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

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:

MedlinePlus related topics: Liver Transplantation

U.S. FDA Resources

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

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:

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Perico N, Benigni A, Bosco E, Rossini M, Orisio S, Ghilardi F, Piccinelli A, Remuzzi G. Acute cyclosporine A nephrotoxicity in rats: which role for renin-angiotensin system and glomerular prostaglandins? Clin Nephrol. 1986;25 Suppl 1:S83-8.

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Gallon L, Akalin E, Lynch P, Rothberg L, Parker M, Schiano T, Abecassis M, Murphy B. ACE gene D/D genotype as a risk factor for chronic nephrotoxicity from calcineurin inhibitors in liver transplant recipients. Transplantation. 2006 Feb 15;81(3):463-8.

Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002 Jul;62(1):237-44.

Parikh CR, Jani A, Mishra J, Ma Q, Kelly C, Barasch J, Edelstein CL, Devarajan P. Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. Am J Transplant. 2006 Jul;6(7):1639-45. PubMed PMID: 16827865.

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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 May 23, 2013