Peritoneal Protein Clearance Is a Function of Local Inflammation and Membrane Area Whereas Systemic Inflammation and Comorbidity Predict Survival of Incident Peritoneal Dialysis Patients.

Zanzhe Yu,Andrew Williams,Mark Lambie,Jun-Young Do,James Chess,Nicholas Topley,Simon J. Davies

doi:10.3389/fphys.2019.00105

Abstract

It is not clear whether the association of increased peritoneal protein clearance (PPCl) with worse survival on peritoneal dialysis (PD) is a consequence of either local or systemic inflammation or indicative of generalized endothelial dysfunction associated with comorbidity. To investigate this we determined the relationship of PPCl to comorbidity, membrane area (equivalent to low molecular weight peritoneal solute transport rate), local and systemic inflammation and hypoalbuminaemia, and for each of these with patient survival. 257 incident patients from three GLOBAL Fluid Study centers were included in this analysis. Clinical profiles were collected at baseline along with a peritoneal equilibration test, 24-h dialysate protein and paired plasma and dialysate cytokine measurements. Although peritoneal protein clearance was associated with increased age and severe comorbidity on univariate analysis, only dialysate IL-6, peritoneal solute transport rate, plasma albumin and cardiac comorbidities (ischaemic heart disease and left ventricular dysfunction) were independent explanatory variables on multivariate analysis. While peritoneal protein clearance and daily peritoneal protein loss were associated with survival in univariate analysis, on multivariate analysis only plasma IL-6, age, residual kidney function, comorbidity, and plasma albumin were independent predictors. Peritoneal protein clearance is primarily a function of peritoneal membrane area and local membrane inflammation. The association with comorbidity and survival is predominantly explained by its inverse relationship to hypoalbuminaemia, especially in diabetics.

Highlights

Peritoneal protein clearance (PPCl) has been shown to relate to comorbidity in several studies (Heaf et al, 2005; Szeto et al, 2005; Johansson and Haraldsson, 2006; Van Biesen et al, 2006; Perl et al, 2009; Sánchez-Villanueva et al, 2009; Balafa et al, 2011) and in many cases to worse survival on peritoneal dialysis (PD)
We have shown that PPCl is predominantly determined by peritoneal membrane area and local inflammation
SD recruited patients from the Stoke-on-Trent Center

Summary

Introduction

Peritoneal protein clearance (PPCl) has been shown to relate to comorbidity in several studies (Heaf et al, 2005; Szeto et al, 2005; Johansson and Haraldsson, 2006; Van Biesen et al, 2006; Perl et al, 2009; Sánchez-Villanueva et al, 2009; Balafa et al, 2011) and in many cases to worse survival on peritoneal dialysis (PD). Local peritoneal but not systemic inflammation is the main predictor of PSTR at the commencement of dialysis, (Lambie et al, 2013) reflecting small pore area, but could increase protein losses by causing a relative increase in large pore area. The purpose of this analysis was to distinguish between local versus systemic determinants of PPCl and determine how these relate to survival using a subgroup of centers in the Global Fluid Study in which peritoneal protein losses were measured

Methods

Results

Conclusion