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Background and objectives For older patients with kidney failure, lowering symptom burden may be more important than prolonging life. Dialysis initiation may affect individual kidney failure-related symptoms differently, but the change in symptoms before and after start of dialysis has not been studied. Therefore, we investigated the course of total and individual symptom number and burden before and after starting dialysis in older patients.Design, setting, participants, & measurements The European Quality (EQUAL) study is an ongoing, prospective, multicenter study in patients >= 65 years with an incident eGFR

Introduction: Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. We aimed to externally validate a recently developed CKD G4+ risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement. Methods: We included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged ≥65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA). Results: The model showed a good discrimination for KRT and “death after KRT,” with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds. Conclusion: This study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries.

Background Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation in patients with advanced CKD is lacking, and most do not account for competing risks. Methods To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration. Results The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average c statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-\18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts. Conclusions Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (≥65 years; estimated glomerular filtration rate ≤20 mL/min/1.73 m2) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off ≤70; 0–100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was –0.12 mL/min/1.73 m2/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03–1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men.

Systemic inflammation and uremic toxins (UT) determine the increased cardiovascular mortality observed in chronic hemodialysis (HD) patients. Among UT, the adipokine Chemerin induces vascular dysfunction by targeting both endothelial and vascular smooth muscular cells (EC and VSMC). As Citrate anion modulates oxidative metabolism, systemic inflammation and vascular function, we evaluated whether citrate-buffered dialysis improves HD efficiency, inflammatory parameters and chemerin-mediated microvascular injury. 45 patients were treated in sequence with acetate, citrate and, again, acetate-buffered dialysis solution (3 months per interval). At study admission and after each treatment switch, we evaluated dialysis efficacy and circulating levels of chemerin and different inflammatory biomarkers. In vitro, we stimulated EC and VSMC with patients’ plasma and we investigated the role of chemerin as UT. Citrate dialysis increased HD efficacy and reduced plasma levels of CRP, fibrinogen, IL6 and chemerin. In vitro, patients’ plasma induced EC and VSMC dysfunction. These effects were reduced by citrate-buffered solutions and paralleled by the decrease of chemerin levels. Consistently, chemerin receptor knockdown reduced EC and VSMC dysfunction. In conclusion, Switching from acetate to citrate improved dialysis efficacy and inflammatory parameters; in vitro, chemerin-induced EC and VSMC injury were decreased by using citrate as dialysis buffer.

COVID-19, a disease caused by a novel coronavirus, is a major global human threat that has turned into a pandemic. This novel coronavirus has specifically high morbidity in the elderly and in comorbid populations. Uraemic patients on dialysis combine an intrinsic fragility and a very frequent burden of comorbidities with a specific setting in which many patients are repeatedly treated in the same area (haemodialysis centres). Moreover, if infected, the intensity of dialysis requiring specialized resources and staff is further complicated by requirements for isolation, control and prevention, putting healthcare systems under exceptional additional strain. Therefore, all measures to slow if not to eradicate the pandemic and to control unmanageably high incidence rates must be taken very seriously. The aim of the present review of the European Dialysis (EUDIAL) Working Group of ERA-EDTA is to provide recommendations for the prevention, mitigation and containment in haemodialysis centres of the emerging COVID-19 pandemic. The management of patients on dialysis affected by COVID-19 must be carried out according to strict protocols to minimize the risk for other patients and personnel taking care of these patients. Measures of prevention, protection, screening, isolation and distribution have been shown to be efficient in similar settings. They are essential in the management of the pandemic and should be taken in the early stages of the disease., Graphical Abstract Graphical Abstract

Background Adherence to low salt diets and control of hypertension remain unmet clinical needs in chronic kidney disease (CKD) patients. Methods We performed a 6-month multicentre randomized trial in non-compliant patients with CKD followed in nephrology clinics testing the effect of self-measurement of urinary chloride (69 patients) as compared with standard care (69 patients) on two primary outcome measures, adherence to a low sodium (Na) diet ( Results In the whole sample (N = 138), baseline UNa and 24-h ABPM were143 ± 64 mmol/24 h and 131 ± 18/72 ± 10 mmHg, respectively, and did not differ between the two study arms. Patients in the active arm of the trial used >80% of the chloride strips provided to them at the baseline visit and at follow-up visits. At the third month, UNa was 35 mmol/24 h (95% CI 10.8–58.8 mmol/24 h; P = 0.005) lower in the active arm than the control arm, whereas at 6 months the between-arms difference in UNa decreased and was no longer significant [23 mmol/24 h (95% CI −5.6–50.7); P = 0.11]. The 24-h ABPM changes as well as daytime and night-time BP changes at 3 and 6 months were similar in the two study arms (Month 3, P = 0.69–0.99; Month 6, P = 0.73–0.91). Office BP, the use of antihypertensive drugs, estimated Glomerular Filtration Rate (eGFR) and proteinuria remained unchanged across the trial. Conclusions The application of self-measurement of urinary chloride to guide adherence to a low salt diet had a modest effect on 24-h UNa and no significant effect on 24-h ABPM.

Background: Depression is the most common psychiatric disorder in long-term dialysis patients and a risk factor for morbidity and mortality. Although there is a relevance of the issue in the dialysis setting, we still know little about possible relationships between depression and uraemia-related biochemical abnormalities. Our aims were to evaluate (1) the prevalence of depression in our haemodialysis (HD) and peritoneal dialysis (PD) population using a validated and easy-to-implement screening tool and (2) the association between depression and the main uraemia-related clinical and biochemical parameter changes. Methods: In this monocentric cross-sectional study, all patients of our centre with at least 3 months of dialysis were screened by Patient Health Questionnaire-9 (PHQ-9), a self-administered depression-screening questionnaire validated in dialysis setting. The impact of depressive symptoms on daily life was also assessed. We then analysed relationships between the PHQ-9-derived depressive score, functional impairment score, demographic, clinical and laboratory variables. Results: In our cohort of 145 patients, depressive symptoms were found in 69 patients (46%). Stratifying for severity, mild, moderate and severe grade accounted for 31, 13 and 2% respectively. Depressive symptoms affected 36% of patients on PD versus 52% of patients on HD. Moreover, the PD patients had significantly less functional impairment derived from depressive symptoms than the HD patients. Simple and multiple regression analysis identified serum phosphorus as the only uraemia-related laboratory parameter that was high statistically associated with depressive score. Conclusions: Using a reliable, simple and fast tool, we found that depressive symptoms affect almost half of dialysis patients, particularly so the HD cohort. Severity of depressive symptoms seems related to serum levels of phosphorus possibly because depression affects compliance to therapy.

