Supplementary Material for: Development and validation of a risk prediction model for citrate accumulation in patients undergoing continuous renal replacement therapy with regional citrate anticoagulation

Introduction: Regional citrate anticoagulation (RCA) is now recommended as the first choice of anticoagulation for continuous renal replacement therapy (CRRT). However, impaired citrate metabolism can lead to citrate accumulation (CA), resulting in severe metabolic acidosis and hypocalcemia, which poses a challenge for clinicians when making decision about the use of RCA.
Methods: In this retrospective cohort study performed in West China Hospital of Sichuan University, we evaluated patients who underwent RCA-based CRRT from 2021 to 2023. Participants were randomly allocated into training and validation groups at a 7:3 ratio. In the training group, significant risk factors for CA were determined by a binary logistic regression analysis and established a risk prediction model, the validation group validated and evaluated the model. A nomogram was constructed to visualize the prediction model, and calibration and receiver operating characteristic (ROC) curves were used to evaluate the prediction accuracy, and decision curve analysis (DCA) was used to evaluate the clinical effectiveness.
Results: Of the 1,259 patients with RCA-CRRT, 882 were randomly stratified into the training group and 377 into the validation group. CA was reported in 16.2% and 16.7%, respectively. We developed and validated a nomogram to predict the risk of CA, incorporating significant factors including male, age, body surface area (BSA), mean hourly citrate dosage, systolic blood pressure (SBP), lactate, total bilirubin (TBIL) and international normalized ratio (INR). The area under the ROC curve of the nomogram was 0.760 (95% CI, 0.737-0.765) and 0.752 (95% CI, 0.744-0.787) in both groups. The calibration curve further confirmed its effective discrimination and calibration abilities. DCA analysis emphasized its clinical utility when the CA probability threshold for intervention is between 11% and 76%.
Conclusion: We developed and validated a useful prediction model for CA in critically ill patients who underwent RCA-CRRT, assisting clinicians in identifying high-risk individuals.

引言：
局部枸橼酸抗凝（Regional citrate anticoagulation, RCA）目前被推荐作为连续性肾脏替代治疗（continuous renal replacement therapy, CRRT）的首选抗凝方案。然而，枸橼酸代谢受损可引发枸橼酸蓄积（citrate accumulation, CA），进而导致严重代谢性酸中毒与低钙血症，这为临床医师决策是否采用RCA带来了挑战。

方法：
本研究为一项回顾性队列研究，于四川大学华西医院开展，纳入2021年至2023年期间接受基于RCA的CRRT治疗的患者。研究对象按7:3的比例随机分为训练集与验证集。在训练集中，通过二元logistic回归分析确定枸橼酸蓄积的显著危险因素，并构建风险预测模型；验证集则用于验证与评估该模型。本研究构建列线图（nomogram）以可视化预测模型，并采用校准曲线与受试者工作特征（Receiver Operating Characteristic, ROC）曲线评估预测准确度，同时使用决策曲线分析（Decision Curve Analysis, DCA）评估其临床有效性。

结果：
在1259例接受RCA-CRRT治疗的患者中，882例被随机分层至训练集，377例被分至验证集。两组的枸橼酸蓄积发生率分别为16.2%与16.7%。本研究构建并验证了一款可预测枸橼酸蓄积风险的列线图（nomogram），纳入的显著危险因素包括男性、年龄、体表面积（Body Surface Area, BSA）、平均每小时枸橼酸给药剂量、收缩压（Systolic Blood Pressure, SBP）、乳酸、总胆红素（Total Bilirubin, TBIL）以及国际标准化比值（International Normalized Ratio, INR）。该列线图的ROC曲线下面积在训练集与验证集中分别为0.760（95%CI：0.737~0.765）与0.752（95%CI：0.744~0.787）。校准曲线进一步证实了其良好的区分度与校准能力。决策曲线分析显示，当干预的枸橼酸蓄积概率阈值介于11%至76%之间时，该模型具有临床应用价值。

结论：
本研究构建并验证了一款可用于预测接受RCA-CRRT治疗的重症患者发生枸橼酸蓄积风险的实用模型，可协助临床医师识别高危人群。