Impact of increasing post-filter ionised calcium target on regional citrate anticoagulation efficacy in ICU continuous renal replacement therapy: the non-inferiority randomised controlled Ca-CIBLE protocol.

INTRODUCTION: Continuous renal replacement therapy (CRRT) is a critical therapeutic intervention for patients with severe acute kidney injury in intensive care. However, premature filter clotting remains a significant challenge during CRRT, impacting treatment efficacy, costs and patient outcomes. Anticoagulation is essential to maintain circuit patency, with regional citrate anticoagulation (RCA) emerging as a preferred strategy due to its favourable bleeding profile. The standard target for post-filter ionised calcium (iCa) concentration during RCA-CRRT is set between 0.25 and 0.35 mmol/L, although evidence supporting this range is limited. We hypothesise that a higher post-filter iCa target (0.35-0.45 mmol/L) can provide comparable circuit patency while potentially reducing adverse effects associated with citrate administration. METHODS AND ANALYSIS: This multicentre randomised controlled non-inferiority trial will compare a low post-filter iCa target (0.25-0.35 mmol/L) with a higher post-filter iCa target (0.35-0.45 mmol/L) in patients undergoing RCA-CRRT in the intensive care unit. A total of 412 CRRT sessions will be randomised with a 1:1 ratio into these two groups. The primary outcome is the incidence of filter clotting. Secondary outcomes include filter lifespan, post-filter iCa levels, citrate infusion rates, the occurrence of metabolic adverse effects, financial costs and blood loss. ETHICS AND DISSEMINATION: The study has obtained approval from the ethics committee (Ethics Committee Est III, Nancy, France) and patients will be included after providing informed consent. The results will be disseminated at academic conferences and in peer-reviewed publications. All procedures were developed in order to assure data protection and confidentiality. TRIAL REGISTRATION NUMBER: NCT05814341.

Switching from acetate to citrate dialysate in a central concentrate delivery system for high-volume online hemodiafiltration: a retrospective cohort study.

Interest in citrate-based dialysate (Cit-D) is growing due to its benefits, including anticoagulation and dialysis efficacy. However, research on safety and efficiency of Cit-D in high-volume hemodiafiltration (HDF) via central concentrate delivery system (CCDS) is scarce. This study aimed to investigate the safety and efficacy of Cit-D when switching from acetate-based dialysate (Acet-D) in high-volume HDF via CCDS. This is a retrospective analysis of 28 patients who underwent post-dilution online HDF via CCDS, who switched from Acet-D to Cit-D. The study period was divided into 3 periods for analysis: 12 weeks using Acet-D (AD period), the first 12 weeks using Cit-D (CD-1 period), and the second 12 weeks using Cit-D (CD-2 period). We collected the laboratory, dialysis, and safety parameters in each period from electrical medical records. After switching from Acet-D to Cit-D, heparin dosage decreased by 17%, whereas the incidence of complications did not increase. Kt/VBUN and urea reduction ratio increased by 4.6% and 2.1%, respectively. Pre-dialysis beta2-microglobulin concentration decreased after using Cit-D. The corrected calcium levels decreased in the CD-1 period compared to the AD period, but in CD-2, they subsequently increased to levels similar to those observed during the AD period. Symptomatic hypocalcemia did not occur, and there was no significant difference in the incidence of hyperparathyroidism. Endotoxin levels and the bacterial culture of ultrapure dialysate were unremarkable throughout all periods. These results might suggest that Cit-D could potentially offer advantages over Acet-D, such as reducing the heparin dose and increasing dialysis efficiency, in patients undergoing high-volume HDF using CCDS.

Automated regional citrate anticoagulation system based on individualized dosing models in nonliver failure patients undergoing PIRRT therapy.

