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Bone mineral abnormalities (defined as Chronic Kidney Disease Mineral Bone Disorder; CKD-MBD) are prevalent and associated with a substantial risk burden and poor prognosis in CKD population. Several lines of evidence support the notion that a large proportion of patients receiving maintenance dialysis experience a suboptimal biochemical control of CKD-MBD. Although no study has ever demonstrated conclusively that CKD-MBD control is associated with improved survival, an expanding therapeutic armamentarium is available to correct bone mineral abnormalities. In this position paper of Lombardy Nephrologists, a summary of the state of art of CKD-MBD as well as a summary of the unmet clinical needs will be provided. Furthermore, this position paper will focus on the potential and drawbacks of a new injectable calcimimetic, etelcalcetide, a drug available in Italy since few months ago.

Among dialysis patients, 40% of deaths are due to cardiovascular causes, and 60% of cardiac deaths are due to an arrhythmia. The purpose of this survey, carried out with the organizational support of the Lombard Section of the Italian Society of Nephrology, is to evaluate the frequency and mode of use of non-invasive instruments for the diagnosis of cardiac arrhythmias in the dialysis centers of Lombardy. Information on the prevalence and type of cardiac devices at December 1, 2016 in this population was also required. Data from 18 centers were collected for a total of 3395 patients in replacement renal therapy, including 2907 (85.6%) in hemodialysis and 488 (14.4%) in peritoneal dialysis. All centers use the 12-lead ECG in case of evocative symptoms of an arrhythmic event and 2/3 perform the exam with programmed cadence (usually once a year). Twenty four-hour ECG Holter is not used as a routine diagnostic tool. The proportion of cardiac devices is relatively high, compared to literature data: n=259, equal to 7.6% of the population. Pace-Maker patients are 166 (4.9%), those with intracardiac defibrillator 52 (1.5%), those with resynchronization therapy 18 (0.5%) and those with resynchronization therapy and intracardiac defibrillator 23 (0.7%). The survey provides interesting information and can be an important starting point for trying to optimize clinical practice and collaboration between nephrologists and cardiologists in front of a major problem like that of arrhythmic disease in patients on renal replacement therapy., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Uremic status results from a malfunctioning of kidneys due to the accumulation of compounds which, under normal conditions, are excreted or metabolized by the kidneys. If these compounds are biologically active, they are called uremic toxins. Such compounds have toxic effects on the cardio-vascular system. An useful classification, published by the European Uremic Toxin Work Group (EUTox) is: 1) small water-soluble compounds; 2) protein-bound compounds; 3) the larger "middle molecules". High-flux membranes and more efficient treatment techniques, like HDF, improve the removal of uremic toxins in the middle molecular-weight range, and recent studies suggest that these strategies have better results on the morbidity and mortality. Today new membranes, medium cut-off membranes (MCO), with increased pore size, allow for the removal of higher molecular-weight toxins, such as kappa and lambda light chains and/or mediators of inflammation. For toxins in the 15 to 45 KD-size range, MCO membranes improve the removal in comparison with high-flux HD and/or HDF. Therefore MCO membrane simplifies the treatment of HD patients with a removal spectrum that extend the current possibilities of the best available therapies for End Stage Renal Disease., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Elevated blood pressure is one of the most significant risk factor for the development of chronic kidney disease (CKD); its treatment is a milestone in CKD management. While it is accepted that a stricter blood pressure control is indicated in patients with proteinuria or microalbuminuria, the exact degree of blood pressure reduction to be obtained in CKD patients is still under debate. Following more recent interpretation of old trials, a BP target for <140/90 mmHg is suggested for non-proteinuric CKD patients. In those with microalbuminuria/proteinuria, the ideal blood pressure target should be ≤130/80 mmHg. Recently, the SPRINT trial put new emphasis on a stricter blood pressure control, mainly from the cardiovascular point of view. The blockers of the renin-angiotensin system (RAS) are recommended as first line treatment in all CKD hypertensive patients with micro or macroalbuminuria either diabetics or not. However, their nephroprotective efficacy is less relevant in non-proteinuric patients. The dual RAS blockade was proposed as an additional option. Despite a greater antiproteinuric effect, some large trials in patients at high cardiovascular risk did not demonstrate significant advantage on hard endpoint. Its use is now contraindicated in diabetic CKD patients. Given that RAS blockers can cause acute derangements in kidney function and hyperkalemia, caution is needed with their use, especially in frail and old patients with cardiovascular disease or in the presence of advanced CKD.