Background: Estimated glomerular filtration rate (eGFR) is a predictor of outcome among patients with non-ST-elevation acute coronary syndrome (NSTE-ACS), but which estimation formula provides the best long-term risk stratification in this setting is still unclear. We compared the prognostic performance of four creatinine-based formulas for the prediction of 10-year outcome in a NSTE-ACS population treated by percutaneous coronary intervention. Methods: In 222 NSTE-ACS patients submitted to percutaneous coronary intervention, eGFR was calculated using four formulas: Cockcroft–Gault, re-expressed modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-Epi), and Mayo-quadratic. Predefined endpoints were all-cause death and a composite of cardiovascular death, non-fatal reinfarction, clinically driven repeat revascularisation, and heart failure hospitalisation. Results: The different eGFR values showed poor agreement, with prevalences of renal dysfunction ranging from 14% to 35%. Over a median follow-up of 10.2 years, eGFR calculated by the CKD-Epi and Mayo-quadratic formulas independently predicted outcome, with an increase in the risk of death and events by up to 17% and 11%, respectively, for each decrement of 10 ml/min/1.73 m2. The Cockcroft–Gault and MDRD equations showed a borderline association with mortality and did not predict events. When compared in terms of goodness of fit, discrimination and calibration, the Mayo-quadratic outperformed the other formulas for the prediction of death and the CKD-Epi showed the best performance for the prediction of events (net reclassification improvement values 0.33–0.35). Conclusions: eGFR is an independent predictor of long-term outcome in patients with NSTE-ACS treated by percutaneous coronary intervention. The Mayo-quadratic and CKD-Epi equations might be superior to classic eGFR formulas for risk stratification in these patients.

Little information have been provided till now regarding the effect of high volume HDF (hv-OL-HDF) in respect to standard bicarbonate dialysis (BHD) in medium-long term protein-bound toxins removal. A randomised cross-over multicentre study (REDERT study) was designed to compare the effects of hv-OL-HDF and low-flux BHD on uremic toxins serum levels in 36 chronic dialysis patients followed for 13 months. Group 1 patients were treated with BHD (Treatment A) for 6 months, and afterwards, they were transferred to hv-OL-HDF for a further 6 months (Treatment B). Group 2 patients were treated with Treatment B for 6 months, and afterwards, they were transferred to Treatment A for a further 6 months. Total and free pre-dialysis indoxyl-sulfate (IS) and p-cresyl-sulfate (pCS) were determined starting a midweek dialysis session at baseline and after six months of hv-OL-HDF or BHD. IS and pCS, were simultaneously measured, by liquid chromatography/electrospray ionization-tandem mass spectrometry, Kt/v and pre and post-dialysis b-2microglobulin (b2MG) levels were measured every three months. Kt/V was significantly increased in hv-OL-HDF (from 1.47 ± 0.24 to 1.49 ± 0.16; p

As currently performed, on line hemodiafiltration reduces, but does not normalize, the micro-inflammation of uremic patients. Recent technological advances make it possible to further reduce the inflammation connected to the dialysis treatment. Short bacterial DNA fragments are pro-inflammatory and can be detected in the dialysis fluids. However, their determination is not currently within normal controls of the quality of the dialysate. The scenario may change once the analysis of these fragments yields reliable, inexpensive, quick and easy to evaluate the results. At variance with standard bicarbonate dialysate, Citrate dialysate induces far less inflammation both for the well-known anti-inflammatory effect of such buffer and also because it is completely acetate free, e.g. a definitely pro-inflammatory buffer. However, the extensive use of citrate dialysate in chronic dialysis is prevented because of concerns about its potential calcium lowering effect. In our view, high convective exchange on line hemodiafiltration performed with dialysate, whose sterility and a-pirogenicity is guaranteed by increasingly sophisticated controls and with citrate buffer whose safety is certified, can serve as the gold standard of dialysis treatments in future.

We report the case of a woman with a history of chronic alcohol abuse who was hospitalized with diarrhea, severe hypokalemia refractory to potassium infusion, nausea, vomiting, abdominal pain, alternations of high blood pressure with phases of hypotension, irritability and increased urinary 5-hydroxyindoleacetic acid and cortisol. Although carcinoid syndrome was hypothesized, abdominal computed tomography and colonoscopy showed non-specific inflammatory bowel disease with severe colic wall thickening, and multiple colic biopsies confirmed non-specific inflammation with no evidence of carcinoid cells. During the following days diarrhea slowly decreased and the patient's condition progressively improved. One year after stopping alcohol consumption, the patient was asymptomatic and serum potassium was normal. Chronic alcohol exposure is known to have several deleterious effects on the intestinal mucosa and can favor and sustain local inflammation. Chronic alcohol intake may also be associated with high blood pressure, behavior disorders, abnormalities in blood pressure regulation with episodes of hypotension during hospitalization due to impaired baroreflex sensitivity in the context of an alcohol withdrawal syndrome, increased urinary 5-hydroxyindoleacetic acid as a result of malabsorption syndrome, and increased urinary cortisol as a result of hypothalamic-pituitary-adrenal axis dysregulation. These considerations, together with the regression of symptoms and normalization of potassium levels after stopping alcohol consumption, suggest the intriguing possibility of a alcohol-related acute inflammatory bowel disease mimicking carcinoid syndrome.

A recent American College of Cardiology Foundation and American Society of Echocardiography document updated previous appropriate use criteria (AUC) for echocardiography. The aim of this study was to explore the application of the new AUC, and the resulting appropriateness rate, in hospitalized patients referred for transthoracic echocardiography (TTE) in a community setting.A total of 931 consecutive inpatients referred for TTE were prospectively recruited in five community hospitals. Patients were categorized as having appropriate, uncertain, or inappropriate indications for TTE according to the AUC. An additional group of 259 inpatients, discharged without having been referred for TTE, was also considered.In the group referred for TTE, the large majority of indications (98.8%) were classifiable according to the AUC with good interobserver reproducibility. Indications were appropriate in 739 patients (80.3%), of uncertain appropriateness in 46 (5.0%), and inappropriate in 135 (14.7%). Compared with patients with appropriate or uncertain indications, those with inappropriate indications were younger and more often referred by noncardiologists. Most common causes of inappropriate indications were related to the lack of changes in clinical status or to the absence of cardiovascular symptoms and signs. Examinations with appropriate or uncertain indications had an impact on clinical decision making more often than those with inappropriate indications (86.7% vs 14.1%, P.0001). In the group discharged without having been referred for TTE, TTE might have been appropriate in 16.2% of cases.Clinical application of the new AUC was highly feasible in a community setting. Although inpatient referral for TTE was appropriate in most patients, strategies aimed at implementing these criteria in clinical practice are desirable.

Kidney function is assessed in clinical practice to screen for kidney disease, to adapt dosage of medications for renal clearance, and to follow the evolution of known kidney disease. Because renal disease has different clinical presentations and patients are often asymptomatic, it is important to assess kidney function as accurately as possible, especially in older adults, since there is a progressive decline in renal function with age. Glomerular filtration rate (GFR) is the best quantification of kidney function,1 but because it cannot be measured directly, it is estimated from serum concentration or urinary clearance of a filtration marker. Exogenous filtration markers such as inulin, which is the criterion standard filtration marker, give accurate estimates of GFR,2 but determining them is complex and expensive, has potential complications, and is inappropriate for general use. Currently, serum creatinine is the most widely used method of assessing renal function in clinical practice, although it has been well established that serum creatinine alone may not be well correlated with true GFR.3,4 Indeed, as renal function declines, tubular creatinine secretion increases, leading to a blunted and delayed rise in serum creatinine concentration, which reaches the abnormal range only when more than half of the total filtration rate is lost.3 Furthermore, because creatinine is derived from the metabolism of creatine in the muscle and from dietary meat intake, factors related to reduced muscle mass, a potential problem in old age, and low dietary meat intake have a strong effect on serum creatinine concentration.4 To account for muscle mass, different estimation equations of GFR adjust serum creatinine concentration for different demographic characteristics and body composition variables. These include the Cockcroft–Gault equation5 or the Modification of Diet in Renal Disease (MDRD) Study equation.6 Despite the fact that serum creatinine is well known to be poorly correlated with GFR, and despite availability of different estimation equations, many clinicians continue to rely solely on serum creatinine as a measure of renal function and interpret a normal serum creatinine as indicating normal renal function. But how many patients with impaired kidney function are missed when relying on serum creatinine alone? Do women have the same risk of misclassification as men? Does this risk change according to body mass index (BMI)? The purpose of this article is to estimate the magnitude of renal function misclassification in a community-dwelling elderly population with normal serum creatinine values and to describe the participant characteristics related to misclassification.

1. Evaluation of the patient1.1 Assessment of dry weight1.2 Measurement of blood pressure and heart rateduring dialysis1.3 Cardiac evaluation2. Lifestyle interventions2.1 Sodium restriction2.2 Food and caffeine intake during dialysis3. Factors relation to the dialysis treatment3.1 Manipulation of ultrafiltration3.1.1 Ultrafiltration profiling3.1.2 Blood volume controlled ultrafiltration3.2 Dialysate composition.3.2.1 High sodium dialysis and sodium profiling3.2.2 Dialysate buffer3.2.3 Dialysate calcium3.2.4 Other components of dialysate3.3 Dialysis membranes/contamination ofdialysate.3.4 Dialysate temperature.3.5 Convective techniques and isolatedultrafiltration.3.5.1 Convective techniques3.5.2 Isolated ultrafiltration3.6 Dialysis duration and frequency.3.7 Switch to peritoneal dialysis.4. Antihypertensive drugs and preventive medication4.1 Antihypertensive drugs4.2 Preventive vasoactive agents4.3 Carnitine5. Stratified approach to prevent IDH6. Treatment of IDH6.1 Trendelenburg position6.2 Stopping ultrafiltration6.3 Infusion fluids6.4 Protocol

Guideline 1. Prevalence of malnutrition and outcomeGuideline 2. Diagnosis and monitoring of malnutrition2.1. Diagnosis of malnutrition2.2. Monitoring and follow-up of nutritionalstatusGuideline 3. Recommendations for protein and energyintake3.1. Recommended protein intake3.2. Recommended energy intakeRecommendation 4. Recommendations for vitamins,minerals and trace elementsadministration in maintenancehaemodialysis patients.4.1. Vitamins4.2. Minerals4.3. Trace elementsGuideline 5. Treatment of malnutrition5.1. Dietary intervention5.2. Oral supplements and enteral feeding5.3. Intradialytic parenteral nutrition5.4. Anabolic agents5.5. Other interventions: daily dialysisGuideline 6. Metabolic acidosisAppendices

