Citrate high volume on-line hemodiafiltration modulates serum Interleukin-6 and Klotho levels: the multicenter randomized controlled study \u201cHephaestus

Background: Studies addressing the anti-inflammatory properties of citrate dialysate enrolled patients in both hemodialysis (HD) and hemodiafiltration (HDF), the latter not adjusted for adequate convective exchange. This is a potential source of confounding in that HDF itself has anti-inflammatory effects regardless of the buffer, and optimal clinical outcomes are related to the amount of convection. Methods: To distinguish the merits of the buffer from those of convection, we performed a 6-month, prospective, randomized, crossover AB-BA study. Comparisons were made during the 3-month study period of on-line HDF with standard dialysate containing three mmol of acetic acid (OL-HDFst) and the 3-month of OL-HDF with dialysate containing one mmol of citric acid (OL-HDFcit). Primary outcome measure of the study was interleukin-6 (IL-6). Klotho, high sensitivity C-reactive protein (hsCRP), fetuin and routine biochemical parameters were also analyzed. Results: We analyzed 47 patients (mean age 64 years, range 27-84 years) enrolled in 10 participating Nephrology Units. Convective volumes were around 25 L/session with 90 percent of sessions > 20 L and f2-microglobulin reduction rate 76% in both HDFs. Baseline median IL-6 values in OL-HDFst were 5.6 pg/ml (25:75 interquartile range IQR 2.9:10.6) and in OL-HDFcit 6.6 pg/ml (IQR 3.4:11.4 pg/ml). The difference was not statistically significant (p 0.88). IL-6 values were lower during OL-HDFcit than during OL-HDFst, both when analyzed as the median difference of overall IL-6 values (p 0.02) and as the median of pairwise differences between the baseline and the 3-month time points (p 0.03). The overall hsCRP values too, were lower during OL-HDFcit than during OL-HDFst (p 0.01). Klotho levels showed a time effect (p 0.02) and the increase was significant only during OL-HDFcit (p 0.01). Conclusions: Citrate buffer modulated IL-6, hsCRP and Klotho levels during high volume OL-HDF. These results are not attributable to differences in the dialysis schedule and may suggest a potential anti-inflammatory and anti-senescent effect of citrate even in dialysis patients with low grade inflammatio

Dosing Penalty after Switching from ESA Originator to Biosimilar: Matched Cohort Study in Stable Hemodialysis Patients

Background: In hemodialysis (HD), switch from ESA originator to biosimilar associates with dosing penalty (DP) of about 10% according to industry-driven studies. However, DP in daily clinical practice is ill-defined. Methods: From 12 non-profit centers, we selected consecutive ESA treated HD patients (2011-14) receiving stable i.v. ESA dose and not transfused in the previous 3 months. Patients switched from originators to biosimilars (BIO, n=153) were matched with those persisting with ESA originator (CON, n=153) to evaluate DP (difference of ESA dose between BIO and CON). Conclusions: In controlled conditions, switch from ESA originator to biosimilar requires doses higher than expected to maintain constant Hb. Besides economic issue, these data call for long-term studies to assess whether the lower efficacy of biosimilars poses a safety threat

Dosing Penalty of Erythropoiesis-Stimulating Agents after Switching from Originator to Biosimilar Preparations in Stable Hemodialysis Patients

To the Editor: The efficacy of ESA biosimilars has been tested mainly in the few studies needed for marketing authorization,1-5 whereas data from individual self-reported clinical experience are lacking. Such information, together with pharmacovigilance data, is key to obtaining reassurance regarding the safety of these products. Of note, 2 studies of efficacy when switching from originator to biosimilar in hemodialysis patients have reported a dosing penalty (ie, requiring higher doses to maintain Hb level) of 4% to 13% for HX575 (epoetin alfa; Binocrit) and 10% to 15% for SB309 (epoetin zeta; Retacrit). 4,5 Dosing penalty for biosimilars is relevant not only for cost reasons, but also when considering the significant association of higher ESA dose with adverse outcomes.6 All manufacturers recommend using the lowest effective dose for correcting anemia

Citrate high volume on-line hemodiafiltration modulates serum Interleukin-6 and Klotho levels: the multicenter randomized controlled study "Hephaestus"

Studies addressing the anti-inflammatory properties of citrate dialysate enrolled patients in both hemodialysis (HD) and hemodiafiltration (HDF), the latter not adjusted for adequate convective exchange. This is a potential source of confounding in that HDF itself has anti-inflammatory effects regardless of the buffer, and optimal clinical outcomes are related to the amount of convection

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] 1615â\u80\u933321), corresponding to a 39.6% (95% CI 24.7â\u80\u9354.6) 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

Risk factors and action thresholds for the novel coronavirus pandemic. Insights from the Italian Society of Nephrology COVID-19 Survey

Over 80% (365/454) of the nation's centers participated in the Italian Society of Nephrology COVID-19 Survey. Out of 60,441 surveyed patients, 1368 were infected as of April 23rd, 2020. However, center-specific proportions showed substantial heterogeneity. We therefore undertook new analyses to identify explanatory factors, contextual effects, and decision rules for infection containment