Genomics of Chronic Renal Allograft Rejection (The GoCAR Study)

NCT00611702 | Completed DMC

• 1 other identifier: DAIT GTCRP-01
• Study Type: observational
• Target: 588
• Locations: 2 countries
• Sites: 5

Brief Summary

Doctors have had success preventing certain types of kidney transplant rejection by suppressing the immune system. However, an individual's genetic make-up and the strength of an immune response to a transplant may also determine whether a transplanted organ is rejected. The purpose of this study is to look at the genetic profile and immune response of people who have had kidney transplants and to correlate the findings with kidney transplant rejection episodes. Donor genetic profiles will also be studied and correlated with the recipient's information.

Conditions

Kidney Transplantation

Keywords

ELISPOT; RT-PCR; Luminex; Genomics

Outcome Measures

Primary Outcomes (3)

• Correlation of chronic rejection with patterns and intensity of recipient alloreactivity

  Throughout study

• Correlation of chronic rejection with recipient gene expression profiles

  Throughout study

• Correlation of chronic rejection with polymorphic variants of specific susceptibility genes in donor and recipient

  Throughout study

Secondary Outcomes (5)

• Correlation of the development of donor specific antibodies after transplant and/or the presence of C4d staining with patterns and intensity of recipient alloreactivity

  Throughout study

• Correlation of the development of donor specific antibodies after transplant and/or the presence of C4d staining with recipient gene expression profiles

  Throughout study

• Correlation of the development of donor-specific antibodies after transplant and/or the presence of C4d staining of peritubular basement membranes on renal biopsy with polymorphic variants of specific susceptibility genes in donor and recipient

  Throughout study

• Correlation of the development of donor-specific antibodies after transplant and/or the presence of C4d staining of peritubular basement membranes on renal biopsy with chronic rejection

  Throughout study

• Correlation of the development of donor-specific antibodies after transplant and/or the presence of C4d staining of peritubular basement membranes on renal biopsy allograft dysfunction as defined by the protocol

  Throughout study

Interventions

Kidney biopsy PROCEDURE

Kidney biopsy (recipients only) will be obtained for RT-PCR, microarray analyses and histology.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals receiving a kidney transplant and individuals who are donating a kidney

You may qualify if:

• Kidney transplant candidates from living or deceased donors
• Male or female, ages 18-75 years
• Subject must be able to understand and provide written informed consent
• Living Donors - Recipient also consents to participate in the study

You may not qualify if:

• Presence of Donor Specific Antibodies in living donor recipients prior to transplantation OR positive cross match according to site-specific technique in cadaveric donor recipients
• Recipients of multiple organ transplants, with the exception of kidney/pancreas transplants.
• Inability or unwillingness to comply with the study protocol.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (5)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mt. Sinai School of Medicine

New York, New York, 10029, United States

Location

University of Wisconsin-Madison

Madison, Wisconsin, 53706, United States

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

Related Publications (10)

• Vitalone MJ, O'Connell PJ, Wavamunno M, Fung CL, Chapman JR, Nankivell BJ. Transcriptome changes of chronic tubulointerstitial damage in early kidney transplantation. Transplantation. 2010 Mar 15;89(5):537-47. doi: 10.1097/TP.0b013e3181ca7389.

  PMID: 20147884 BACKGROUND

• Vitalone MJ, O'Connell PJ, Jimenez-Vera E, Yuksel A, Wavamunno M, Fung CL, Chapman JR, Nankivell BJ. Epithelial-to-mesenchymal transition in early transplant tubulointerstitial damage. J Am Soc Nephrol. 2008 Aug;19(8):1571-83. doi: 10.1681/ASN.2007050580. Epub 2008 May 14.

  PMID: 18480317 BACKGROUND

• Dinavahi R, George A, Tretin A, Akalin E, Ames S, Bromberg JS, Deboccardo G, Dipaola N, Lerner SM, Mehrotra A, Murphy BT, Nadasdy T, Paz-Artal E, Salomon DR, Schroppel B, Sehgal V, Sachidanandam R, Heeger PS. Antibodies reactive to non-HLA antigens in transplant glomerulopathy. J Am Soc Nephrol. 2011 Jun;22(6):1168-78. doi: 10.1681/ASN.2010111183. Epub 2011 May 12.

