Trial reportJournal of nephrology2021
Citrate high volume on-line hemodiafiltration modulates serum Interleukin-6 and Klotho levels: the multicenter randomized controlled study "Hephaestus".
Trial report in Journal of nephrology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02863016 (tHe Effects of Postdilution Online Hemodiafiltration With AcEtate-free Citrate dialySis Fluid on Inflammation Markers in TUscan Prevalent Hemodialysis patientS), which is not on this map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
tHe Effects of Postdilution Online Hemodiafiltration With AcEtate-free Citrate dialySis Fluid on Inflammation Markers in TUscan Prevalent Hemodialysis patientS: HEPHAESTUS Study
Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- High-flux hemodialysis with polymethylmethacrylate membranes reduces soluble CD40L, a mediator of cardiovascular disease in uremia.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Trial
- The effect of citrate in cardiovascular system and clot circuit in critically ill patients requiring continuous renal replacement therapy.Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs · 2023Trial
- Plasma from Cardiac Surgery Patients Induces Endothelial and Tubular Epithelial Cell Damage: Potential Role in Acute Kidney Injury Development-A Preliminary Report.International journal of molecular sciences · 2026Article
- Impact of citrate dialysate on middle molecular weight uremic toxin adsorption and removal in high-flux and MCO dialysis membranes.Scientific reports · 2025Article
- Switching from acetate to citrate dialysate in a central concentrate delivery system for high-volume online hemodiafiltration: a retrospective cohort study.Renal failure · 2024Article
- Comparison of citrate dialysate in pre- and post-dilution online hemodiafiltration: effect on clot formation and adequacy of dialysis in hemodialysis patients.Renal failure · 2024Article
- Citric acid-based bicarbonate dialysate attenuates aortic arch calcification in maintenance hemodialysis patients: a retrospective observational study.Journal of nephrology · 2023Observational
- Clinical Safety of Expanded Hemodialysis Compared with Hemodialysis Using High-Flux Dialyzer during a Three-Year Cohort.Journal of clinical medicine · 2022Article
- Has time come to replace the residual acetate with citrate in the dialysis fluid?Journal of nephrology · 2022Article
- The Next Evolution of HemoDialysis eXpanded: From a Delphi Questionnaire-Based Approach to the Real Life of Italian Dialysis Units.Blood purification · 2022Article
- Fibroblast Growth Factor-23-Klotho Axis in Cardiorenal Syndrome: Mediators and Potential Therapeutic Targets.Frontiers in physiology · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStudies 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.
methodsTo 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.
resultsWe 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 ß2-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).
conclusionsCitrate buffer modulated IL-6, hsCRP and Klotho levels during high volume OL-HDF. These results are not attributable to differences in the dialysis technology that was applied and may suggest a potential biological effect of citrate on CKD-associated inflammatory state. ClinicalTrials.gov identifier NCT02863016.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.