Affordable Access

Publisher Website

Complement Activation in Peritoneal Dialysis-Induced Arteriolopathy.

  • Bartosova, Maria1
  • Schaefer, Betti1
  • Bermejo, Justo Lorenzo2
  • Tarantino, Silvia3
  • Lasitschka, Felix4
  • Macher-Goeppinger, Stephan5
  • Sinn, Peter4
  • Warady, Bradley A6
  • Zaloszyc, Ariane7
  • Parapatics, Katja8
  • Májek, Peter8
  • Bennett, Keiryn L8
  • Oh, Jun9
  • Aufricht, Christoph3
  • Schaefer, Franz1
  • Kratochwill, Klaus3, 10
  • Schmitt, Claus Peter11
  • 1 Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine.
  • 2 Department of Medical Biometry, Institute of Medical Biometry and Informatics, and.
  • 3 Department of Pediatrics and Adolescent Medicine and.
  • 4 Department of General Pathology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany. , (Germany)
  • 5 Department of Pathology, University Medical Center Mainz, Mainz, Germany. , (Germany)
  • 6 Division of Pediatric Nephrology, Children's Mercy Hospital, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
  • 7 Department of Pediatrics 1, University Hospital of Strasbourg, Strasbourg, France. , (France)
  • 8 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria; and. , (Austria)
  • 9 Department of Pediatric Nephrology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. , (Germany)
  • 10 Christian Doppler Laboratory for Molecular Stress Research in Peritoneal Dialysis, Medical University of Vienna, Vienna, Austria. , (Austria)
  • 11 Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, [email protected]
Published Article
Journal of the American Society of Nephrology
American Society of Nephrology
Publication Date
Jan 01, 2018
DOI: 10.1681/ASN.2017040436
PMID: 29046343


Cardiovascular disease (CVD) is the leading cause of increased mortality in patients with CKD and is further aggravated by peritoneal dialysis (PD). Children are devoid of preexisting CVD and provide unique insight into specific uremia- and PD-induced pathomechanisms of CVD. We obtained peritoneal specimens from children with stage 5 CKD at time of PD catheter insertion (CKD5 group), children with established PD (PD group), and age-matched nonuremic controls (n=6/group). We microdissected omental arterioles from tissue layers not directly exposed to PD fluid and used adjacent sections of four arterioles per patient for transcriptomic and proteomic analyses. Findings were validated in omental and parietal arterioles from independent pediatric control (n=5), CKD5 (n=15), and PD (n=15) cohorts. Transcriptomic analysis revealed differential gene expression in control versus CKD5 arterioles and in CKD5 versus PD arterioles. Gene ontology analyses revealed activation of metabolic processes in CKD5 arterioles and of inflammatory, immunologic, and stress-response cascades in PD arterioles. PD arterioles exhibited particular upregulation of the complement system and respective regulatory pathways, with concordant findings at the proteomic level. In the validation cohorts, PD specimens had the highest abundance of omental and parietal arteriolar C1q, C3d, terminal complement complex, and phosphorylated SMAD2/3, a downstream effector of TGF-β Furthermore, in the PD parietal arterioles, C1q and terminal complement complex abundance correlated with the level of dialytic glucose exposure, abundance of phosphorylated SMAD2/3, and degree of vasculopathy. We conclude that PD fluids activate arteriolar complement and TGF-β signaling, which quantitatively correlate with the severity of arteriolar vasculopathy. Copyright © 2018 by the American Society of Nephrology.

Report this publication


Seen <100 times