Related Experiment Video
Updated: Jun 6, 2025
A Murine Model of Hemodialysis Access-Related Hand Dysfunction
Published on: May 31, 2022
The contact system in chronic kidney disease and hemodialysis - A cross-sectional study
Yaseelan Palarasah1, Rikke Borg2, Else-Marie Bladbjerg3
1Department 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.
Insights
Contact system activation is altered in chronic kidney disease (CKD) patients undergoing hemodialysis (HD) or peritoneal dialysis (PD), showing reduced kallikrein generation, but HD does not activate the contact system (CAS). Further research should explore CAS in CKD independent of dialysis.
Area of Science:
- Immunology
- Hematology
- Nephrology
Background:
- The contact activation system (CAS) plays roles in immunity and coagulation.
- CAS involvement in chronic kidney disease (CKD) and dialysis is known but poorly understood.
- Conflicting data necessitates clarification of CAS activation in CKD patients undergoing different renal replacement therapies.
Purpose of the Study:
- To compare CAS activation in patients with CKD undergoing hemodialysis (HD) versus peritoneal dialysis (PD).
- To assess CAS activation in CKD patients not on dialysis compared to healthy controls.
- To evaluate the impact of a single HD session on CAS markers from pre- to post-dialysis.
Main Methods:
- Cross-sectional analysis of blood samples from 106 HD patients, 40 PD patients, 60 CKD patients, and 80 healthy controls.
- Measurement of CAS components (factor XII, prekallikrein, high-molecular-weight kininogen, cleaved HK, C1-inhibitor) and functional kallikrein generation.
- Pre- and post-dialysis CAS assessment in HD patients using linear regression and mixed models.
Main Results:
- HD patients exhibited altered prekallikrein, factor XII, and cleaved HK levels compared to other groups.
- HD patients showed increased C1-inhibitor and reduced functional kallikrein generation, similar to PD and CKD patients versus controls.
- No evidence of CAS activation was detected during the HD procedure itself.
Conclusions:
- CKD, particularly with HD or PD, is linked to reduced functional kallikrein generation and altered CAS components, suggesting ongoing CAS activation.
- No significant factor XII-mediated CAS activation occurred during hemodialysis.
- Future studies should investigate the role of CAS in CKD independently of dialysis modality.
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.
Related Concept Videos
01:27Dialysis
Acute kidney injury develops suddenly and can be caused by pre-renal causes (e.g., hypovolemia, shock), intrinsic renal causes (e.g., acute tubular necrosis), or post-renal causes (e.g., urinary obstruction). In contrast, chronic renal failure progresses gradually over time and is often...
01:20Renal Corpuscle
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...
01:17Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
01:10Nephrons
01:24Renal Tubule and Collecting Duct
Proximal Convoluted Tubule (PCT):
The PCT is the initial segment of the renal tubule, extending from the Bowman's capsule that encloses the glomerulus. Its convoluted structure and microvilli-lined cells increase the surface area for reabsorption. The PCT reabsorbs glucose, amino acids, sodium, and water from the filtrate, ensuring essential...
01:22Heart Failure Drugs: Diuretics