Department of Renal Medicine, St James’s University Hospital, Leeds, UK, Nephrology Department, Reina Sofia University Hospital, Cordoba, Spain, Division of Nephrology and Dialysis, Bolognini Hospital, Seriate, Italy, Department of Medicine, Division of Nephrology, Ege University Medical Faculty, Izmir, Turkey, Nephrology, Dialysis and Intensive Care Unit, Lapeyronie University Hospital, Montpellier, France, Departement de Nephrologie JE 2411 Denutrition des Maladies Chroniques, Hopital E Herriot, France, Department of Diagnostic and Interventional Radiology, Helios Klinikum Wuppertal, University Hospital Witten/Herdecke, Germany, Medical Faculty University of Cologne, Medicine Clinic I, Hospital Merheim, Germany (retired), Department of Internal Medicine, Division of Nephrology, University Hospital Maastricht, The Netherlands, Nephrology Unit, SM Annunziata Hospital, Florence, Italy, Department of Surgery, University Hospital Maastricht, The Netherlands, Department of Nephrology, Nutrition and Dietetics, Guy’s and St Thomas’ NHS Foundation Trust, London, UK (retired), Department of Medicine, Division of Nephrology, University Hospital, Wurzburg, Germany, Department of Nephrology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands and Nephrology Section, Department of Internal Medicine, University Hospital, Ghent, Belgium

Benefits and risks of angiotensin converting enzyme inhibitors (ACE-I) in advanced chronic kidney disease (CKD) are controversial. We tested the role of ACE-I in slowing the progression of renal damage in a real-world elderly population with CKD stage 5. We evaluated all patients consecutively referred to our CKD stage 5 outpatient clinic from January 2002 to December 2013. Chronicity was defined as two consecutive estimated glomerular filtration rate (eGFR) measurements below 15 ml/min/1.73 m2. We retrieved parameters of interest at baseline and assessed eGFR reduction rate during follow-up. We estimated GFR by the 4-variable Modification of Diet in Renal Disease (MDRD) formula. Mean age of the 342 subjects analyzed was 72 years and eGFR 10 ml/min/1.73 m2. In the 188 patients on ACE-I at baseline, the subsequent annual rate of eGFR reduction was less than a third of that found in the 154 patients off ACE-I. Across phosphate quartiles, baseline eGFR significantly decreased while its annual reduction rate significantly increased. Of the original cohort, 60 patients (17 %) died, 201 (59 %) started dialysis and 81 (24 %) were still in conservative treatment at the end of the study. Multivariate analysis identified age, phosphate, proteinuria, baseline eGFR and its rate of progression as independent risk factors directly or inversely predictive of progression to dialysis. ACE-I use significantly reduced by 31 % the risk of dialysis. Our study shows that proteinuria independently predicts further renal damage progression even in end-stage renal disease patients not yet in dialysis. In our cohort of elderly patients with very advanced CKD, ACE-I was effective in slowing down further renal damage progression.

Knowledge about mineral bone disorder (MBD) management in non-dialysis chronic kidney disease (ND-CKD) patients is scarce, although essential to identifying areas for therapeutic improvement. We prospectively evaluated current management of CKD-MBD in two visits, performed 6 months apart, in 727 prevalent ND-CKD stage 3b–5 patients from 19 nephrology clinics. Therapeutic inertia was defined as lack of treatment despite hyperphosphatemia and/or hypocalcemia, and/or hyperparathyroidism. The primary endpoint was the prevalence of achieved target for CKD-MBD parameters and related treatments (phosphate binders, vitamin D and calcium supplements). The secondary endpoint was the assessment of prevalence and clinical correlates of therapeutic inertia. Over 65 % of patients did not reach parathormone (PTH) targets, while 15 and 19 % did not reach phosphate and calcium targets, respectively. The proportion of untreated patients decreased from stage 3b to 5 (at baseline, from 60 to 16 %, respectively). From baseline to the 6-month visit, the achievement of targets remained stable. Low protein diet was prescribed in 26 % of patients, phosphate binders in 17.3 % (calcium-based binders 15.5 %, aluminium binders 1.8 %), and vitamin D in 50.5 %. The overall prevalence of therapeutic inertia at the 6-month visit was 34.0 % (for hyperphosphatemia, 54.3 %). Compared to CKD stage 3, the likelihood of therapeutic inertia was 40 and 68 % lower at stage 4 and 5, respectively. PTH, calcium and phosphate targets were not reached in a significant proportion of patients. One-third of patients with at least one MBD parameter not-at-target remained untreated. Therapeutic inertia regarding CKD-MBD treatment may be a major barrier to optimizing the prevention and cure of CKD-MBD.

Background: Previous studies reported significant increases in epoetin dosages when converting hemodialysis patients from subcutaneous (SC) to intravenous (IV) administration. More recent studies that corrected for iron deficiency found a much lower, if any, increase in epoetin dosage and/or decrease in hemoglobin (Hb) level after conversion from SC to IV epoetin administration. Therefore, the matter is still open for debate. Methods: This multicenter observational study evaluated stable hemodialysis patients without iron deficiency who had a stable SC epoetin dosage and Hb level of 10 g/dL or greater (≥100 g/L) at the time of study enrollment. Data for epoetin dosage, anemia, and inflammatory markers were collected retrospectively during the last 6 months of SC epoetin treatment and prospectively for 6 months after conversion to IV administration. The primary efficacy assessment was difference in Hb levels and epoetin dosages between patients administered epoetin SC and IV. Changes in values for iron stores, C-reactive protein, intact parathyroid hormone, and albumin were monitored as control parameters. Results: Data were analyzed for 262 hemodialysis patients from 6 Italian centers. Overall, mean Hb levels were similar with SC and IV epoetin administration (11.49 g/dL [114.9 g/L] and 11.44 g/dL [114.4 g/L]). Mean epoetin dosages also were similar with SC and IV administration (7,185 and 7,270 IU/wk). In patients requiring epoetin dosages of 12,000 IU/wk or greater at study entry, mean dosages tended to decrease after conversion to IV administration. There were no significant changes in control parameters. Conclusion: Conversion from SC to IV epoetin administration did not result in changes in Hb levels or epoetin dosage requirements in iron-replete hemodialysis patients.

