Icodextrin Effects on Glucose Transporter Activation and Mediators of Fibrosis
| Status: | Recruiting |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | 19 - 100 |
| Updated: | 4/21/2016 |
| Start Date: | May 2014 |
| End Date: | May 2017 |
| Contact: | Leslie Jackson, R.N. |
| Email: | lesliea@uab.du |
| Phone: | 205-996-2227 |
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.
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.
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.
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.
Inclusion Criteria:
- 19 years of age or older
- On Peritoneal Dialysis
Exclusion Criteria:
We found this trial at
1
site
Birmingham, Alabama 35294
Principal Investigator: Eric Wallace, MD
Phone: 205-975-9676
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