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Complement activation during CAPD
G A Young1, S Kendall, A M Brownjohn
1Renal Research Unit, General Infirmary, Leeds, UK.
Insights
Complement activation occurs in the peritoneum during continuous ambulatory peritoneal dialysis (CAPD). This may increase infection risk, with findings suggesting alternative pathway generation in the peritoneum.
Area of Science:
- Immunology
- Nephrology
- Complement System Biology
Background:
- Continuous ambulatory peritoneal dialysis (CAPD) involves direct contact of dialysis fluid with the peritoneal membrane.
- The role of complement system activation within the peritoneal cavity during CAPD is not fully understood.
Purpose of the Study:
- To investigate complement activation pathways in CAPD patients compared to healthy individuals.
- To determine the site of complement activation (plasma vs. peritoneum) during CAPD.
Main Methods:
- Measurement of complement components (C3, C4, Factor B) and activation markers (Bb, C4d, iC3b, SC5b-9/MAC) in plasma and dialysate.
- Comparison between 20 CAPD patients and 20 normal individuals.
Main Results:
- Elevated levels of soluble membrane attack complex (SC5b-9) in CAPD plasma, not solely due to plasma activation.
- Higher concentrations of iC3b, Bb, and SC5b-9 in dialysate suggest peritoneal generation, primarily via the alternative pathway.
- Low levels of C3, C4, and Factor B in dialysate indicate vascular leakage, while C4d suggests minor classical pathway activation.
Conclusions:
- Complement activation demonstrably occurs within the peritoneal cavity during CAPD.
- Peritoneal complement activation, particularly via the alternative pathway, may contribute to inflammatory complications and infection risk in CAPD patients.
Abstract:
Complement activation was monitored in 20 CAPD patients and 20 normal individuals using markers of the alternative (Bb fragment), classical (C4d fragment), common (iC3b) and terminal pathways (SC5b-9, the soluble form of the membrane attack complex, MAC), together with C3, C4 and factor B. CAPD plasma SC5b-9 was higher than normal although this was not due to increased complement activation in the plasma. The calculated cleavage for C3, C4 and factor B to iC3b, C4d and Bb respectively, due to spontaneous activation, was similar in both groups. C3, C4 and factor B in dialysate were less than 1% of plasma concentration, consistent with vascular leakage, whereas iC3b, Bb and SC5b-9 were at higher concentrations, suggesting generation in the peritoneum by the alternative pathway. 2.4% C4d is consistent with leakage of this small molecule but may indicate slight classical activation. It is concluded that complement activation occurs in the peritoneum during CAPD. MAC and the anaphylatoxins which are also generated may contribute to an increased risk of infection and other inflammatory complications.