Comparing the efficacy and safety of nafamostat mesylate versus citrate for anticoagulation in continuous renal replacement therapy: a systematic review and meta-analysis

Background Anticoagulation is pivotal to the successful implementation of continuous renal replacement therapy (CRRT). Systematic comparative studies between nafamostat mesylate (NM) and citrate are scarce. There is currently a lack of evidence-based support for clinical practice. Objective To systematically compare the efficacy and safety of NM versus citrate for anticoagulation in CRRT. Methods We performed a comprehensive literature search in PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database (Wanfang), China Science and Technology Journal Database (VIP), and China Biological Medicine Database (CBM). Two researchers conducted literature screening, data extraction, and quality assessment using standardized procedures and double-blinded methods. Statistical analyses were performed using Review Manager V.5.4 and STATA 15.1. Statistical heterogeneity among studies was quantified using the Chi-square and I-square tests, and publication bias was evaluated using Egger’s test and funnel plots. Results A total of 18 studies involving 2,247 CRRT patient episodes were included. The meta-analysis showed no significant differences in filter lifespan or clotting events between NM and citrate (MD = −0.11, 95%CI: −1.87 to 1.65, p = 0.90; RR = 0.63, 95%CI: 0.25–1.59, p = 0.33). NM reduced the risk of bleeding events compared with citrate (RR = 0.54, 95%CI: 0.36–0.82, p = 0.003), subgroup analyses showed that NM was associated with a lower risk of bleeding events in high-risk bleeding, low-dose NM, and randomized controlled trials (RCTs) subgroups (RR = 0.47, 95%CI: 0.25–0.88, p = 0.02; RR = 0.39, 95%CI: 0.23–0.66, p < 0.001; RR = 0.21, 95%CI: 0.07–0.66, p = 0.007). No significant differences were found between NM and citrate in platelet (PLT), activated partial thromboplastin time (APTT), or prothrombin time (PT) (MD = 0.88, 95%CI: −5.83 to 7.59, p = 0.80; MD = −0.42, 95%CI: −2.74 to 1.91, p = 0.73; MD =-0.38, 95%CI: −1.45 to 0.68, p = 0.48). Conclusion NM suggests anticoagulant efficacy comparable to citrate in CRRT, with a lower risk of bleeding, particularly in high bleeding risk situations, among patients receiving low-dose NM. For CRRT patients with contraindications to citrate or high bleeding risk, NM may be an anticoagulant alternative that combines efficacy with safety. The overall certainty of the evidence from this study is low to very low; further multi-center, large-sample, high-quality RCTs are required to validate these findings. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251182609 , identifier CRD420251182609.