Study Supports Citrate Over Heparin Anticoagulation For Continuous Dialysis

A large randomized controlled trial supports the use of regional citrate over heparin anticoagulation to help prevent blood clot formation at the filter in patients receiving continuous dialysis therapies.

dialysis filter life was 15 hours longer in the regional citrate anticoagulation group compared to the heparin group, Dr. Alexander Zarbock reported October 23 during the "high-impact" clinical trials session at the Kidney Week 2020 virtual annual meeting. The study was simultaneously published in JAMA.

Blood clot formation at the filter is a common complication in patients receiving continuous dialysis therapies. Systemic use of heparin and regional citrate are the two main anticoagulant strategies. Current guidelines recommend the use of citrate over heparin, but the evidence level is considered low.

Dr. Zarbock, from University Hospital Munster in Germany, and colleagues conducted the RICH trial to test whether regional citrate anticoagulation prolongs dialysis filter life and reduces 90-day all-cause mortality in critically ill adults requiring continuous renal replacement therapy.

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The trial, conducted at 26 centers in Germany, included 596 patients (mean age, 67.5 years; 30.7% women), with 300 randomly allocated to regional citrate anticoagulation and 296 to systemic heparin anticoagulation.

Median filter lifespan was 47 hours with citrate anticoagulation versus 26 hours with heparin (P<0.001). There was no significant difference in 90-day all-cause mortality (51.2% vs 53.6%), although the trial was underpowered to reach conclusions regarding mortality, Dr. Zarbock noted.

As for secondary outcomes, the bleeding rate was significantly lower with regional citrate than with heparin (5.1% vs 16.9%; P<0.001), "but surprisingly," the rate of new infections was significantly higher with regional citrate (68.0% vs 55.4%; P=0.002), Dr. Zarbock noted in his presentation. This observation has to be investigated in greater detail in future trials, he said.

Patients in the regional citrate group more frequently developed severe alkalosis (2.4% vs 0.3%) and hypophosphatemia (15.4% vs 6.2%). Hyperkalemia was more frequent in the heparin group (1.4% vs 0%). Gastrointestinal complications were lower in the regional citrate group (0.7% vs 3.4%). "All other adverse events didn't differ between the two groups," Dr. Zarbock reported.

Commenting on the RICH trial results in email to Reuters Health, Dr. Ankur Shah noted that current guidelines recommend citrate over heparin "due to greater efficacy and a lower risk of bleeding shown in a 2020 meta-analysis of smaller randomized controlled trials, a recommendation which is supported by this much larger clinical trial."

Dr. Shah, with the Division of Kidney Diseases and Hypertension, Warren Alpert Medical School of Brown University, Providence, Rhode Island, said, the RICH trial provides "stronger support to the current recommendation to use citrate as an anticoagulant and may support clinicians who do not use citrate to begin doing so."

He agrees that the finding of increased infections is "surprising as citrate has been shown to have antimicrobial effects in vitro and numerous studies have demonstrated an association between line thrombosis and infection. This finding should help inform treating physicians to have a higher index of suspicion for infection in patients receiving citrate and would benefit from further study in the future."

The RICH study was funded by the German Research Foundation. Dr. Zarbock has received grants from Baxter, Fresenius, Astute Medical, and Astellas and personal fees from Fresenius, AM Pharma, and BioMerieux.

—Megan Brooks

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