Efficacy and safety of a novel 18 mmol/L sodium citrate hemofiltration solution in continuous renal replacement therapy for critically ill patients: a retrospective cohort study

Introduction

Continuous renal replacement therapy (CRRT) includes a range of extracorporeal blood purification modalities designed for the continuous and gradual elimination of fluids and solutes. It is routinely implemented in intensive care unit (ICU) for the management of patients who are critically ill with acute kidney injury (AKI), acute-on-chronic renal insufficiency, acute respiratory distress syndrome, acute heart failure, sepsis, and other life-threatening conditions. The selection of an appropriate anticoagulation strategy and replacement solution is essential, as effective and safe anticoagulation is necessary to maintain uninterrupted therapy. An optimal anticoagulation approach should be straightforward to administer and monitor, reduce the risk of adverse events, and support cost-effectiveness (1). Regional citrate anticoagulation (RCA) is currently recommended as the anticoagulant of choice for CRRT in international clinical guidelines. Existing recommendations favor RCA over heparin, except in cases where citrate is contraindicated (1-3). Critically ill patients often present with multiple organ dysfunction, particularly involving impaired liver function and acid-base regulation. When conventional high-concentration sodium citrate anticoagulation is used, these patients are more susceptible to complications such as metabolic alkalosis, hypernatremia, and citrate accumulation. The low-concentration sodium citrate hemodiafiltration replacement fluid (with a citrate concentration of 18 mmol/L) can significantly reduce sodium and alkali loads, thereby helping to maintain acid-base and electrolyte balance while lowering the risk of citrate accumulation. Additionally, the fast-paced and high-intensity nature of ICU work means that traditional regional citrate anticoagulation (tRCA) requires frequent replacement of infusion bags and the use of multiple infusion pumps, which not only increases the nursing workload but also raises the risk of operational errors. By integrating the anticoagulant with the replacement fluid, sodium citrate hemodiafiltration replacement fluid simplifies the CRRT procedure, reduces the number of infusion pumps required and the frequency of bag changes, thereby improving clinical efficiency and patient safety.

Although both international and domestic studies have reported the safety and efficacy of sodium citrate hemofiltration replacement solutions in CRRT, these studies relied on institutionally compounded formulations due to the prior unavailability of commercial preparations. A ready-to-use formulation that integrates citrate anticoagulant with a replacement solution has recently been commercialized in China and approved for insurance reimbursement for use in CRRT anticoagulation. However, its safety, efficacy, and clinical workflow efficiency in intensive care settings remain to be validated through large-scale, multicenter clinical trials, and such evidence is currently lacking. This study was designed to assess the safety, efficacy, and clinical convenience of sodium citrate hemofiltration replacement solution in CRRT among critically ill patients. Our study may also provide real-world evidence regarding the application of sodium citrate hemofiltration replacement fluid in the complex ICU environment, which will help inform the design and implementation of subsequent randomized controlled trials. We present this article in accordance with the STROBE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-1-1001/rc).

Methods

Study population

Critically ill patients with an indication for CRRT were enrolled from the ICU of Beijing Electric Power Hospital between July 1, 2025 and September 30, 2025. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethical Committee of Beijing Electric Power Hospital (No. 2025-KY-11-01-01), and all patients provided written informed consent.

Definition of critical illness

Critically ill patients were defined as individuals who, with or without pre-existing conditions, developed life-threatening condition or transient/sustained organ dysfunction requiring life-support interventions, such as mechanical ventilation or vasopressor therapy, and had a Sequential Organ Failure Assessment (SOFA) score ≥2 (4).

Inclusion criteria

Patients were included if (I) CRRT was administered; (II) RCA was used; and (III) age was greater than 18 years.

Exclusion criteria

Exclusion criteria were (I) presence of contraindications to citrate anticoagulation, such as severe hepatic dysfunction [defined as total bilirubin ≥10× upper limit of normal or international normalized ratio (INR) ≥1.5]; severe hypoxemia [partial pressure of arterial oxygen (PaO₂)/fraction of inspired oxygen (FiO₂) <100 mmHg] and/or tissue hypoperfusion (lactate >5 mmol/L or norepinephrine-equivalent dose >1 µg/kg/min); or known hypersensitivity to any component of the solution; (II) diagnosis of psychiatric illness or inability to cooperate with treatment; (III) pregnancy or lactation.

