Protocol Number: 04-DK-0193

Title:

Identification and Mechanistic Investigations of Tolerant Kidney Transplant Patients

Number:

04-DK-0193

Summary:

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.

Sponsoring Institute:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Participants for this study will be renal transplant recipients or living-related donors who are:

1. 18 years of age or older

2. meet the criteria for inclusion in one of the study groups

3. provide informed consent

4. participants who agree to a biopsy must have a International Normalized Ratio (INR) (minimum value less than 1.6) completed and/or a bleeding time of less than 9 minutes, to ensure that their risk of bleeding is minimal.

EXCLUSION CRITERIA:

1. AIDS [includes all HIV-infected persons who have less than 200 cells/mm(3) CD4+ T-lymphocytes/microL, or a CD4+ T-lymphocyte percent of total lymphocytes less than 14, or who have been diagnosed with an AIDS-defining condition as defined by the Center for Disease Control (CDC)

2. current malignancy requiring recent surgery, ongoing chemotherapy or radiation

3. acute systemic infections within 30 days prior to enrollment

4. pregnancy

Patients meeting any of the exclusion criteria, if identified to have been clinically tolerant prior to the occurrence of the excluding condition, will be enrolled and demographic data collected for the registry; however the decision as to whether or not to collect blood, urine, and tissue samples will be deferred until the patient's condition improves and the clinically tolerant state persists.

Special Instructions: Currently Not Provided

Keywords:

Tolerance

Renal

Allograft

Rejection

Immunosuppression

Recruitment Keywords:

Kidney Transplant

Conditions:

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Benfield MR, Herrin J, Feld L, Rose S, Stablein D, Tejani A. Safety of kidney biopsy in pediatric transplantation: a report of the Controlled Clinical Trials in Pediatric Transplantation Trial of Induction Therapy Study Group. Transplantation. 1999 Feb 27;67(4):544-7.

Hergesell O, Felten H, Andrassy K, Kuhn K, Ritz E. Safety of ultrasound-guided percutaneous renal biopsy-retrospective analysis of 1090 consecutive cases. Nephrol Dial Transplant. 1998 Apr;13(4):975-7.

Heeger PS, Greenspan NS, Kuhlenschmidt S, Dejelo C, Hricik DE, Schulak JA, Tary-Lehmann M. Pretransplant frequency of donor-specific, IFN-gamma-producing lymphocytes is a manifestation of immunologic memory and correlates with the risk of posttransplant rejection episodes. J Immunol. 1999 Aug 15;163(4):2267-75.

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