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.

[The history of home hemodialysis and its likely revival]. / Storia dell'emodialisi domiciliare e della sua probabile rinascita.

The home extracorporeal hemodialysis, which aroused a great interest in the past, has not kept its promises due to the complexity and expectations for family involvement in treatment management. In the United States NxStage One portable system was proposed and designed for home use. In this work we describe, starting from the history of home hemodialysis, the method with NxStage system by comparing it with the conventional HD in 5 patients. The dialysis efficiency was similar between the two treatments, even if home hemodialysis showed a reduction in serum urea, creatinine and phosphorus. At the same time phosphate binders use decreased with an increase in serum calcium while hemoglobin increased reducing doses of erythropoietin. The method was successful in the training of the patients and their partners during hospital training and at home. Patients have shown great enthusiasm at the beginning and during the therapy, which is developed around the users personal needs, being able to decide at its own times during 24 hours according to personal needs, in addition to faster recovery after the dialysis. This method certainly improved the patients' wellness and increased their autonomy.

[Is the Sodium Thiosulfate Therapy useful for vascular calcification in dialysis Pts?]. / È utile la terapia con Tiosolfato di sodio nel trattamento delle calcificazioni vascolari nei pazienti emodializzati?

Vascular calcifications in uremic patients are associated with a significant increase in cardiovascular morbidity and mortality. Sodium thiosulfate (STS) has been shown to reduce the progression of uremic calcifications in haemodialysis patients. In our study we evaluated the effects on evolution of aortic calcifications of the drug infused during the last 2 hours of dialysis sessions at a dose of 10 grams. 18 hemodialysis patients were evaluated as regards the calcifications index according to Kauppila, calcium-phosphorus metabolism, PTH, and oral chelation therapy. The side effects of STS and the symptomatic effects reported by the patient, were also evaluated using a questionnaire delivered to patients. After 6 months of therapy, a modest reduction of the Kauppila's index (from 16.4 5.5 to 15.1 4.6) was detected. No significant change was detected in blood tests. Even chelation therapy did not suffer variations. It was also showed a clear and statistically significant improvement in signs and symptoms of leg pain, a moderate improvement of' power reserve and a reduction of muscle fatigue. The results of our study, although preliminary and on a small number of patients, confirm a positive effect of STS on vasculopatic symptoms and progression of vascular calcifications.

Effects of the association of potassium citrate and agropyrum repens in renal stone treatment: results of a prospective randomized comparison with potassium citrate.

OBJECTIVES: To evaluate by a prospective randomized controlled study the efficacy of the association of potassium citrate and dry extract of couch grass (Agropyrum repens) (CalcoMEV) in renal stone treatment. MATERIALS AND METHODS: 50 patients with nephrolithiasis associated with one or more active metabolic alterations that constitute an indication to the use of potassium citrate were randomly divided in two equal unblinded treatment groups. A group of patients was assigned to treatment with the association of potassium citrate and couch grass (at the dose of 24 mEq of potassium citrate and 100 mg of dry extract of Agropyrum repens bis in die) and the other group to potassium citrate (at a dose of 20 mEq ter in die). Each form of main treatment was associated, depending on the results of metabolic basal assessment, to allopurinol and/or an association of amiloride and hydrochlorothiazide and/or pyridoxine. Patients of both groups were advised the same diet based on a reduced intake of sodium, foods rich in oxalate and protein of animal origin, a normalized intake of calcium and an increase in fluid intake (> 2 liters every day). RESULTS: At the end of the 5-month follow-up period, the group treated with the association of potassium citrate and couch grass showed a significant reduction in the total number of stones (-1.0 +/- 0.2 vs. 0.0 +/- 0.2 stones) and in the larger diameter of the stones (-3.6 +/- 0.9 mm vs. 0.0 +/- 0.8 mm), as well as a statistically significant reduction of uric acid urinary excretion (-164.7 +/- 45.3 vs -38 +/- 42 mg/24 h). No significant differences in the two groups were observed with respect to urinary citrate, oxalate and calcium urinary excretions and urinary pH. CONCLUSIONS: This prospective randomized study demonstrates the superiority of the association of potassium citrate and dry extract of couch grass, in combination with standard pharmacological and dietary treatment, in reducing the number and size of urinary stones with respect to potassium citrate in association with the same pharmacological and dietary regimen.

Divert to ULTRA: differences in infused volumes and clearance in two on-line hemodiafiltration treatments.

BACKGROUND: Mixed diffusive-convective dialysis therapies offer greater removal capabilities than conventional dialysis. The aim of this study was to compare two different on-line, post-dilution hemodiafiltration (HDF) treatments with regard to achieved convective volume and middle-molecule dialysis efficiency: standard volume control (sOL-HDF) and automated control of the transmembrane pressure (TMP) (UC-HDF). METHODS: We enrolled 30 ESRD patients (55.9 ± 14.0 years, 20/10 M/F) in a randomized, prospective, cross-over study. The patients received a 3-month period of sOL-HDF followed by UC-HDF for a further 3 months, or vice versa, using the same dialysis machine. In sOL-HDF, fixed exchange volumes were set according to a filtration fraction greater than or equal to 25%. In UC-HDF therapy, the exchanged volume was driven by a biofeedback system controlling the TMP and its set point in a double loop. Patients maintained their treatment time, dialyzer, blood flow rate, and anticoagulant regimen unchanged throughout the study. RESULTS: Greater convective volumes were achieved in UC-HDF than in sOL-HDF (23.8 ± 3.9 vs.19.8 ± 4.8 L; p<0.001) with high pre-dialysis Ht value (sOL-HDF 34.0 ± 4.5% and UC-HDF 34.0 ± 4.4%; p = 0.91). The average clearance values of ß2m and P were higher in UC-HDF than in sOL-HDF (respectively 123 ± 24 vs. 111 ± 22 ml/min, p<0.002 and 158 ± 26 vs. 152 ± 25 ml/min, p<0.05). Moreover, the UC-HDF mode led to a significantly increased rate of call-free sessions from 88% to 97% (p<0.0001). CONCLUSIONS: This study showed that the biofeedback module, applied to the automatic control of TMP in on-line HDF, results in higher convective volumes and correspondingly higher ß2m and P clearances. By making the HDF treatment more automated and less complex to perform, it significantly reduced the staff workload.