INTRODUCTION: Regional citrate anticoagulation is a preferred option for renal replacement therapy in critically ill patients. However, current implementations ignore individual differences that may exist in the fluctuation of patients' ionized calcium levels. To address this problem, individualized citrate and calcium supplementation models were established based on the pharmacokinetic and clearance characteristics of citrate, and an automated regional citrate anticoagulation system was built with these models as its core to facilitate the treatment of clinical patients. This study was designed to preliminarily evaluate the safety and efficacy of this system, the SuperbMed® RCA-SP100 automated regional citrate anticoagulation system, in prolonged intermittent renal replacement therapy. METHODS: Seven patients undergoing prolonged intermittent renal replacement therapy completed treatment with the SuperbMed® RCA-SP100 system. In vivo and in vitro ionized calcium levels were measured every hour before and after the start of dialysis. The accuracy and alarm sensitivity of the pumps were also monitored. RESULTS: During seven treatments, the average extracorporeal ionized calcium level was 0.34 ± 0.02 mmol/L, and the mean ionized calcium level in vivo was 1.09 ± 0.07 mmol/L. No patient required intervention, and there was no filter coagulation. The pumps all had an absolute accuracy less than 5%, and alarms could be triggered precisely. CONCLUSIONS: We reported on an automated system that allows for individualized citrate and calcium supplementation in prolonged intermittent renal replacement therapy and enables the precise and secure implementation of regional citrate anticoagulation.

An in situ bioadhesive foam as a large intestinal delivery platform for antibody fragment to treat inflammatory bowel disease.

Biologics have been widely used as injectables in the treatment of inflammatory bowel disease (IBD). Different local treatment attempts have been developed in recent years. However, maintaining systemic levels of biologics is still crucial for achieving colitis remission. An equilibrium between systemic and local concentrations of biologics is therefore essential for treatment of colitis. Current formulations struggle to create optimal balance between drug concentrations in plasma and the colonic wall. Addressing this challenge, we developed a rectally delivered in situ foam that generates CO2via a reaction between potassium bicarbonate (PB) and citric acid (CA) without the aid of an external device. An anti-TNF-α antibody fragment (Fab) was loaded into the foam formulation, which promoted prolonged colon retention and improved Fab distribution up to proximal colon following rectal administration to mice. In addition, we observed increased plasma Fab concentrations in mice receiving the rectal Fab foam compared to a Fab solution. In a non-everted rat gut ex vivo model, a single exposure to the CO2-containing foam improved macromolecule transepithelial flux across colonic tissue by over ten-fold. Foam efficacy for Fab was investigated in a range of colitis mouse models, from acute to chronic. This non-invasive formulation platform demonstrates potential to overcome existing limitations in delivering biologics to inflamed colonic tissue.

Regional citrate anticoagulation with continuous renal replacement therapy as a cause of hypercalcemia.

CLINICAL RELEVANCE: Awareness of the causes of hypercalcemia is essential for timely diagnosis of calcium disorders and optimal treatment. Citrate is commonly used as an anticoagulant during continuous renal replacement therapy (CRRT). Accumulation of citrate in the systemic circulation during CRRT may induce several metabolic disturbances, including total hypercalcemia and ionized hypocalcemia. The aim of the present study is to increase awareness of citrate accumulation and toxicity as a cause of hypercalcemia by relating three cases and reviewing the pathophysiology and clinical implications. OBSERVATIONS: We utilized electronic health records to examine the clinical cases and outlined key studies to review the consequences of citrate toxicity and general approaches to management. CONCLUSIONS: Citrate toxicity is associated with high mortality. A safe threshold for tolerating hypercalcemia during citrate anticoagulation is not clearly defined, and whether citrate toxicity independently increases mortality has not been resolved. Greater attention to citrate toxicity as a cause of hypercalcemia may lead to earlier detection, help to optimize the management of systemic calcium levels, and foster interest in future clinical studies.

The CATERPILLAR study: an assessor-blinded randomized controlled trial comparing a taurolidine-citrate-heparin lock solution to a heparin-only lock solution for the prevention of central-line-associated bloodstream infections in paediatric oncology patients.

