EMT in Peritoneal Dialysis Patients
| Status: | Not yet recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 18 - 90 |
| Updated: | 12/30/2018 |
| Start Date: | January 2019 |
| End Date: | December 2023 |
| Contact: | Isaac Teitelbaum, MD |
| Email: | isaac.teitelbaum@ucdenver.edu |
| Phone: | 720/848-7601 |
Epithelial to Mesenchymal Transition (EMT) in Peritoneal Dialysis Patients
Approximately 10-11% of end stage kidney disease patients worldwide utilize peritoneal
dialysis (PD) as their method of renal replacement therapy. Over time, the peritoneal
membrane often undergoes anatomic and functional changes due to the process of epithelial to
mesenchymal transition (EMT). EMT is characterized by increases in pro-inflammatory and
pro-angiogenic cytokines. In this process, the mesothelial cells lining the peritoneal
membrane are denuded and change their morphology to one more closely resembling fibroblasts.
These fibroblasts invade the submesothelial zone of the peritoneal membrane resulting in
marked fibrosis, and the pro-angiogenic cytokines cause an increase in neovascularization.
Jointly, these processes culminate in impaired function of the peritoneal membrane and often
limit the duration of effective PD therapy.
In vitro studies in cultured human peritoneal mesothelial cells (HPMCs) and in vivo studies
in rodent models of PD have demonstrated that the use of active Vitamin D receptor agonists
or statins may attenuate this process of EMT. These are both classes of drugs that are
commonly in use by patients on PD. The investigators goal is to determine whether either or
both of these drugs might attenuate the process of EMT in patients performing PD.
dialysis (PD) as their method of renal replacement therapy. Over time, the peritoneal
membrane often undergoes anatomic and functional changes due to the process of epithelial to
mesenchymal transition (EMT). EMT is characterized by increases in pro-inflammatory and
pro-angiogenic cytokines. In this process, the mesothelial cells lining the peritoneal
membrane are denuded and change their morphology to one more closely resembling fibroblasts.
These fibroblasts invade the submesothelial zone of the peritoneal membrane resulting in
marked fibrosis, and the pro-angiogenic cytokines cause an increase in neovascularization.
Jointly, these processes culminate in impaired function of the peritoneal membrane and often
limit the duration of effective PD therapy.
In vitro studies in cultured human peritoneal mesothelial cells (HPMCs) and in vivo studies
in rodent models of PD have demonstrated that the use of active Vitamin D receptor agonists
or statins may attenuate this process of EMT. These are both classes of drugs that are
commonly in use by patients on PD. The investigators goal is to determine whether either or
both of these drugs might attenuate the process of EMT in patients performing PD.
Patients will perform a standard 2 Liter overnight dwell with the usual 2.5% dextrose PD
solution. This will be done the night before a routinely scheduled visit to the home dialysis
clinic. In the clinic the fluid will be drained in usual fashion and the fluid- which would
otherwise be discarded- will be analyzed as below:
HPMCs will be isolated as previously described by Kinashi et al. and stored at -80 degrees
until analysis. Changes in the protein expression of EMT markers such as E-cadherin, alpha
smooth muscle actin (a-SMA), Snail, and fibronectin in the HPMCs will be evaluated by Western
blot analysis.
solution. This will be done the night before a routinely scheduled visit to the home dialysis
clinic. In the clinic the fluid will be drained in usual fashion and the fluid- which would
otherwise be discarded- will be analyzed as below:
HPMCs will be isolated as previously described by Kinashi et al. and stored at -80 degrees
until analysis. Changes in the protein expression of EMT markers such as E-cadherin, alpha
smooth muscle actin (a-SMA), Snail, and fibronectin in the HPMCs will be evaluated by Western
blot analysis.
Inclusion Criteria:
- Patients > 18 years of age
- Patients on Peritoneal dialysis, and
- Patients that meet at least one of the criteria noted in the Population Description.
Exclusion Criteria:
- Patients with Recent peritonitis
We found this trial at
1
site
13001 E 17th Pl
Aurora, Colorado 80045
Aurora, Colorado 80045
(303) 724-5000
Phone: 720-848-7601
University of Colorado Anschutz Medical Campus Located in the Denver metro area near the Rocky...
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