Study design

In this retrospective cohort study, the two groups consist of contemporaneous cases, patients were assigned to either the sodium citrate hemofiltration solution group or the traditional RCA group according to the anticoagulation method used. Treatment assignment was determined by the attending clinicians based on the patient’s clinical condition and product availability. This study was approved by the Ethics Committee for Clinical Trials of Beijing Electric Power Hospital (No. 2025-KY-11-01-01).

CRRT protocol

Vascular access was obtained using an 11.5-Fr double-lumen hemodialysis catheter (Guangdong Baihe Medical Technology Co., Ltd., Foshan, China), which was inserted into either the femoral or internal jugular vein. CRRT was performed with the MultiFiltrate system (Fresenius Medical Care, Bad Homburg, Germany), Tianyihao extracorporeal circuit tubing (Ningbo Tianyi Medical Appliance Co., Ltd., Ningbo, China), and the Ultraflux AV600S hemofilter (Fresenius Medical Care). All treatments were administered using continuous veno-venous hemofiltration (CVVH) with RCA in a pre-dilution mode at 1,500 mL/h, combined with a post-dilution mode at 1,000 mL/h, and a blood flow rate of 150 mL/min.

Sodium citrate hemofiltration solution group: in the pre-dilution phase, a sodium citrate hemofiltration solution (Shanghai Changzheng Fumin Jinshan Pharmaceutical Co., Ltd., Shanghai, China) containing 18 mmol/L citrate, 140 mmol/L sodium, and 86 mmol/L chloride was administered at 10 times the blood flow rate (1,500 mL/h). In the post-dilution phase, a hemofiltration replacement solution (Shijiazhuang No. 4 Pharmaceutical Co., Ltd., Shijiazhuang, China) containing 10.6 mmol/L anhydrous glucose, 118 mmol/L total chloride, 0.797 mmol/L magnesium, 1.6 mmol/L calcium, and 113 mmol/L sodium was infused at a rate of 1,000 mL/h (Figure 1).

Figure 1 Schematic diagram of the sodium citrate hemofiltration replacement solution group. CVVH, continuous venovenous hemofiltration.

Post-filter ionized calcium levels were monitored to assess anticoagulation efficacy. When post-filter ionized calcium concentrations fell below 0.2 mmol/L or exceeded 0.4 mmol/L, the citrate solution rate was adjusted in increments of 1× blood flow rate (150 mL/h).

Traditional RCA group: An anticoagulant citrate solution (Shanghai Transfusion Technology Co., Ltd., Shanghai, China) containing 136 mmol/L citrate and 408 mmol/L sodium was administered via the arterial port using an infusion pump. The initial infusion rate was calculated as [blood flow (mL/min) + pre-dilution rate (mL/h) ÷ 60] × 1.5, resulting in an approximate rate of 260 mL/h. The replacement solution used in both the pre-dilution and post-dilution phases was identical in composition to the post-dilution solution described above, with infusion rates of 1,500 mL/h for pre-dilution and 1,000 mL/h for post-dilution (Figure 2). Post-filter ionized calcium concentrations were monitored to assess anticoagulation status, and dose adjustments of 10–20 mL/h were made when levels deviated from the target range of 0.2–0.4 mmol/L.

Figure 2 Schematic diagram of the tRCA group. CVVH, continuous venovenous hemofiltration; tRCA, traditional regional citrate anticoagulation.

The composition of the sodium citrate hemofiltration solution, anticoagulant citrate solution, and hemofiltration replacement solution is summarized in Table 1. In both groups, 5% sodium bicarbonate was administered intravenously via infusion pump, initiated at a rate of 30 mL/h and adjusted to maintain serum bicarbonate concentrations within the range of 22–26 mmol/L. Calcium gluconate 10% was infused through the venous line using a syringe pump at 10% of the blood flow rate (15 mL/h), with dose adjustments made in 1–2 mL/h increments based on serum ionized calcium levels. When serum ionized calcium levels decreased below 0.9 mmol/L, a 60 mL bolus of 10% calcium gluconate was administered intravenously, and the continuous infusion rate was increased by 2 mL/h to maintain serum ionized calcium between 1.0 and 1.2 mmol/L (5).

