Association between Serum Complement AnaphylatoxinC5a and Thrombotic Events in Patients Receiving Maintenance Hemodialysis

Abstract

Several primary kidney and systemic disorders lead to end-stage renal disease (ESRD), which is manifested as renal failure. Although renal dialysis is a lifesaving procedure, patients undergoing this treatment are at risk for various complications, including thrombosis. Thrombotic complications are thought to be a net outcome of both underlying kidney disease, complicated by renal failure, and its management through dialysis. The increased risk of thrombosis during hemodialysis is a complex mechanism and still not well understood. However, several studies have pointed to inflammation as an important contributor to thrombotic complications in hemodialyzed patients. Indeed, ESRD is currently perceived as a state of chronic or recurrent inflammation. It was postulated that activation of complement and subsequent generation of the complement anaphylatoxin C5a contribute to up-regulation of tissue factor (TF), a major trigger of coagulation in vivo, in patients with antiphospholipid syndrome (APS). Although considerable progress has been made in reducing this activation through modifications of the surfaces of the biomaterials used to manufacture hemodialysis filters and elements of extracorporeal circuits, activation of complement as a result of bioincompatibility still induces adverse reactions in patients maintained on hemodialysis. More importantly, blockade of C5a and C5aR with neutralizing polyclonal antibodies has been shown to significantly improve survival rate, prevent Multiorgan Failure, and ameliorate dysfunction of the coagulation and fibrinolysis system in a caecal ligation/puncture model of sepsis in rats and mice. Interestingly, the growth of aerobic bacteria, cultured from the spleen and liver of septic animals, was significantly reduced following neutralization of C5a. It is interpreted that the generation of C5a during sepsis suppresses polymorphonuclear function, and this leads to decreased bacterial clearance by mechanisms, such as leukotriene (LT) B4 or IL8, perhaps by heterologous desensitization. Together, inhibition of the C5a/C5aR pathway in sepsis could be an attractive therapeutic approach.

Aim of the work: To find the association between complement components (C5a) and thrombosis in hemodialysis patients. Patient and methods: This study was conducted in hemodialysis unit in El Zaitoun specialized hospital. 50 patients were included in this study; all patients received hemodialysis sessions three times per week for four hours with bicarbonate solution and polysulfone dialysis membrane. Blood samples were collected 30 minutes from the start of the hemodialysis session. The patients were divided into two groups: Group (A): included 25 HD patients with thrombotic events e.g AVF thrombosis, DVT….etc. Group (B): included 25 HD patients without any thrombotic events (control group).