Observational pilot study: A comparison of amino acids and derangement of intestinal function between healthy ageing subjects and patients affected by chronic kidney disease stage CKD3b-4 in conservative management.

BACKGROUND AND AIMS: A comparison of the amino acid (AA) plasma profile and markers of intestinal absorption-inflammation between healthy subjects aged 65-70 years and age-matched patients affected by stage 3b-4 chronic kidney disease (CKD3b-4) was performed. METHODS: Eleven healthy volunteers were compared with 12 CKD3b-4 patients at their first outpatient control (T0) and after 12-months (T12). Adherence to a low protein diet (LPD, 0.6 ± 0.1 g/kg/day) was assessed by Urea Nitrogen Appearance. The following parameters were assessed: renal function, nutritional parameters, bioelectrical impedance analysis, plasma levels of 20 total amino acids (TAAs), both essential (EAAs) including branched-chain amino acids (BCAAs) and non-essential (NEAAs). Zonulin and faecal Calprotectin markers were used to evaluate intestinal permeability/inflammation. RESULTS: Four patients dropped out of the study; in the remaining 8 residual kidney function (RKF) remained stable, their LPD adherence had risen to 0.89  g/kg/day, anaemia had worsened and extracellular body fluid had increased. In comparison to healthy subjects, TAA levels of histidine, arginine, asparagine, threonine, glycine, and glutamine had all increased. No variation in BCAAs was observed. A significant increase was detected in faecal calprotectin and zonulin levels in CKD patients as the disease progressed. CONCLUSIONS: This study confirms the finding in aged patients of an alteration in plasmatic levels of several AAs secondary to uraemia. Intestinal markers provide confirmation of a relevant alteration to the intestinal function in CKD patients.

Effects of a Metabolic Mixture on Gut Inflammation and Permeability in Elderly Patients with Chronic Kidney Disease: A Proof-of-Concept Study.

Intestinal barrier dysfunction is a risk factor for the progression of Chronic Kidney Disease (CKD). In this proof-of-concept study, we tested the effects of a mixture of Essential Amino Acids (EAAs) and mitochondrial substrates on intestinal inflammation and permeability of CKD patients. Eight patients with stage 3b-4 CKD and 11 healthy controls after overnight fasting underwent fecal measures of calprotectin and zonulin levels (indicators of gut inflammation and permeability, respectively) and determinations of plasma amino acids. Only CKD patients were supplemented with the mixture (8 g/d diluted in water). Compared to controls, baseline fecal calprotectin, zonulin and plasma levels of some AA in CKD patients were significantly higher (p = 0.005; p = 0.001 and p = 0.02 to 0.003, respectively). After six months of supplementation, CKD baseline fecal levels of calprotectin and zonulin significantly (borderline for zonulin) decreased (p = 0.008 and p = 0.05, respectively). Plasma AA concentrations, including glutamine and alanine, were higher than at the baseline (p: 0.05 to 0.008). The supplementation of this mixture was associated with improved intestinal barrier dysfunction. Increased plasma AA levels might contribute to the improvement of gut barrier dysfunction.

Effects of a Novel Amino Acid Formula on Nutritional and Metabolic Status, Anemia and Myocardial Function in Thrice-Weekly Hemodialysis Patients: Results of a Six-Month Randomized Double-Blind Placebo-Controlled Pilot Study.

(1) Background: Chronic Kidney Disease (CKD) induces metabolic derangement of amino acid (AA) kinetics, eliciting severe damage to the protein anabolism. This damage is further intensified by a significant loss of AAs through hemodialysis (HD), affecting all tissues with a high metabolic turnover, such as the myocardium and body muscle mass. (2) Aim: to illustrate the effects of a novel AA mixture in boosting mitochondrial energy production. (3) Methods: A strict selection of 164 dialysis patients was carried out, allowing us to finally identify 22 compliant patients who had not used any form of supplements over the previous year. The study design envisaged a 6-month randomized, double-blind trial for the comparison of two groups of hemodialysis patients: eleven patients (67.2 ± 9.5 years) received the novel AA mix (TRG), whilst the other eleven (68.2 ± 10.5 years) were given a placebo mix that was indistinguishable from the treatment mix (PLG). (4) Results: Despite the 6-month observation period, the following were observed: maintenance of target hemoglobin values with a reduced need for erythropoiesis-stimulating agents in TRG > 36% compared to PLG (p < 0.02), improved phase angle (PhA) accompanied by an increase in muscle mass solely in the TRG group (p < 0.05), improved Left Ventricular Ejection Fraction (LVEF > 67%) in the TRG versus PLG group (p < 0.05) with early but marked signs of improved diastolic function. Increased sensitivity to insulin with greater control of glycemic levels in TRG versus PLG (p = 0.016). (5) Conclusions: the new AA mix seemed to be effective, showing a positive result on nutritional metabolism and cardiac performance, stable hemoglobin levels with the need for lower doses of erythropoietin (EPO), insulin increased cell sensitivity, better muscle metabolism with less loss of mass.