Background: Given the public health challenge and burden of chronic kidney disease, the Italian Society of Nephrology (SIN) promoted acensusof the renal and dialysis units to analyse structural and human resources, organizational aspects, activities and workload referring to theyear 2014., Methods: An online questionnaire, including 64 items exploring structural and human resources, organization aspects, activities and epidemiological data referred to 2014, was sent to chiefs of any renal or dialysis unit., Results: Renal and dialysis activity was performed by over 2718 physicians (45 pmp). The management of the acute renal failure was one of the most frequent activities in the public renal units (12,206 patients in ICU and 140.00 dialysis sessions). There were performed about 9000 AV fistulas and 1700 central vascular catheters insertions. In the census, there are a lot of data regarding organization, workforce and workload of the renal unit in Italy. The benchmark data derived from this census show interesting comparisons between centres, regions and groups of regions. These data realised the clinical management of renal disease in Italy.

Background: Given the public health challenge and burden of chronic kidney disease, the Italian Society of Nephrology (SIN) promoted a census of the renal and dialysis units to analyse structural and human resources, organizational aspects, activities and workload referring to the year 2014., Methods: An online questionnaire, including 64 items exploring structural and human resources, organization aspects, activities and epidemiological data referred to 2014, was sent to chiefs of any renal or dialysis unit., Results: 615 renal units were identified. From these 615 units, 332 were public renal centres (of which 318 centres answered to the census) and 283 were private dialysis centres (of which 113 centres answered to the census). The results show 6 public renal units pmp. Renal biopsies were 4624 (81 pmp). The nephrology beds are about 41 pmp. There are 7.304 nurses working in HD wards, 1.692 in the nephrology wards and only 613 for outpatients clinics. The benchmark data derived from this census show interesting comparisons between centres, regions and groups of regions. These data realised the clinical management of renal disease in Italy.

Background/aims: Hemodialysis (HD) patients often show impaired response to erythropoiesis-stimulating agents (ESAs). Extended HD membrane permeability may potentially improve ESA response., Methods: Twenty-four prevalent HD patients were randomly assigned to 12 weeks use of high cut-off (HCO) membrane (in every second dialysis treatment) or continued treatment with high-flux membrane. We monitored changes in hemoglobin (Hb), ESA dose, and key biochemical markers., Results: The Hb level increased in the study group (from 11.6 ± 1.0 to 12.5 ± 1.5 g/dl; p = 0.038) but was stable in the control group. Variation over time in ESA dose and ESA resistance index did not differ between groups. HCO membrane usage for 12 weeks led to decreased hepcidin level, from 303 ± 189 to 157 ± 83 ng/ml (p = 0.024); serum albumin level decreased and stabilized 15 ± 6% below baseline., Conclusions: These results indicate that use of a more permeable dialysis membrane may improve ESA responsiveness in iron-replete HD patients. Extensive albumin removal may preclude long-term use of the HCO membrane., (© 2015 S. Karger AG, Basel.)

The ERA-EDTA codes for primary renal disease (ERA-EDTA PRD code) were implemented many years ago as a tool to use during the annual census of the European Register. They encompassed all those kidney diseases that terminate in uremia, grouped together in various sections, to produce a document that, in a pre-computer age, would guarantee the simplicity of use required at the time, when the census was compiled manually. Over the years, the refinement of diagnostic techniques and the evolution of medical knowledge in general has limited the use of these codes. In addition, the expansion of computer technology has simplified word search in documents thereby permitting the use of far more complex lists containing greater numbers of codes. For this reason, ERA-EDTA has initiated a comprehensive revision of the PRD codes, producing a new list (ERA-EDTA PRD code 2012) which is considerably more detailed and thorough: for example, renal disease not leading to uremia is included, thereby extending the use of codes for scientific applications not restricted to dialysis. In addition, it is amenable to 'recoding' into different encoding systems, including ICD-10, SNOMED-CT data and the Mendelian Inheritance in Man. The new ERA-EDTA codes are accompanied by detailed notes to guide the user. Both codes and notes have been translated accurately into Italian and are now available on the site of the Italian Dialysis Register www.sin-ridt.org together with further information and a search tool for ease of use. This article introduces thenew codesand describesthe Italian language translation process.

