EMT in Peritoneal Dialysis Patients

NCT ID: NCT03458819

Last Updated: 2021-02-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 22 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-03-20
• Study Completion Date: 2019-05-22

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.

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.

Conditions

Peritoneal Dialysis Complication

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Control

Patients on neither active Vitamin D or a statin

Isolation of peritoneal mesothelial cells

Intervention Type: 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.

Vit D

Patients on active Vitamin D but not a statin

Isolation of peritoneal mesothelial cells

Intervention Type: 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.

Statin

Patients on a statin but not active Vitamin D

Isolation of peritoneal mesothelial cells

Intervention Type: 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.

D + Statin

Patients on both active Vitamin D and a statin

Isolation of peritoneal mesothelial cells

Intervention Type: 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.

Interventions

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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Isaac Teitelbaum, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Countries

United States

Other Identifiers

18-0401

Identifier Type: -

Identifier Source: org_study_id