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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.
New immunosuppressive drugs have improved short-term transplant survival but have not affected long-term transplant survival. Rejection is caused by both immunological and non-immunological factors from both the donor and the recipient. Although the exact cause of chronic rejection is not known, it is associated with the presence of C4d, a degradation product of the antibody response cascade, and the presence of circulating donor-specific antibodies (DSAs). The purpose of this study is to determine the role of cell- and antibody-mediated responses in chronic rejection of transplants, to determine the gene expression profile associated with the development of chronic rejection, and to determine whether variants of specific genes cause susceptibility to rejection.
This is an observational study of people who will be receiving kidney transplants and participants will be followed for 2 years. Study visits for kidney transplant recipients will occur at study entry and at months 3, 6, 12, 18, and 24 after transplant. At these visits, adverse event assessment, rejection assessment, medication history questionnaire, and blood collection will occur. At some visits, a physical exam and a kidney biopsy will occur. Blood will also be collected from living kidney donors at the time of donation if both donor and recipient agree to be in the study. This study will be take place at 4 clinical sites: Mount Sinai School of Medicine, University of Wisconsin-Madison, Westmead Hospital, and Northwestern Memorial Hospital. Brigham and Women's Hospital and Massachusetts General Hospital will also participate in the study as central laboratories.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Kidney biopsy | Procedure | Kidney biopsy (recipients only) will be obtained for RT-PCR, microarray analyses and histology. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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Individuals receiving a kidney transplant and individuals who are donating a kidney
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| Name | Affiliation | Role |
|---|---|---|
| Barbara T. Murphy, MD | Division of Nephrology, Mt. Sinai School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern Memorial Hospital | Chicago | Illinois | 60611 | United States | ||
| University of Michigan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20147884 | Background | 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. | |
| 18480317 | 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. |
| Label | URL |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | View source |
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Blood from both kidney donor and recipient and transplant kidney biopsy samples
| 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 |
| Ann Arbor |
| Michigan |
| 48109 |
| United States |
| Mt. Sinai School of Medicine | New York | New York | 10029 | United States |
| University of Wisconsin-Madison | Madison | Wisconsin | 53706 | United States |
| Westmead Hospital | Sydney | New South Wales | 2145 | Australia |
| 21566057 | 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. |
| 19218437 | 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. |
| 17924997 | 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. |
| 20883548 | 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. |
| 21115619 | 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. |
| 20019169 | 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. |
| 24103111 | 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. |
| 27452608 | Derived | 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. |