Uric acid is an end product of the purine metabolism. The total production is about 700-900 mg/day. Two thirds are eliminated by the kidney; the total amount delivered is about 6-12% of the filtered uric acid. Also fructose raises the uric acid concentration as a result of the activation of fructokinase with ATP consumption and stimulation of AP deaminase. Several studies have demonstrated that uric acid plays a role in renal and cardiovascular disease but none of these studies evaluated its real role as an independent risk factor. Despite studies to find an answer, the current evidence still cannot definitively prove or refute the hypothesis that a high uric acid level can directly induce chronic renal injury.

Background: To understand how peritoneal dialysis (PD) was being used in Italy in 2005 and 2008, a census of all centers was carried out., Methods: In 2005 and 2008, data were collected from, respectively, 222 and 223 centers, with respect to 4432 and 4094 prevalent patients., Results: In the two periods, the PD incidence remained stable (24.3% vs 22.9%), varying from center to center. Continuous ambulatory PD (CAPD) was the main initial method (55%), but APD was more widespread among prevalent patients (53%). Among patients returning to dialysis from transplantation (Tx), PD was used in 10%. The use of incremental CAPD increased significantly from 2005 to 2008, in terms both of the number of centers (27.0% vs 40.9%) and of patients (13.6% vs 25.7%). Late referrals remained stable at 28%, with less use of PD. The overall drop-out rate (episodes/100 patient-years) remained unchanged (31.0 vs 32.8), with 13.1 and 12.9 being the result of death, and 11.8 and 12.4 being the result of a switch to hemodialysis, mainly after peritonitis. A dialysis partner was required by 21.8% of the PD patients. The incidence of peritonitis was 1 episode in 36.5 and 41.1 patient-months, with negative cultures occurring in 17.1% of cases in both periods. The incidence of encapsulating peritoneal sclerosis (episodes/100 patient-years) was 0.70, representing 1.26% of patients treated. The catheter types used and the sites and methods of insertion varied widely from center to center., Conclusions: These censuses confirm the good results of PD in Italy, and provide insight into little-known aspects such as the use of incremental PD, the presence of a dialysis partner, and the incidence of encapsulating peritoneal sclerosis.

Background: Large observational studies have shown a reduction in morbidity and mortality in patients on high-flux haemodialysis (HD) or convective techniques, compared with low-flux HD. An index to evaluate treatment efficiency in middle molecule (MM) removal would be recommended. Since beta-2-microglobulin (beta2-M) is a recognized MM marker, we evaluated an easy approach for Kt/V(beta2-M) assessment on a routine basis, avoiding other complex methods., Methods: An equation that estimates single-pool (sp) Kt/V(beta2-M) was derived from Leypoldt's formula, which calculates beta2-M dialyser clearance (K(beta2-M)) from the post/pre-dialysis beta2-M concentration (C(t)/C(0)) ratio and the weight loss/end-dialysis weight (Delta W/W) ratio. Our equation, spKt/V(beta2-M) = 6.12 Delta W/W [1 - ln(C(t)/C(0))/ln(1 + 6.12 Delta W/W)], was derived by assuming urea distribution volume (V(u)) as 49% of W and beta2-M volume (V(beta2-M)) as V(u)/3, in agreement with the average patient values in the HEMO Study. The spKt/V(beta2-M) values calculated with our equation (F) in 129 patients on 407 sessions of different high-flux treatments were compared with those calculated with the method applied in the HEMO Study (HM). Equilibrated beta2-M concentration (C(eq)) of the same sessions was also estimated with the equation for C(eq) by Tattersall, and equilibrated Kt/V (eKt/V(beta2-M)) was calculated by introducing Tattersall's equation into our simplified spKt/V(beta2-M) formula., Results: Mean results of our spKt/V(beta2-M) equation (F) were very close to those of the HM method (1.48 +/- 0.38 vs 1.47 +/- 0.37). The difference was less than +/-0.1 in 95% of cases. A mean end-session beta2-M rebound of 44 +/- 14% was predicted, which caused a mean reduction in actual Kt/V(beta2-M) of ~27% (eKt/V(beta2-M) = 1.08 +/- 0.26)., Conclusions: The method proposed to estimate spKt/V(beta2-M) and eKt/V(beta2-M) could become a simple tool to monitor the efficiency of high-flux HD and convective techniques and to evaluate the adequacy of treatments in terms of MM removal. Moreover, it might help to better understand the effects of different dialysis schedules. Validation on a larger dialysis population is required.

