PB0792 - Initiation of the contact activation system (CAS) and complement system during hemodialysis: A prospective observational cohort study

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

YP

Yaseelan Palarasah, MSc, PhD

Associate professor
Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark
Odense, Syddanmark, Denmark
RB

Rikke Borg

MD
Department of Nephrology, Zealand University Hospital, Roskilde, Denmark
Roskilde, Sjelland, Denmark
EJ

Emma Kathrine Jungjohan Johansen

Master student
Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark
Odense, Syddanmark, Denmark
Stephanie Thuy Duong Pham, MSc (she/her/hers)

PhD student
Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
Odense C, Syddanmark, Denmark
CN

Christian Nielsen

MSc, PhD
Department of Clinical Immunology, Odense University Hospital, Odense, Denmark
Odense, Syddanmark, Denmark
EP

Erik Bo Pedersen

MD
Department of Nephrology, Odense University Hospital, Odense, Denmark
Odense, Syddanmark, Denmark
PJ

Per Bruno Jensen

MD
Department of Nephrology, Odense University Hospital, Odense, Denmark
Odense, Syddanmark, Denmark
HT

Helle Charlotte Thiesson

MD
Department of Nephrology, Odense University Hospital, Odense, Denmark.
Odense, Syddanmark, Denmark

Presenting Author(s)

Katrine Pilely, PhD (she/her/hers)

Postdoc
Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Odense, Syddanmark, Denmark

Background: Patients with end-stage renal disease in hemodialysis are burdened with high mortality rates. Cardiovascular complications and bloodstream infections account for the majority of deaths in hemodialysis-patients. The contact activation system (CAS) mediates proinflammatory and procoagulant responses that could contribute to or accelerate cardiovascular and infection risk. Our understanding of hemodialysis-mediated CAS activation remains limited and studies addressing in vivo CAS activation in patients undergoing hemodialysis have reported inconsistent results. We hypothesize that CAS is activated during hemodialysis, promoting the coagulability of blood and increasing chronic inflammation, thus increasing overall risk of infection and cardiovascular disease in hemodialysis-patients.

Aims: The aim of this study is to investigate the effect of hemodialysis on CAS in a prospective observational cohort study.

Methods: Patients with chronic kidney disease (CKD) in hemodialysis (n=106) are included and plasma is collected before and after dialysis. The plasma levels of CAS and complement components and activation markers (FXII; kallikrein; high-molecular-weight kininogen (HK); cleaved-HK; kallistatin; kallistatin-generation; C1-inhibitor; C3dg; sC5b-9) and coagulation factors are analyses by in-house available assays. The levels of CAS- and complement components in the hemodialysis group is compared to three control groups: patients with CKD in peritoneal-dialysis (n=40); patients with CKD not in dialysis (n=60); and healthy blood donors (n=100). Clinical background information and information on number of infections and cardiovascular events is collected at baseline and at two- and five-year follow-up.

Results: Participants were included from April 2022. As of January 2023, 106 hemodialysis-patients; 20 CKD-patients in peritoneal-dialysis; 21 CKD-patients not in dialysis; and 100 healthy blood donors have been included. The remaining participants will be included during January-February 2023. The analysis of plasma samples and statistical analysis is done in Marts-June 2023.

Conclusion(s): Results from this study will increase our understanding of hemodialysis-mediated CAS activation, potentially contributing to future efforts aiming to increase the life span of hemodialysis-patients.