Circulating lncRNA and CV Morbidities in CKD and ESRD

NCT ID: NCT02304471

Last Updated: 2014-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

360 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-11-30

Study Completion Date

2018-12-31

Brief Summary

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Cardiovascular disease is the major cause of morbidity and death in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). The mechanisms linking impaired renal function and increased risk for cardiovascular diseases, however, remain elusive.

Long non-coding RNAs (lncRNAs) is a heterogeneous group of non-coding transcripts longer than 200 nucleotides. While the roles of lncRNAs in human diseases including cancer and neurodegenerative disorders are beginning to emerge, it remains unclear how lncRNA regulation contributes to cardiovascular complications in patients with renal dysfunction.

In this proposal, the investigators seek to apply next-generation sequencing technology to investigate circulating lncRNA expression in control subjects and in patients with CKD and ESRD. The investigators will test the hypothesis that circulating lncRNA expression signature can reflect the underlying kidney disease states in patients with CKD and ESRD. A gene co-expression network analysis will be conducted to identify lncRNAs that are functionally involved in the pathogenesis of CKD and ESRD. Next, the investigators will identify circulating lncRNAs that are indicative of cardiovascular dysfunction in ESRD patients. Finally, the investigators propose to test the hypothesis that circulating lncRNAs can be novel prognostic biomarkers to predict cardiovascular outcomes and renal function progression in CKD patients. The results from these experiments will lead to better understanding of how circulating lncRNAs contribute to uremic cardiovascular complications and renal function progression.

Detailed Description

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Cardiovascular disease is the major cause of morbidity and death in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Patients with CKD and ESRD are at high risk for myocardial dysfunction, ischemia and heart failure. The mechanisms linking impaired renal function and increased risk for cardiovascular diseases, however, remain elusive. In addition, conventional therapeutics proven effective in reducing cardiovascular events in general population fail to provide similar benefits in uremic patients. There is a clear need to identify novel mediators of cardiovascular complications in uremic patients to provide insights into the pathogenesis, to tailor clinical care based on cardiovascular risks, and to develop new therapeutic strategies.

It has become increasingly clear that the transcription of the eukaryotic genome is far more pervasive and complex than previously appreciated. While the expression of messenger RNAs (mRNAs) and microRNAs (miRNAs) account for only \~1% of all transcribed species, up to 90% of the mammalian genome is transcribed as long non-coding RNAs (lncRNAs), a heterogeneous group of non-coding transcripts longer than 200 nucleotides. LncRNAs have been shown to be functional and involved in specific physiological and pathological processes through epigenetic, transcriptional and post-transcriptional mechanisms. While the roles of lncRNAs in human diseases including cancer and neurodegenerative disorders are beginning to emerge, it remains unclear how lncRNA regulation contributes to cardiovascular complications in patients with renal dysfunction.

In this proposal, we seek to apply next-generation sequencing technology to investigate circulating (plasma and peripheral blood mononuclear cells \[PBMC\]) lncRNA expression in control subjects and in patients with CKD and ESRD. We will test the hypothesis that circulating lncRNA expression signature can reflect the underlying kidney disease states in patients with CKD and ESRD. A gene co-expression network analysis will be conducted to identify lncRNAs that are functionally involved in the pathogenesis of CKD and ESRD. Next, we will identify circulating lncRNAs that are indicative of cardiovascular dysfunction in ESRD patients. The hypothesis that circulating lncRNAs can be used to predict the progression of myocardial dysfunction, the occurrence of adverse cardiovascular events and death among patients with ESRD, will be tested. The sensitivity and specificity of using circulating lncRNAs to predict cardiovascular function/outcomes in ESRD patients will be tested prospectively in an independent ESRD population. Finally, we propose to test the hypothesis that circulating lncRNAs can be novel prognostic biomarkers to predict cardiovascular outcomes and renal function progression in CKD patients. The results from these experiments will lead to better understanding of how circulating lncRNAs contribute to uremic cardiovascular complications and renal function progression. These experiments will also help to design better diagnostic and prognostic tools in CKD/ESRD patients, as well as to develop novel therapeutic strategies to treat or prevent CKD progression and uremic cardiovascular complications.

Conditions

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Chronic Kidney Disease End-stage Renal Disease

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Control

healthy subjects

No interventions assigned to this group

CKD

chronic kidney disease

No interventions assigned to this group

ESRD

end-stage renal disease

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* 1.Adult patients with various stages 1-5 of CKD will be enrolled at outpatient clinic. Definition and staging of CKD were defined by estimated glomerular filtration rate by the Modification of Diet in Renal Disease study equation.
* 2.Patients with ESRD under maintenance hemodialysis or peritoneal dialysis will also be included.

Exclusion Criteria

* 1.age younger than 20 years or older than 80 years.
* 2.pregnant woman.
* 3.patients already received kidney transplantation.
* 4.recent hospitalization within previous one month.
* 5.for ESRD patients, receiving maintenance hemodialysis or peritoneal dialysis for less than 3 months.
Minimum Eligible Age

20 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Taiwan University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Chun-Fu Lai, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

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National Taiwan University Hospital

Taipei, Taiwan, Taiwan

Site Status RECRUITING

Countries

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Taiwan

Central Contacts

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Chun-Fu Lai, M.D.

Role: CONTACT

+886-2-23123456 ext. 63921

Facility Contacts

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Chun-Fu Lai, M.D.

Role: primary

+886-2-23123456 ext. 63921

Other Identifiers

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201409019RINB

Identifier Type: -

Identifier Source: org_study_id