The Impact of Delflex on Mesothelial Cell Viability and Peritoneal Transport
The Impact of Delflex on Mesothelial Cell Viability and Peritoneal Transport
The purpose of this study is to evaluate the impact of Delflex neutral pH (a biocompatible
 peritoneal dialysis solution) on mesothelial cell viability and peritoneal transport.
In spite of its benefits, many peritoneal dialysis patients ultimately have to switch
 dialysis therapy to hemodialysis secondary to technique failure. Numerous etiologies for
 peritoneal dialysis treatment failure exist and include the continuous exposure of the
 peritoneal membrane to bioincompatible dialysis solutions with acidic pH and high content of
 glucose degradation products. These factors have been implicated in mesothelial cell loss,
 fibrosis and neovascularization, resulting in alterations in solute transport and
 ultrafiltration failure. Novel peritoneal dialysis solutions with neutral pH and low
 concentrations of glucose degradation products have recently been developed to improve
 biocompatibility and ameliorate the consequences of membrane damage with conventional
 peritoneal dialysis solutions. While novel peritoneal dialysis solutions have been available
 outside the United States for several years, Delflex Neutral pH has only recently been
 approved for use in the United States. Thus, the majority of all the data supporting the
 benefits of these novel solutions comes from locations outside of the United States.

 The central question regarding the novel peritoneal dialysis solution is whether long term
 use will result in better preservation of the peritoneal membrane to support dialysis.
 Ultimately, this can only be determined with studies comparing long term outcomes of patients
 using the various solutions. However, given the expected availability in the United States
 and the potential benefits of the novel peritoneal dialysis solutions long term studies
 comparing outcomes with conventional solutions raises ethical concerns. Therefore, surrogate
 markers for peritoneal membrane integrity are necessary. Short term studies using various
 surrogate markers to assess mesothelial cell mass and peritoneal inflammation such as Cancer
 Antigen 125 (CA125) and pro-inflammatory cytokines have been reported, but it is uncertain
 how well these markers predict long term outcome. Recently, a novel approach to predict
 outcome has been reported, using mesothelial cell shedding and apoptosis. The number of
 mesothelial cells and the number of apoptotic mesothelial cells in a standard 8 hour dialysis
 dwell were reported to correlate well with deterioration of peritoneal dialysis
 characteristics over a one year follow-up. The authors concluded that mesothelial cell
 shedding and apoptosis are reliable predictors of peritoneal membrane deterioration.

 The purpose of this study is to evaluate the impact of Delflex neutral pH (a biocompatible
 peritoneal dialysis solution) on mesothelial cell viability and peritoneal transport. The
 study will specifically compare mesothelial cell shedding and apoptosis in the peritoneal
 dialysis effluent after exposure to Delflex neutral pH solution and conventional peritoneal
 dialysis solution. Cancer Antigen 125 (CA125)levels (indicative of mesothelial cell mass) and
 connective tissue growth factor (CTGF) levels (a marker of inflammation) will be measured in
 the spent dialysate to determine whether these markers correlate with cell shedding and
 apoptosis. The study will also characterize the transport of glucose degradation products
 (GDPs) and advanced glycosylation end products (AGEs) across the mesothelial cells after
 exposure to Delflex neutral pH solution versus conventional peritoneal dialysis solution.
Inclusion Criteria:

 -  ≥ 18 years of age

 -  Incident or prevalent patients with End Stage Kidney disease treated with either CAPD
 (continuous ambulatory peritoneal dialysis) or CCPD (continuous cycling peritoneal
 dialysis)

 -  Patients must maintain modality of either CAPD or CCPD throughout duration of study

 -  Able to provide informed consent

 Exclusion Criteria:

 -  Pregnant or lactating women

 -  Recent (< 3 months) history of peritonitis

 -  CCPD utilizing Baxter cycler (due to inability to connect Delflex solution to cycler)

 -  Anticipated renal transplant within 6 months of enrollment