Protection of Residual Renal Function and Nutritional Treatment: First Step Strategy for Reduction of Uremic Toxins in End-Stage Kidney Disease Patients.

The retention of uremic toxins and their pathological effects occurs in the advanced phases of chronic kidney disease (CKD), mainly in stage 5, when the implementation of conventional thrice-weekly hemodialysis is the prevalent and life-saving treatment. However, the start of hemodialysis is associated with both an acceleration of the loss of residual kidney function (RKF) and the shift to an increased intake of proteins, which are precursors of uremic toxins. In this phase, hemodialysis treatment is the only way to remove toxins from the body, but it can be largely inefficient in the case of high molecular weight and/or protein-bound molecules. Instead, even very low levels of RKF are crucial for uremic toxins excretion, which in most cases are protein-derived waste products generated by the intestinal microbiota. Protection of RKF can be obtained even in patients with end-stage kidney disease (ESKD) by a gradual and soft shift to kidney replacement therapy (KRT), for example by combining a once-a-week hemodialysis program with a low or very low-protein diet on the extra-dialysis days. This approach could represent a tailored strategy aimed at limiting the retention of both inorganic and organic toxins. In this paper, we discuss the combination of upstream (i.e., reduced production) and downstream (i.e., increased removal) strategies to reduce the concentration of uremic toxins in patients with ESKD during the transition phase from pure conservative management to full hemodialysis treatment.

Evaluation of Residual Kidney Function during Once-Weekly Incremental Hemodialysis.

BACKGROUND: The initial once-weekly administration of incremental hemodialysis to patients with residual kidney function (RKF) has recently attracted considerable interest. METHODS: The aim of our study was to assess the performance of a series of different methods in measuring serum urea nitrogen and serum Cr (sCr) RKF in patients on once-weekly hemodialysis (1WHD). Evaluations were carried out by means of 24-h predialysis urine collection (Kr-24H) or 6-day inter-dialysis collection (Kr-IDI) and estimation of glomerular filtration rate based on (KrSUN + KrsCr)/2 for the purpose of identifying a simple reference calculation to be used in assessing RKF in patients on 1WHD dialysis. Ninety-five urine samples were collected from 12 1WHD patients. A solute solver urea and Cr kinetic modeling program was used to calculate residual urea and Cr clearances. Mann-Whitney U test, Pearson's correlation coefficient (R), and linear determination coefficient (R2) were used for statistical analysis. RESULTS: 1WHD patients displayed a mean KrSUN-IDI of 4.5 ± 1.2 mL/min, while KrSUN-24H corresponded to 4.1 ± 0.9 mL/min, mean KrsCr-IDI to 9.1 ± 4.0 mL/min, and KrsCr 24H to 8.9 ± 4.2 mL/min, with a high regression between IDI and 24-h clearances (for IDI had R2 = 0.9149 and for 24H had R2 = 0.9595). A good correlation was also observed between KrSUN-24H and (KrSUN + KrsCR/2) (R2 = 0.7466, p < 0.01. DISCUSSION: Urine collection over a 24-h predialysis period yielded similar results for both KrSUN and KrsCr compared to collection over a longer interdialytic interval (KrSUN + KrsCr)/2 could be applied to reliably assess RKF in patients on 1WHD. CONCLUSION: The parameters evaluated are suitable for use as a routine daily method indicating the commencement and continued use of the 1WHD Incremental Program.

Hemodialysis-Nutritional Flaws in Diagnosis and Prescriptions. Could Amino Acid Losses be the Sharpest "Sword of Damocles"?