BACKGROUND: Taurolidine-citrate(-heparin) lock solutions (TCHL) are suggested as a promising and safe method for the prevention of central-line-associated bloodstream infections (CLABSI). AIM: To investigate the efficacy of TCHL for the prevention of CLABSI in paediatric oncology patients. METHODS: An assessor-blinded randomized controlled trial at the Princess Máxima Centre for paediatric oncology, the Netherlands, was performed from 2020 to 2023. Paediatric oncology patients receiving a tunnelled central venous access device (CVAD) were eligible. A total of 462 patients were required to compare the TCHL to the heparin-only lock (HL). Patients were followed-up for the first 90 days after CVAD insertion. The primary outcome was the incidence of the first CLABSI from CVAD insertion until the end of follow-up. Intention-to-treat and per-protocol analyses were performed. FINDINGS: In total, 232 were randomized in the HL and 231 in the TCHL group. A total of 47 CLABSIs were observed. The intention-to-treat analysis showed that a CLABSI was observed in 26 (11.2%) of the HL group patients versus 21 (9.1%) of the TCHL group patients; incidence rate ratio (IRR) of 0.81 (95% confidence interval (CI): 0.46-1.45) in favour of the TCHL group. The per-protocol analysis showed that a CLABSI was observed in 10 (7.9%) of the HL group patients versus 6 (4.8%) of the TCHL group patients; IRR of 0.59 (95% CI: 0.21-1.62) in favour of the TCHL group. Adverse events were more common in the TCHL group but rarely reported. CONCLUSION: No difference was detected between the TCHL and HL in the incidence of CLABSI in paediatric oncology patients.

A randomized prospective study comparing the effect of low-volume bowel preparations for colonoscopy preparation in China.

AIM: To evaluate the effect of sodium picosulfate/magnesium citrate (SPMC) and 3 L split-dose polyethylene glycol (PEG) with or without dimethicone on bowel preparation before colonoscopy. METHODS: In this multicenter, prospective, randomized, controlled study conducted from April 2021 to December 2021, consecutive adult patients scheduled for colonoscopy were prospectively randomized into four groups: SPMC, SPMC plus dimethicone, 3 L PEG, and 3 L PEG plus dimethicone. Primary endpoint was colon cleansing based on Boston Bowel Preparation Scale (BBPS). Secondary endpoints were bubble score, time to cecal intubation, adenoma detection rate (ADR), patient safety and compliance, and adverse events. RESULTS: We enrolled 223 and 291 patients in SPMC and 3 L PEG group, respectively. The proportion with acceptable bowel cleansing, total BBPS score and cecal intubation time were similar in all four subgroups (p > 0.05). Patient-reported acceptability and tolerability was significantly greater in SPMC than 3 L PEG group (p < 0.001); adverse events were significantly lower in SPMC than latter group (p < 0.001). ADR in both groups was greater than 30%. CONCLUSION: SPMC had significantly higher acceptability and tolerability than 3 L PEG, however, was similar in terms of bowel-cleansing effect and cecal intubation time and hence can be used before colonoscopy preparation.

A safe and effective protocol for postdilution hemofiltration with regional citrate anticoagulation.

BACKGROUND: Regional citrate anticoagulation (RCA) is recommended during continuous renal replacement therapy. Compared to systemic anticoagulation, RCA provides a longer filter lifespan with the risk of metabolic alkalosis and impaired calcium homeostasis. Surprisingly, most RCA protocols are designed for continuous veno-venous hemodialysis or hemodiafiltration. Effective protocols for continuous veno-venous hemofiltration (CVVH) are rare, although CVVH is a standard treatment for high-molecular-weight clearance. Therefore, we evaluated a new RCA protocol for postdilution CVVH. METHODS: This is a monocentric prospective interventional study to evaluate a new RCA protocol for postdilution CVVH. We recruited surgical patients with stage III acute kidney injury who needed renal replacement therapy. We recorded dialysis and RCA data and hemodynamic and laboratory parameters during treatment sessions of 72 h. The primary endpoint was filter patency at 72 h. The major safety parameters were metabolic alkalosis and severe hypocalcemia at any time. RESULTS: We included 38 patients who underwent 66 treatment sessions. The mean filter lifespan was 66 ± 12 h, and 44 of 66 (66%) filters were patent at 72 h. After censoring for non-CVVH-related cessation of treatment, 83% of all filters were patent at 72 h. The delivered dialysis dose was 28 ± 5 ml/kgBW/h. The serum levels of creatinine, urea and beta2-microglobulin decreased significantly from day 0 to day 3. Metabolic alkalosis occurred in one patient. An iCa++ below 1.0 mmol/L occurred in four patients. Citrate accumulation did not occur. CONCLUSIONS: We describe a safe, effective, and easy-to-use RCA protocol for postdilution CVVH. This protocol provides a long and sustained filter lifespan without serious adverse effects. The risk of metabolic alkalosis and hypocalcemia is low. Using this protocol, a recommended dialysis dose can be safely administered with effective clearance of low- and middle-molecular-weight molecules. TRIAL REGISTRATION: The study was approved by the medical ethics committee of Heinrich-Heine University Duesseldorf (No. 2018-82KFogU). The trial was registered in the local study register of the university (No: 2018044660) on 07/04/2018 and was retrospectively registered at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT03969966) on 31/05/2019.

