Let's stop talking about 'citrate toxicity'

Curr Opin Nephrol Hypertens. 2024 Mar 1;33(2):181-185. doi: 10.1097/MNH.0000000000000953. Epub 2023 Nov 14.


Purpose of review: Continuous renal replacement therapy (CRRT) is a vital medical intervention used in critically ill patients with acute kidney injury (AKI). One of the key components of adequate clearance with CRRT is the use of anticoagulants to prevent clotting of the extracorporeal circuit. Regional citrate anticoagulation is the most often recommended modality. The term 'citrate toxicity' is used to describe potential adverse effects of accumulation of citrate and subsequent hypocalcemia. However, citrate is itself not inherently toxic. The term and diagnosis of citrate toxicity are questioned in this review.

Recent findings: Citrate is being increasingly used for regional anticoagulation of the CRRT circuit. Citrate accumulation is infrequent and can cause hypocalcemia and metabolic alkalosis, which are potential adverse effects. Citrate itself, however, is not a toxic molecule. The term 'citrate toxicity' has been used to denote hypocalcemia and metabolic acidosis. However, citrate administration is well known to cause systemic and urinary alkalinization and under certain circumstances, metabolic alkalosis, but is not associated itself with any 'toxic' effects.We review the existing literature and debunk the perceived toxicity of citrate. We delve into the metabolism and clearance of citrate and question current data suggesting metabolic acidosis occurs as the result of citrate accumulation.

Summary: In conclusion, this article calls into question prevailing concerns about 'citrate toxicity'. We emphasize the need for a more nuanced understanding of its safety profile. We recommend discarding the term 'citrate toxicity' in favor of another frequently used, but more meaningful term: 'citrate accumulation'.

Publication types

  • Review

MeSH terms

  • Acidosis / chemically induced
  • Acute Kidney Injury* / therapy
  • Alkalosis / chemically induced
  • Anticoagulants / adverse effects
  • Citrates* / adverse effects
  • Humans
  • Hypocalcemia / chemically induced
  • Renal Replacement Therapy* / adverse effects


  • Anticoagulants
  • Citrates