Green Nephrology: Citrate, the Green Alternative to Heparin in Hemodialysis.
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ABSTRACT:
SUBMITTER: van der Meulen J
PROVIDER: S-EPMC10851001 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
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Green Nephrology: Citrate, the Green Alternative to Heparin in Hemodialysis.
Kidney international reports 20231130 2
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Project description:BackgroundRegional citrate anticoagulation (RCA) is the gold standard of anticoagulation for continuous renal replacement therapy but is rarely used for intermittent hemodialysis (IHD) in ICU. Few studies assessed the safety and efficacy of RCA during IHD in ICU; however, no data are available comparing RCA to heparin anticoagulation, which are commonly used for IHD. The aim of this study was to assess the efficacy and safety of RCA compared to heparin anticoagulation during IHD.MethodsThis retrospective single-center cohort study included consecutive ICU patients treated with either heparin anticoagulation (unfractionated or low-molecular-weight heparin) or RCA for IHD from July to September in 2015 and 2017. RCA was performed with citrate infusion according to blood flow and calcium infusion by diffusive influx from dialysate. Using a propensity score analysis, as the primary endpoint we assessed whether RCA improved efficacy, quantified with Kt/V from the ionic dialysance, compared to heparin anticoagulation. The secondary endpoint was safety. Exploratory analyses were performed on the changes in efficacy and safety between the implementation period (2015) and at long term (2017).ResultsIn total, 208 IHD sessions were performed in 56 patients and were compared (124 RCA and 84 heparin coagulation). There was no difference in Kt/V between RCA and heparin (0.95 ± 0.38 vs. 0.89 ± 0.32; p = 0.98). A higher number of circuit clotting (12.9% vs. 2.4%; p = 0.02) and premature interruption resulting from acute high transmembrane pressure (21% vs. 7%; p = 0.02) occurred in the RCA sessions compared to the heparin sessions. In the propensity score-matching analysis, RCA was associated with an increased risk of circuit clotting (absolute differences = 0.10, 95% CI [0.03-0.18]; p = 0.008). There was no difference in efficacy and safety between the two time periods (2015 and 2017).ConclusionRCA with calcium infusion by diffusive influx from dialysate for IHD was easy to implement with stable long-term efficacy and safety but did not improve efficacy and could be associated with an increased risk of circuit clotting compared to heparin anticoagulation in non-selected ICU patients. Randomized trials to determine the best anticoagulation for IHD in ICU patients should be conducted in a variety of settings.
| S-EPMC7822996 | biostudies-literature
Project description:BACKGROUND:Non-tunneled hemodialysis catheters are currently used for critically ill patients with acute kidney injury requiring extracorporeal renal replacement therapy. Strategies to prevent catheter dysfunction and infection with catheter locks remain controversial. METHODS:In a multicenter, randomized, controlled, double-blind trial, we compared two strategies for catheter locking of non-tunneled hemodialysis catheters, namely trisodium citrate at 4% (intervention group) versus unfractionated heparin (control group), in patients aged 18 years or older admitted to the intensive care unit and in whom a first non-tunneled hemodialysis catheter was to be inserted by the jugular or femoral vein. The primary endpoint was length of event-free survival of the first non-tunneled hemodialysis catheter. Secondary endpoints were: rate of fibrinolysis, incidence of catheter dysfunction and incidence of catheter-related bloodstream infection (CRBSI), all per 1000 catheter-days; number of hemorrhagic events requiring transfusion, length of stay in intensive care and in hospital; 28-day mortality. RESULTS:Overall, 396 randomized patients completed the trial: 199 in the citrate group and 197 in the heparin group. There was no significant difference in baseline characteristics between groups. The duration of event-free survival of the first non-tunneled hemodialysis catheter was not significantly different between groups: 7 days (IQR 3-10) in the citrate group and 5 days (IQR 3-11) in the heparin group (p = 0.51). Rates of catheter thrombosis, CRBSI, and adverse events were not statistically different between groups. CONCLUSIONS:In critically ill patients, there was no significant difference in the duration of event-free survival of the first non-tunneled hemodialysis catheter between trisodium citrate 4% and heparin as a locking solution. Catheter thrombosis, catheter-related infection, and adverse events were not statistically different between the two groups. Trial registration Registered with Clinicaltrials.gov under the number NCT01962116. Registered 14 October 2013.
| S-EPMC6603108 | biostudies-literature
Project description: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.