Data collection

Baseline characteristics

Baseline data included sex, age, primary diagnosis, and comorbidities (hypertension, diabetes mellitus, and chronic kidney disease). Additional variables recorded were the use of mechanical ventilation and vasopressors, SOFA score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, as well as laboratory parameters including serum creatinine, blood urea nitrogen, total bilirubin, INR, and platelet count.

Intra-treatment monitoring

Post-filter ionized calcium, serum ionized calcium, bicarbonate, potassium, sodium, pH, lactate, total calcium, and magnesium levels were measured at 0, 2, 6, 12, 24, 36, and 48 hours. Magnesium supplementation was administered when serum magnesium levels decreased below 0.66 mmol/L, and both the administered dose and corresponding clinical response were documented.

CRRT parameters

CRRT-related parameters included treatment duration, incidence of filter loss due to clotting, hourly increase in transmembrane pressure, reason for treatment termination, frequency of solution bag changes per hour, and the number of syringes and infusion pumps required.

Complications

Complications monitored during treatment included citrate accumulation, metabolic alkalosis, hypernatremia, and hypomagnesemia. Citrate accumulation was defined as a ratio of total calcium to ionized calcium >2.5. Metabolic alkalosis was defined as arterial blood pH >7.45 and serum HCO₃⁻ >27 mmol/L. Hypernatremia was defined as an elevated serum sodium level >145 mmol/L induced by CRRT, which was not present before CRRT initiation. Hypomagnesemia was defined as serum magnesium <0.7 mmol/L.

Statistical analysis

Data were analyzed using SPSS version 22.0. The Kolmogorov-Smirnov test was used to assess the normality of the distribution. Continuous variables with normal distribution were presented as mean ± standard deviation and compared using the independent-samples t-test. Non-normally distributed continuous variables were expressed as median [interquartile range (IQR)] and compared using the Wilcoxon rank-sum test. Categorical variables were presented as number (percentage) and compared using the χ² test. For the primary outcome (filter lifespan), univariate Cox regression analysis was first performed to evaluate the association between various potential confounding factors and filter survival time. Variables with P<0.10 in the univariate analysis, along with the primary exposure variable (group), were included in a multivariable Cox proportional hazards model to adjust for confounding. The results were presented as hazard ratios (HR) with their 95% confidence intervals (CI). A P value of <0.05 was considered statistically significant.

Results

Baseline characteristics

A total of 157 CRRT sessions were performed in the ICU of Beijing Electric Power Hospital between July 1 and September 30, 2025. After excluding 48 sessions that used systemic anticoagulation and 4 sessions that received anticoagulation-free CRRT due to liver failure, 105 sessions were included in the final analysis, comprising 53 sessions in the sodium citrate hemofiltration solution group and 52 in the tRCA group. Patient age ranged from 28 to 96 years, with a median age of 74 (IQR, 52–83) years. Primary diagnoses included AKI, sepsis, post-cardiac arrest, acute heart failure, and acute cerebrovascular disease. No statistically significant differences were observed between the two groups in terms of sex distribution, comorbidities (hypertension, diabetes mellitus, and chronic kidney disease), or indicators of disease severity, including SOFA score, APACHE II score, mechanical ventilation requirements, and vasopressor use. Laboratory parameters reflecting coagulation status, hepatic function, and renal function were comparable between groups. Femoral venous access was used in 36 patients (67.9%) in the citrate replacement solution group and 34 patients (65.4%) in the traditional RCA group (P=0.79). Concomitant systemic anticoagulation was administered to 7 patients (13.2%) in the citrate replacement solution group and 9 patients (17.3%) in the tRCA group due to hypercoagulable states (P=0.56). Detailed baseline characteristics are presented in Table 2.

Anticoagulation efficacy

The duration of CRRT was significantly longer in the sodium citrate hemofiltration solution group compared to the tRCA group (50.91±13.07 vs. 45.19±10.83 hours, P=0.02). Comparisons of CRRT-related parameters are presented in Table 3. Univariate Cox regression analysis identified CRRT anticoagulation methods, sex, age, mechanical ventilation status, and APACHE II score as factors associated with filter survival. These variables were subsequently entered into a multivariable Cox regression model to adjust for potential confounding. After adjustment, the use of sodium citrate hemofiltration solution remained independently associated with significantly prolonged filter survival compared with tRCA (adjusted HR =0.615, 95% CI: 0.404–0.935, P=0.02).

