Clinical trial NCT03458819: EMT in Peritoneal Dialysis Patients
Official title: Epithelial to Mesenchymal Transition (EMT) in Peritoneal Dialysis Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Peritoneal Dialysis Complication
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2018-03-08
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

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

Primary outcomes:
measure: Changes in the protein expression of EMT markers
timeFrame: One year or at the end of the study, whichever occurs first.
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Isaac Teitelbaum, MD
role: PRINCIPAL_INVESTIGATOR
References: