Citrate confers less filter-induced complement activation and neutrophil degranulation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients

Schilder, Louise; Nurmohamed, Shaikh A.; Wee, Pieter M. ter; Paauw, Nanne J.; Girbes, Armand R.J.; Beishuizen, Albertus; Beelen, Robert H.J.; Groeneveld, A. B. Johan

doi:10.1186/1471-2369-15-19

Cited by 30 publications

(30 citation statements)

References 19 publications

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“…While heparin was associated with a reduction in tumor necrosis factor-α, prefilter myeloperoxidase levels were significantly higher compared with citrate. Similarly, heparin has been shown to activate complement and induce neutrophil degranulation in the extracorporeal circuit to a greater extent when compared with citrate [52]. Whether these observations are also impacted by citrate being associated with longer filter survival and reduced episodes of bleeding and need for transfusion is plausible but remains uncertain [53].…”

Section: Impact Of Rrt On Recoverymentioning

confidence: 99%

Effects of Renal Replacement Therapy on Renal Recovery after Acute Kidney Injury

Schneider

Bagshaw

2014

Nephron Clin Pract

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Recovery of kidney function following an episode of acute kidney injury (AKI) is now acknowledged as a vital patient-centered outcome with clear health economic implications. In approximately 5-8% of critically ill patients with more severe forms of AKI, support with renal replacement therapy (RRT) is provided. Recent data have suggested that rates of RRT utilization in AKI are increasing. Despite advances in our understanding of how best to prescribe acute RRT in critically ill patients with AKI, additional aspects remain uncertain, predisposing to suboptimal delivery and variation in practice. Importantly, if, when, how, and by what principles we apply acute RRT for AKI are all treatment decision-related factors that are modifiable and may interact with recovery of kidney function. Limited data, mostly from observational studies and secondary analyses, have explored the specific association between acute RRT and recovery. Available data are not able to clarify whether providing any RRT in otherwise eligible patients with AKI impacts recovery. They are also unable to inform whether the timing or circumstance under which RRT is started impacts recovery. No studies have evaluated whether there is an optimal time to start RRT to maximize the probability of recovery. Accumulated evidence, mostly derived from observational studies, suggests initial therapy in critically ill patients with AKI with continuous RRT, compared with intermittent modalities, improves the probability of recovery to dialysis independence. Evidence from high-quality randomized trials failed to show any association between delivered dose intensity of RRT and recovery. The use of biocompatible membranes for acute RRT may improve recovery in AKI; however, data are inconsistent. Limited data have evaluated the impact of membrane flux properties on recovery. Preliminary data have suggested that circuit anticoagulation with citrate, which results in a reduction in membrane-induced oxidative stress and leukocyte activation, may be associated with improved recovery; however, further corroborative data are needed. Additional evidence, ideally from randomized trials, is clearly needed to inform best practice in the delivery of acute RRT to optimize probability of recovery of kidney function for survivors of AKI.

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Section: Impact Of Rrt On Recoverymentioning

confidence: 99%

Effects of Renal Replacement Therapy on Renal Recovery after Acute Kidney Injury

Schneider

Bagshaw

2014

Nephron Clin Pract

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“…Citrate anticoagulates the extracorporeal circuit by chelating ionized calcium (10,11,22), the key cofactor of many steps of the clotting cascade (23). Additional antihemostatic and anti-inflammatory activities of citrate may indirectly derive from its effects on blood cell components, including reduced activation of white blood cells and platelets (24)(25)(26)(27)(28)(29), and protective effects against endothelial-cell inflammation and dysfunction (30). Furthermore, citrate may be directly involved as a signal molecule in several cellular processes related to inflammation and balance of oxidative species (31).…”

Section: Rca: Basic Principles and Citrate Metabolismmentioning

confidence: 99%

Regional Citrate Anticoagulation for RRTs in Critically Ill Patients with AKI

Morabito

Pistolesi

Tritapepe

et al. 2014

Clinical Journal of the American Society of Nephrology

127

130

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Hemorrhagic complications have been reported in up to 30% of critically ill patients with AKI undergoing RRT with systemic anticoagulation. Because bleeding is associated with significantly increased mortality risk, strategies aimed at reducing hemorrhagic complications while maintaining extracorporeal circulation should be implemented. Among the alternatives to systemic anticoagulation, regional citrate anticoagulation has been shown to prolong circuit life while reducing the incidence of hemorrhagic complications and lowering transfusion needs. For these reasons, the recently published Kidney Disease Improving Global Outcomes Clinical Practice Guidelines for Acute Kidney Injury have recommended regional citrate anticoagulation as the preferred anticoagulation modality for continuous RRT in critically ill patients in whom it is not contraindicated. However, the use of regional citrate anticoagulation is still limited because of concerns related to the risk of metabolic complications, the complexity of the proposed protocols, and the need for customized solutions. The introduction of simplified anticoagulation protocols based on citrate and the development of dialysis monitors with integrated infusion systems and dedicated software could lead to the wider use of regional citrate anticoagulation in upcoming years.

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“…Both heparin and citrate have been reported to affect the pro‐ versus anti‐inflammatory balance differently, depending on the model used . They are postulated to influence the inflammatory response either directly or through some of its key mediators.…”

Section: Discussionmentioning

confidence: 99%

Regional Citrate Anticoagulation for Intermittent Hemodialysis in Dogs

Francey

Schweighauser

2017

Veterinary Internal Medicne

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BackgroundThe traditional systemic heparinization used for anticoagulation in extracorporeal therapies may cause fatal complications in animals at risk of bleeding.Hypothesis/ObjectivesTo develop and validate a protocol of regional citrate anticoagulation (RCA) for intermittent hemodialysis in dogs.AnimalsA total of 172 dogs treated with hemodialysis for acute kidney injury.MethodsIn vitro titration was performed, adding trisodium citrate and calcium chloride to heparinized canine blood. A tentative protocol was used first in 66 treatments with additional heparinization and subsequently in 518 heparin‐free treatments. Safety and adequacy of RCA were assessed based on clinical and laboratory monitoring, dialyzer pressure gradient, treatment completion, and visual scoring of the extracorporeal circuit.ResultsAddition of 1 mmol/L citrate to heparinized blood decreased the ionized calcium concentration by 0.23 mmol/L (95% confidence interval [CI], 0.16–0.30) and 1 mmol/L calcium increased it by 0.62 mmol/L (95% CI, 0.45–0.79). Heparin‐free treatments were initiated with infusion of trisodium citrate (102 mmol/L) at 2.55 mmol/L blood and calcium chloride (340 mmol/L) at 0.85 mmol/L. Citrate and calcium administrations were adjusted in 27 and 34% of the treatments, respectively. Overall, anticoagulation was satisfactory in 92% of the treatments, with expected azotemia reduction in 95% (urea) and 86% (creatinine), stable dialyzer pressure gradient in 82%, and clean extracorporeal circuits in 92% of the treatments. Eighteen treatments (3.5%) were discontinued prematurely, 9 because of clotting and 9 for reasons unrelated to the RCA procedure.Conclusions and Clinical ImportanceRegional citrate anticoagulation allows safe and efficient heparin‐free hemodialysis in dogs at risk of bleeding.

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Citrate confers less filter-induced complement activation and neutrophil degranulation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients

Cited by 30 publications

References 19 publications

Effects of Renal Replacement Therapy on Renal Recovery after Acute Kidney Injury

Effects of Renal Replacement Therapy on Renal Recovery after Acute Kidney Injury

Regional Citrate Anticoagulation for RRTs in Critically Ill Patients with AKI

Regional Citrate Anticoagulation for Intermittent Hemodialysis in Dogs

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