Clinical Trial: Icodextrin Effects on Glucose Transporter Activation and Mediators of Fibrosis

Study Status: Completed
Recruit Status: Completed
Study Type: Observational [Patient Registry]

Official Title: Icodextrin Effects on Glucose Transporter Activation and Mediators of Fibrosis

Brief Summary:

The time on peritoneal dialysis may be limited for a significant number of patients that use this modality of renal replacement therapy due to the inability of the peritoneal membrane to clear solutes or achieve adequate ultrafiltration, termed peritoneal membrane failure (PMF). This can be devastating for patients who have become accustomed to the quality of life provided by peritoneal dialysis and who otherwise have done well on this therapy. There is clinical evidence suggesting that icodextrin preserves the peritoneal membrane transport characteristics which may be linked to reduced cumulative glucose exposure of the peritoneal mesothelial cells. Theories to explain the role of dextrose in PMF have focused for the most part on the high intracellular concentrations of glucose without consideration to the potential pathogenic role of the glucose transporters which allow glucose entry into the cell. Experimental evidence in non-mesothelial cell lines indicate that some cellular processes that occur under high glucose conditions may not be related to intracellular glucose metabolism but to the type of glucose transporter allowing glucose entry. 3,4 However, little is known about these glucose transporters in peritoneal mesothelial cells and their potential role in the development of PMF.

We hypothesize the following

• The presence of Sodium Glucose Co-transporter (SGLT1) on peritoneal mesothelial cells plays a role in PMF under hyperglycemic conditions.
• Regulation of pro-fibrotic mediators such as reactive oxidative species,transforming growth factor β, and vascular endothelial growth factor are modulated by SGLT1 activation by glucose rather than glucose metabolism or concentration.
• Icodextrin does not activate the SGL
  

  Detailed Summary:

  Participants enrolled in this study will have pertinent clinical information entered into a database. Participants will then have spent peritoneal dialysate collected at least every 6 months and analyzed for markers of fibrosis. Patients undergoing a special type of peritoneal dialysis start call urgent start peritoneal dialysis will have spent peritoneal dialysate collected more frequently at the start of peritoneal dialysis and then every 6 months. The results from the analysis of the peritoneal dialysate will then be correlated with data in the patient registry.

  Quality assurance- As this is a single center trial all data will be monitored by the PI. Data will be entered in a prospective manner into the database by a research coordinator. Every 6 months data will be checked for accuracy by comparing to data collected for routine clinical purposes by both the home dialysis unit which tracks all hospitalizations, peritonitis, exit site infections, technique failures. As well as the dialysis access database maintained by the University of Alabama at Birmingham.

  Source data verification- Data will come from both the history and physical of the primary investigator as well as electronic medical records at the University of Alabama at Birmingham and Falcon Electronic Health Record from Davita.

  Data Dictionary is as follows. Variable / Field Name study_id Is the patient restarting Peritoneal dialysis after stopping If the patient is restarting are they restarting with the same catheter or a new catheter Date of 1st Access Length of time catheter placed prior to use How was the catheter placed: Surgically vs. Interventional Radiology Open versus laparoscopic Lysis of Adhesions Omentopexy Type of PD Catheter Has the patient had a second access procedure Medical Record Number Davi
  Sponsor: University of Alabama at Birmingham
  

  Current Primary Outcome: Change in glucose transporter expression on peritoneal mesothelial cells [ Time Frame: baseline to 3 years ]
  
  

  Original Primary Outcome: Same as current
  
  

  Current Secondary Outcome:
  
  

  Original Secondary Outcome:
  
  Information By: University of Alabama at Birmingham
  

  Dates:
  Date Received: April 30, 2014
  Date Started: May 2014
  Date Completion:
  Last Updated: April 17, 2017
  Last Verified: April 2017