Background. In patients on on-line convective treatments, given the considerable quantity of dialysis fluid re-infused, the small amount of acetate present in bicarbonate dialysis fluid as a pH stabilizing factor may allow a significant transfer of that anion to the patient, possibly inducing cytokine activation. Methods. To verify this hypothesis, we performed on-line haemodiafiltration (OL-HDF) with (3 mmol/l) and without acetate in dialysis fluid in a cross-over randomized order on 12 prevalent patients. Results. In comparison with the pre-treatment values, plasma acetate levels were unchanged during and after acetate-free OL-HDF, while they were 5–6 times higher in the course of OL-HDF containing acetate in dialysis fluid; plasma acetate levels returned to basal values 2 h after the end of the procedure. The total increase of bases in the patient attributable to acetate was 36%. Plasma bicarbonate values at the end of treatment were significantly lower in treatments without acetate, as compared to those with acetate. Interleukin-6 plasma levels were super-imposable at the beginning and in the course of the two methods compared, but there was a tendency towards a greater increase at an interval of 2 h following OL-HDF with acetate. Conclusions. Our preliminary results confirm the assumption that body gain of acetate is particularly high in convective treatments, while acetate-free OL-HDF slows down acetate burden. Clinical advantages due to these effects should be evaluated in properly designed prospective studies.

Parameters derived by ultrasonic myocardial characterization in dialysis patients are associated with mortality.BackgroundAutopsy studies have shown that hypertrophic hearts of uremic patients have peculiar characteristics. Changes in tissue structure are detectable by ultrasound as changes in echo reflectivity.MethodsWe studied 96 dialysis patients, 18 hypertensive subjects with normal renal function and 52 healthy subjects. The echo pattern of interventricular septum was assessed by videodensitometry (VDT) (i.e., a computer-assisted quantitative analysis of gray levels). For each pixel a numerical value from 0 (black) to 255 (white) was assigned. From the resulting histogram of gray level frequency distribution, we obtained indexes of central tendency (reflectivity) and of homogeneity of distribution (uniformity).ResultsFor the same septum thickness, dialysis patients showed a significantly greater reflectivity (87 ± 19 and 70 ± 17) (P < 0.001) and lower uniformity (137 ± 32 and 184 ± 71) (P < 0.007) compared with hypertensives. Hypertensive patients showed VDT parameters similar to control subjects in spite of significantly higher septum thickness (P < 0.003). Followed up after 5 years, dialysis patients with a reduced homogeneity of distribution of gray levels (lower uniformity) showed a significantly shorter survival (HR by Cox 2.5, 95% CI 1.21-5.27).ConclusionFor a similar degree of cardiac hypertrophy, dialysis patients differed widely from hypertensives in their VDT parameters. By contrast, the hypertensive heart differed from the normal heart in the degree of hypertrophy but not in terms of VDT parameters. VDT parameters are independent predictors of all-cause mortality in dialysis patients.

BACKGROUND In haemodialysis (HD) patients, anaemia is associated with reduced survival. Despite treatment with erythropoiesis-stimulating agents (ESAs), a large number of patients with chronic kidney disease show resistance to this therapy and require much higher than usual doses of ESAs in order to maintain the recommended haemoglobin (Hb) target, and recent studies suggest that hepcidin (HEP) may mediate the ESA resistance index (ERI). High-volume online haemodiafiltration (HV-OL-HDF) has been shown to improve anaemia and to reduce the need for ESAs in HD patients; this effect is associated with a reduced inflammatory state in these patients. The aim of the REDERT study (role of haemodiafiltration on ERI) was to investigate the effect of different dialysis techniques on ERI and HEP levels in chronic dialysis patients. METHODS A single cross-over, randomized, multicentre study (A-B or B-A) was designed. Forty stable HD patients from seven different dialysis units (male 65%, mean age 67.6 ± 14.7 years and mean dialytic age 48 ± 10 months) were enrolled. Patients were randomized to the standard bicarbonate dialysis (BHD) with low-flux polysulfone (PS) membrane group or to the HV-OL-HDF group with high-flux PS membranes and exchange volume of >20 L/session. After 6 months, patients were shifted to the other dialytic group for a further 6 months. Clinical data, Hb, ESA doses and iron metabolism were recorded every month. HEP, beta2-microglobulin (b2MG) and C-reactive protein (CRP) were determined every 3 months, and ERI was calculated monthly as the weekly ESA dose per kilogram of body weight divided by Hb level. Data were analysed using paired-samples t-test, Wilcoxon signed-rank test and Spearman's correlation coefficient. RESULTS Dialysis efficiency for small molecules assessed as Kt/V was significantly increased in HV-OL-HDF from 1.47 ± 0.24 to 1.49 ± 0.16; P < 0.01. A significant reduction of b2MG was obtained in HV-OL-HDF from month 3 whereas CRP values were not significantly changed during the study period either in BHD or HV-OL-HDF.ERI was significantly reduced in HV-OL-HDF at month 3 and 6 (from 9.1 ± 6.4 UI/weekly/Kg/Hb to 6.7 ± 5.3 UI/weekly/Kg/Hb; P < 0.05) due to a higher ESA consumption in BHD in spite of similar Hb levels. HEP levels were reduced in HV-OL-HDF with respect to BHD after 3 and 6 months. Iron consumption was not significantly different during BHD or HV-OL-HDF treatment as well as transferrin, ferritin and TSAT levels. A significant positive linear correlation between HEP and ERI (r(2) = 0.258, P < 0.001) was observed. CONCLUSIONS In a uraemic patient population with low-grade inflammation treated with HV-OL-HDF, we observed a significant reduction of ERI values as well as HEP levels. The positive correlation between these two parameters supports a role for HEP in the development of ERI in the dialytic population. Moreover, the lower b2MG and the higher Kt/V achieved in HV-OL-HDF confirms the better depurative effect of this technique in comparison with BHD with respect to middle molecules and small-molecular-weight molecules.