| S-EPMC5787180 | biostudies-literature
Project description:Heparin is commonly given during hemodialysis (HD). Patients undergoing HD have a high rate of gastrointestinal bleeding (GIB). It is unclear whether or when it is safe to give heparin after acute GIB. We describe the patterns and safety of heparin use with outpatient HD following an acute GIB.We identified patients aged ? 67 who, from 2004-2008, experienced GIB requiring hospitalization within 2 days of receiving maintenance HD with heparin. We used Cox regression to estimate the risk of recurrent GIB and death associated with receiving heparin the day they resumed outpatient HD post-GIB.Of the 1,342 patients who had GIB, 1,158 (86%) received heparin at a median dose of 4,000 units with their first outpatient HD session after discharge from GIB. On average, their post-GIB doses were slightly lower than their pre-GIB doses (mean change: -214 ± 3,266 units, p < 0.02). However, only 27% of patients had a decrease in their dose, while 21% had their dose increased. We did not find an increased risk of death or recurrent GIB associated with using heparin post-GIB (HR; 95% confidence interval (CI), for death: 1.01; 0.69-1.48; for recurrent GIB: 0.78; 0.39-1.57).The vast majority of these high-risk patients received heparin on the very first day they resumed outpatient HD post-GIB, and the majority at unchanged doses to those received pre-GIB. Even if the practice was not associated with increased risks of death or re-bleeding, it highlights an area for possible system-based improvement to the care for patients on HD.
| S-EPMC4246045 | biostudies-literature
Project description:Currently, there is no consensus regarding the mechanism underlying Aspergillus niger citrate biosynthesis and secretion. We hypothesise that depending on the experimental setup, extracellular citrate accumulation can have fundamentally different underlying transcriptomic landscapes. We show that varying the amount and type of supplement of an arginine auxotrophic A. niger strain results in transcriptional down-regulation of citrate metabolising enzymes in the condition in which more citrate is accumulated extracellularly. This contrasts with the transcriptional adaptations when increased citrate production is triggered by iron limitation. By combining gene expression data obtained from these two very distinct experimental setups with hidden Markov models and transporter homology approaches, we were able to compile a shortlist of the most likely citrate transporter candidates. Two candidates (An17g01710 and An09g06720m.01) were heterologously expressed in the yeast Saccharomyces cerevisiae, and one of the resultant mutants showed the ability to secrete citrate. Our findings provide steps in untangling the complex interplay of different mechanisms underlying A. niger citrate accumulation, and we demonstrate how a comparative transcriptomics approach complemented with further bioinformatics analyses can be used to pinpoint a fungal citrate exporter.
| S-EPMC6502548 | biostudies-literature
Project description:Evidence-informed decision making in clinical care and policy in nephrology is undermined by trials that selectively report a large number of heterogeneous outcomes, many of which are not patient centered. The Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) Initiative convened an international consensus workshop on November 7, 2015, to discuss the identification and implementation of a potential core outcome set for all trials in hemodialysis. The purpose of this article is to report qualitative analyses of the workshop discussions, describing the key aspects to consider when establishing core outcomes in trials involving patients on hemodialysis therapy. Key stakeholders including 8 patients/caregivers and 47 health professionals (nephrologists, policymakers, industry, and researchers) attended the workshop. Attendees suggested that identifying core outcomes required equitable stakeholder engagement to ensure relevance across patient populations, flexibility to consider evolving priorities over time, deconstruction of language and meaning for conceptual consistency and clarity, understanding of potential overlap and associations between outcomes, and an assessment of applicability to the range of interventions in hemodialysis. For implementation, they proposed that core outcomes must have simple, inexpensive, and validated outcome measures that could be used in clinical care (quality indicators) and trials (including pragmatic trials) and endorsement by regulatory agencies. Integrating these recommendations may foster acceptance and optimize the uptake and translation of core outcomes in hemodialysis, leading to more informative research, for better treatment and improved patient outcomes.