Mean post-filter ionized calcium concentrations remained within the target range at all measured time points in both groups. Relevant results are presented in Table 4. At 48 hours, the post-filter ionized calcium concentration in the sodium citrate hemofiltration replacement fluid group was significantly lower than that in the tRCA group (0.28±0.05 vs. 0.32±0.06 mmol/L, P=0.02). No significant differences were observed between the two groups at other time points. Calcium gluconate 10% supplementation requirements were lower in the citrate replacement solution group compared to the tRCA group [15 (IQR, 14–16) vs. 16 (IQR, 15–17) mL/h, P=0.002]. Although the rate of increase in transmembrane pressure was lower in the citrate replacement solution group [0.64 (IQR, 0.35–1.27) vs. 1.07 (IQR, 0.05–1.38) mmHg/h], this difference was not statistically significant (P=0.608). Circuit failure due to clotting within 24 hours occurred in two patients (3.8%) in the tRCA group, while no such events were reported in the citrate replacement solution group (P=0.15). This may reflect differences in anticoagulation stability and circuit performance between the two protocols. Comparisons of CRRT-related parameters are presented in Table 3.

Complications

Significant differences in complication rates were observed between the two groups. Citrate accumulation was not reported in the citrate replacement solution group (0%) but was observed in 7.7% (4 cases) of the tRCA group (P=0.04). Metabolic alkalosis occurred in 3.8% (2 cases) of the citrate replacement solution group, compared with 17.3% (9 cases) in the tRCA group (P=0.02).

No cases of hypernatremia were reported in either group. However, hypomagnesemia was more frequently observed in the citrate replacement solution group [9.4% (5 cases) vs. 0%, P=0.02], a finding consistent with the absence of magnesium in the formulation of the sodium citrate hemofiltration solution. Relevant results are presented in Table 5.

Clinical workflow efficiency

Medical resource utilization differed significantly between the two groups. Fewer syringes and infusion pumps were required in the citrate replacement solution group compared to the tRCA group [2 (IQR, 2–2) vs. 3 (IQR, 3–3) devices, P<0.001]. Nursing workload, as assessed by the hourly frequency of solution bag exchanges, was significantly lower in the citrate replacement solution group [0.57 (IQR, 0.51–0.59) vs. 1.17 (IQR, 1.15–1.19) changes/hour, P<0.001, Figure 3].

Figure 3 Comparison of syringe and infusion pump requirements and solution bag-exchange frequency. tRCA, traditional regional citrate anticoagulation.

Discussion

CRRT serves as a vital organ support intervention for critically ill patients, with effective anticoagulation being essential to ensure uninterrupted and successful treatment. A substantial proportion of individuals admitted to ICUs present with conditions such as severe infections, stress-related mucosal bleeding, thrombocytopenia, coagulopathy, or active hemorrhage, all of which constitute contraindications to systemic anticoagulation. In the absence of anticoagulation, CRRT is frequently associated with clot formation within the filter and venous drip chamber, thereby hindering the achievement of therapeutic goals and contributing to coagulation factor consumption and blood loss. RCA has been identified as an effective alternative in such clinical contexts. Multiple studies have demonstrated that RCA is associated with a reduction in bleeding risk and incidence of thrombocytopenia, while extending filter and circuit lifespan (6-8). Furthermore, several studies have indicated that survival outcomes and renal recovery rates with RCA are comparable to those observed with heparin anticoagulation (9,10). Considering this evidence, international guidelines recommend RCA as the preferred anticoagulation strategy for CRRT (1-3). RCA is particularly suitable for patients without contraindications to citrate, especially those at elevated or potential risk of bleeding.

