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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      Maintaining Normal Levels of Ionized Calcium during Citrate-Based Renal Replacement Therapy Is Associated with Stable Parathyroid Hormone Levels

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          Abstract

          Background/Aims: Citrate is an effective anticoagulant during continuous renal replacement therapy (CRRT). Previous studies showed raised parathyroid hormone (PTH) levels when aiming for serum ionized calcium [Ca<sub>i</sub>] between 0.8 and 1.1 mmol/l. Our objective was to assess whether citrate-based CRRT with physiologic target systemic [Ca<sub>i</sub>] between 1.12 and 1.20 mmol/l could maintain stable PTH levels. Methods: Measurement of intact PTH (PTHi) in 30 consecutive critically ill patients treated with citrate-based CRRT. Results: Thirty patients [mean age: 70.4 (SD 11.3) years; 56.7% males] were enrolled. Mean serum [Ca<sub>i</sub>] was 1.16 mmol/l (SD 0.09), 1.13 mmol/l (SD 0.09), 1.17 mmol/l (SD 0.05) and 1.16 mmol/l (SD 0.04) at baseline, 12, 24 and 48 h, respectively (p = 0.29). Median PTHi levels (interquartile range) at baseline, 12, 24 and 48 h were 66.5 (43-111), 109 (59.5-151.5), 88.5 (47-133) and 85 pg/ml (53-140), respectively. The differences between baseline and 12 h and across all time points were statistically not significant (p = 0.16 and p = 0.49, respectively). In a mixed-effects model, each 0.1 mmol/l increase in serum [Ca<sub>i</sub>] was associated with a 31.2% decrease in PTHi (p < 0.001). Results were unchanged after adjustment for age, gender, magnesium, phosphate, arterial pH and time spent on CRRT. Conclusions: Maintaining systemic [Ca<sub>i</sub>] within the physiologic range was associated with stable PTHi levels.

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          Citrate anticoagulation for continuous venovenous hemofiltration.

          Heleen Oudemans-van Straaten, Rob J Bosman, Matty Koopmans … (2009)
          Continuous venovenous hemofiltration (CVVH) is applied in critically ill patients with acute renal failure for renal replacement. Heparins used to prevent circuit clotting may cause bleeding. Regional anticoagulation with citrate reduces bleeding, but has metabolic risks. The aim was to compare the safety and efficacy of the two. Randomized, nonblinded, controlled single-center trial. General intensive care unit of a teaching hospital. Adult critically ill patients needing CVVH for acute renal failure and without an increased bleeding risk. Regional anticoagulation with citrate or systemic anticoagulation with the low-molecular weight heparin nadroparin. End points were adverse events necessitating discontinuation of study anticoagulant, transfusion, metabolic and clinical outcomes, and circuit survival. Of the 215 randomized patients, 200 received CVVH per protocol (97 citrate and 103 nadroparin). Adverse events required discontinuation of citrate in two patients (accumulation and clotting) of nadroparin in 20 (bleeding and thrombocytopenia) (p < 0.001). Bleeding occurred in 6 vs. 16 patients (p = 0.08). The median number of red blood cell units transfused per CVVH day was 0.27 (interquartile range, 0.0-0.63) for citrate, 0.36 (interquartile range, 0-0.83) for nadroparin (p = 0.31). Citrate conferred less metabolic alkalosis (p = 0.001) and lower plasma calcium (p < 0.001). Circuit survival was similar. Three-month mortality on intention-to-treat was 48% (citrate) and 63% (nadroparin) (p = 0.03), per protocol 45% and 62% (p = 0.02). Citrate reduced mortality in surgical patients (p = 0.007), sepsis (p = 0.01), higher Sepsis-Related Organ Failure Assessment score (p = 0.006), and lower age (p = 0.009). The efficacy of citrate and nadroparin anticoagulation for CVVH was similar, however, citrate was safer. Unexpectedly, citrate reduced mortality. Less bleeding could only partly explain this benefit, less clotting could not. Post hoc citrate appeared particularly beneficial after surgery, in sepsis and severe multiple organ failure, suggesting interference with inflammation.
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            Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study.

