This study will investigate tolerance in kidney transplant patients. One of the most common complications of kidney transplantation is organ rejection, which occurs because the body's immune system tries to attack (reject) the newly transplanted kidney. To prevent this, patients are given immunosuppressive, or anti-rejection, drugs. Most patients who stop taking these drugs reject their transplanted kidney; however, some patients do not reject the transplanted kidney and it continues to work well. These patients are said to "tolerate" the transplanted kidney, and this condition is referred to as tolerance. This study will establish a database of clinical and laboratory information that may help to identify unique characteristics of tolerant patients.
Patients 18 years of age and older who have had a kidney transplant and people who donated their kidneys for these patients may be eligible for this study. Patients are divided into 6 groups, according to the medicines they are currently taking and the status of their kidney function. A seventh group comprises patients who received a kidney from an identical twin, and an eighth group comprises kidney donors. Patients are screened with a medical history and a skin test to determine how well their immune system responds to foreign substances.
Patients in group 1 (patients who have stopped taking immunosuppressive medications for at least 1 year and whose transplanted kidney functions in a normal and stable manner) are required only to undergo the screening assessment, but may choose to participate in the following procedures, which are required for groups 2-7:
- Baseline visit - Review of medical history and demographic information; routine blood tests; 24-hour urine sample; blood draw by standard method (phlebotomy) or by leukapheresis for tolerance tests. For leukapheresis, a needle is placed in a vein in each arm. Blood is collected from one arm and directed to a machine that separates it into its components. Some of the white blood cells are removed, and the rest of the blood is returned to the patient through the needle in the other arm.
- Visits 1-6 (months 6, 12, 18, 24, and 36) - Review of medical history, including status of transplanted kidney; blood and urine samples for routine laboratory tests. If kidney function declines during the course of the study, patients will be asked to provide: additional blood and urine samples for routine laboratory tests; a 24-hour urine sample; and blood for tolerance tests, collected by standard phlebotomy or leukapheresis.
Patients in all groups may be asked to provide a biopsy sample of their transplanted kidney for tolerance assays and for microscopic examination. The biopsy may be repeated if kidney function worsens. For this procedure, a small piece of the transplanted kidney is removed with a special needle. Biopsies are an optional procedure.
Kidney donors provide blood samples for tolerance assays. They may be asked to provide additional samples if the kidney they donated deteriorates in function. The donor may choose to provide the blood sample by leukapheresis or by phlebotomy.
| Estimated Enrollment: |
210 |
| Study Start Date: |
May 2004 |
This study is designed to obtain information from Kidney Transplant recipients and donors that will help scientists understand those factors causing and preventing transplant rejection. Approximately 210 renal transplant recipients and donors will be recruited into the study. The recruitment period for this study will be for 3 years after the first participant is enrolled. Based on the Network Executive Committee (NEC) and Tolerance Assay Sub-Group's annual review of the recruitment status of the study, the recruitment period may be adjusted. Participants will be classified into one of eight study groups and, once the participant has been assigned to a particular group, they will remain in that group until the end of the trial, regardless of change of status during the course of the study.
Each participant will be asked to provide consent for the collection of extensive demographic/clinical information and medical histories, and blood, urine and tissue (biopsy) samples upon study entry and during the study depending on the study group. Blood, urine and tissue samples (when provided) will be used to perform specific assays, to help define mechanism(s) of tolerance. In addition, specimens collected may be archived for use in future research assays. Participants will be asked to provide permission before any specimens are utilized in future research not described within this protocol. Information will be obtained regarding the donor of the renal allograft from the recipient's medical records. Living donors may be informed of this study by the recipient of their organ. The donor of the renal allograft may then contact study personnel if they are interested in participating in the study. The donor participants will be asked to consent to joining the study and asked to provide medical histories and blood samples. Information and archived blood and/or tissue samples from cadaveric donors will be requested from the Organ Procurement Organization (OPO) or UNOS (United Network for Organ Sharing) based on the unique UNOS number assigned to the donated kidney.
Purpose