Traditional RCA involves the continuous infusion of 4% sodium citrate solution administered pre-filter, accompanied by calcium chloride or calcium gluconate infusion at the venous return line to offset citrate binding, in combination with a hemofiltration replacement solution. Citrate derived from the 4% sodium citrate solution is metabolized to supraphysiological concentrations of bicarbonate. Furthermore, the sodium content of this anticoagulant reaches 408 mmol/L, which is significantly higher than the physiological concentration, contributing to an elevated risk of acid-base imbalance and electrolyte disturbances. The currently used calcium-containing hemodiafiltration basal solution increases the required dosage of sodium citrate, consequently raising the amount of calcium citrate entering the body. Within the mitochondria of organs such as the liver, muscles, and kidneys, calcium citrate is broken down into bicarbonate ions (HCO₃⁻) and calcium ions (Ca²⁺) via the tricarboxylic acid cycle. However, critically ill patients often present with concurrent conditions such as hypoxemia, septic shock, and liver dysfunction, which impede the metabolism of calcium citrate. This leads to an increased risk of citrate accumulation and unstable anticoagulation efficacy. Tsujimoto et al. assessed a composite endpoint comprising metabolic alkalosis, metabolic acidosis, and other metabolic derangements, and reported a higher incidence of metabolic disturbances with RCA compared to systemic heparin therapy (9). During RCA, inadequate calcium supplementation or excessive systemic circulation of citrate leading to binding of serum calcium may result in hypocalcemia. In a systematic review, Liu et al. reported that RCA significantly increased the risk of hypocalcemia in comparison with heparin anticoagulation (11). In addition, the procedure necessitates the use of separate infusion pumps and frequent solution bag changes by nursing staff, contributing to increased workflow complexity and placing a greater burden on clinical personnel. Citrate accumulation remains a clinical concern, particularly among critically ill patients in the ICU setting.

Although the overall incidence is low, given that most calcium-citrate complexes are eliminated via the extracorporeal circuit and residual citrate is metabolized to bicarbonate, an increased risk is present in individuals with acute hepatic injury, hypoxemia, or peripheral hypoperfusion associated with multiorgan failure. The reported incidence of citrate accumulation in individuals with hepatic failure is approximately 3% (12); however, a standardized threshold of hepatic dysfunction that predisposes to citrate accumulation has not been established. Despite its low frequency, citrate accumulation requires close monitoring due to the potential for severe consequences if recognition is delayed or management is inadequate. The citrate-containing hemodiafiltration replacement fluid is calcium-free, resulting in a relatively reduced dose of sodium citrate entering the body. This helps alleviate the patient’s base load and lowers the risk of citrate toxicity.

Advancements in technology and clinical understanding have facilitated the international adoption of a novel low-concentration citrate replacement solution in the practice of CRRT. The term “low-concentration” refers to its 0.5% sodium citrate content, corresponding to 18 mmol/L citrate, which is substantially lower than the 136 mmol/L citrate content in traditional 4% sodium citrate anticoagulant formulations. This solution contains 140 mmol/L sodium, 86 mmol/L chloride, and 18 mmol/L citrate. The sodium concentration in the sodium citrate anticoagulant is 408 mmol/L, which is significantly higher than the physiological level. The introduction of citrate-containing hemodiafiltration replacement fluid is expected to reduce the patient’s sodium load. In 2006, the successful implementation of low-concentration (0.5%) RCA was first reported by Tolwani et al., demonstrating effective metabolic control and prolonged filter survival (13).

A single-center retrospective cohort study conducted in Canada included 53 critically ill patients undergoing a total of 80 CRRT sessions, comparing low-concentration RCA (0.5% citrate), high-concentration RCA (4% citrate), and systemic heparin anticoagulation, all delivered via continuous veno-venous hemodiafiltration (CVVHDF) (14). When compared to traditional 4% RCA, the use of the low-concentration citrate solution significantly reduced the proportion of treatment time during which ionized calcium levels fell outside the target range (6.8% vs. 23%, P=0.03) and decreased the incidence of hypocalcemia (16% vs. 72%, P<0.001). In addition, daily calcium monitoring requirements were significantly reduced (P<0.05). Filter clotting occurred in 3.8% of sessions using the citrate solution, compared with 16.9% for high-concentration RCA and 28.3% for heparin anticoagulation, indicating improved filter survival. These findings suggested that the low-concentration citrate solution provided more stable regional anticoagulation and significantly enhanced calcium management. Filter lifespan was extended to 79.8 hours with the citrate solution, compared to 62.0±2.6 hours with traditional RCA and 60.0±4.6 hours with heparin (14). Furthermore, the incidence of metabolic alkalosis (P<0.001) and hypernatremia (P=0.003) was significantly lower with the low-concentration citrate solution than with high-concentration RCA. Although risks of hypocalcemia and citrate accumulation were reduced, the magnesium-free formulation of the solution was associated with an increased risk of hypomagnesemia. At the time of the study, no commercial preparation of the low-concentration citrate solution was available; instead, the solution was prepared by diluting commercially available 4% sodium citrate anticoagulant.