The optimal timing of dialysis initiation is still unclear. We aimed to ascertain whether a strict clinical follow-up can postpone need for dialysis in chronic kidney disease (CKD) stage 5 patients. We reviewed records of all consecutive adult patients attending our conservative CKD stage 5 outpatient clinic from 2001 to 2010. Chronicity was defined as two consecutive estimated glomerular filtration rate (eGFR) measurements below 15 ml/min/1.73 m2. Characteristics of subjects, including comorbidities, were assessed at baseline; blood pressure and serum markers of uremia were assessed both at first and last visit. GFR was estimated by the 4-variable Modification of Diet in Renal Disease (MDRD) formula. In the 312 patients analyzed baseline eGFR was 9.7 ± 2.7 ml/min, which declined by 1.93 ± 4.56 ml/min after 15.6 ± 18.2 months. Age was inversely related to eGFR decline (r −0.27, p = 0.000). During conservative follow-up 55 subjects (18 %) died. In comparison with those eventually entering dialysis, deceased subjects were older and had a longer follow-up with no CKD progression. Multivariate analysis identified age, proteinuria and lower baseline K values as the only independent determinants of death. One hundred ninety-four subjects (66 %) started dialysis with an average eGFR of 6.1 ± 1.9 ml/min. During 35.8 ± 24.7 months of dialysis follow-up, 84 patients died. Multivariate analysis identified age as the main determinant of death (hazard ratio [HR] for every year 1.07, 95 % confidence interval [CI] 1.04–1.11, p 0.000). Patients starting dialysis with eGFR below the median, e.g.

Calcimimetics are effective in lowering serum parathyroid hormone (PTH) levels in hyperparathyroidism (HPT). However, they failed to reduce PTH levels in the long term in the setting of primary malignant HPT. A haemodialysis patient suffering from severe longstanding secondary HPT underwent total parathyroidectomy with autotransplantation of parathyroid tissue in her left arm. In the following years, she developed a severe HPT sustained by cancerous transformation of the parathyroid transplanted tissue and resistant both to pharmacological and repeated surgical treatments. The calcimimetic 'cinacalcet' was able to effectively reduce serum PTH levels over a 3-year follow-up and to induce disappearance of the neoplastic lesion on radionuclide imaging. Biochemical control of HPT was associated with a remarkable improvement in cardiac function.

Background. Citrate has anticoagulative properties and favorable effects on inflammation, but it has the potential hazards of inducing hypocalcemia. Bicarbonate dialysate (BHD) replacing citrate for acetate is now used in chronic haemodialysis but has never been tested in postdilution online haemodiafiltration (OL-HDF).Methods. Thirteen chronic stable dialysis patients were enrolled in a pilot, short-term study. Patients underwent one week (3 dialysis sessions) of BHD with 0.8 mmol/L citrate dialysate, followed by one week of postdilution high volume OL-HDF with standard bicarbonate dialysate, and one week of high volume OL-HDF with 0.8 mmol/L citrate dialysate.Results. In citrate OL-HDF pretreatment plasma levels of C-reactive protein andβ2-microglobulin were significantly reduced; intra-treatment plasma acetate levels increased in the former technique and decreased in the latter. During both citrate techniques (OL-HDF and HD) ionized calcium levels remained stable within the normal range.Conclusions.Should our promising results be confirmed in a long-term study on a wider population, then OL-HDF with citrate dialysate may represent a further step in improving dialysis biocompatibility.

Multiple solitary plasmacytoma (MSP) is a rare plasma cell dyscrasia, characterised by multiple lesions of neoplastic monoclonal plasma cells. It differs from multiple myeloma by the lack of hypercalcaemia, renal insufficiency, anaemia and pathological monoclonal plasmocytosis on a random bone biopsy. We present the case of an MSP described for the first time in a patient on peritoneal dialysis. There are only few cases of MSP described in literature, and we performed a review of these cases trying to systematise the topic. The increasing clinical use of CT, MRI and positron emission tomography will enhance in the future the correct diagnosis of MSP.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase implicated in several age-related biological mechanisms such as telomere shortening and cell senescence. We tested the hypothesis that ADMA blood level is an independent predictor of mortality in elderly. This is a longitudinal population-based cohort study. Participants are a representative cohort of 1,025 men and women (age range 65–102 years) living in Chianti area, Tuscany, Italy. The plasma ADMA was measured by liquid chromatography–tandem mass spectrometry. During the follow-up (95 ± 32 months), 384 individuals died, of whom 141 (37 %) died of cardiovascular (CV) causes. In adjusted analyses, the plasma ADMA was the strongest predictor of all-cause mortality (HR (0.1 μMol/L) 1.26, 95 % CI 1.10–1.44, P 60 μMol/L. Notwithstanding the association of ADMA with all-cause mortality was robust, this biomarker failed to add predictive power to a simple model based on the risk factors in the elderly (area under the ROC curve 0.85 ± 0.01 vs. 0.84 ± 0.01). ADMA is a strong independent predictor of mortality in the older population, and l-arginine modifies the effect of ADMA on survival. The mechanisms for this association should be targeted by future studies.

In the management of anemia in patients with chronic kidney disease stage 5 undergoing dialysis (CKD-5D), maintaining hemoglobin (Hb) within the range recommended by the guidelines is challenging.The CARISMA study aim was to evaluate the efficacy, safety and tolerability of a once-monthly continuous erythropoietin receptor activator (CERA) for the treatment of anemia in CKD-5D patients. In this single-arm, multicenter, open-label, phase IIIb study, we screened adult patients from 66 centers in Italy receiving intravenous epoetin alfa or beta or darbepoetin alfa. Eligible patients entered the CERA dose titration phase (DTP), followed by an efficacy evaluation period (EEP) and a long-term safety period (LTSP). Patients were analyzed by intention-to-treat (ITT), per protocol (PP) and safety populations.The rate of patients maintaining Hb within the range 10.0-12.0 g/dL throughout the EEP was 63.22% (220/348), and concentration from baseline to any postbaseline time point. CERA may thus offer a convenient and effective treatment 73.94% (122/165) in the ITT and PP population, respectively, periods in both populations. The rate of patients requiring a dose change was higher during the DTP (69.2%) and the LTSP (73.0%) than during the EEP (54.5%), as expected. CERA treatment was generally well tolerated.Once-monthly CERA administered to CKD-5D patients was associated with negligible changes in mean Hb option for these patients.

