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

Peritoneal Dialysis International, vol. 44, pp. 37–47

Abstract

Background: Despite several advantages compared to haemodialysis (HD), peritoneal dialysis (PD) remains an underused dialysis technique due to its high technique failure rate related to membrane fibrosis and peritonitis events. Previous work has suggested a harmful role for the complement system in these processes, highlighting the need for a more comprehensive examination in PD. Methods: Plasma levels of C1q, mannose-binding lectin (MBL), Properdin, Factor D, C3d/C3-ratio and soluble membrane attack complex (sC5b-9) were determined in PD patients ( n = 55), HD patients ( n = 41), non-dialysis chronic kidney disease (CKD) patients ( n = 15) and healthy controls ( n = 14). Additionally, C1q, MBL, Properdin, Factor D and sC5b-9 levels were assessed in the peritoneal dialysis fluid (PDF). In a subgroup, interleukin-6, matrix metalloproteinase-2 (MMP-2), myeloperoxidase (MPO) and elastase were measured in the PDF. Results: PD patients had significantly higher systemic levels of sC5b-9 compared to healthy controls, CKD and HD patients ( p < 0.001). Plasma levels of C1q and C3d/C3-ratios were significantly associated with systemic sC5b-9 levels ( p < 0.001). Locally, sC5b-9 was detected in the PDF of all PD patients, and levels were approximately 33% of those in matched plasma, but they did not correlate. In the PDF, only Properdin levels remained significantly associated with PDF sC5b-9 levels in multivariate analysis ( p < 0.001). Additionally, PDF levels of sC5b-9 positively correlated with elastase, MPO and MMP-2 levels in the PDF ( p < 0.01). Conclusions: Our data reveal both systemic and local complement activation in PD patients. Furthermore, these two processes seem independent considering the involvement of different pathways and the lack of correlation.

Authors 11

1. Bernardo Faria

   University Medical Center Groningen · University of Groningen · Universidade do Porto · i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto

   Affiliation as printed

   Department of Medicine, Faculty of Medicine, University of Porto, Portugal

   Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, The Netherlands

   Nephrology and Infectious Disease R&D Group, INEB, Institute of Investigation and Innovation in Health (i3S), University of Porto, Portugal

2. Mariana Gaya da Costa

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Anesthesiology, University Medical Center Groningen, University of Groningen, The Netherlands

   Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, The Netherlands

3. Stefan P. Berger

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, The Netherlands

4. Carla Lima

   Hospital São Teotónio

   Affiliation as printed

   Division of Nephrology, Hospital São Teotônio, Viseu, Portugal

5. Cátia Pêgo

   Hospital São Teotónio

   Affiliation as printed

   Division of Nephrology, Hospital São Teotônio, Viseu, Portugal

6. Jacob van den Born

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, The Netherlands

7. Casper F. M. Franssen

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, The Netherlands

8. Mohamed R. Daha Aachen Department of Nephrology, Leiden University Medical Centre

   Leiden University · University Medical Center Groningen · University of Groningen · Leiden University Medical Center

   Affiliation as printed

   Department of Nephrology, Leiden University Medical Center, University of Leiden, The Netherlands

   Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, The Netherlands

9. Manuel Pestana

   Universidade do Porto · i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto

   Affiliation as printed

   Department of Medicine, Faculty of Medicine, University of Porto, Portugal

   Nephrology and Infectious Disease R&D Group, INEB, Institute of Investigation and Innovation in Health (i3S), University of Porto, Portugal

10. Marc A. Seelen

    University Medical Center Groningen · University of Groningen

    Affiliation as printed

    Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, The Netherlands

11. Felix Poppelaars corresponding

    University Medical Center Groningen · University of Groningen

    Affiliation as printed

    Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, The Netherlands