EMT in Peritoneal Dialysis Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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Epithelial to Mesenchymal Transition (EMT) in Peritoneal Dialysis Patients

Conditions
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Peritoneal Dialysis Complication

Intervention / Treatment
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* Diagnostic Test: Isolation of peritoneal mesothelial cells


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control<br>Patients on neither active Vitamin D or a statin | Diagnostic Test: Isolation of peritoneal mesothelial cells<br>* 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.<br>|
| Vit D<br>Patients on active Vitamin D but not a statin | Diagnostic Test: Isolation of peritoneal mesothelial cells<br>* 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.<br>|
| Statin<br>Patients on a statin but not active Vitamin D | Diagnostic Test: Isolation of peritoneal mesothelial cells<br>* 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.<br>|
| D + Statin<br>Patients on both active Vitamin D and a statin | Diagnostic Test: Isolation of peritoneal mesothelial cells<br>* 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.<br>|

What is the study measuring?
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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. |