The contact system in chronic kidney disease and hemodialysis - A cross-sectional study

Yaseelan Palarasah; Rikke Borg; Else-Marie Bladbjerg; Stephanie Thuy Duong Pham; Anna Mejldal; Christian Nielsen; Erik Bo Pedersen; Per Bruno Jensen; Helle Charlotte Thiesson; Katrine Pilely

doi:10.1016/j.thromres.2024.109229

The contact system in chronic kidney disease and hemodialysis - A cross-sectional study

Thromb Res. 2024 Nov 19:245:109229. doi: 10.1016/j.thromres.2024.109229. Online ahead of print.

Affiliations

¹ Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark; Department of Regional Health Research, University of Southern Denmark, Esbjerg, Denmark; Department of Clinical Biochemistry, Unit for Thrombosis Research, University Hospital of Southern Denmark, Esbjerg, Denmark.
² Department of Medicine, Zealand University Hospital, Roskilde, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
³ Department of Regional Health Research, University of Southern Denmark, Esbjerg, Denmark; Department of Clinical Biochemistry, Unit for Thrombosis Research, University Hospital of Southern Denmark, Esbjerg, Denmark.
⁴ Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.
⁵ Odense Patient Data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark.
⁶ Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.
⁷ Department of Nephrology, Odense University Hospital, Odense, Denmark.
⁸ Department of Nephrology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
⁹ Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark; Department of Nephrology, Odense University Hospital, Odense, Denmark. Electronic address: Kapi@sdu.dk.

PMID: 39577039
DOI: 10.1016/j.thromres.2024.109229

Abstract

Background and hypothesis: The contact system (CAS) is a part of both the immune system and the coagulation system. The involvement of the CAS in chronic kidney disease (CKD) and hemodialysis (HD) has been documented, yet conflicting findings have hindered a comprehensive understanding. This study aimed to investigate whether CAS activation occurs in patients with chronic kidney failure undergoing HD compared with those undergoing peritoneal dialysis (PD), patients with CKD not receiving replacement therapy, or healthy controls and to assess the impact of HD on CAS from pre- to post-dialysis during a single session of HD.

Methods: In this cross-sectional study, blood samples from HD patients (n = 106), PD patients (n = 40), CKD patients (n = 60), and healthy control subjects (n = 80) were analyzed. The levels of CAS components, including factor XII, prekallikrein, high-molecular-weight kininogen (HK), cleaved HK (cHK), and C1-inhibitor, and functional kallikrein generation were determined. Among HD patients, CAS measures were evaluated both pre- and post-dialysis. Linear regression models and linear mixed models were employed to analyze associations and changes.

Results: HD patients had altered levels of prekallikrein, factor XII, and cHK compared with PD patients, CKD patients, and the healthy control group. Moreover, HD patients demonstrated increased levels of C1-inhibitor and reduced functional kallikrein generation, a pattern also observed in PD patients and, to a lesser degree, in CKD patients when compared with healthy controls. Notably, no CAS activation was detected during HD.

Conclusions: Impaired kidney function, especially in patients undergoing HD or PD, was associated with reduced functional kallikrein generation and altered levels of CAS components, implying continuous CAS activation in CKD. There was no indication of significant activation of factor XII-mediated CAS during HD. The role of CAS in CKD, independently of dialysis, should be addressed in future research.

Keywords: Chronic kidney diseases; Contact system; Factor XII; Hemodialysis; High molecular weight Kininogen; Prekallikrein.