• Correlation of chronic rejection with patterns and intensity of recipient alloreactivity [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Correlation of chronic rejection with recipient gene expression profiles [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Correlation of chronic rejection with polymorphic variants of specific susceptibility genes in donor and recipient [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  

• Correlation of the development of donor specific antibodies after transplant and/or the presence of C4d staining with patterns and intensity of recipient alloreactivity [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Correlation of the development of donor specific antibodies after transplant and/or the presence of C4d staining with recipient gene expression profiles [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• 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 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• 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 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• 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 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  

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.

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

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.