EMT in Peritoneal Dialysis Patients

Peritoneal Dialysis Complication Clinical Trial

Official title:

Epithelial to Mesenchymal Transition (EMT) in Peritoneal Dialysis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03458819
• Other study ID #: 18-0401
• Status: Completed
• Start date: March 20, 2018
• Est. completion date: May 22, 2019

Study information

• Verified date: February 2021
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: May 22, 2019
• Est. primary completion date: May 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Peritoneal Dialysis Complication

Intervention

Diagnostic Test:
• Isolation of peritoneal mesothelial cells
HPMCs will be isolated and stored at -80 degrees until analysis. Changes in the protein expression of EMT markers such as E-cadherin, a- SMA, Snail, and fibronectin in the HPMCs will be evaluated by Western blot analysis.

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in the protein expression of EMT markers	The goal of this study is to determine whether either or both of these drugs, Vitamin D receptor agonists or statins, might attenuate the process of EMT in peritoneal mesothelial cells. Changes in the protein expression of EMT markers such as E-cadherin, a- SMA, Snail, and fibronectin in the HPMCs will be evaluated by Western blot analysis.	One year or at the end of the study, whichever occurs first.