EMT in Peritoneal Dialysis Patients

NCT03458819 | Completed

• 1 other identifier: 18-0401
• Study Type: observational
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Peritoneal Dialysis Complication

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (4)

Control

Patients on neither active Vitamin D or a statin

Diagnostic Test: Isolation of peritoneal mesothelial cells

Vit D

Patients on active Vitamin D but not a statin

Diagnostic Test: Isolation of peritoneal mesothelial cells

Statin

Patients on a statin but not active Vitamin D

Diagnostic Test: Isolation of peritoneal mesothelial cells

D + Statin

Patients on both active Vitamin D and a statin

Diagnostic Test: Isolation of peritoneal mesothelial cells

Interventions

Isolation of peritoneal mesothelial cells DIAGNOSTIC_TEST

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.

Control; D + Statin; Statin; Vit D

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• Patients \> 18 years of age
• Patients on Peritoneal dialysis, and
• Patients that meet at least one of the criteria noted in the Population Description.

You may not qualify if:

• Patients with Recent peritonitis

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Isolated human peritoneal mesothelial cells

Study Officials

• Isaac Teitelbaum, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2018
• First Posted: March 8, 2018
• Study Start: March 20, 2018
• Primary Completion: May 22, 2019
• Study Completion: May 22, 2019
• Last Updated: February 25, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)