Systemic and local complement activation in peritoneal dialysis patients via conceivably distinct pathways

Area of Science:

• Nephrology and Immunology
• Complement System Biology
• Renal Replacement Therapy

Background:

• Peritoneal dialysis (PD) is underutilized due to high failure rates linked to membrane fibrosis and peritonitis.
• The complement system's role in PD complications requires further investigation.
• Previous research suggests complement activation may harm PD patients.

Purpose of the Study:

• To investigate systemic and local complement activation in patients undergoing peritoneal dialysis.
• To compare complement activation markers in PD patients versus hemodialysis (HD) patients, chronic kidney disease (CKD) patients, and healthy controls.
• To explore the relationship between systemic and local complement activation in PD.

Main Methods:

• Measured plasma levels of complement factors (C1q, MBL, Properdin, Factor D, C3d/C3-ratio, sC5b-9) in PD, HD, CKD, and control groups.
• Assessed complement factors (C1q, MBL, Properdin, Factor D, sC5b-9) in peritoneal dialysis fluid (PDF).
• Quantified inflammatory markers (IL-6, MMP-2, MPO, elastase) in PDF from a subgroup of PD patients.

Main Results:

• PD patients showed significantly higher systemic levels of soluble membrane attack complex (sC5b-9) compared to other groups (p < 0.001).
• Systemic sC5b-9 levels correlated with plasma C1q and C3d/C3-ratios (p < 0.001).
• Local sC5b-9 in PDF correlated with PDF Properdin levels (p < 0.001) and inflammatory markers (elastase, MPO, MMP-2) (p < 0.01), but not with systemic sC5b-9.

Conclusions:

• Peritoneal dialysis patients exhibit distinct systemic and local complement activation.
• These systemic and local complement activation processes appear independent.
• Further research into complement pathways may offer strategies to improve PD technique survival.