Background: EPREX®/ERYPO®/PROCRIT® (epoetin alfa, Janssen-Cilag GmbH) was the first available recombinant human erythropoietin (rHuEPO) and was universally reference product as per the recommendation provided by European Medicines Agency. EPIAO® is a biosimilar formulation of EPREX®, and making it a 1:1 dose conversion from EPREX® according to recommendation of European Medicines Agency. This study evaluated the clinical efficacy and safety of EPIAO® in subjects with end-stage renal disease receiving hemodialysis after intravenous administration. Methods: This study was a multicenter, prospective, randomized, double-blind, parallel-group, 2-cohort, maintenance phase, therapeutic equivalence study to evaluate a 1:1 dose conversion from EPREX® to EPIAO® in terms of clinical efficacy and safety that was conducted at 20 sites in 2 countries in patients with end-stage renal disease on hemodialysis. Eligible subjects were treated with EPREX® (reference product of epoetin) for a period of at least 3 months before the treatment period, and then were randomly assigned to the group of EPREX® or EPIAO®. Primary endpoints were mean absolute change in hemoglobin level and mean absolute change in weekly epoetin dosage from baseline to 6 months after treatment with EPIAO®/EPREX® in parallel groups. Results: A total of 200 people received the random intervention and were included in the safety set. After 6, 9, and 12 months of treatment with EPIAO® or EPREX®, there were no significant differences in the hemoglobin levels of the 2 groups compared with baseline. The 95% confidence interval for the treatment difference was within the predetermined acceptable range: ±0.5 g/dL. There were no significant differences in the epoetin dosage of the 2 groups compared with the baseline. The 95% confidence interval for the treatment difference was within the predetermined acceptable range: ± 45 IU/kg. There were no significant differences in the incidence of adverse events between the EPIAO® and EPREX® groups. Most adverse events were mild to moderate and were reverted/resolved. Conclusion: EPIAO® demonstrated promising effectiveness and manageable safety in patients with end-stage renal disease on hemodialysis.

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Background and Aims Malnutrition is a prevalent condition in patients with chronic kidney disease (CKD) receiving replacement therapy by peritoneal dialysis (PD). Geriatric nutritional risk index (GNRI) is an effective tool for screening nutritional status in maintenance hemodialysis patients. The purpose of this study was to determine the information content of GNRI for the diagnosis of protein-energy malnutrition in patients with CKD receiving replacement therapy with PD when compared to malnutrition inflammation score (MIS) and 7-point subjective global assessment (7p-SGA). Method A prospective cohort study included 222 adults PD-patients (man 100, female 112, age 44±14). All patients received continuous ambulatory peritoneal dialysis. Median duration PD before inclusion in the study was 12 months, the observation period of patients was 36 months. Nutritional status assessment included anthropometric (body mass index, triceps skinfold thickness, midupper arm muscular area) and biochemical (albumin, C-reactive protein, total iron-binding capacity, total cholesterol, hemoglobin and others) examinations as well as bioelectrical impedance analysis (BIA – fat mass). GNRI calculated according to the formula GNRI = 1.489 × albumin (g/dL)] + [41.7 × (body wt/ideal body wt)], where the ideal body weight for women is: height (cm)–100–[(height–152) × 0.2], ideal body weight for men is equal to: height (cm) -100 - [(height - 152) × 0.4]. We used MIS and 7p-SGA as a reference standard, a score ≥6 and ≤5, respectively, defined malnutrition. The cutoff of GNRI the diagnosis of malnutrition were derived from these ROC-analysis. Results Most of the individual nutritional indexes, including the anthropometric, biochemical and BIA indexes, were significantly (P<0.001) lower in the patients with MIS score ≥6 and 7p-SGA score ≤5, thus both nutritional screening tools were considered reasonable as a reference standard to determine the information content GNRI in PD-patients. The GNRI fluctuated in the range 66–126 (median 99), MIS score – 2–24 (median 7) and 7p-SGA score – 2–7 (median 5). The GNRI showed a significantly negative correlation with MIS (r = -0,708, p<0.0001) and a significantly positive correlation with 7p-SGA (r = 0.636, p<0.0001) (Fig. 1). The most accurate GNRI cutoff to identify a malnourished patient according to the MIS was ≤99 (Fig. 2). The frequency of malnutrition among the observed patients was 52.3% when using GNRI≤99, 55.9% when using MIS≥6 and 51.4% when using 7p-SGA≤5 (n.s.). The values for sensitivity and specificity with a GNRI of ≤99 in predicting malnutrition based on the MIS were 77.4% (95%CI 69.0-84.4%) and 79.6% (95%CI 70.3-87.1%) respectively. Positive predictive value and negative predictive value also had high scores respectively 73.7% (95%CI 64.9-80.9%) and 72.2 (95%CI 63.1-79.8%). The application of the GNRI to the PD-patients found significant (p<0.001) differences in the various nutrition-related indexes (anthropometric, biochemical and BIA) between the group with a GNRI≤99 and that with GNRI>99. Mortality from all causes among patients with GNRI>99 was one case per 54.9 patient-years, among patients with GNRI≤99 was one case per 29.7 patient-years. Conclusion In PD-patients GNRI closely correlates with MIS and 7p-SGA, characterized by high sensitivity and specificity. GNRI can be used to determine the nutritional status of PD patients.

