CITRATE ACCUMULATION IN PATIENTS USING REGIONAL ISOTONIC CITRATE ANTICOAGULATION DURING CONTINUOUS KIDNEY REPLACEMENT THERAPY

Regional citrate anticoagulation (RCA) is effective for anticoagulation during continuous kidney replacement therapy (CKRT). Citrate accumulation is the most concerning complication of RCA and can result in metabolic derangements including severe hypocalcemia if left undetected. While citrate accumulation is generally rare in literature, higher rates have been reported in Asian populations. This study aimed to determine the incidence rate and identify risk factors for citrate accumulation among patients undergoing CKRT with RCA. 

This was a retrospective, single-center study which included consecutive patients undergoing CKRT using RCA from 01/08/2022 to 15/05/2025 for at least 6 hours. All patients underwent continuous veno-venous hemodiafiltration. Regiocit (Vantive, USA), a form of isotonic citrate which contains citrate 18 mmol/L was used as the replacement fluid, together with Biphozyl (Vantive, USA), a non-calcium containing dialysate.  Citrate dose was 2.5 mmol/L and initial blood flow was 150 mL/min, with initial total effluent dose 30 mL/kg/hour. Citrate accumulation was defined as total-to-ionized calcium ratio of ≥ 2.5. The primary outcome was incidence of citrate accumulation and risk factors for the development of citrate accumulation. Baseline demographics and dialysis characteristics were collected. Univariate and multivariate analysis were used to determine the risk factors of citrate accumulation. Ethics approval was obtained.

659 patients had CKRT ordered in the study period, with 74 patients who used 120 filters comprising our analytic cohort. The median Regiocit dose was 1250 mL/h, median dialysate dose was 700 mL/hour (Interquartile range [IQR] 650). Citrate accumulation occurred in 23 patients (31.1%), with similar baseline characteristics between accumulation and non-accumulation groups. Univariate analysis identified weight, age, gender, peripheral vascular disease, dialysate dose, effluent dose, baseline bicarbonate, and base excess as associated with citrate accumulation. Lactic acidosis and liver impairment were not associated with citrate accumulation. Logistic regression showed higher weight to be protective for citrate accumulation (odds ratio 0.922, p=0.005, confidence interval 0.863-0.971). Sub-analysis according to weight categories showed stepwise reduced rates of citrate accumulation with increasing weight. The median time to citrate accumulation was 12 hours. Citrate accumulation did not affect in-hospital morbidity and mortality.

Our study identified a high incidence of citrate accumulation despite a low citrate dose and few patients with liver impairment. Weight was the only significant risk factor associated with citrate accumulation. As our current protocol uses an initial replacement fluid rate of 1250 mL/hour, dialysate doses are low in patients with low body weight, thus leading to a lower calcium-citrate extraction ratio. Our findings are similar to what has been observed in other Asian studies which may suggest the influence of geographic, demographic or protocol related factors for this. The results of this study will drive protocol modifications – options include reduction of the blood flow hence citrate delivery and/or increasing the dialysate component. Further prospective studies to evaluate the impact of these changes on rates of citrate accumulation are needed.