Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis

Gritters, Mareille; Grooteman, Muriël P.C.; Schoorl, Margreet; Schoorl, Marianne; Bartels, P. C. M.; Scheffer, P; Teerlink, Tom; Schalkwijk, Casper G.; Spreeuwenberg, Marieke; Nubé, Menso J.

doi:10.1093/ndt/gfi069

Cited by 144 publications

(110 citation statements)

References 20 publications

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“…Heparin has been known to activate platelets and white blood cells, whereas citrate does not (6). Furthermore, acetate in concentrations present in regular bicarbonate dialysate is also reported to be proinflammatory, increasing cellular activation (7).…”

Section: Discussionmentioning

confidence: 99%

Increased Efficiency of Hemodialysis with Citrate Dialysate

Kossmann¹,

Gonzales

Callan

et al. 2009

Clinical Journal of the American Society of Nephrology

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Background and objectives: A bicarbonate dialysate acidified with citrate (CD) has been reported to have local anticoagulant effect. This study examines the effect of CD on dialysis efficiency, measured as eKt/Vurea, and predialysis concentrations of BUN, creatinine, phosphate, and ␤-2 microglobulin in chronic dialysis units.Design, settings, participants, & measurements: Three outpatient chronic hemodialysis units with 142 patients were switched to CD for 6 mo. Using each patient's prior 6 mo on regular bicarbonate dialysate acidified by acetate (AD) as control, eKt/Vurea was compared with that of CD. Follow-up data for 7 mo after the study were collected from about one-half of the participants remaining on CD and the others returned to AD.Results: eKt/Vurea, increased (P < 0.0001) from pre-CD value of 1.51 ؎ 0.01 to 1.57 ؎ 0.01 with CD. During CD use ␤-2 microglobulin levels declined (P ‫؍‬ 0.0001) from 28.1 ؎ 10.0 to 25.9 ؎ 10.0. Similarly, the concentrations of BUN, creatinine, and phosphate also decreased on CD (P < 0.008). In the poststudy period, eKt/Vurea for the patients staying on CD remained unchanged at 1.60 ؎ 0.17 versus 1.59 ؎ 0.18 (P ‫؍‬ NS), whereas in those returning to AD the eKt/Vurea decreased from 1.55 ؎ 0.20 to 1.52 ؎ 0.17 (P < 0.0001).Conclusions: Data suggest that CD use is associated with increased solute removal.

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Section: Discussionmentioning

confidence: 99%

Increased Efficiency of Hemodialysis with Citrate Dialysate

Kossmann¹,

Gonzales

Callan

et al. 2009

Clinical Journal of the American Society of Nephrology

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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

124

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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“…The low molecular weight citrate anion is removed by diffusion/ convection, with the patient's citrate load eventually resulting from the balance between citrate administration and its removal by RRT (12). Longer circuit survival with lower bleeding rates (15,16) and improved biocompatibility (17)(18)(19)(20) are recognized advantages of the citrate-based continuous RRT modalities.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of a Citrate-Based Protocol for Sustained Low-Efficiency Dialysis in AKI Using Standard Dialysis Equipment

Fiaccadori¹,

Regolisti²,

Cademartiri³

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives A simple anticoagulation protocol was developed for sustained low-efficiency dialysis (SLED) in patients with AKI, based on the use of anticoagulant citrate dextrose solution formulation A (ACD-A) and standard dialysis equipment. Patients' blood recalcification was obtained from calcium backtransport from dialysis fluid.Design, setting, participants, & measurements All patients treated with SLED (8-to 12-hour sessions) for AKI in four intensive care units of a university hospital were studied over a 30-month period, from May 1, 2008 to September 30, 2010. SLED interruptions and their causes, hemorrhagic complications, as well as coagulation parameters, ionized calcium, and blood citrate levels were recorded.Results This study examined 807 SLED sessions in 116 patients (mean age of 69.7 years [SD 12.1]; mean Acute Physiology and Chronic Health Evaluation II score of 23.8 [4.6]). Major bleeding was observed in six patients (5.2% or 0.4 episodes/100 person-days follow-up while patients were on SLED treatment). Citrate accumulation never occurred, even in patients with liver dysfunction. Intravenous calcium for ionized hypocalcemia (, 3.6 mg/dl or , 0.9 mmol/L) was needed in 28 sessions (3.4%); in 8 of these 28 sessions (28.6%), low ionized calcium was already present before SLED start. In 92.6% of treatments, SLED was completed within the scheduled time (median 8 hours). Interruptions of SLED by impending/irreversible clotting were recorded in 19 sessions (2.4%). Blood return was complete in 98% of the cases. In-hospital mortality was 45 of 116 patients (38.8%).Conclusions This study protocol affords efficacious and safe anticoagulation of the SLED circuit, avoiding citrate accumulation and, in most patients, systematic calcium supplementation; it can be implemented with commercial citrate solutions, standard dialysis equipment, on-line produced dialysis fluid, and minimal laboratory monitoring.

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Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis

Abstract: This study shows first, that HD-induced PMN and platelet degranulation are early, most probably calcium-dependent processes and, secondly, that the formation of ox-LDL is clearly dependent on the type of anticoagulant applied.

Cited by 144 publications

References 20 publications

Increased Efficiency of Hemodialysis with Citrate Dialysate

Increased Efficiency of Hemodialysis with Citrate Dialysate

Regional Citrate Anticoagulation for RRTs in Critically Ill Patients with AKI

Efficacy and Safety of a Citrate-Based Protocol for Sustained Low-Efficiency Dialysis in AKI Using Standard Dialysis Equipment

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