Citrate and low-dose heparin combined anticoagulation in pediatric continuous renal replacement therapy.

There remains no optimal anticoagulation protocol for continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in pediatric patients with elevated D-dimer levels. We aimed to assess the effects of different anticoagulation strategies on the risk of CRRT filter clotting in these patients. Pediatric patients undergoing CRRT were retrospectively grouped based on pre-CRRT D-dimer levels and anticoagulant: D-RCA group (normal D-dimer, RCA only, n = 22), D+ RCA group (elevated D-dimer, RCA only, n = 50), and D+ RCA+ systemic heparin anticoagulation (SHA) group (elevated D-dimer, RCA combined with SHA, n = 55). The risk of filter clotting and incidence of bleeding were compared among the groups. Among the groups, the D+ RCA+ SHA group had the longest filter lifespan; further, the incidence of bleeding was not increased by concurrent use of low-dose heparin for anticoagulation. Moreover, concurrent heparin anticoagulation was associated with a decreased risk of filter clotting. Contrastingly, high pre-CRRT hemoglobin and D-dimer levels and post-filter ionized calcium level > 0.4 mmol/L were associated with an increased risk of filter clotting. RCA combined with low-dose heparin anticoagulation could reduce the risk of filter clotting and prolong filter lifespan without increasing the risk of bleeding in patients with elevated D-dimer levels undergoing CRRT.

Early experience of using regional citrate anticoagulation for continuous renal replacement therapy in critically ill patients in a resource-limited setting.

AIM: Despite the superiority of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT), its application is limited in resource-limited settings. We aim to explore the cost and safety of RCA for CRRT in critically ill patients, compared to usual care. METHODS: This prospective observational study included patients requiring CRRT in a tertiary intensive care unit (ICU) from February 2022 to January 2023. They were classified to either the RCA or usual care groups based on the anticoagulation technique chosen by the treating physician, considering contraindications. The CRRT prescription follows the institutional protocol. All relevant data were obtained from the ICU CRRT-RCA charts and electronic medical records. A cost analysis was performed. RESULTS: A total of 54 patients (27 per group) were included, with no demographic differences. Sequential Organ Failure Assessment score and lactate levels were significantly higher in the usual care group. The number of filters used were comparable (p = .108). The median filter duration in the RCA group was numerically longer (35.00 [15.50-56.00] vs. 23.00 [17.00-29.00] h), but not statistically significant (p = .253). The duration of mechanical ventilation, vasopressor requirement, and mortality were similar, but the RCA group had a significantly longer ICU stay. The rate of adverse events was similar, with four severe metabolic alkalosis cases in the RCA group. The RCA group had higher total cost per patient per day (USD 611 vs. 408; p = .013). CONCLUSION: In this resource-limited setting, RCA for CRRT appeared safe and had clinically longer filter lifespan compared with usual care, albeit the increased cost.

Can regional anticoagulation with calcium-free dialysate be extended to maintenance hemodialysis?

BACKGROUND: Regional anticoagulation in hemodialysis avoids the use of heparin, which is responsible for both hemorrhagic and non-hemorrhagic complications. Typically, blood is decalcified by injecting citrate into the arterial line of the extracorporeal circuit. Calcium-free dialysate improves anticoagulation efficacy but requires injection of a calcium-containing solution into the venous line and strict monitoring of blood calcium levels. Recent improvements have made regional anticoagulation with calcium-free dialysate safer and easier. OBSERVATIONS: (1) Adjusting the calcium injection rate to ionic dialysance avoids the risk of dyscalcemia, thus making unnecessary the monitoring of blood calcium levels. This adjustment could be carried out automatically by the hemodialysis monitor. (2) As calcium-free dialysate reduces the amount of citrate required, this can be supplied by dialysate obtained from currently available concentrates containing citric acid. This avoids the need for citrate injection and the risk of citrate overload. (3) Calcium-free dialysate no longer needs the dialysate acidification required for avoiding calcium carbonate precipitation in bicarbonate-containing dialysate. CONCLUSIONS: Regional anticoagulation with calcium-free dialysate enables an acid- and heparin-free procedure that is more biocompatible and environmentally friendly than conventional bicarbonate hemodialysis. The availability of specific acid-free concentrates and adapted hemodialysis monitors is required to extend this procedure to maintenance hemodialysis.

