Clinical trial NCT02513615: Epigenetic Determinants of Peritoneal Fibrosis
Official title: Epigenetic Determinants of Peritoneal Fibrosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Peritoneal Fibrosis
Keywords: Fibrosis
Peritoneal Dialysis
Epigenetics
Peritoneal membrane injury
Glucose exposure
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2015-07-31
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with end stage renal disease recently started on peritoneal dialysis. Patients will be over the age of 18.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Patients with end stage renal disease recently started on peritoneal dialysis. Patients will be over the age of 18.

Exclusion Criteria:

-

Primary outcomes:
measure: DNA methylation pattern
timeFrame: 12 months
Secondary outcomes:
measure: DNA methylation and solute transport
timeFrame: 12 months
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare
state: Ontario
Study officials:
affiliation: McMaster University
name: Peter J Margetts, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: