Genetic Predisposition-Chronic Nephrotoxicity From CI-Liver Transplant Recipients-Potential Correlation-Urinary Biomarkers

This study has been completed.
Sponsor:
Collaborator:
Northwestern Memorial Hospital
Information provided by (Responsible Party):
Lorenzo Gallon, Northwestern University
ClinicalTrials.gov Identifier:
NCT00857844
First received: March 6, 2009
Last updated: May 1, 2013
Last verified: May 2013
  Purpose

The purpose of this study is to determine the relationship between genomic variants of components of the renin-angiotensin system and the development of kidney problems due to Calcineurin-inhibitors post liver transplant.Also the investigator will evaluate the relationship between chronic renal failure post liver transplant and the risk of death. A sample of blood and urine wil be examined to see how the patient's genes are arranged in order to determine the difference in genes between people which may explain who will develop chronic renal failure after having received a liver transplant.

The results may help us classify patients according to their risk and allow us to target their treatment to their individual need. In addition, it may ultimately lead to treatments that slows or prevents the development of chronic rejection.


Condition
Complication of Transplanted Liver

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Genetic Predisposition of Chronic Nephrotoxicity From Calcineurin Inhibitors in Liver Transplant Recipients, Potential Correlation With Urinary Biomarkers

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • To investigate, in liver transplant patients, the role of urinary biomarkers as indirect indices of chronic nephrotoxicity from CI and associate, where possible, urinary biomarkers to genomic variants of the angiotensin converting [ Time Frame: At time of enrollment ] [ Designated as safety issue: No ]
    Blood draw (20cc) and urine collection (80cc).


Secondary Outcome Measures:
  • The study will also evaluate if specific demographic characteristics are associated with an increased risk of nephrotoxic damage from CI. [ Time Frame: At time of enrollment ] [ Designated as safety issue: No ]
    Blood draw (20cc)

  • Organ transplant tolerance in subjects who are currently using immunosuppressant medications. [ Time Frame: One additional blood draw - follow-up time point ] [ Designated as safety issue: No ]
    Blood draw (18cc).


Biospecimen Retention:   Samples With DNA
  • Urine will be collected from all patients in the 3 groups and analyzed for biomarkers of interstitial fibrosis and proximal tubule injury. Specific biomarkers that will be tested are: urinary TGF-beta1, kidney injury molecule-1 and angiotensinogen. Urinary biomarkers will be normalized to creatinine and analyzed using an ELISA assay.
  • An additional 18mls of blood will be collected. This blood will be used to study organ transplant tolerance in subjects who are currently using immunosuppressant medications.

Enrollment: 207
Study Start Date: July 2007
Study Completion Date: May 2012
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts
Group 1
Normal GFR (>90ml/min/1.73m2). Stage I CKD
Group 2
GFR between 30-59ml/min/1.73m2. Stage III CKD
Group 3
GFR between 15-29ml/min/1.72m2. Stage IV CKD

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

This study will be conducted in liver transplant recipients. We are planning to collect data and genotyping in 650 liver transplant recipients. Patients who satisfy the following inclusion/exclusion criteria will be eligible for the study:

Criteria

Inclusion Criteria:

  • Informed consent
  • Males and females > 18 years old
  • Liver transplant recipients who have received a liver transplant at least 6 months ago
  • Liver transplant recipients receiving a maintenance immunosuppression.

Exclusion Criteria:

  • Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the study
  • Pre-existing known kidney disease before liver transplantation
  • Multi-organ transplant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00857844

Locations
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Northwestern Memorial Hospital
Investigators
Principal Investigator: Lorenzo Gallon, M.D. Northwestern University, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation
  More Information

Publications:
Amer H, Lieske J, Grande J, Stegall M, Larson T. Urinary TGF-beta1 predicts progressive renal allograft fibrosis on one year protocol biopsies. Abstract, ASN, 2006. San Diego

Responsible Party: Lorenzo Gallon, Associate Professor, Northwestern University
ClinicalTrials.gov Identifier: NCT00857844     History of Changes
Other Study ID Numbers: STU8309 0773-018
Study First Received: March 6, 2009
Last Updated: May 1, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Northwestern University:
Chronic Nephrotoxicity
Kidney dysfunction post liver transplant
Urinary biomarkers of chronic nephrotoxicity from CI

Additional relevant MeSH terms:
Disease Susceptibility
Genetic Predisposition to Disease
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on October 20, 2014