Kidney transplantation and hyperparathyroidism

Objective: to assess the prevalence of hyperparathyroidism (HPT) and the factors affecting its development in kidney transplant recipients. Materials and methods. The single-center observational cohort study included 97 kidney transplant recipients – 40 men, 57 women, age 50 ± 9 years. Inclusion criteria: more than 12 months of post-transplant period, 3 months of stable renal transplant function. Non-inclusion criterion: therapy with vitamin D, with its alternatives or with cinacalcet. Dialysis ranged from 0 to 132 months (median 18); 46% of patients had pre-operative secondary HPT. A comprehensive laboratory study included evaluation of serum concentrations of parathyroid hormone (PTH), 25-OH vitamin D, calcium, phosphorus, magnesium, total alkaline phosphatase (ALP) activity, albumin, creatinine and daily proteinuria. At the dialysis stage, the target PTH range of 130–585 pg/ ml was used, in the post-transplant period – ≤130 pg/ml. Glomerular filtration rate (eGFR) was calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula. Results. Patients were divided into two groups based on PTH threshold level (130 pg/ml): the first with HPT (PTH >130 pg/ml, median 203), the second without HPT (PTH ≤130 pg/ml, median 101). Both groups were comparable in terms of gender, age, primary renal disease, dialysis modality, post-transplant follow-up, and immunosuppressive therapy regimen. In group 1 and group 2 recipients, dialysis therapy, pre-transplant median PTH level, incidence of reoperation and incidence of immediate renal graft function were 30 (14; 50) and 14 (6; 28) months (p = 0.004), 681 (538; 858) and 310 (182; 556) pg/ml (p < 0.001), 17% and 2% (p = 0.028), 51% and 80% (p = 0.005), respectively. At the time of the study, 72% of group 1 recipients had eGFR <60 ml/min, versus 36% of group 2 (p >< 0.001). Among HPT biochemical parameters, there were differences for ionized serum calcium (1.32 ± 0.07 versus 1.29 ± 0.04 mmol/l, p = 0.017) and ALP activity (113 ± 61 versus 75 ± 19 u/l, p = 0.021). Serum vitamin D in both groups reduced in equal measures – 14 ± 4 and 15 ± 6 ng/ml. Conclusion. Persistent HPT in the long-term post-transplant period reaches 48.5%. Risk factors for its development included dialysis for more than 18 months, pre-operative secondary HPT, repeated kidney transplantation, delayed graft function, and eGFR <60 ml/min.

amino acids in both serum and daily volume of peritoneal dialysis solution were determined using liquid chromatography.Dietary protein consumption in PD patients was 1.06 70.09 vs. 1.21 7 0.05 g/kg/day (p o0.05) in the control group. Decreased serum levels of 6 essential amino acids were registered (valine, lysine, threonine, and tyrosine -almost 2 fold (p o0.05), leucine and isoleucine -by 28 and 34% (p o 0.05), accordingly, as well as normal concentration of phenylalanine and methionine -0.6 72.3 and 9.47 2.1 mg/L, correspondingly, vs. 11.1 70.8 and 11.3 7 0.8 mg/L in the control (p4 0.05), and increased level of histidine -32.7 76.8 vs. 14.6 7 0.5 mg/L in the control. The ratios essential/nonessential amino acids and branched/ replaceable amino acids as well as Fisher's index were 0.54 70.05, 0.25 70.05 and 2.0 705, correspondingly, vs. 1.35 7 0.15, 0.55 70.05 and 3.27 0.2 in the control (po 0.05). Daily excretion of essential amino acids with dialysis solution fluctuated between 314 and 522 mg, and that of conditionally essential amino acids -between 156 and 337 mg. Direct correlation was revealed between daily excretion of essential amino acids, on the one hand, and both peritoneal transport (p ¼0.001) and daily excretion of isoleucine, threonine, histidine, and their serum levels, on the other (p ¼0.04, p ¼0.001, and p¼ 0.01, accordingly). Direct correlation between daily excretion of essential amino acids and that of tyrosine and its serum level was only near reliable value (p ¼0.055). PD patients are characterized by the markedly unbalanced level of essential amino acids. The deficiency of the majority of essential amino acids in PD patients is due to their high loss through dialysis solution and insufficient protein consumption.http://dx.

Renal failure is a complicating factor in the maintenance of vitamin D adequate levels, which can interfere in the patients' nutritional status. The aim of this study was to evaluate the association of serum 25hydroxyvitamin D [25(OH)D] with clinical and nutritional parameters. Prevalent hemodialysis (HD) patients were submitted to a single evaluation about demographic characteristics, clinical data and laboratory measurements. Anthropometric measurements and electrical bioimpedance were performed to obtain BMI, percentage of standard MAMC (%MAMC), fat percentage (%Fat) and phase angle (PA). Deficiency was defined as a 25(OH)D level o15 ng/mL, insufficiency as 15-30 ng/mL and sufficiency as4 30 ng/mL. Univariate models were constructed and the variables associated with 25(OH)D sufficiency were included subsequently in the multiple regression model. Statistical significance was po 0.05.One hundred twelve patients (59 male, 53 female) were included. Twenty seven (24.1%) were 25(OH)D deficient, 43 (38.4%) insufficient and 42 (37.5%) sufficient. In univariate regression, creatinin, albumin and PA were positively associated with serum 25(OH)D, while age, glucose, BMI and %MAMC were negatively associated. In multivariate regression, age and %MAMC were negatively associated with sufficiency. Most studied sample showed inadequate 25(OH)D levels. In our study, the result to be highlighted was the negative associations of 25(OH)D sufficiency with age and %MAMC, but all the findings suggest that fat interferes with vitamin D stores in HD patients.http://dx.