Effect of Calcium Correction on Rates of Identified Citrate Accumulation During Continuous Kidney Replacement Therapy

Background: Citrate accumulation is a serious complication during continuous kidney replacement therapy (CKRT), often assessed by the total-to-ionized calcium ratio (tCa/iCa). However, the impact of correcting total calcium for hypoalbuminemia on the identification of citrate accumulation remains unclear. Methods: We retrospectively analyzed patients undergoing CKRT with citrate anticoagulation at University of Iowa Hospitals from 2022 to 2024. Citrate accumulation was defined as a tCa/iCa ratio ≥2.5. We compared the frequency of citrate accumulation using both uncorrected and albumin-corrected total calcium and examined associated in-hospital mortality using both unadjusted binary logistic models and models adjusted for age, gender, liver disease, and SOFA score. Results: Based on uncorrected calcium, 3.4% (3/88) of patients had ratios ≥2.5. After correcting for albumin, this increased to 16.5% (14/85). All 3 high-ratio patients in the uncorrected group died, and mortality was also significantly higher in the corrected high-ratio group (13/14, 93%) compared to the normal-ratio group (39/71, 55%). The Figure shows differences in corrected tCa/iCa ratios between survivors and non-survivors (p=0.001). Univariate analysis showed a significant association between corrected tCa/iCa ratio ≥2.5 and mortality (OR 5.33, 95% CI 1.12-25.39, p=0.04), with a trend towards increased mortality after adjustments for covariates (OR 3.75, 95% CI 0.70-20.13, p=0.1). Conclusion: Correction of total calcium for albumin substantially increases the detection of citrate accumulation, and identifies a CKRT cohort at especially high risk for mortality. Further research should externally validate the findings and also explore whether additional metrics such as change in bicarbonate or CO2 improve detection of clinically relevant citrate accumulation.