Citrate Pharmacokinetics in Critically Ill Patients with Acute Kidney Injury

PLoS One. 2013 Jun 18;8(6):e65992. doi: 10.1371/journal.pone.0065992. Print 2013.

Abstract

Introduction: Regional citrate anticoagulation (RCA) is gaining popularity in continous renal replacement therapy (CRRT) for critically ill patients. The risk of citrate toxicity is a primary concern during the prolonged process. The aim of this study was to assess the pharmacokinetics of citrate in critically ill patients with AKI, and used the kinetic parameters to predict the risk of citrate accumulation in this population group undergoing continuous veno-venous hemofiltration (CVVH) with RCA.

Methods: Critically ill patients with AKI (n = 12) and healthy volunteers (n = 12) were investigated during infusing comparative dosage of citrate. Serial blood samples were taken before, during 120 min and up to 120 min after infusion. Citrate pharmacokinetics were calculated and compared between groups. Then the estimated kinetic parameters were applied to the citrate kinetic equation for validation in other ten patients' CVVH sessions with citrate anticoagulation.

Results: Total body clearance of citrate was similar in critically ill patients with AKI and healthy volunteers (648.04±347.00 L/min versus 686.64±353.60 L/min; P = 0.624). Basal and peak citrate concentrations were similar in both groups (p = 0.423 and 0.247, respectively). The predicted citrate curve showed excellent fit to the measurements.

Conclusions: Citrate clearance is not impaired in critically ill patients with AKI in the absence of severe liver dysfunction. Citrate pharmacokinetic data can provide a basis for the clinical use of predicting the risk of citrate accumulation.

Trial registration: ClinicalTrials.gov Identifier NCT00948558.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / metabolism*
  • Adolescent
  • Adult
  • Aged
  • Anticoagulants / pharmacokinetics*
  • Citric Acid / pharmacokinetics*
  • Critical Illness*
  • Female
  • Hemofiltration / adverse effects
  • Humans
  • Male
  • Middle Aged

Substances

  • Anticoagulants
  • Citric Acid

Associated data

  • ClinicalTrials.gov/NCT00948558

Grant support

This study was supported, in part, by grants from the National Natural Science Foundation of China (No: 81270850, 81070609), the Science and Technology Commission of Shanghai Municipality (No: 09411961500,11441901401) (to FD), the Board of Health of Shanghai Municipality (20124Y126) (to JL), and the Scientific Research foundation of Huashan Hospital (to YZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.