Research note: A scald water surfactant combined with an organic acid carcass dip reduces microbial contaminants on broiler carcasses during processing.

Organic acids are applied to poultry carcasses during processing to reduce foodborne pathogens and spoilage microorganisms. Scald water surfactant agents employed to improve feather removal may enhance the efficacy of organic acids during processing. This study investigated the effects of concurrent application of a scald water surfactant and organic acid dip on microbial contamination of carcasses processed in a small-scale production model. Broilers were reared in litter floor pens to 47 d of age and slaughtered using standard practices. Carcasses were scalded in either control or surfactant scald water initially and dipped in either a 2% organic acid blend or water after feather removal to complete a 2 × 2 factorial arrangement with n = 15 carcasses per treatment group. The commercially available scald water additive was a slightly alkaline surfactant solution labelled as a feather removal aid. The organic acid dip consisting of lactic and citric acid was maintained at pH of 2.5. Approximately 10 g of neck skin was collected 1-min postdipping and placed in buffered peptone water with an added neutralizing agent, sodium thiosulfate. Serial dilutions were performed to determine general coliform (GC), E. coli (EC), and aerobic plate (APC) counts as CFU per gram of skin sample. A significant 0.61, 0.76, and 1.6 log reduction of GC, EC, and APC, respectively, was attributed to use of the organic acid carcass dip (P ≤ 0.01). There were no significant differences in carcass microbial reduction due to surfactant scald water alone. A 0.69, 0.73 (P ≤ 0.05), and 1.96 log reduction of GC, EC, and APC, respectively, was observed in surfactant-scalded, acid-dipped carcasses compared to water-scalded, water-dipped control groups. These data demonstrated that a surfactant scald water additive and an organic acid carcass dip can have beneficial effects of microbial reduction when employed simultaneously during broiler processing.

Safety and Feasibility of Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy With Calcium-Containing Solutions: A Randomized Controlled Trial.

BACKGROUND: Calcium-free (Ca-free) solutions are theoretically the most ideal for regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT). However, the majority of medical centers in China had to make a compromise of using commercially available calcium-containing (Ca-containing) solutions instead of Ca-free ones due to their scarcity. This study was designed to probe into the potential of Ca-containing solution as a secure and efficient substitution for Ca-free solutions. METHODS: In this prospective, randomized single-center trial, 99 patients scheduled for CRRT were randomly assigned in a 1:1:1 ratio to one of three treatment groups: continuous veno-venous hemodialysis Ca-free dialysate (CVVHD Ca-free) group, continuous veno-venous hemodiafiltration calcium-free dialysate (CVVHDF Ca-free) group, and continuous veno-venous hemodiafiltration Ca-containing dialysate (CVVHDF Ca-containing) group at cardiac intensive care unit (CICU). The primary endpoint was the incidence of metabolic complications. The secondary endpoints included premature termination of treatment, thrombus of filter, and bubble trap after the process. RESULTS: The incidence of citrate accumulation (18.2% vs. 12.1% vs. 21.2%) and metabolic alkalosis (12.1% vs. 0% vs. 9.1%) did not significantly differ among three groups (p > 0.05 for both). The incidence of premature termination was comparable among the groups (18.2% vs. 9.1% vs. 9.1%, p = 0.582). The thrombus level of the filter and bubble trap was similar in the three groups (p > 0.05 for all). CONCLUSIONS: In RCA-CRRT for CICU population, RCA-CVVHDF with Ca-containing solutions and traditional RCA with Ca-free solutions had a comparable safety and feasibility. TRIAL REGISTRATION: ChiCTR2100048238 in the Chinese Clinical Trial Registry.