A study conducted in Hong Kong included 35 patients who underwent 45 CRRT sessions using CVVH (15). In the pre-dilution phase, a low-concentration citrate solution (Prismocitrate 18/0, Baxter Gambro, USA; 18 mmol/L citrate) was used, while the post-dilution phase employed a replacement solution (Phoxilium, USA). The median circuit lifespan was 44 hours, with an interquartile range of 29–55 hours. The incidences of metabolic acidemia, hypophosphatemia, and hypomagnesemia were 8.3%, 3.5%, and 40.2%, respectively. No cases of hypokalemia or citrate accumulation were reported. The findings indicated that the low-concentration citrate solution provided effective anticoagulation while maintaining a more stable electrolyte and acid-base balance. However, the magnesium-free composition of Prismocitrate 18/0 was associated with an increased risk of hypomagnesemia. A domestic retrospective study compared a self-prepared, citrate-containing, calcium-free replacement solution (11.3 mmol/L citrate) with a traditional sodium citrate anticoagulant during CRRT using the CVVH mode (16). The filter lifespan was significantly prolonged with the citrate-containing solution (30.0±10.93 vs. 24.3±8.19 hours, P=0.04). However, the preparation of in-house solutions necessitates strict aseptic technique and rigorous quality control, thereby increasing the risk of preparation errors, nosocomial infections, and clinical workload. The 2017 Acute Disease Quality Initiative (ADQI) guidelines cautioned that self-preparation is associated with high risk, requires oversight by a pharmacist, and poses substantial challenges for standardized implementation and large-scale clinical adoption (17).

The sodium citrate hemofiltration solution is currently the only citrate anticoagulant with regulatory approval for use in CRRT and the only CRRT replacement solution approved for use across all age groups, including pediatric patients. In a comparative study, Soltysiak et al. assessed citrate solution versus heparin anticoagulation in a pediatric population, reporting a significantly longer filter lifespan with RCA (58.04 ± 51.18 vs. 37.64 ± 32.51 hours, P<0.05) and a markedly lower incidence of filter clotting (11.63% vs. 34.15%) (18). No significant differences were observed between groups in the incidence of metabolic acidosis or alkalosis. Cappoli et al. assessed citrate solution anticoagulation in critically ill pediatric patients, infants, and neonates, including those with hepatic failure (19). For pediatric patients with hepatic failure, an initial citrate dose of 2 mmol/L was administered using the CVVHDF mode. The mean filter lifespan reached 54.5±18.2 hours, with 42.5% of filters operating beyond 70 hours. Ionized calcium concentrations were maintained at 1.15±0.13 mmol/L systemically and 0.38±0.07 mmol/L post-filter. Transient citrate accumulation occurred in six children, all of whom resolved spontaneously without the need for intervention. CRRT is predominantly being used beyond renal support, emerging as an important therapeutic modality in the management of multiorgan failure among critically ill patients (20).

Research on hemofiltration replacement solutions remains limited, consisting primarily of single-center studies with small sample sizes that utilized institution-prepared citrate formulations. A commercially available sodium citrate hemofiltration solution has recently been introduced to the Chinese market with approved indications for anticoagulation in CRRT; however, domestic clinical data remain scarce. In this study, the sodium citrate hemofiltration solution was compared with traditional RCA. CRRT duration was significantly prolonged in the group receiving the citrate replacement solution. Multivariable Cox regression analysis was performed to adjust for potential confounders, including sex, age, mechanical ventilation status, and APACHE II score. After adjustment, the use of sodium citrate hemofiltration solution remained independently associated with significantly longer filter survival compared with tRCA (adjusted HR =0.615, 95% CI: 0.404–0.935, P=0.02). Mean post-filter ionized calcium concentrations remained within the target range at all measured time points in both groups, indicating effective anticoagulation. In terms of safety, lower incidences of citrate accumulation and metabolic alkalosis were observed with the citrate replacement solution. However, due to the absence of magnesium in the formulation, an increased incidence of hypomagnesemia was noted. The citrate replacement solution eliminates the need for a separate anticoagulant infusion, thereby reducing the number of infusion pumps required. Furthermore, the combined anticoagulant-replacement formulation significantly decreases the frequency of solution bag changes, resulting in a simplified clinical workflow. With the product approved for insurance reimbursement for CRRT, out-of-pocket treatment costs per hour are also reduced. A separate study also demonstrated the superior cost-effectiveness of the citrate replacement solution in adult CRRT applications (21).

