Incidence, severity, and predictors of citrate accumulation during continuous kidney replacement therapy in the critically ill

Critical Care volume 29, Article number: 468 (2025) Published: 03 November 2025

Background

Regional citrate anticoagulation (RCA) is the recommended anticoagulation strategy for continuous kidney replacement therapy (CKRT). However, the safety of RCA in patients with liver dysfunction and/or shock remains controversial due to the risk of citrate accumulation. This study assesses the associations of citrate accumulation with liver dysfunction, circulatory shock, and mortality, and investigates lactate and the vasoactive inotropic score (VIS) as early predictors.

Methods

This retrospective cohort study included critically ill patients requiring RCA-based CKRT between January 2018 and March 2022. Lactate, VIS and parameters of organ failure were investigated as predictors of citrate accumulation. An albumin-corrected total calcium to ionized calcium ratio ≥ 2.5 was used to define citrate accumulation. Regression models were employed to investigate the association of predictors with outcomes.

Results

Nine hundred eleven patients were included, citrate accumulation was observed in 159 individuals (17%). Factors related to liver dysfunction, but not circulatory shock, were attributed to citrate accumulation. After multivariable adjustment, citrate accumulation was not associated with mortality. Lactate measured before onset of CKRT showed an improved discriminative performance compared to the VIS. The odds of citrate accumulation increased by 2.34 (CI 1.94–2.85, p < 0.001) for each one-unit increase in lactate on the logarithmic scale (log mmol/L). The probability for citrate accumulation ranged from 3.3 (CI 2.06–5.28) % at lactate levels of 0.3 mmol/L to 59.8 (CI 48.88–69.78) % at levels of 25 mmol/L.

Conclusion

Lactate is a reliable predictor for assessing the risk of citrate accumulation in patients undergoing CKRT. Further research is needed to develop and validate predictive algorithms for various anticoagulation strategies to offer reliable support for personalized decision-making in clinical practice.