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

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

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

Metformin-Associated Lactic Acidosis Undergoing Renal Replacement Therapy in Intensive Care Units: A Five-Million Population-Based Study in the North-West of Italy

Background: Metformin-associated lactic acidosis (MALA) is a severe complication of drug administration with significant morbidity and mortality. So far no study in large population areas have examined the incidence, clinical profile and outcome of acute kidney injury (AKI)-MALA patients admitted in intensive care units (ICUs) and treated by renal replacement therapy (MALA-RRT). Methods: Retrospective analysis over a 6-year period (2010-2015) in Piedmont and Aosta Valley regions (5,305,940 inhabitants, 141,174 diabetics treated with metformin) of all MALA-RRT cases. Results: One hundred and seventeen cases of AKI-MALA-RRT were observed (12.04/100,000 metformin treated diabetics, 1.45% of all RRT-ICU patients). Survival rate was 78.3%. The average duration of RRT was 4.0 days at mean dialysis effluent of 977 mL/kg/day. At admission most patients were dehydrated, and experienced shock and oliguria. Conclusion: Our data showed that MALA-RRT is a common complication, needing more prevention. Adopted policy of early, extended, continuous and high efficiency dialysis could contribute to an observed high survival rate

Safety and efficacy of COVID-19 vaccines in patients on dialysis: a multicentre cohort study in Italy

Background The aim of this study was to evaluate the efficacy and safety of COVID-19 vaccines in patients undergoing haemodialysis in Italy compared to the general population.Methods In this cohort study, 118 dialysis centres from 18 Italian Regions participated. Individuals older than 16 years on dialysis treatment for at least 3 months, who provided informed consent were included. We collected demographic and clinical information, as well as data on vaccination status, hospitalisations, access to intensive care units and adverse events. We calculated the incidence, hospitalisation, mortality, and fatality rates in the vaccinated dialysis cohort, adjusted for several covariates. The incidence rates of infection in the dialysis cohort and the general population were compared through Standardised Incidence Rate Ratio.Results The study included 6555 patients vaccinated against SARS-CoV-2 infection according to the schedule recommended in Italy. Between March 2021 and May 2022, there were 1096 cases of SARS-CoV-2 infection, with an incidence rate after completion of the three-dose vaccination cycle of 37.7 cases per 100 person-years. Compared to the general population, we observed a 14% reduction in the risk of infection for patients who received three vaccine doses (Standardised Incidence Rate Ratio: 0.86; 95% Confidence Interval: 0.81-0.91), whereas no statistically significant differences were found for COVID-19-related hospitalisations, intensive care unit admissions or death. No safety signals emerged from the reported adverse events.Conclusions The vaccination program against SARS-CoV-2 in the haemodialysis population showed an effectiveness and safety profile comparable to that seen in the general population