Disenchantment: the overstated impact of citrate concentration on accumulation risk

Citrate accumulation is a relevant complication of continuous kidney replacement therapy (CKRT). In response to the commentary by Wang and Li, we reassessed findings from a cohort of 911 critically ill patients, in whom bilirubin levels, technical parameters, and CKRT modality were independently associated with citrate accumulation. Continuous venovenous haemodiafiltration (CVVHDF) was associated with a lower risk compared with continuous venovenous haemodialysis (CVVHD). While this difference was initially hypothesised to reflect transmembrane flux and membrane patency, Wang and Li highlighted potential confounding by device-specific citrate concentrations. We acknowledge this limitation, as CVVHDF was delivered exclusively using the Prismaflex system, whereas CVVHD was performed with the multiFiltrate device that both use different citrate regimens. Although multiFiltrate was associated with a higher citrate load, total citrate load was not independently associated with citrate accumulation at therapy initiation or at the time of accumulation. Importantly, treatment modality remained significantly associated with citrate accumulation after multivariable adjustment. These findings suggest that factors beyond citrate load contribute to citrate accumulation, warranting further investigation.