Citrate pharmacokinetics and calcium levels during high-flux dialysis with regional citrate anticoagulation

Nephrol Dial Transplant. 2009 Jul;24(7):2244-51. doi: 10.1093/ndt/gfp017. Epub 2009 Feb 5.


Background: Regional citrate anticoagulation is a very effective anticoagulation method for haemodialysis. However, it is not widely used, primarily due to the risk of hypocalcaemia. We studied citrate and calcium kinetics to better understand safety aspects of this anticoagulation method.

Methods: During 15 haemodialysis treatments with a calcium-free dialysis solution, citrate was infused pre-dialyser and calcium was substituted post-dialyser. Systemic and extracorporeal citrate and calcium concentrations were repeatedly measured to calculate citrate and calcium pharmacokinetics.

Results: Removal by dialysis constituted the major elimination pathway of citrate (83 +/- 5%). Systemic citrate load and concentrations were low (17 +/- 7 mmol/4 h, 0.3 +/- 0.15 mmol/l). Combined use of calcium-free dialysate and citrate infusion increased diffusible calcium to 80% of total calcium and induced substantial dialytic loss of calcium (43 +/- 4 mmol/4 h). Since calcium was substituted, systemic calcium balances were positive (approximately +5 mmol) and concentrations stable. Calcium supplementation correlated with calcium dialytic losses, which in turn were dependent on total calcium and haematocrit.

Conclusions: When using calcium-free dialysate during citrate anticoagulation, hypocalcaemia is very likely unless calcium is re-infused, because large amounts of calcium are lost in the dialysate. However, an accumulation of citrate in the patient's systemic circulation is an unlikely cause of hypocalcaemia since most of the citrate is removed by dialysis. Calcium substitution and monitoring are the most important safety measures. We propose a rational approach based on haematocrit and total calcium for the choice of the starting calcium supplementation rate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage*
  • Calcium Chloride / pharmacokinetics*
  • Citrates / pharmacokinetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Renal Dialysis* / methods
  • Sodium Citrate


  • Anticoagulants
  • Citrates
  • Sodium Citrate
  • Calcium Chloride