This review aims to highlight the strengths and weaknesses emerging from diagnostic evaluations and prescriptions in an intent to prevent progression over time of malnutrition and/or protein-energy wasting (PEW) in hemodialysis (HD) patients. In particular, indications of the most effective pathway to follow in diagnosing a state of malnutrition are provided based on a range of appropriate chemical-clinical, anthropometric and instrumental analyses and monitoring of the nutritional status of HD patients. Finally, based on the findings of recent studies, therapeutic options to be adopted for the purpose of preventing or slowing down malnutrition have been reviewed, with particular focus on protein-calorie intake, the role of oral and/or intravenous supplements and efficacy of some classes of amino acids. A new determining factor that may lead inexorably to PEW in hemodialysis patients is represented by severe amino acid loss during hemodialysis sessions, for which mandatory compensation should be introduced.

Differences and Effects of Metabolic Fate of Individual Amino Acid Loss in High-Efficiency Hemodialysis and Hemodiafiltration.

OBJECTIVE: The objective of the study was to quantify the loss and arterial blood concentration of the three main classes of amino acids (AAs)-nonessential amino acids (NEAAs), essential amino acids (EAAs), and branched-chain amino acids-as resulting from high-efficiency hemodialysis (HED) and hemodiafiltration (HDF). We moreover aimed to identify the different fates and metabolic effects manifested in patients undergoing hemodialysis and the consequences on body composition and influence of nutritional decline into protein energy wasting. DESIGN AND METHODS: Identical dialysis monitors, membranes, and dialysate/infusate were used to ensure consistency. Ten patients were recruited and randomized to receive treatment with on-line modern HED and HDF. Arterial plasma concentrations of individual AAs were compared in healthy volunteers and patients undergoing hemodialysis, and AA levels outflowing from the dialyzer were evaluated. Baseline AA plasma levels of patients undergoing hemodialysis were compared with findings obtained 1 year later. RESULTS: A severe loss of AA with HED/HDF was confirmed: a marked loss of total AAs (5 g/session) was detected, corresponding to more than 65% of all AAs. With regard to individual AAs, glutamine displayed a consistent increase (+150%), whereas all other AAs decreased after 12 months of HD/HDF. Only a few AAs, such as proline, cysteine, and histidine maintained normal levels. The most severe metabolic consequences may result from losses of EAAs such as valine, leucine, and histidine and from NEAAs including proline, cysteine, and glutamic acid eliciting the onset of hypercatabolism threatening muscle mass loss. CONCLUSION: Dialysis losses, together with the effect of chronic uremia, resulted in a reduction of fundamental EAAs and NEAAs, which progressively led our patients after 12 months to a deterioration of lean mass toward sarcopenia. Therefore, the reintroduction of a correctly balanced AA supplementation in patients undergoing HD to prevent or halt decline of hypercatabolism into cachexia is recommended.

The production of on-line dialysis water for extracorporeal dialysis: proposals for an increased safety upgrade: a viewpoint.

INTRODUCTION: At the start of the 2000s, the progressive diffusion of high-flux extracorporeal dialysis and membranes saw an increased use of high infusion volumes injected into the patient's blood circuit following the advent of on-line water production plants. METHODOLOGY: Our 15-year experience with on-line extracorporeal methodologies using very high infusion volumes has led to the detection of errors and weaknesses, thus allowing us to correct and provide for the implementation of appropriate technology in dialysis water production plants with the aim of ensuring a higher chemical-physical, bacteriological and endotoxin quality. The initial procedures had already been outlined in the 2005 Italian Guidelines, although still today Health Technicians and Nephrologists operating in the field are unable to take on board specific integrations for on-line methods due to a lack of upgrading of documentation in both European and non-European Guidelines. RESULTS: After more than 17 years' experience, and in view of the technological implementations developed since 2005, we wish to put forward a series of suggestions in an attempt to improve the safety of on-line water, with uses ranging from drinking water, pre-treatment, osmosis, distribution circuit, hemodialysis monitors up to the most recent update of microbiological cultures. DISCUSSION: Additional, more stringent measures are required to prevent the occurrence of acute accidents during dialysis sessions and to reduce chronic inflammation-oxidation deriving from the use of not totally ultra-pure/sterile dialysis fluids. CONCLUSION: Our point of view based on our long-standing experience, the proposals made relate to procedures to be applied in technological maintenance, which the consultant nephrologist and other relevant personnel such as microbiologists, biologists, and technical operators should adhere to rigorously to ensure that the production of dialysis water on-line is viewed on a par with a pharmacological administration.

Could there be Haemodynamic Stress Effects on Pro-Inflammatory CD14+CD16+ Monocytes during Convective-Diffusive Treatments? A Prospective Randomized Controlled Trial.

