Regional citrate trumps systemic heparin for extending dialysis filter lifespan

Using regional citrate for anticoagulation during dialysis significantly extends the lifespan of dialysis filter compared with systemic heparin anticoagulation, although this has no impact on the patients’ mortality rate over 1 year, according to the RICH study presented at ASN 2020.

“Acute kidney injury [AKI] is a common complication in critically ill patients. Approximately 50 percent of all ICU patients will develop AKI, with some requiring renal replacement therapy,” said lead investigator Professor Alexander Zarbock from the University of Münster, Germany.

“Normally, critically ill patients undergoing dialysis receive anticoagulants to reduce filter clotting and prolong filter lifetime,” he continued. “If it clots, you cannot retransfuse the blood that is in the system. [Consequently,] the workload becomes higher and the costs also increase.”

“The KDIGO* guidelines for acute kidney injury recommend the use of regional citrate anticoagulation in this setting. However, the evidence is based on small randomized clinical trials and is therefore only a weak suggestion,” Zarbock explained. 

In the multicentre clinical trial, 596 critically ill patients (mean age 67.5 years, 30.7 percent women) with severe acute kidney injury (AKI) or indications for kidney replacement therapy were randomized 1:1 to anticoagulation with regional citrate (target ionized calcium level 1.0–1.40 mg/dL) or systemic heparin (target activated partial thromboplastin time of 45–60 seconds). [ASN 2020, abstract FR-OR57]

Use of regional citrate anticoagulation significantly lengthened the filter life span by 11.2 hours compared with systemic heparin anticoagulation (mean, 44.9 vs 33.3 hours; p<0.001).

The rates of 90-day all-cause mortality were 51.2 percent in the regional citrate group compared with 53.6 percent in the systemic heparin group, which were not significantly different between the two groups (adjusted hazard ratio [HR], 0.91; p=0.38).

“This finding was true for the 90-day mortality as well as the 1-year mortality,” reported Zarbock.

“However, the trial was terminated early and was therefore underpowered to reach definitive conclusions about the comparative effect of these anticoagulation strategies on mortality,” the researchers pointed out.

Compared with systemic heparin anticoagulation, patients on regional citrate anticoagulation had significantly lower bleeding complications (5.1 percent vs 16.9 percent; odds ratio, 0.27; p<0.001).

“The potential advantage of citrate anticoagulation for continuous kidney replacement therapy is that it may reduce the occurrence of adverse events [AEs] as systemic effects on anticoagulation are avoided,” explained Zarbock and co-authors.

“[On the other hand,] metabolic derangements are a potential disadvantage of using citrate anticoagulation,” they suggested. “Metabolic derangements are closely linked to the use of certain solutions for kidney replacement therapy. For instance, citrate solutions of higher concentrations are associated with higher occurrence of metabolic alkalosis.”

Infection rate was also significantly higher in the regional citrate than the systemic heparin group (68.0 percent vs 55.4 percent; p=0.002).

*KDIGO: The Kidney Disease: Improving Global Outcomes