibrin deposits during CAPD can cause poor outflow of peritoneal fluid and recurrent peritonitis. In order to treat this complication, 75,000 IU of diluted Urokinase (UK) were infused into catheters obstructed by fibrin in 10 CAPD patients (4 of which had peritonitis), without adverse reactions. After 60 minutes, a 2 liter exchange of peritoneal fluid was performed. In all the cases a normal outflow was restored. Hemostasis parameters (PT, PTT, TT, Fibrinogen, FDP, Fibrin monomers, BT, AT III) and blood cells count (RBC, HGB, HCT, WBC, PTL), were assayed before and two hours after the UK infusion, and did not show any significant variation, except for a decrease of white blood cells, which remained, however, within the normal range. No peritonitis episode occurred in the follow-up period. UK fibrinolytic therapy is safe and effective in treating fibrin obstruction of CAPD catheters without catheter removal and prevents recurrent peritonitis.

To investigate if age of patients, time on CAPD, episodes of peritonitis, or systemic illness (diabetes) may affect the permeability of the peritoneal membrane to small solutes, 51 patients (eight diabetic) 57.2 +/- 9.4 years of age undergoing long-term CAPD were enrolled in a prospective study of peritoneal clearances (PC), started in January 1982. The studies were repeated, when possible, every 6 months after peritonitis episodes. The results were divided according to osmolality of solutions and dwell time. The age of patients had no influence on results. Significantly positive correlations were found between PC (1.36%) of creatinine, uric acid, phosphate, and time on CAPD. Uric acid PC (3.86%) correlated directly with time on CAPD. The PC in diabetic and nondiabetic patients were similar. Patients who had more than three episodes of peritonitis showed PC similar to those observed in patients who had less than three episodes, despite a longer time on CAPD. The stability of PC in patients undergoing long-term peritoneal dialysis suggests that CAPD may permit effective dialysis over many years.