BACKGROUND: The main aim is to compare the pro-inflammatory CD14+CD16+ monocytes blood levels in patient in end-stage renal disease (ESRD) undergoing Mixed online Haemodiafiltration (Mixed OL-HDF) vs. post-dilution OL-HDF and online high-efficiency haemodialysis. METHODS: The study is a prospective double-blind randomized controlled cross-over trial. Dialysis monitor, membrane, duration and dialytic adequacy, volume ultrapure dialysate/infusion were the same in all treatments. Monocyte CD14+CD16+, CD14-CD16+, IL-2R, TNFα, IL-1ß, IL-8, IL-6, IL-10, ß2-microglobulin outcome were measured. RESULTS: Mixed OL-HDF showed a less expression on the activated monocytes CD14+CD16+, CD14-CD16+ (-15.5%). There was no difference between cytokines and high sensitivity C-reactive protein and in other haemato-chemical inflammatory parameters except a significative decrease of TNF-α during Mixed OL-HDF. CONCLUSION: We found that Mixed OL-HDF could inhibit the CD14+CD16+ peripheral blood lymphocytes related to a less hemorheology stress inside capillary dialysis filter but in this study there is not still ascertainable its superiority compared to post OL-HDF and post OL-HEH.

Differences in Amino Acid Loss Between High-Efficiency Hemodialysis and Postdilution and Predilution Hemodiafiltration Using High Convection Volume Exchange-A New Metabolic Scenario? A Pilot Study.

OBJECTIVE: The objective of the study was to quantify the loss of total amino acids (TAAs), nonessential amino acids, essential amino acids, and branched chain amino acids (BCAAs) produced by high-efficiency hemodialysis (HEHD), postdilution hemodiafiltration (HDFpost), and predilution hemodiafiltration (HDFpre) using high ultrafiltration volumes; and to define the specific AA losses registered in HEHD, HDFpost, and HDFpre; to identify a potential metabolic and nutritional decline into protein energy wasting; to compare AA analysis of arterial blood samples taken from healthy controls and patients with end-stage renal disease undergoing hemodialysis. DESIGN AND METHODS: Identical dialysis monitors, membranes, and dialysate/infusate were used to homogenize extracorporeal body influence. Ten patients were recruited and randomized to receive treatment with HEHD, HDFpost, and HDFpre it was used on-line dialytic water methodologies (OL); patients' AA arterial concentrations were measured at the start and on completion of dialysis; TAA from the dialyzer filter was calculated, and baseline levels were subsequently compared with findings obtained 1 year later. Finally, the results obtained were compared with the data from a study of 8 healthy volunteers conducted using bioimpedance analysis and laboratory blood tests to assess nutritional status. RESULTS: A higher convective dose results in a higher weekly loss of TAA, nonessential AAs, essential AAs, and BCAAs (HEHD: 15.7 g; HDFpost-OL: 16.1 g; HDFpre-OL: 16.3 g, P < .01). After 12 months, the same hemodialys patients showed a reduced body and water intracellular mass and reduced phase angle. Arterial concentrations of TAAs and BCAAs were lower than those detected in healthy subjects (P < .01). CONCLUSION: The study shows that the AA losses in dialytic liquid are greater after high exchange volume HDF techniques, especially HDFpre. The AA losses are not metabolically compensated, so these increase the derangements of predialytic arterial plasma AA levels. Both AA losses and arterial AA perturbations further worsened body composition already after 12 months of additional dialysis.

[Nutritional diet therapy in the management of the patient with Chronic Kidney Disease in advanced phase to delay the beginning and reduce the frequency of dialysis. An option also in the pre-emptive transplant program].

The Italian nephrology has a long tradition and experience in the field of dietetic-nutritional therapy (DNT), which is an important component in the conservative management of the patient suffering from a chronic kidney disease, which precedes and integrates the pharmacological therapies. The objectives of DNT include the maintenance of an optimal nutritional status, the prevention and / or correction of signs, symptoms and complications of chronic renal failure and, possibly, the delay in starting of dialysis. The DNT includes modulation of protein intake, adequacy of caloric intake, control of sodium and potassium intake, and reduction of phosphorus intake. For all dietary-nutritional therapies, and in particular those aimed at the patient with chronic renal failure, the problem of patient adherence to the dietetic-nutritional scheme is a key element for the success and safety of the DNT and it can be favored by an interdisciplinary and multi-professional approach of information, education, dietary prescription and follow-up. This consensus document, which defines twenty (20) essential points of the nutritional approach to patients with advanced chronic renal failure, has been written, discussed and shared by the Italian nephrologists together with representatives of dietitians (ANDID) and patients (ANED).