There are several limitations in this study. A total of 105 CRRT cases were included, representing a modest sample size given the recent clinical introduction of the sodium citrate hemofiltration solution. Future investigations should incorporate larger cohorts to improve statistical power and reliability. The magnesium-free formulation of the citrate replacement solution was associated with an increased incidence of hypomagnesemia. Critically ill patients are inherently at high risk for arrhythmias and electrolyte disturbances. The use of magnesium-free citrate-containing hemodiafiltration replacement fluid may further exacerbate the risk of hypomagnesemia, potentially trigger malignant arrhythmias and increase the incidence of ICU-acquired weakness. Therefore, when using citrate-containing hemodiafiltration replacement fluid, routine monitoring of blood magnesium levels and timely magnesium supplementation are recommended. Future research could assess the effects of adding magnesium sulfate to the solution or propose modifications to the commercial formulation, specifically, the inclusion of appropriate magnesium content to mitigate this risk. Additionally, bicarbonate-based replacement solutions are now commercially available. The combined use of a pre-dilution citrate solution and post-dilution bicarbonate solution may further simplify clinical workflows. However, many critically ill patients in the ICU present with severe metabolic acidosis or alkalosis, and fixed-composition bicarbonate solutions may not allow for adequate titration based on individual patient needs. Validation through large-scale, multicenter clinical trials remains necessary.

This study is a single-center retrospective cohort study rather than a randomized controlled trial, representing a reasonable choice based on both the characteristics of the study population and the developmental stage of the new formulation. The study subjects are critically ill ICU patients with severe conditions and significant individual variability, requiring personalized CRRT protocols. Implementing strict randomization and standardized interventions as required by an RCT would not only be clinically challenging but could also compromise patient safety and violate ethical principles. Furthermore, the citrate-containing hemodiafiltration replacement fluid is a newly launched commercial product in China with no prior clinical data available. A retrospective cohort study is essential to first clarify its clinical differences compared to traditional protocols, thereby laying the groundwork for future research. Real-world evidence is highly valuable in evaluating new commercial formulations. By utilizing actual clinical data, this study has elucidated the anticoagulation efficacy, safety advantages, and operational convenience of this new formulation, while also identifying its association with a higher incidence of hypomagnesemia. These findings fill a gap in the domestic clinical application of this formulation and provide an optimized research framework for subsequent multicenter, large-sample RCTs.

Conclusions

In conclusion, the sodium citrate hemofiltration solution provides effective anticoagulation while concurrently functioning as a replacement fluid during CRRT. In terms of anticoagulation efficacy, it demonstrated superiority over traditional RCA, with longer CRRT duration, fewer metabolic complications, and reduced procedural complexity. As a replacement fluid, its near-physiologic electrolyte composition was associated with a lower risk of electrolyte disturbances and acid-base imbalance. Therefore, the sodium citrate hemofiltration solution appears to be a safe and effective option for CRRT anticoagulation in critically ill ICU patients, with promising potential for clinical implementation.

Acknowledgments

We would like to express our sincere gratitude to all staff involved in this study for their hard work and dedication.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-1-1001/rc

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-1-1001/dss

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-1-1001/prf

Funding: This study was supported by Scientific Research Project of Fengtai District Health and Wellness System in 2025 (No. 2025-046) and College-level Research Project of 2026 (No. Y2026-37).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-1-1001/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethical Committee of Beijing Electric Power Hospital (No. 2025-KY-11-01-01), and all patients provided written informed consent.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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