TY - JOUR
T1 - The contact system in chronic kidney disease and hemodialysis - A cross-sectional study
AU - Palarasah, Yaseelan
AU - Borg, Rikke
AU - Bladbjerg, Else-Marie
AU - Pham, Stephanie Thuy Duong
AU - Mejldal, Anna
AU - Nielsen, Christian
AU - Pedersen, Erik Bo
AU - Jensen, Per Bruno
AU - Thiesson, Helle Charlotte
AU - Pilely, Katrine
PY - 2025/1
Y1 - 2025/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.thromres.2024.109229
DO - 10.1016/j.thromres.2024.109229
M3 - Journal article
C2 - 39577039
SN - 0049-3848
VL - 245
JO - Thrombosis Research
JF - Thrombosis Research
M1 - 109229
ER -