  PMID: 21566057 BACKGROUND

• Kruger B, Krick S, Dhillon N, Lerner SM, Ames S, Bromberg JS, Lin M, Walsh L, Vella J, Fischereder M, Kramer BK, Colvin RB, Heeger PS, Murphy BT, Schroppel B. Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3390-5. doi: 10.1073/pnas.0810169106. Epub 2009 Feb 13.

  PMID: 19218437 BACKGROUND

• Wavamunno MD, O'Connell PJ, Vitalone M, Fung CL, Allen RD, Chapman JR, Nankivell BJ. Transplant glomerulopathy: ultrastructural abnormalities occur early in longitudinal analysis of protocol biopsies. Am J Transplant. 2007 Dec;7(12):2757-68. doi: 10.1111/j.1600-6143.2007.01995.x. Epub 2007 Oct 6.

  PMID: 17924997 BACKGROUND

• Gurkan S, Luan Y, Dhillon N, Allam SR, Montague T, Bromberg JS, Ames S, Lerner S, Ebcioglu Z, Nair V, Dinavahi R, Sehgal V, Heeger P, Schroppel B, Murphy B. Immune reconstitution following rabbit antithymocyte globulin. Am J Transplant. 2010 Sep;10(9):2132-2141. doi: 10.1111/j.1600-6143.2010.03210.x.

  PMID: 20883548 BACKGROUND

• Farris AB, Adams CD, Brousaides N, Della Pelle PA, Collins AB, Moradi E, Smith RN, Grimm PC, Colvin RB. Morphometric and visual evaluation of fibrosis in renal biopsies. J Am Soc Nephrol. 2011 Jan;22(1):176-86. doi: 10.1681/ASN.2009091005. Epub 2010 Nov 29.

  PMID: 21115619 BACKGROUND

• Schroppel B, Kruger B, Walsh L, Yeung M, Harris S, Garrison K, Himmelfarb J, Lerner SM, Bromberg JS, Zhang PL, Bonventre JV, Wang Z, Farris AB, Colvin RB, Murphy BT, Vella JP. Tubular expression of KIM-1 does not predict delayed function after transplantation. J Am Soc Nephrol. 2010 Mar;21(3):536-42. doi: 10.1681/ASN.2009040390. Epub 2009 Dec 17.

  PMID: 20019169 BACKGROUND

• Luan Y, Mosheir E, Menon MC, Wilson D, Woytovich C, Ochando J, Murphy B. Monocytic myeloid-derived suppressor cells accumulate in renal transplant patients and mediate CD4(+) Foxp3(+) Treg expansion. Am J Transplant. 2013 Dec;13(12):3123-31. doi: 10.1111/ajt.12461. Epub 2013 Sep 18.

  PMID: 24103111 BACKGROUND

• O'Connell PJ, Zhang W, Menon MC, Yi Z, Schroppel B, Gallon L, Luan Y, Rosales IA, Ge Y, Losic B, Xi C, Woytovich C, Keung KL, Wei C, Greene I, Overbey J, Bagiella E, Najafian N, Samaniego M, Djamali A, Alexander SI, Nankivell BJ, Chapman JR, Smith RN, Colvin R, Murphy B. Biopsy transcriptome expression profiling to identify kidney transplants at risk of chronic injury: a multicentre, prospective study. Lancet. 2016 Sep 3;388(10048):983-93. doi: 10.1016/S0140-6736(16)30826-1. Epub 2016 Jul 22.

  PMID: 27452608 DERIVED

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)

Biospecimen

Retention: SAMPLES WITH DNA

Blood from both kidney donor and recipient and transplant kidney biopsy samples

Study Officials

• Barbara T. Murphy, MD

  Division of Nephrology, Mt. Sinai School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2008
• First Posted: February 11, 2008
• Study Start: June 1, 2008
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: May 14, 2015

Record last verified: 2015-05

Locations

AU (1); US (4)