Peritoneal Fibrosis Clinical Trial
Official title:
Epigenetic Determinants of Peritoneal Fibrosis
Peritoneal dialysis (PD) is a type of kidney replacement therapy for patients with chronic kidney disease where the peritoneal membrane is used to filter the blood. Exposure to PD fluid results in scarring of the peritoneal membrane and increased blood vessel growth. This condition can progress even when peritoneal dialysis is stopped. Therefore, the investigators hypothesize glucose in the dialysis fluid may result in DNA modifications called epigenetic changes. These changes modify how genes are expressed and how cells function. The investigators want to study these epigenetic changes and the effect on peritoneal membrane scarring, blood vessel growth and peritoneal membrane function.
There is considerable evidence that epigenetic changes in effector cells underlie the
progressive nature of fibrogenic diseases. The investigators have developed an ex-vivo
mesothelial cell culture system based on work by Aroeira and colleagues. Ex vivo cell
cultures were treated with the DNA methyltransferase inhibitor 5-AZA for 72 hours. Overall,
the investigators found that 11 of 14 patients' cells showed an increase in the
E-Cad/alpha-SMA ratio with treatment to 5-AZA, indicating a return to a more epithelial-like
phenotype and supporting an epigenetic mechanism of progressive fibrosis. The investigators
hope to identify DNA methylation patterns associated with glucose exposure and peritoneal
membrane solute transport in PD patients.
The investigators will take the peritoneal effluent from an overnight dwell from patients
within one month of initiation of dialysis. The overnight effluent is centrifuged and the
pellet is washed and cells are grown in DMEM medium. At confluence, cells are passaged into 2
flasks then taken for DNA and RNA. At 12 months, a second overnight peritoneal effluent
sample will be obtained. The investigators will also gather demographic data (patient's age,
diabetes, occurrence of peritonitis, cumulative PD prescription including total glucose
exposure, use of icodextrin, and the results of a peritoneal equilibrium test carried out for
clinical purposes between 3 and 12 months from the start of peritoneal dialysis). The
investigators will use whole genome DNA methylation analysis to assess epigenetic changes in
mesothelial cells from incident PD patients.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT00173056 -
The Factors Predicting Change of Peritoneal Transport Characters in Peritoneal Dialysate
|
N/A |