            Mehran Monchi, Denis Berghmans, Didier Ledoux … (2004)
            To compare the efficacy and safety of adjusted-dose unfractionated heparin with that of regional citrate anticoagulation in intensive care patients treated by continuous venovenous hemofiltration (CVVH). Prospective, randomized, clinical trial in a 32-bed medical and surgical ICU in a university teaching hospital. ICU patients with acute renal failure requiring continuous renal replacement therapy, without cirrhosis, severe coagulopathy, or known sensitivity to heparin. Before the first CVVH run patients were randomized to receive anticoagulation with heparin or trisodium citrate. Patients eligible for another CVVH run received the other study medication in a cross-over fashion until the fourth circuit. Forty-nine circuits (hemofilters) were analyzed: 23 with heparin and 26 with citrate. The median lifetime of hemofilters was 70 h (interquartile range 44-140) with citrate anticoagulation and 40 h (17-48) with heparin (p=0.0007). One major bleeding occurred during heparin anticoagulation and one metabolic alkalosis (pH=7.60) was noted with citrate after a protocol violation. Transfusion rates (units of red cells per day of CVVH) were, respectively, 0.2 (0.0-0.4) with citrate and 1.0 (0.0-2.0) with heparin (p=0.0008). Regional citrate anticoagulation seems superior to heparin for the filter lifetime and transfusion requirements in ICU patients treated by continuous renal replacement therapy.
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              Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients.

              Demetrios J Kutsogiannis, R T Noel Gibney, Daniel E Stollery … (2005)
              We determined the effect of regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill subjects suffering from acute renal failure who were not at high risk for hemorrhagic complications. Between April 1999 and June 2002, 30 critically ill subjects requiring continuous renal replacement therapy and using 79 hemofilters were randomly assigned to receive regional citrate or systemic heparin anticoagulation. The median hemofilter survival time was 124.5 hours (95% CI 95.3 to 157.4) in the citrate group, which was significantly longer than the 38.3 hours (95% CI 24.8 to 61.9) in the heparin group (P < 0.001). Increasing illness severity score, male gender, and decreasing antithrombin-III levels were independent predictors of an increased relative hazard of hemofilter failure. After adjustment for illness severity, antithrombin-III levels increased significantly more over the period of study in the citrate as compared to the heparin group (P= 0.038). Moreover, after adjustment for antithrombin-III levels and illness severity score, the relative risk of hemorrhage with citrate anticoagulation was significantly lower than that with heparin (relative risk of 0.14; 95% CI 0.02 to 0.96, P= 0.05). Compared with systemic heparin anticoagulation, regional citrate anticoagulation significantly increases hemofilter survival time, and significantly decreases bleeding risk in critically ill patients suffering from acute renal failure and requiring continuous renal replacement therapy.
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                Author and article information

                Journal
                Journal ID (publisher-id): NEC
                Journal ID (nlm-ta): Nephron Clin Pract
                Journal ID (doi): 10.1159/issn.1660-2110
                Title: Nephron Clinical Practice
                Publisher: S. Karger AG
                ISSN (Electronic): 1660-2110
                Publication date Subscription-year: 2013
                Publication date (Print): December 2013
                Publication date (Electronic): 02 November 2013
                Volume: 124
                Issue: 1-2
                Pages: 124-131
                Affiliations
                aDepartment of Critical Care, Guy's and St Thomas' Foundation Hospital, King's Health Partners and bDivision of Health and Social Care Research, King's College London, London, UK; cHospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
                Author notes
                *Marlies Ostermann, PhD, MD, FRCP, Consultant in Critical Care and Nephrology, Department of Critical Care Medicine, King's College London, Guy's and St Thomas' Foundation Hospital, London SE1 7EH (UK), E-Mail Marlies.Ostermann@gstt.nhs.uk
                Article
                Publisher ID: 355860 Other ID: Nephron Clin Pract 2013;124:124-131
                DOI: 10.1159/000355860
                PubMed ID: 24192818
                SO-VID: be74e51d-0e93-45f1-a0e4-571accea9d25
                Copyright © © 2013 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 15 April 2013
                Date accepted : 17 September 2013
                Page count
                Figures: 1, Tables: 4, Pages: 8
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Acute kidney injury,Citrate,Continuous renal replacement therapy,Parathyroid hormone
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Acute kidney injury, Citrate, Continuous renal replacement therapy, Parathyroid hormone

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