The National Society of Nephrology has promoted the development of specific Italian Guidelines for dialysis fluids. Two previous national inquiries showed a wide variety in the type and frequency of both microbiological and chemical controls concerning dialysis water, reinforcing the need for specific standards and recommendations. An optimal water treatment system should include tap water pre-treatment and a double reverse osmosis process. Every component of the system, including the delivery of the treated water to the dialysis machines, should prevent microbiological contamination of the fluid. Regular chemical and microbiological tests and regular disinfection of the system are necessary. 1. Chemical quality (Table: see text). Treated tap water used to prepare dialysis fluid should be within European Pharmacopoeia limits at the water treatment system inlet and at the reverse osmosis outlet. In addition dialysate, concentrate and infusion fluids must comply with specific Pharmacopoeia limits. The physician in charge of the dialysis unit is advised to institute a multidisciplinary team to evaluate the requirement for added chemical controls in the presence of local hazards. 2. Microbiological quality (Table: see text). High microbiological purity of dialysis fluid--regularly verified--is a fundamental prerequisite for dialysis quality and every dialysis unit should aim as a matter of course to obtain "ultra-pure" dialysate (microbial count <0.1 UFC/mL, endotoxins <0.03 U/mL). On-line dialysate ultrafiltration and regular disinfection of dialysis machines greatly enhance microbiological purity. On-line dialysate reinfusion requires specific devices used according to corresponding instructions and to more frequent microbiological tests. Dialysis fluids for home dialysis should comply with the same chemical and bacteriological quality. The appendix reports the water treatment system's technical characteristics, sampling and analytical methods, monitoring time-tables, as well as the origin and effects of the main toxic substances. Suggestions and questions concerning these guidelines are welcome to nefrologia@sin-italy.org.

The medical care of renal anaemia has received much attention over the past decade, as nephrologists have recognized the increased therapeutic value of erythropoiesis-stimulating agents. The European Best Practice Guidelines and the US National Kidney Foundation's Kidney Disease Outcome Quality Initiative Guidelines have provided evidence-based advice on the optimal treatment of renal anaemia, and have recommended a target haemoglobin (Hb) level of 11 g/dl or 11-12 g/dl. Achieving this target Hb level has been shown to improve quality of life and reduce the rate of hospitalization; there is also good evidence to suggest that achieving adequate Hb levels reduces morbidity and mortality in patients with end-stage renal disease. In recent years, a number of factors have been identified that may counteract the positive action of epoetin therapy. These treatment-influencing factors include inadequate haemodialysis, absolute and functional iron deficiency, anticoagulant use, inflammation and infection. Each factor on its own may result in a substantial decrease in Hb levels, or an increase in epoetin requirements of up to 100%. Therefore, optimal and cost-effective treatment can only be achieved by adequately managing all of the factors that potentially can influence anaemia in patients with chronic kidney disease. Large-scale, cross-sectional surveys, such as the European Survey on Anaemia Management and the Dialysis Outcomes and Practice Patterns Study, have shown that there is still room for improving the efficacy and efficiency of anaemia therapy. The Optimal Treatment of Renal Anaemia (OPTA) initiative aims to help both physicians and nurses improve renal anaemia management by "translating" the standards set in published guidelines into practical clinical advice.