Continuous Kidney replacement Therapy Dosage and Mortality in Critically Ill Patients: a Retrospective Cohort Study using Marginal Structural Model.

Abstract Background Continuous kidney replacement therapy (CKRT) is a crucial intervention for hemodynamically unstable patients with acute kidney injury (AKI). Despite the recommendations to offer a CKRT dose of 20-25 mL/kg/h, the optimal CKRT dose remains uncertain, especially whether low-dose CKRT is associated with poor outcomes. This study investigated the association between low CKRT dosage and 90-day mortality using a marginal structural model (MSM). Methods Using the MIMIC-IV database, adult patients who received CKRT for more than 24 hours were included. Data on time-fixed and time-dependent variables were collected. Patients were categorized based on CKRT dose thresholds of 13 and 20 ml/kg/h. Results Among the 1,329 patients, the 90-day mortality rate was 49.6%. The median age of the patients was 62 years (IQR: 52-72). Changes in CKRT dosing during treatment were frequent. Patients with a reduced delivered CKRT dose (<20 and < 13 ml/kg/h) generally exhibited low values during the initial days of CKRT, with an increase in the delivered CKRT dose. After adjusting only for baseline variables (traditional Cox regression model), patients receiving CKRT doses <13 ml/kg/h had significantly greater 90-day mortality (HR: 1.70, 95% CI 1.16-2.49) than those receiving CKRT doses ≥13 ml/kg/h. However, after adjusting for time-dependent variables, the CKRT dose was not significantly associated with mortality at either the 13 or 20 ml/kg/h threshold. Additionally, there were no significant associations between the delivered CKRT dose and 90-day mortality within the range of 5 to 40 ml/kg/h. Conclusion This study highlights the impact of methodological approaches on the association between CKRT dose and mortality and that with personalized adjustments, there may not be a lower limit of the unsafe CKRT dose. However, lower CKRT doses were initially associated with higher mortality, and adjusting for time-dependent variables nullified this association.