Soluble CD59 in peritoneal dialysis: a potential biomarker for peritoneal membrane function

Abstract

Introduction Various studies have reported the importance of complement regulators in preventing mesothelial damage during peritoneal dialysis (PD). Its assessment, however, is limited in clinical practice due to the lack of easy access to the peritoneal membrane. Recently, a soluble form of the complement regulatory protein CD59 (sCD59) has been described. We therefore aimed to investigate the role of sCD59 in PD. Methods Plasma sCD59 was measured in 48 PD patients, 41 hemodialysis patients, 15 non-dialysis patients with chronic kidney disease and 14 healthy controls by ELISA (Hycult; HK374-02). Additionally, sCD59 and sC5b-9 were assessed in the peritoneal dialysate. Results sCD59 and sC5b-9 were detectable in the peritoneal dialysate of all patients, and marginally correlated (r = 0.27, P = 0.06). Plasma sCD59 levels were significantly higher in PD patients than in patients with chronic kidney disease and healthy controls, but did not differ from hemodialysis patients. During follow-up, 19% of PD patients developed peritoneal membrane failure and 27% of PD patients developed loss of residual renal function. In adjusted models, increased sCD59 levels in the dialysate (HR 3.44, 95% CI 1.04–11.40, P = 0.04) and in plasma (HR 1.08, 95% CI 1.01–1.17, P = 0.04) were independently associated with the occurrence of peritoneal membrane failure. Higher plasma levels of sCD59 were also associated with loss of residual renal function (HR 1.10, 95% CI 1.04–1.17, P < 0.001). Conclusions Our study suggests that sCD59 has potential as a biomarker to predict peritoneal membrane function and loss of residual renal function in PD, thereby offering a tool to improve patient management. Graphic abstract

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

“…However, the PDF/plasma ratio of Factor D (24 kDa) was similar to those predicted by the three-pore model (14.5%) and regression lines (14.6%), 10,23 as well as to ratios found for other molecules of similar size (16% for sCD59 [18–21 kDa]). 11 Furthermore, considering that levels of C1q, MBL and Properdin correlated with protein loss and generally corresponded to 1–2% of plasma levels, vascular leakage seems the most likely source for complement in the PDF. 15 In addition, complement activation has previously been suggested to further enhance protein loss, which may partially explain the correlations between complement levels and protein loss to the PDF.…”

“…2 However, we have recently demonstrated that shedding of CD59 is not associated with local complement activation in PD. 11 Other proposed mechanisms of complement activation in PD include (i) microorganisms due to the presence of the peritoneal catheter and (ii) cellular debris as a result of peritoneal damage by bioincompatible solutions as well as direct effects of glucose and glucose degradation products (GDP) exposure on complement, in addition to leakage of complement proteins from the circulation to the peritoneal cavity leading to their accumulation and activation. 9,10 The current study aims to investigate whether PD is associated with systemic and/or local complement activation in stable adult patients without peritonitis.…”

Long-term peritoneal dialysate exposure modulates expression of membrane complement regulators in human peritoneal mesothelial cells

“…With the use of conventional low-pH PDF, impairment of CD55 expression was shown in injured peritoneum ( 13 ). In peritoneal vessels under long-term PD therapy, impairment of CD59 was also reported and soluble CD59 was increased in PDF ( 23 ). Although CD55 expression correlated inversely with D/P Cr in our previous report ( 14 ), D/P Cr did not significantly change in the present cases during 1 year of observation, and no significant changes in CD55 expression were observed in HPMCs.…”

Current Insights into Cellular Determinants of Peritoneal Fibrosis in Peritoneal Dialysis: A Narrative Review

“…Several other molecular markers are also mentioned as having the potential to be used in the diagnosis and monitoring of peritoneal membrane inflammation, for example, microRNA and aquaporin-1 (AQP1), which are excreted by mesothelium cells [ 6 , 20 ]. Secreted protein acidic and rich in cysteine or SPARC (osteonectin), monocyte chemoattractant protein (MCP)-1, and soluble cluster differentiation (sCD)-59 were also identified as potential biomarkers in PD effluent, where their increase is associated with peritoneal membrane failure and death [ 40 , 41 ]. Another study documented the potential of effluent decoy receptor 2 (eDcR2) as a biomarker of peritoneal fibrosis in PD patients.…”