The effects of citrate dialysate in hemodialysis on polymorphonuclear elastase interaction with tissue factor and its inhibitor

Abstract

Background: This study aimed to investigate whether hemodialysis (HD) affects tissue factor (TF), tissue factor pathway inhibitor (TFPI), and polymorphonuclear elastase (PMNE) in endstage renal disease (ESRD) patients when eliminating the effects of heparin. Also, to explore the interaction of TF, TFPI, and PMNE throughout a single HD session. Methods: We enrolled 57 ESRD patients who had undergone hemodialysis for >3 months as an experimental group. Plasma levels of TF, TFPI and PMNE were measured by ELISA in 24 ERSD patients on intermittent HD using low-molecular-weight heparin (LMWH) as anticoagulation (LMWH group) and 33 ESRD patients using citrate as anticoagulation (citrate group) at the start and at 1, 2 and 5 h of the HD session. Meanwhile,28 ESRD patients not on dialysis were enrolled as a control group and fasting venous blood samples were taken in the morning. Results: Compared with the control group, the plasma TFPI levels of the LMWH group and the citrate group were significantly higher (P=0.000, P=0.002, respectively) under baseline conditions as well as the plasma PMNE levels (P=0.001, P=0.02,respectively), whereas TF showed no difference (P=0.186). During HD with citrate, plasma TFPI decreased slightly (P=0.012) and PMNE increased significantly (P=0.008) at 1 h. The plasma TFPI levels of the citrate group correlate with PMNE at 2 and 5 h (P=0.001, P=0.008, respectively). Conclusions: ESRD patients on HD have significantly higher TFPI and PMNE levels compared to patients not on HD under baseline conditions, while TF levels were similar between the three groups. TFPI and PMNE are differently regulated, but the plasma levels correlated during HD in the citrate group. It might be possible that PMNE plays a role in anticoagulative activity through TFPI.

What is the role of the neutrophil extracellular traps in the cardiovascular disease burden associated with hemodialysis bioincompatibility?

“…In addition, MPO release, one of the main protein components of NETs, has been evidenced during HD sessions. Furthermore, the serine protease elastase, another component of NETs, which is significantly increased in end-stage kidney disease patients, is further enhanced after 1 h of HD ( 68 ). Exacerbated elastase activity in uremic patients prior to dialysis sessions has been reported by Khatib-Massalha and colleagues ( 69 ) and elastase concentration increases progressively during dialysis sessions ( 70 ).…”

“…Additionally, cirDNA has been proposed as a potential biomarker of renal damage ( 91 ). MPO and elastase levels have been reported to be elevated in chronic kidney diseases prior to dialysis ( 69 , 92 , 93 ) but they are enhanced in dialysis patients compared with end-stage renal failure patients ( 68 ). On the other hand, the disappearance rate of NETs after a dialysis session is unknown.…”

Advances in Enhancing Hemocompatibility of Hemodialysis Hollow-Fiber Membranes

“…During the hemodialysis process, the activation of the intrinsic coagulation (contact activation) pathway may be the main reason inducing the initial clotting process. Important considerations are (1) membrane-induced thrombosis is mainly triggered by the contact activation pathway; (2) the use of FXIIa antagonists can effectively avoid thrombosis during extracorporeal blood therapy [ 192 ], and the potential of FXIa inhibitors should also be investigated; and (3) the concentration of TF during hemodialysis shows limited change [ 193 ]. However, in the case of anticoagulant-free hemodialysis, this argument needs to be reconsidered.…”