Use of phytase and citric acid supplementation on growth performance and nutrient digestibility of Cirrhinus mrigala fingerlings fed on canola meal based diet / Uso de suplementação de fitase e ácido cítrico no desempenho do crescimento e digestibilidade de nutrientes de dedos Cirrhinus mrigala alimentados em dieta à base de refeição de canola

Fishmeal; being a limited and costly feed ingredient is continuously been substituted with locally available plant proteins. However, the occurrence of anti-nutritional factors in plant meal suppresses its potential to be fully replaced. Therefore, in this study we aimed to study the synergistic effects of dietary additives like citric acid and phytase enzyme supplementation on growth performance and nutrient digestibility of Cirrhinus mrigala fingerlings. Canola meal (CM) was used as a test ingredient to replace fishmeal (FM) as; 0%, 25%, 50% and 75%. These four diets were further supplemented by varying levels of phytase (0 and 750 FTU kg-1) and citric acid (0% and 2.5%) to formulate total sixteen test diets as T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, T12, T13, T14, T15 and T16. Each treatment contained three replicates; applied to fish groups having 15 fingerlings each; following 3×3 factorial arrangement. 1% of chromic oxide was added as an inert marker. Maximum weight gain% (288%) and the lowest value of FCR (1.07) were recorded when fish was fed on diet T12 as compared to fish fed control diet (T1). Similarly, optimum nutrient digestibility values such as crude protein (77%), crude fat (84%) and gross energy (70%) were noted on same level. It was concluded that 50% canola meal can optimally replace fishmeal when supplemented with phytase and citric acid at the levels of 750 FTU kg-¹ and 2.5%, respectively.

A farinha de peixe, por ser um ingrediente alimentar limitado e caro, é continuamente substituída por proteínas vegetais disponíveis localmente. No entanto, a ocorrência de fatores antinutricionais na farinha de plantas suprime seu potencial de ser totalmente substituída. Portanto, neste estudo objetivamos estudar os efeitos sinérgicos de aditivos dietéticos como ácido cítrico e suplementação com enzima fitase sobre o desempenho de crescimento e digestibilidade de nutrientes de alevinos de Cirrhinus mrigala. A farinha de canola (CM) foi usada como ingrediente de teste para substituir a farinha de peixe (FM) como: 0%, 25%, 50% e 75%. Essas quatro dietas foram suplementadas por níveis variados de fitase (0 e 750 FTU kg-1) e ácido cítrico (0% e 2,5%) para formular um total de 16 dietas de teste como T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, T12, T13, T14, T15 e T16. Cada tratamento continha três repetições; aplicado a grupos de peixes com 15 alevinos cada; seguindo o arranjo fatorial 3 × 3. 1% de óxido crômico foi adicionado como um marcador inerte. % de ganho de peso máximo (288%) e o valor mais baixo de FCR (1,07) foram registrados quando os peixes foram alimentados com dieta T12 em comparação com peixes alimentados com dieta controle (T1). Da mesma forma, valores ótimos de digestibilidade de nutrientes, como proteína bruta (77%), gordura bruta (84%) e energia bruta (70%) foram anotados no mesmo nível. Concluiu-se que 50% da farinha de canola pode substituir de forma ideal a farinha de peixe quando suplementada com fitase e ácido cítrico nos níveis de 750 FTU kg-¹ e 2,5%, respectivamente.

Regional Citrate Anticoagulation: A Tale of More Than Two Stories.

Calcium is a key clotting factor, and several inorganic molecules that bind to calcium have been found to reduce the clotting propensity of blood. Citrate, a calcium chelator, is used as inhibitor of the coagulation cascade in blood transfusion. Also, it is used as an anaticoagulant during dialysis to maintain patency of the extracorporeal circuit, known as regional citrate anticoagulation (RCA). The amount of citrate should be chosen such that ionized calcium concentrations in the extracorporeal circuit are reduced enough to minimize propagation of the coagulation cascade. The dialytic removal of the calcium-citrate complexes combined with reduced ionized calcium concentrations makes necessary calcium supplementation of the blood returning to the patient. This can be achieved in different ways. In classical RCA, citrate and calcium are infused in the afferent and efferent tubing, respectively, whereas the dialysate does not contain calcium. This setup has been shown to be highly efficacious with a very low clotting propensity. Strict monitoring of blood electrolytes is required. Alternatively, the use of a high-calcium dialysate leads to calcium loading, obviating the need for a separate calcium infusion pump. The main advantages are simplified delivery of RCA and less fluctuation of systemic calcium concentrations. Currently, citric acid is sometimes added to the acid concentrate as a replacement for acetic acid. Differences and similarities between RCA and citrate-containing dialysate are discussed. RCA is an excellent alternative to heparin for patients at high risk of bleeding.