Epigenetic Determinants of Peritoneal Fibrosis
調査の概要
状態
条件
詳細な説明
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.
研究の種類
入学 (実際)
連絡先と場所
研究場所
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Ontario
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Hamilton、Ontario、カナダ、L8N 4A6
- St. Joseph's Healthcare
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- Patients with end stage renal disease recently started on peritoneal dialysis. Patients will be over the age of 18.
Exclusion Criteria:
-
研究計画
研究はどのように設計されていますか？
デザインの詳細
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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DNA methylation pattern
時間枠：12 months
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DNA methylation pattern will be measured after 12 months of glucose exposure compared with a baseline sample.
Gene expression will be measured by Genome wide methylation analysis.
In the incident patients, a within-subject analysis will be carried out between the naive and 12 month cell culture sample.
Gene expression analysis will be performed with the statistical software R and "BioConductor", a collection of tools for gene expression analysis.
Gene-level summaries from Human HT-12 BeadChip data will be generated using the widely used Bioconductor package lumi, which includes background correction, variance stabilization and normalization of expression data.
The Linear Models for Microarray Analysis (LIMMA) package of Bioconductor will be used for differential expression analysis.
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12 months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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DNA methylation and solute transport
時間枠：12 months
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The investigators will correlate changes in DNA methylation with solute transport measured by a peritoneal equilibrium test and peritoneal glucose exposure.
Solute transport is calculated from the dialysate to plasma creatinine ratio which is obtained from the peritoneal equilibrium test.
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12 months
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協力者と研究者
スポンサー
捜査官
- 主任研究者：Peter J Margetts, MD PhD、McMaster University
研究記録日
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研究開始
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研究の完了 (実際)
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QC基準を満たした最初の提出物
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最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- 14CECPDNA1006
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