Clinical Management of Chronic Kidney Disease Patients in Italy: Results from the IRIDE Study.

BACKGROUND: Lack of adequate management of chronic kidney disease (CKD) often results in delayed diagnosis and inadequate treatment. This study assessed the clinical management and outcome of stages 1-5 CKD patients. METHODS: Patients were prospectively followed for 3 years in 25 nephrology centers across Italy. Clinical characteristics were measured at baseline and every 6 months. Outcome measures included CKD staging, presence of comorbidities, treatment, mineral bone disorder (MBD) parameters, and patient outcomes. RESULTS: Of 884 enrolled patients (59.7% males, aged 66.2 ± 14.6 years), 587 (66.4%) completed the study. The majority of patients were referred by a general practitioner (44.7%) and had stage 3 or 4 CKD (40.9 and 23.8% respectively). Data reveal that 91.3% of patients had at least 1 concomitant disease, most frequently hypertension (80.1%) and dyslipidemia (42.5%); 94.6% of patients were receiving cardiovascular medication and 52.6% were receiving lipid-lowering medication. Approximately 40% of patients had proteinuria and intact parathyroid hormone levels outside the normal range. As expected, stages 4 and 5 CKD patients had a higher prevalence of proteinuria (68 and 74%), MBD (59 and 88%) and anemia (28 and 73%), as well as a higher risk of hospitalization (34.3 and 51.9%) and need for dialysis (69.5 and 70%). The overall probability of survival over 36 months was 90.6%. CONCLUSIONS: This is the first Italian prospective study performed with a large cohort of CKD patients over a 3-year period. Considering the multifactorial burden of diseases associated with CKD patients, the need for greater attention to CKD and related disorders is paramount.

Nutritional treatment of advanced CKD: twenty consensus statements.

The Italian nephrology has a long tradition and experience in the field of dietetic-nutritional therapy (DNT), which is an important component in the conservative management of the patient suffering from a chronic kidney disease, which precedes and integrates the pharmacological therapies. The objectives of DNT include the maintenance of an optimal nutritional status, the prevention and/or correction of signs, symptoms and complications of chronic renal failure and, possibly, the delay in starting of dialysis. The DNT includes modulation of protein intake, adequacy of caloric intake, control of sodium and potassium intake, and reduction of phosphorus intake. For all dietary-nutritional therapies, and in particular those aimed at the patient with chronic renal failure, the problem of patient adherence to the dietetic-nutritional scheme is a key element for the success and safety of the DNT and it can be favored by an interdisciplinary and multi-professional approach of information, education, dietary prescription and follow-up. This consensus document, which defines twenty essential points of the nutritional approach to patients with advanced chronic renal failure, has been written, discussed and shared by the Italian nephrologists together with representatives of dietitians (ANDID) and patients (ANED).

[Infrequent and incremental dialysis: differences and definitions].

The purpose of this review is to give dignity at the Incremental Dialysis, which cannot be confused with the term and the therapeutic choice defined as Infrequent Dialysis. The Infrequent Dialysis is defined by each and every hemodialytic therapeutic choice like rhythms below thrice-weekly-hemodialytic treatments. Nonetheless, Infrequent Dialysis is a choice of replacement hemodialysis therapy with pays more special clinical attentions and nutritional monitoring and should also be accompanied by a slightly hypoproteic controlled nutrition. When talking about the Incremental Dialysis (CDDP) it is defined as a well-defined therapeutic program that requires a significant clinical attention. The CDDP begins with the pre-dialysis outpatient clinic in the short period of time when the patient passes, after a severe nutrition compliance assessment with a VFG of 5-10 mL / min / 1.73mq, from the conservative treatment to an hypoproteic diet composed of 0.6g/ Kg / day with or without essential amino acids and hyposaline diet supplemented by One-Weekly Dialysis. The Incremental Dialysis program is strictly tailored on the trend of Residual Renal Function (FRR). CDDP is a time variable therapeutic "bridge" that must provide a good metabolic status and a good quality of life of the treated patients. Recent studies have shown a lower mortality compared with thrice-weekly-dialysis and a neutral input/output balance of phosphorus pool due to the phosphaturia contribution compared to the thrice-weekly-patients who lose early their FRR. Further studies are needed to confirm the safety and validity of this therapeutic choice.