Over the years hemo(dia)filtration therapies have received considerable impetus owing to the simplified techniques and optimal hydraulic management. Today, these technological improvements allow large amounts of on-line fluid exchange with the resulting clinical benefits. After a brief historical review, this article describes the main characteristics of predilution and postdilution hemodiafiltration based on the current literature, emphasizing the technical peculiarities as well as the clinical advantages in terms of patient survival. Particular attention is paid to the physical and hydraulic principles, and to new programs that optimize dialysis efficiency.

This paper reports the analysis of the second part of the data obtained from the second SIN census and illustrates the management model of the Italian dialysis centers, highlighting its strengths but also its limits. The census was carried out between March and December 2008 with a webbased survey using fillable PDF forms. The survey was validated by comparing the data with those sent to the Italian Dialysis and Transplant Register (Registro Italiano di Dialisi e Trapianti, RIDT) and hence it refers to December 31, 2008, the date of the last RIDT report. Forty-two percent of dialysis centers, which altogether take care of 50% of Italian dialysis patients, participated in the census. The participation percentage was very variable among Italian regions (from 5% to 100% of dialysis centers). By excluding the three regions with a participation rate below 10%, the survey reached a participation rate of 68% of all Italian dialysis centers and is therefore sufficient to give an estimate of the Italian dialysis situation. However, because of this variability it was not possible to compare regional situations, and the data were evaluated only by analyzing the ''complex'' and ''simple'' dialysis centers separately. The state of affairs of dialysis in Italy on the whole proved to be complicated. It is striking, for example, that 15% of the ''complex'' dialysis centers do not have their own hospital beds and some of them lack traceability programs. Noteworthy are also the increasing use of central venous catheters and the number of patients that need an ambulance to get to the dialysis center. Despite its limits due to the reduced participation in the census, this work offers a fair description of the state of affairs of dialysis in Italy, where there is certainly space for qualitative improvement. First of all, however, every effort should be made to implement and improve the use of the existing structures and to standardize protocols and behaviors in all Italian dialysis centers.

This paper reports on a first analysis of data of the second survey promoted by the Italian Society of Nephrology (SIN), with particular regard to data referring to the nephrologist's workload. The survey was carried out through a Web-based questionnaire that participants could fill in online between March and December 2010. The data were validated against those of the Italian Dialysis and Transplant Registry (RIDT) and therefore refer to 31 December 2008, the date of the last RIDT report. Accurate completion of the questionnaires and reminders were monitored by the presidents of the regional sections of the SIN and the regional registries' chairpersons under the coordination of four area managers and a census committee. The response to the survey represented 42% of all nephrology centers, treating about 50% of all dialysis patients in Italy. The response percentage varied widely among regions (from 5% to 100% of the centers). After exclusion of the three regions with responses below 10%, it reached 68%, which was sufficient to give an idea of the state of nephrology in Italy. However, due to this wide variability, it was not possible to make an overall comparison of the regional situations, hence data for complex and simple structures were assessed separately. Despite the limits due to the incomplete participation in the survey, this article provides a clear description of the state of nephrology in Italy. The results confirm the hypothesis presented in the work of Bocconi Cergas, namely that the nephrology market is broader than nephrologists are able to control. The work of the nephrologist, which still seems to be focused mainly on dialysis in its various forms, should be directed more towards the development of methods for early detection of kidney disease and close follow-up. The ultimate aim is the early diagnosis of kidney disease and hence prevention of its complications, so that the focus no longer needs to be on ESKD treatment systems.

The aim of this study was to assess the kidney function of an older community-dwelling population at baseline and appraise its evolution after 3 years of follow-up in terms of chronic kidney disease (CKD) stage progression, magnitude of glomerular filtration rate (GFR) changes, and value of serum creatinine. This was a prospective population-based study of 676 Italian participants, aged 65 years and older. GFR was estimated using the Cockcroft-Gault equation and the Modification of Diet in Renal Disease Study equation. Using the Cockcroft-Gault equation. A total of 33% of participants had criteria of CKD (GFR < 60 mL/min) at baseline; among them, the majority remained stable, 10% improved, and 7% progressed to more severe CKD stages at follow-up. Loss of GFR in participants with GFR < 60 mL/min was significantly lower (1.4 mL/min per year) than in participants with GFR >/= 60 mL/min (3.3 mL/min per year) at baseline. Most participants classified with CKD stage 2 (GFR 60-89 mL/min) or stage 3 (GFR 30-59 mL/min) at baseline did not change stage, whereas 55% of people with CKD stage 1 (GFR > 90 mL/min) at baseline worsened to stage 2 and 10% worsened to stage 3. An abnormal high level of serum creatinine at baseline did not help to predict who might worsen at follow-up. Older people with CKD displayed a low progression of renal disease and therefore are at higher risk for co-morbidities related to CKD than for progression to end-stage renal disease.

