EFFECT OF NAFAMOSTAT MESYLATE ON BRADYKININ PRODUCTION AND BLOOD PRESSURE STABILITY DURING LDL APHERESIS IN CHRONIC LIMB-THREATENING ISCHEMIA

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Abstract Title *

EFFECT OF NAFAMOSTAT MESYLATE ON BRADYKININ PRODUCTION AND BLOOD PRESSURE STABILITY DURING LDL APHERESIS IN CHRONIC LIMB-THREATENING ISCHEMIA

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Co-author 1

Yusuke Yoshimura yoshimura@toranomon.gr.jp Toranomon Hospital Nephrology Center Tokyo Japan *

Co-author 2

Takaya Handa kitanohanda@gmail.com Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai Department of Nephrology and Dialysis Osaka Japan -

Co-author 3

Susumu Tsunoda s.tsunoda1997@gmail.com Toranomon Hospital Nephrology Center Tokyo Japan -

Co-author 4

Hisashi Sugimoto hisashi0223capy@gmail.com Toranomon Hospital Nephrology Center Tokyo Japan -

Co-author 5

Yoshifumi Ubara yoshifumitora_0418@yahoo.co.jp Toranomon Hospital Nephrology Center Tokyo Japan -

Co-author 6

Takehiko Wada twada-tky@umin.ac.jp Toranomon Hospital Nephrology Center Tokyo Japan -

Co-author 7

Takeshi Matsubara t-matsubara@kitano-hp.or.jp Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai Department of Nephrology and Dialysis Osaka Japan -

Co-author 8

Naoki Sawa naokis@toranomon.gr.jp Toranomon Hospital Nephrology Center Tokyo Japan -

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

LDL apheresis is indicated for severe chronic limb-threatening ischemia (CLTI) refractory to revascularization. Negative charge of dextran sulfate in the apheresis column can activate the kallikrein–kinin system and induce bradykinin-mediated hypotension, compromising procedural safety. We investigated whether using the positively charged anticoagulant nafamostat mesylate (NM), instead of standard heparin (HP), could neutralize the dextran sulfate charge, suppress bradykinin production, and improve hemodynamic stability.

Main contributions: (1) quantification of bradykinin kinetics during LDL apheresis in CLTI; (2) direct comparison of NM versus HP on intraprocedural plasma bradykinin concentration and blood pressure; (3) demonstration of a practical strategy to optimize apheresis tolerability in vascular disease.

Methods

The retrospective study included seven CLTI patients from two centers who underwent LDL apheresis using Rheocarna® (Kaneka Corporation, Osaka, Japan). Plasma bradykinin concentrations were measured by ELISA at baseline, 30, and 120 minutes during each session. Intraprocedural blood pressure changes and clinical outcome were also assessed.

Results

In the HP group, bradykinin increased significantly from 890 ± 168 pg/mL at baseline to 6,850 ± 843 pg/mL at 30 min and 3,876 ± 372 pg/mL at 120 min (p < 0.01 vs. baseline). The NM group showed a decrease at 30 min (979 ± 177 to 669 ± 134 pg/mL, p = 0.01), with no significant difference between baseline and 120 min (866 ± 169 pg/mL, p = 0.59). Systolic blood pressure in the HP group fell from 131 ± 4.89 mmHg at baseline to 111 ± 4.52 mmHg at 30 min (p < 0.01) and returned to 128 ± 4.86 mmHg at 120 min (p = 0.56), while the NM group remained stable (124 ± 3.95, 126 ± 3.64, 126 ± 3.82 mmHg; p = 0.15, 0.71). Limb outcomes were similar in both groups.

Conclusion

For CLTI patients experiencing hypotension during LDL apheresis, switching from HP to NM may help stabilize blood pressure and enhance treatment tolerability by attenuating bradykinin production.

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