This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a relative with the same (or nearly the same) blood cell type as the transplant recipient. An investigational medication will be given prior to and after the transplant to help protect the transplanted kidney from attack by the body's immune system.

Of the two currently available treatments for kidney failure, long-term dialysis and kidney transplantation, only kidney transplantation provides a potential cure. After a kidney transplant, the body's immune system recognizes the kidney as foreign and tries to attack and destroy it in a process called rejection. To avoid rejection, participants must take medications called immunosuppressants or anti-rejection drugs. It is believed that by transplanting bone marrow at the same time as a solid organ such as a kidney, a state of "mixed chimerism" (a mixing of the donor and recipient's immune system) can be achieved. Mixed chimerism may prevent rejection without the need for anti-rejection drugs.

Participants in this study will receive a simultaneous bone marrow and kidney transplant from the same living related donor in an attempt to establish mixed chimerism. Prior to transplantation, participants will undergo a "conditioning regimen" involving cyclophosphamide chemotherapy, radiation to the thymus gland, and four immunosuppressive medications: cyclosporine A, a man-made antibody known as rituximab to suppress B cells, a short course of steroids, and a T-cell depleting antibody known as MEDI-507. MEDI-507 is an investigational medication that has not been approved by the FDA. The primary goal of the study is to investigate the safety of the conditioning regimen and its ability to promote mixed chimerism so that the transplanted kidney is not destroyed. The study will also determine whether participants with mixed chimerism can eventually be safely removed from long-term immunosuppressive therapy following transplantation.

Participants will be assessed before and after transplantation and will be followed ≤36 months.

Inclusion Criteria:

• End-stage renal disease (ESRD) without prior sensitization (defined as Panel Reactive Antibody [PRA] greater than 20%) within the 60 days prior to transplant as measured by cytotoxicity assays, ELISA, and flow cytometry;
• Undergoing a first or second transplant;
• Receiving a transplant from a living related donor who is ABO (blood type) compatible and haploidentical (3, 4, or 5 antigen match by serologic typing);
• Cardiac ejection fraction greater than 40%;
• Forced expiratory volume (FEV1) greater than 50%;
• Liver function tests, bilirubin, and coagulation studies less than 2 X normal;
• White blood cells greater than 2000/mm^3; abd
• Platelets greater than 100,000/mm^3

Exclusion Criteria:

• Positive donor lymphocyte cross-match;
• HIV-1 infected;
• Positive hepatitis B surface antigen (HbsAg);
• Hepatitis C virus infected;
• History of cancer;
• Prior dose-limiting radiation therapy;
• Pregnant, breastfeeding, or planning pregnancy within the time frame of the study;
• Enrolled in another investigational drug study within 30 days prior to study entry; or
• Receiving maintenance immunosuppression within 3 months before the conditioning regimen begins