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Comparison of nafamostat mesilate to citrate anticoagulation in pediatric continuous kidney replacement therapy

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Abstract

Background

Regional citrate anticoagulation (RCA) is the preferred continuous kidney replacement therapy (CKRT) anticoagulation strategy for children in the USA. Nafamostat mesilate (NM), a synthetic serine protease, is used widely for CKRT anticoagulation in Japan and Korea. We compared the safety and efficacy of NM to RCA for pediatric CKRT.

Methods

Starting June 2019, the most recent 100 medical records of children receiving CKRT with either RCA or NM were reviewed retrospectively, at one children’s hospital in Japan (NM) and one in the USA (RCA). The number of hours a single CKRT filter was in use, was the primary outcome. Safety was assessed by bleeding complications for the NM group and citrate toxicity leading to RCA discontinuation or electrolyte imbalance in the RCA group.

Results

Eighty patients received NM and 78 patients received RCA. Median filter life was longer for the NM group (NM: 38 [22, 74] vs. RCA: 36 [17, 66] h, p = 0.02). When filter life was censored for discontinuation other than clotting, the 60-h survival rate was higher for RCA (71% vs. 54%). The hazard ratio comparing NM over RCA varied over time (HR 0.7; 0.2–1.5, p = 0.33 at 0 h to HR 5.5; 1.3–23.7, p = 0.334 at 72 h). The lack of difference in filter survival persisted controlling for filter surface area, catheter diameter, and pre-CKRT platelet count. Major bleeding rates did not differ between groups (NM: 5% vs. RCA: 9%).

Conclusions

RCA and NM provide satisfactory anticoagulation for CKRT in children with no difference in major bleeding rates.

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Acknowledgements

We thank Dr. Heather Baer (Department of Epidemiology, Harvard T.H. Chan School of Public Health), Dr. John Orav (Department of Biostatistics, Harvard T.H. Chan School of Public Health) and Dr. Takahiro Kinoshita (Philips Research North America) for methodological advice.

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Authors and Affiliations

  1. Center for Acute Care Nephrology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 7022, Cincinnati, OH, 45229, USA

    Mai J. Miyaji, Kelli A. Krallman, Danielle Lazear & Stuart L. Goldstein

  2. Critical Care Medicine, National Center for Child Health and Development, Tokyo, Japan

    Mai J. Miyaji, Kentaro Ide, Kohei Takashima & Mikiko Maeno

  3. Master of Science Program, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Mai J. Miyaji

  4. University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Stuart L. Goldstein

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  1. Mai J. Miyaji
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Contributions

MJM designed the study, analyzed the data, and drafted the paper; KI and KAK contributed to IRB preparation and subject screening; MM and KT contributed data collection; SLG guided the study and critically revised the paper; all authors approved the final version of the manuscript.

Corresponding author

Correspondence to Stuart L. Goldstein.

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Conflict of interest

MJM serves as a consultant to Lowell Therapeutics, Inc, which has licensed NM in the US. At the current time, NM is not approved for marketing in the US. Lowell did not have input into the design of this study, access to the raw data or development of any aspect of this manuscript.

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Miyaji, M.J., Ide, K., Takashima, K. et al. Comparison of nafamostat mesilate to citrate anticoagulation in pediatric continuous kidney replacement therapy. Pediatr Nephrol 37, 2733–2742 (2022). https://doi.org/10.1007/s00467-022-05502-8

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  • DOI: https://doi.org/10.1007/s00467-022-05502-8

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