[Practical procedures to launch a once-weekly-dialysis program integrated into a personalized hypoproteic nutrition (CDDP)].

This work is aimed for showing in detail to the nephrologists the methodology applied in the Combined Diet Dialysis Program (CDDP) in selected patients especially with the use of the Urea Nitrogen Appearance which allows to verify the sustainability and collaboration of patients on the 0.6 g/Kg/day hypoproteic diet by calculating the Protein Catabolic Rate in patients with metabolic steady state. It is also confirmed that the combined action of nutrition and the minimal contact with hemodialysis may allow a longer maintenance of the residual renal function with the further possibility of a greater excretion of Protein Bound Uremic Toxins and to obtain a phosphate balance thanks for a good maintenance of phosphaturia. In this paper are described in detail all the necessary steps and calculations. But it is mandatory a greater clinical commitment to achieve the achievement of a personalized therapeutic protocol like CDDP that is easily applicable in everyday clinical practice.

Fabry Disease in Southern Sardinia: epidemiological results from screening in an extensive area. / Risultati dello screening epidemiologico sulla malattia di Fabry nell'area sud-est della Sardegna.

INTRODUCTION: Epidemiological data relating to the prevalence and incidence of Fabry disease (FD) and other Lysosomal Storage diseases (LSDs) are largely underestimated and not yet well known. Distribution of the disease varies according to geographical area and to ethnic origin. Heterozygous females are also at risk of contracting severe and multi-symptomatic forms of FD. AIM: To demonstrate the results obtained in outpatient surgeries situated in an area comprising 319,340 inhabitants. METHODS: Out of a total of 2710 nephrologist visits, 150 patients with suspected FD (73 undergoing dialysis and 77 conservative management) were selected. The relatives of one female patient on dialysis who had tested positive were investigated and a further 11 patients thus identified (total: 4 males and 7 females) within a micro-area of 21,822 inhabitants, i.e. a prevalence rate of one positive case every 1,818 inhabitants. These data relate to the first 18 months of screening. CONCLUSIONS: In the field of nephrology, patients with high levels of proteinuria or microalbuminuria (150-200 mg/day) should be screened for FD, particularly in areas with a high incidence and/or prevalence of kidney disease. Once positive patients of both sexes have been identified, they should immediately be referred for cardiologic and neurological assessment.

Effectiveness of Switch to Erythropoiesis-Stimulating Agent (ESA) Biosimilars versus Maintenance of ESA Originators in the Real-Life Setting: Matched-Control Study in Hemodialysis Patients.

BACKGROUND: In hemodialysis (HD), switching from erythropoiesis-stimulating agent (ESA) originators to biosimilars is associated with the need for doses approximately 10% higher, according to industry-driven studies. OBJECTIVE: The aim of this study was to evaluate the efficacy on anemia control of switching from ESA originators to biosimilars in daily clinical practice. METHODS: We retrospectively selected consecutive HD patients receiving stable intravenous ESA doses, and who had not been transfused in the previous 6 months, from 12 non-profit Italian centers. Patients switched from originators to biosimilars (n = 163) were matched with those maintained on ESA originators (n = 163) using a propensity score approach. The study duration was 24 weeks, and the primary endpoint was the mean dose difference (MDD), defined as the difference between the switch and control groups of ESA dose changes during the study (time-weighted average ESA dose minus baseline ESA dose). RESULTS: Age (70 ± 13 years), male sex (63%), diabetes (29%), history of cardiovascular disease (40%), body weight (68 ± 14 kg), vascular access (86% arteriovenous fistula), hemoglobin [Hb] (11.2 ± 0.9 g/dL) and ESA dose (8504 ± 6370 IU/week) were similar in the two groups. Hb remained unchanged during the study in both groups. Conversely, ESA dose remained unchanged in the control group and progressively increased in the switch group from week 8 to 24. The time-weighted average of the ESA dose was higher in the switch group than in the control group (10,503 ± 7389 vs. 7981 ± 5858 IU/week; p = 0.001), leading to a significant MDD of 2423 IU/week (95% confidence interval [CI] 1615-3321), corresponding to a 39.6% (95% CI 24.7-54.6) higher dose of biosimilars compared with originators. The time-weighted average of Hb was 0.2 g/dL lower in the switch group, with a more frequent ESA hyporesponsiveness (14.7 vs. 2.5%). Iron parameters and other resistance factors remained unchanged. CONCLUSIONS: In stable dialysis patients, switching from ESA originators to biosimilars requires 40% higher doses to maintain anemia control.