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)).

Survival is not enough. We need to build a health system starting from patients' needs without wasting the resources of our grandchildren and great-grandchildren. We have to switch from curative to preventive medicine by firing managers who think they can resolve all problems by cutting expenditures. We need to educate a new cadre of managers able to govern by centering the system on the patients. Managers should consider health care as an asset and should reinforce clinical research. Such a program has been recently adopted in France.

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.

Angiotensin converting enzyme inhibitors (ACE-i) and angiotensin II receptor blockers (ARB) are considered to be equally effective for patients with diabetic kidney disease, while only ACE-i have been shown to determine a significant reduction in the risk of all-cause mortality, predominantly cardiovascular, in these patients. Studies on the cardio-renal efficacy of combined therapy with ACE-i and ARB are not available or not conclusive, in a population with cardiovascular risk with micro- or macroalbuminuria. In this paper, we present the protocol of a randomized controlled clinical trial that will address the question. The LIRICO (Long-term Impact of RAS Inhibition on Cardiorenal Outcomes) study will evaluate the comparative efficacy for cardiovascular and renal outcomes of combined therapy with ACE-i and ARB versus monotherapy with ACE-i or ARB in micro/macroalbuminuric individuals at cardio-renal risk. The study will enrol 2100 patients allocated to monotherapy with ACE-i, ARB or combined treatment with ACE-i + ARB. The LIRICO study is a randomized comparative trial, with PROBE (Prospective Randomized Open Blinded End-Point) design. The study has been approved and funded by the Agenzia Italiana del Farmaco (AIFA) within the 2005 funding plan for independent research on drugs. Availability of funding for this study provides, for the first time in our Country, an opportunity to organize a collaborative national network of nephrology, internal medicine and diabetology outpatient clinics to develop a large multicentre trial collaboration. The results of this trial will establish the optimal therapy for micro/macroalbuminuric individuals with cardiovascular and renal risk.

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.

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.

The serum concentrations of total and free thyroid hormones and of TSH have been determined in 10 trained subjects before, during and after exercise on a bicycle ergometer. The concentrations of T4 and FT4 increase during the muscular exercise and reduce 30 minutes after the end of work; the decrease is statistically meaningful for the T4. The concentrations of TSH and T3 reduce 30 minutes after the end of work on a bicycle ergometer. The serum concentration of FT3 and of hematocrit doesn't presents any statistically meaningful variation during and after the muscular exercise. The results achieved in our work are in support of the hypothesis that the physic and intense exercise would involve the thyroid gland exalting its activity.

The transmembrane transfer of calcium during hemodialysis is related to many factors (calcium gradient, plasma volume flow, plasma concentration of phosphate). During biofiltration the high ultrafiltration rate reduces the net transfer of calcium from dialysate to patient. Prolonged metabolic alkalosis occurs during biofiltration, lowering the ionized calcium/total calcium ratio. These two factors may stimulate PTH secretion, with negative long-term effects in dialysis bone disease.

We have valued in 8 individuals subjected to muscular moderate work the degree of use of glucose in the body tissues, measured by means of K-Conard, and the role that holds the insulin hormone in this particular condition. The IVGTT was carried out in 8 individuals, at first, in condition of relax. In the same individuals, the day after, the IVGTT was carried out after 5 minutes from the beginning of muscular work to cycloergometer set a 50 watts for a term of 30 minutes. The study demonstrates that, during the muscular moderate work, we have an improvement, statistically significant, of the use of glucose, measured by means of K-Conard (t = 2.42; P less than 0.05). Then, it demonstrates that the muscular moderate work has not any influence on plasmatic concentrations of insulin.