Icodextrin Effects on Glucose Transporter Activation and Mediators of Fibrosis
Condition: End Stage Renal Disease
MeSH terms: Kidney Failure, Chronic; Fibrosis
Study type: Observational [Patient Registry]

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 SGLT1 transporter establishing a mechanism that may
           explain the beneficial effects of icodextrin on peritoneal membrane transport.
    

Detailed description: 
      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 Davita Medical Record Number Person Entering Data
      first_name last_name Date of Birth sex race address Is the patient new to dialysis? Has the
      patient previously been on peritoneal dialysis. transfer Why was peritoneal dialysis stopped.
      Type of Start: Urgent start versus traditional start Anuric Urgent Start: Inpatient or
      Outpatient Admit Date for PD Initiation Date of Discharge for pd initiation Did the patient
      require hemodialysis during urgent start period Indication for Hemodialysis Number of
      Hemodialysis sessions Nonsurgical catheter issues Date of PD start Age at PD start Date of PD
      graduation Length of time to PD graduation Reason for Urgent start PD first_dialysis_modality
      Predialysis education type_predialysis_education Glomerular filtration rate at time of PD
      start Has the patient stopped PD Did the patient stop Peritoneal dialysis or did they
      transfer out? Date PD was stopped Length of time on dialysis Age PD stopped Reason PD stopped
      When the patient transferred, did they transfer with an access or a permacath Cause of death
      Cause of End Stage Renal Disease (ESRD) Comorbidities Has the patient had a kidney transplant
      Previous abdominal surgeries? Type of previous abdominal surgeries height Indication for
      Peritoneal Equilibration Test (PET Date of PET Type of PET 2 hour D/P Creatinine 4 hour D/P
      Creatinine Transporter type 2 hour D/D0 Glucose 4 hour D/D0 Glucose Initial PET glucose PD
      Glucose 4 hours Glucose Absorption PET Drain Volume Ultrafiltration PD Sodium 0 Hour PD
      Sodium 1 Hour PD Sodium 2 hour PD Sodium 4 Hour Serum Sodium Minimum PD Sodium Level Systolic
      Blood Pressure Diastolic Blood Pressure Mean Arterial Pressure Weight Body Mass Index
      Hemoglobin Albumin Ferritin Iron Transferrin Saturation Hemoglobin A1c Creatinine Potassium
      BUN Sodium Hco3 Total Protein total cholesterol HDL LDL Vitamin D 25 Phosphorus Calcium PTH
      Kt/V Does the patient have a last fill Icodextrin versus dianeal Midday Total Liters per day
      Total Liters Total 6 month glucose exposure Is the patient on icodextrin Date of Icodextrin
      start Length of time on icodextrin Kt/v prior to icodextrin Kt/V after icodextrin Reason
      icodextrin stopped Date Icodextrin stopped Length of time on icodextrin Has the patient had
      peritonitis Date of infection Polymicrobial Pathogen Gram Positive Methicillin Resistant Gram
      Negative Ciprofloxacin Resistant Fungal Did the patient have antibiotics prior to fungal
      peritonitis What antibiotic Did the patient receive fungal prophylaxis Is this relapsing or
      recurrent Has the patient been hospitalized Date of admission Length of time to first
      admission Date of Discharge Length of stay Reason for admit Hospitalization Outcome Cause of
      death

      Standard Operating Procedures: Patient recruitment will be from the University of Alabama at
      Birmingham Home Dialysis unit.

      Sample size: As there are no data on which to base the power calculation for this unique
      study on glucose transporters and their role in peritoneal membrane fibrosis, descriptive
      statistics will be used to gain insight into the proposed research questions. Continuous
      variables will be summarized with mean and standard deviation or median and interquartile
      range depending on the distribution. Categorical variables will be summarized with frequency
      and percentage.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        All patients over the age of 19 on Peritoneal Dialysis at the University of Alabama at
        Birmingham
      
Biospecimen description: 
      Biospecimens will be retained. Cells harvested from spent peritoneal dialysate will have RNA
      isolated and then cDNA will be preserved.

      Supernatent of spent peritoneal dialysate will be kept.
    
Keywords: Peritoneal Dialysis; Peritoneal Fibrosis; Glucose Transporters