| S-EPMC5369351 | biostudies-literature
Project description: Not available
| S-EPMC8694695 | biostudies-literature
Project description:BackgroundLow molecular weight heparins (LMWH) have been extensively studied and became the treatment of choice for several indications including pulmonary embolism. While their efficacy in hemodialysis is considered similar to unfractionated heparin (UFH), their safety remains controversial mainly due to a risk of bioaccumulation in patients with renal impairment. The aim of this systematic review was to evaluate the safety of LMWH when compared to UFH for extracorporeal circuit (ECC) anticoagulation.MethodsWe used Pubmed, Embase, Cochrane central register of controlled trials, Trip database and NICE to retrieve relevant studies with no language restriction. We looked for controlled experimental trials comparing LMWH to UFH for ECC anticoagulation among end-stage renal disease patients undergoing chronic hemodialysis. Studies were kept if they reported at least one of the following outcomes: bleeding, lipid profile, cardiovascular events, osteoporosis or heparin-induced thrombocytopenia. Two independent reviewers conducted studies selection, quality assessment and data extraction with discrepancies solved by a third reviewer. Relative risk and 95% CI was calculated for dichotomous outcomes and mean weighted difference (MWD) with 95% CI was used to pool continuous variables.ResultsSeventeen studies were selected as part of the systematic. The relative risk for total bleeding was 0.76 (95% CI 0.26-2.22). The WMD calculated for total cholesterol was -28.70 mg/dl (95% CI -51.43 to -5.98), a WMD for triglycerides of -55.57 mg/dl (95% CI -94.49 to -16.66) was estimated, and finally LDL-cholesterol had a WMD of -14.88 mg/dl (95% CI -36.27 to 6.51).ConclusionsLMWH showed to be at least as safe as UFH for ECC anticoagulation in chronic hemodialysis. The limited number of studies reporting on osteoporosis and HIT does not allow any conclusion for these outcomes. Larger studies are needed to evaluate properly the safety of LMWH in chronic hemodialysis.
| S-EPMC5463373 | biostudies-literature
Project description:BackgroundAlthough heparin is used to anticoagulate the extracorporeal circuit for most patients on maintenance hemodialysis (HD), some patients undergo heparin-free HD. We describe the determinants of heparin-free HD and its association with adverse outcomes using data from a national dialysis provider merged with Medicare claims.MethodsWe identified patients aged ≥67 years with no recent history of warfarin use who initiated maintenance HD from 2007 to 2008. We applied the Cox regression to a propensity score-matched cohort to estimate the hazards of all-cause mortality, bleeding (gastrointestinal hemorrhage, hemorrhagic stroke, other hemorrhage), atherothrombosis (ischemic stroke, myocardial infarction) and venous thromboembolism (VTE) (deep vein thrombosis, pulmonary embolism).ResultsAmong 12 468 patients, 836 (6.7%) were dialyzed heparin-free. In multivariable-adjusted analyses, a history of gastrointestinal bleeding, hemorrhagic stroke and lower hemoglobin and platelet counts were associated with higher odds of heparin-free HD. Heparin-free HD use also varied as much as 4-fold by facility region. We found no significant association of heparin-free HD with all-cause mortality [hazard ratio (HR) 1.08; 95% confidence interval (CI): 0.94-1.26], bleeding (HR 1.15; 95% CI: 0.83-1.60), atherothrombosis (HR 1.09, 95% CI: 0.90-1.31) or VTE (HR 1.23, 95% CI: 0.93-1.64) compared with HD with heparin.ConclusionsPatient markers of increased risk of bleeding and facility region associated with heparin-free HD use. Despite the potential benefits of avoiding heparin use, heparin-free HD was not significantly associated with decreased hazards of death, bleeding or thrombosis, suggesting that it may be no safer than HD with heparin.
| S-EPMC3888305 | biostudies-literature
Project description:BackgroundThere is an unmet need to develop safe and successful heparin-free regional anticoagulation modalities in haemodialysed patients at risk of bleeding. Whether the addition of citrate as a prefilter injection or in the dialysate itself is required to reach anticoagulation objectives when calcium-free dialysate is used as regional anticoagulation remains unclear.MethodsIn this monocentric retrospective study, we report our experience of 908 dialysis sessions performed with a calcium-free citrate-containing dialysate and calcium reinjection according to the ionic dialysance, without additional heparin.ResultsPremature termination for filter clotting occurred in 20 sessions (2.2%) and duration of session was >4.5 h in 135 (15%; maximum duration 6 h). In addition, we could investigate the citrate, calcium and acid-basis status during haemodialysis sessions performed with (citrate group, n = 20 sessions) or without (citrate-free group, n = 19 sessions) citrate in the dialysate. In 20 sessions performed in patients with underlying liver disorders and using calcium-free citrate-containing dialysate, patients' ionized calcium (iCa) and serum citrate levels were stable and remained within the normal range, respectively. Post-filter iCa was below 0.4 mmol/L in 19/20 sessions and citrate was 0.304 mmol/L (range: 0.011; 0.548). In 19 sessions that used calcium and citrate-free dialysate, post-filter iCa was 0.41 mmol/L (0.34; 0.5) and all sessions extended to 4 h or beyond.ConclusionsRegional anticoagulation of haemodialysis with a calcium-free dialysate and calcium reinjection according to the ionic dialysance is safe. Adding citrate to the dialysate is not mandatory to prevent dialysis circuit clotting in most patients.
| S-EPMC8690133 | biostudies-literature