Chronic kidney disease (CKD) is a major public health problem and can result in end-stage renal disease with need for dialysis or transplantation. In Europe up to 12% of the adult population had some renal impairment, while in the United States the end stage of CKD has increased dramatically from 209.000 in 1991 to 472.000 in 2004. Diabetes and hypertension are major causes of kidney pathology. Infection, particularly ascending infection, is more common with increasing age, as both immune function declines and associated pathology predisposing to infection, such as obstructive uropathy, becomes more common. Most pathological changes in the kidney appear to be initiated by oxidative stress, followed by an inflammatory reaction. Oxidative stress results from an imbalance between free radicals and their detoxification by endogenous and exogenous scavengers, including polyunsaturated fatty acids (PUFA). Recent studies showed that PUFA supplementation slowed the rate of loss of renal function in patients with IgA nephropathy. Then, studies of omega-3 supplementation in dialysis patients describe salutary effects on triglyceride levels and dialysis access patency. We examined the relationship between total plasma PUFA levels and change in creatinine clearance over a three-year follow-up in the older persons enrolled in the InCHIANTI study, a population-based epidemiology study conducted in Tuscany, Italy. This study showed that older adults with low total plasma PUFA levels have a greater decline in creatinine clearance over three years of follow-up. These findings suggest that a higher dietary intake of PUFA may be protective against progression to chronic kidney disease.

Detection of subjects with early chronic kidney disease (CKD) is important because some will progress up to stage 5 CKD, and most are at high risk of cardiovascular morbidity and mortality. While validity and precision of estimated glomerular filtration rate (eGFR) equations in tracking true GFR have been repeatedly investigated, their prognostic performance for mortality has not been hitherto compared. This is especially relevant in an elderly population in whom the risk of death is far more common than progression.We analysed data of participants in the InCHIANTI study, a community-based cohort study of older adults. Twenty-four-hour creatinine clearance (Ccr), Cockcroft-Gault (C-G) and Modification of Diet in Renal Disease (MDRD)-derived equations (six and four input variables) were calculated at enrolment (1998-2000), and all-cause mortality and cardiovascular mortality were prospectively ascertained by Cox regression over a 6-year follow-up.Of the 1270 participants, 942 (mean age 75 years) had complete data for this study. The mean renal function ranged from 77 ml/min/1.73 m(2) by Ccr to 64 ml/min/1.73 m(2) by C-G. Comparisons among equations using K/DOQI staging highlight relevant mismatches, with a prevalence of CKD ranging from 22% (MDRD-4) to 40% (C-G). Reduced renal function was a strong independent predictor of death. In a Cox model--adjusted for demographics, physical activity, comorbidities, proteinuria and inflammatory parameters-participants with Ccr 60-90 ml/min/1.73 m(2) and Ccr60 ml/min/1.73 m(2) were, respectively, 1.70 (95% CI: 1.02-2.83) and 1.91 (95% CI: 1.11-3.29) times more likely to die over the follow-up compared to those with Ccr90 ml/min/1.73 m(2). For the C-G, the group with values60 ml/min/1.73 m(2) had a significant higher all-cause mortality compared to those with values90 ml/min/1.73 m(2) (HR 2.59, 95% CI: 1.13-5.91). The classification based on the MDRD formulae did not provide any significant prognostic information. The adjusted risk of all-cause mortality followed a similar pattern when Ccr and estimating equations were introduced as continuous variables or dichotomized as higher or lower than 60 ml/min. C-G was the best prognostic indicator of cardiovascular mortality. Possibly, Ccr and C-G are better prognostic indicators than MDRD-derived equations because they incorporate a stronger effect of age.In a South-European elderly population, the prevalence of CKD is high and varies widely according to the method adopted to estimate GFR. Researchers and clinicians who want to capture the prognostic information on mortality related to kidney function should use the Ccr or C-G formula and not MDRD equations. These results highlight the importance of strategies for early detection and clinical management of CKD in elderly subjects.

Twenty-five years have passed since our groupdescribed for the first time the role played byTemperature (T) in cardiovascular stability. ‘Cold’treatments prevented the hypotension induced by‘warm’ treatments, whether in haemodialysis (HD) orin isolated ultrafiltration [1] or in haemofiltration [2,3].Though some notes of caution were sounded [4],all researchers studying the problem in the years thatfollowed confirmed the role played by T in short-term[5–9] as well as in long-term studies [10,11]. Ascompared to standard HD or ‘warm’ HD, that iswith dialysate T of 37–37.58C, ‘cold’ HD, that is withdialysate T of 35–35.58C, ensures better cardiovascularstability. In 1997, reduction of dialysate T wasrecommended by the DOQI Guidelines as a meansto prevent intradialytic hypotension [12]. A systematicreview recently published found that ‘intradialytichypotension occurred 7.1 (95% CI, 5.3–8.9) times lessfrequently with cool-temperature dialysis. A total of 22studies comprising 408 patients were included, all studieswere of crossover design and relatively short duration’[13]. Lastly, the European Best Practice Guidelinesson cardiovascular instability, announced at the 2006ERA-EDTA Congress, scored only cold dialysis withevidence level I, among the different dialysis techniquesusually adopted to prevent intradialytic hypotension.The terms ‘warm’ and ‘cold’ HD, though immedi-ately understandable, are in reality too simplistic todescribe the complex interrelations between the ther-mal profile of the dialytic treatment and its impact onthe patient’s body T and cardiocirculatory function.Since 1984a good correlation (r¼0.75) betweenvariations in dialysate T in the 34–388C range andconcomitant changes in patients’ body T has beenfound [14]. However, in standard HD with a dialysateT of 378C no thermal exchanges, on average, took placein the extracorporeal circuit, in that the T of the bloodin the venous line was equal to or slightly lower thanthat of the arterial line [14]. Despite this thermoneutralbehaviour however, an average rise in patient’s body Tof 0.5–0.78C takes place [14,15], and this is the reasonfor defining standard HD as a ‘warm’ treatment.However, further analysing the behaviour of individualpatients, differentiated responses (with some subjectswho tended to warm up and others to cool down), forthe same T of the dialysate were described [15].To better understand the physio-pathologicalmechanisms and the clinical implications underlyingdialytic hyperthermia, it is useful to review thephysiology of the relations between T and arterialpressure, to evaluate whether the haemodynamicprofile during HD is in accordance with physiologyand finally, to study what determines thermal balancein the course of HD.