EMT in Peritoneal Dialysis Patients

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.

Study Overview

• Status: Completed
• Conditions: Peritoneal Dialysis Complication
• Intervention / Treatment: Diagnostic test: Isolation of peritoneal mesothelial cells

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 22

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

PD patients > 18 years old. We propose to study 4 groups of 6 patients each:

1. Patients taking neither an active Vitamin D analogue nor a statin
2. Patients already taking an active Vitamin D analogue
3. Patients already taking a statin
4. Patients already taking both an active Vitamin D analogue and a statin

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control; Patients on neither active Vitamin D or a statin	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.
Vit D; Patients on active Vitamin D but not a statin	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.
Statin; Patients on a statin but not active Vitamin D	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.
D + Statin; Patients on both active Vitamin D and a statin	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Isaac Teitelbaum, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2018
• Primary Completion (Actual): May 22, 2019
• Study Completion (Actual): May 22, 2019

Study Registration Dates

• First Submitted: February 26, 2018
• First Submitted That Met QC Criteria: March 1, 2018
• First Posted (Actual): March 8, 2018

Study Record Updates

• Last Update Posted (Actual): February 25, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 18-0401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No