A vitamin E-coated polysulfone membrane reduces serum levels of inflammatory markers and resistance to erythropoietin-stimulating agents in hemodialysis patients: results of a randomized cross-over multicenter trial.

BACKGROUND: Oxidative stress is prevalent in dialysis patients and has been implicated in the pathogenesis of cardiovascular disease and anemia. Vitamin E is a fat-soluble antioxidant that plays a central role in reducing lipid peroxidation and inhibiting the generation of reactive oxygen species. The aim of this cross-over randomized study was to compare the effects of a vitamin E-coated polysulfone (Vit E PS) membrane and a non-vitamin E-coated polysulfone (PS) membrane on inflammatory markers and resistance to erythropoietin-stimulating agents (ESAs). METHODS: After a 1-month run-in period of standard bicarbonate dialysis with a synthetic membrane, 62 patients of both genders, and older than 18 years, dialysis vintage 48 ± 27 months, BMI 22 ± 3 (from 13 different dialysis units) were randomized (A-B or B-A) in a cross-over design to Vit E PS (treatment A) and to PS (treatment B) both for 6 months. C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations were determined by a sandwich enzyme immunoassay at baseline and every 2 months; red blood cell count, ESA dose and ESA resistance index (ERI) were assessed monthly. RESULTS: Hemoglobin (Hb) levels significantly increased in the Vit E PS group from 11.1 ± 0.6 g/dl at baseline to 11.5 ± 0.7 at 6 months (p < 0.001) and remained unchanged in the PS group. Although ESA dosage remained stable during the observation periods in both groups, ERI was significantly reduced in the Vit E PS group from 10.3 ± 2.2 IU-dl/kg/g Hb week at baseline to 9.2 ± 1.7 at 6 months (p < 0.001). No significant variation of ERI was observed in the PS group. A significant reduction in plasma CRP and IL-6 levels was observed in the Vit E PS group: CRP from 6.7 ± 4.8 to 4.8 ± 2.2 mg/l (p < 0.001) and IL-6 from 12.1 ± 1.4 to 7.5 ± 0.4 pg/ml (p < 0.05). In the PS group, CRP varied from 6.2 ± 4.0 to 6.4 ± 3.7, and IL-6 from 10.6 ± 2.1 to 9.6 ± 3.5 (p = n.s.). CONCLUSIONS: Treatment with Vit E PS membranes seems to lead to a reduction in ESA dosage in HD patients; in addition, a low chronic inflammatory response may contribute to a sparing effect on exogenous ESA requirements.

Endothelial dysfunction in patients with kidney failure and vascular risk factors: acute effects of hemodialysis.

BACKGROUND: Patients with kidney failure present endothelial dysfunction, which was shown to be partly corrected by hemodialysis. No data exist on the effects of hemodialysis on endothelial dysfunction in kidney failure patients with associated vascular risk factors. The aim of this study was to evaluate the acute effects of hemodialysis on endothelial dysfunction in patients with kidney failure and associated vascular risk factors and to assess the role of endothelium-toxic substances. METHODS: We assessed endothelial dysfunction in 13 patients with chronic renal failure and other vascular risk factors before and after hemodialysis and in 13 healthy controls and simultaneously measured nitric oxide (NO) synthesis and activity. Endothelial dysfunction was studied using an echographic method as flow-mediated dilation (FMD) of the brachial artery; plasma NO2- and NO3-, cyclic guanosine-5-monophosphate (cGMP), plasma homocysteine levels and low molecular mass-advanced glycation end-products (LMM-AGEs) were simultaneously measured. RESULTS: As compared with healthy controls, patients with renal failure showed a reduced FMD (2.89 +/- 1.43 vs. 7.81 +/- 1.54%, p < 0.01) which was not corrected by dialysis (after dialysis 2.40 +/- 1.65%, p = NS vs. pre). Plasma NO2- and NO3- were normal or slightly increased and remained unchanged after dialysis. Plasma cGMP levels were reduced and remained unchanged after dialysis. Homocysteine and LMM-AGE plasma levels were raised and, although significantly reduced by dialysis, remained higher than in controls. CONCLUSIONS: Patients with kidney failure and associated vascular risk factors show an endothelial dysfunction related to defective NO activity, which is not corrected by hemodialysis despite the reduction, though not to normal, in homocysteine and LMM-AGE levels. Endothelial dysfunction may contribute to the progression of atherosclerosis in patients with kidney failure and vascular risk factors.