A prospective study on serum citrate levels and clinical correlations in patients receiving regional citrate anticoagulation

Lay Summary Regional citrate anticoagulation (RCA) is gaining popularity across the world as the first-line anticoagulation strategy for continuous renal replacement therapy (CRRT). Citrate accumulation (CA) remains a feared complication limiting the widespread application of RCA. Diagnosis of CA currently requires consideration of multiple biochemical parameters including the total calcium:ionized calcium ratio, which can be complex to interpret and subject to inaccuracies. This prospective study is the first of its kind to examine the serum citrate profile at predefined time points in 133 patients who received RCA CRRT. Serum citrate levels were shown to have good diagnostic value for CA. The 2-h citrate level taken early in the course of RCA CRRT had good predictive value for CA development, suggesting a potential role of direct citrate measurement in patients at high risk of developing CA. Background Current ways to diagnose citrate accumulation (CA) in patients receiving regional citrate anticoagulation (RCA) continuous renal replacement therapy (CRRT) are confounded by various clinical factors. Serum citrate measurement emerges as a more direct way to diagnose CA, but its clinical utility and optimal cut-off values remain undefined. This study examined serum citrate kinetics and its diagnostic performance for CA in patients receiving RCA CRRT. Methods A multicentre prospective study was carried out in two tertiary referral centre intensive care units in Hong Kong with serum citrate levels measured at baseline and 2, 6, 12, 24, 36, 48 and 72 h after initiation of RCA CRRT and their relationships with the development of CA. Results Among the 133 patients analysed, 18 patients (13.5%) developed CA. The serum citrate levels at baseline and 2, 6 and 12 h after initiation of RCA CRRT in patients who had CA were significantly higher than the non-CA group (P < .001 for all). The CA group also had higher serum citrate levels than the non-CA group {median 0.93 mmol/L [interquartile range (IQR) 0.81-1.16) versus 0.37 mmol/L (IQR 0.26-0.57), P < .001}. Using a cut-off of 0.85 mmol/L, the serum citrate level had a sensitivity of 0.77 and a specificity 0.96 for the diagnosis of CA [area under the receiver operating characteristics curve (AUROC) 0.90, P < .001]. The 2-h and 6-h serum citrate levels had good discriminatory abilities for predicting subsequent development of CA (AUROC 0.86 and 0.83 for 2-h and 6-h citrate levels using cut-off values of 0.34 and 0.63 mmol/L, respectively; P < .001). Conclusion Serum citrate levels were significantly higher in patients with CA compared with patients without CA. Serum citrate levels showed good performance in diagnosing and predicting the development of CA.

Automated summary

This prospective study examined the diagnostic and predictive value of serum citrate levels for citrate accumulation (CA) in patients receiving regional citrate anticoagulation (RCA) continuous renal replacement therapy (CRRT). The study found that serum citrate levels showed good performance in diagnosing and predicting the development of CA.