In this extension study we will be extending our clinical observation of the STN patients from two to five years. It is expected that a Calcinerium Inhibitor (CNI) sparing regimen will be associated with better preservation of kidney function and fewer cardiovascular events.
STN is a prospective multi-center study that has completed enrollment of 305 first time recipients of kidney allografts from 27 centers. The enrollees were randomly assigned either to continue the center-specific CNI regimen (assigned at the time of transplantation) or were switched to replace the CNI with sirolimus therapy. Either CNI or sirolimus are being used in combination with CellCept therapy with or without the use of maintenance steroids, based on individual center preferences. Induction therapy was also center-specific.
In the present long-term follow-up study we will approach patients previously enrolled in the STN study and offer them the opportunity to enroll to be followed for another 3 years. There will be no changes in immunosuppression unless clinically indicated. The majority of the effort is standard care with every 6 month follow-up appointments.They will be required to be consented to participate in the three year extension study.
The only inclusion criteria is willingness to sign the consent form for the extension study, after successful completion of the two year STN study.
Study entry is defined as the point at which they sign the consent form, and agree to participate in the study extension.All patients will be followed for 3 years from their initial screening visit. There will be 7 visits during the study period. All procedures will be standard care for long-term transplant follow-up, with no changes in immunosuppression unless clinically indicated. The only exception to standard of care is obtaining a 24 hour urine for protein and creatinine clearance every 6 months during the follow-up.
Visit 1 (Study entry) 1. Review of inclusion/exclusion criteria 2. Medical history, recipient's age, gender and race 3. Complete transplant information i. date of transplant ii. tissue and ABO typing iii. B-Cell cross match, PRA iv. Patient/donor EBV and CMV serology
The patients will stay on the same immunosuppression as they were receiving in the STN study, unless medications were changed due to medical reasons. They will be routinely monitored as per center practice.
The drugs are given as standard of care and the extension of this study does not alter the participants' medication regimen.
The following laboratory evaluations are typically performed at each visit.
- Tacrolimus / sirolimus trough concentration. Immunosuppressive regimen will be reviewed and changed or adjusted as necessary.
- CBC with differential
- Chemistry panel: glucose, Na, K, Cl, CO2, Ca, P, Mg, blood urea nitrogen (BUN), albumin and total protein, AST, ALT, bilirubin (total), alkaline phosphatase and serum creatinine 4 Estimated GFR from blood and urine data.
5. Fasting lipid profile: total cholesterol, LDL, HDL, HDL/LDL ratio, triglycerides
The following clinical assessments will also be performed and recorded in each visit: 1. Vital signs 2. Weight measurements 3. Concomitant medications 4. Adverse events 5. Opportunistic infections 6. Malignancies 7. Clinical evaluation of signs or symptoms of rejection
Number of patients with adverse events will be summarized by body system and each adverse event. Incidence of adverse events will also be summarized by severity and relationship to study medication. Any serious adverse events or deaths will be summarized separately. patient death, graft loss, the need to be withdrawn from the original assigned calcineurin inhibitor therapy patients who return to dialysis for 6 or more consecutive weeks, patients who experience adverse events that lead to premature withdrawal or loss to follow-up. Patients will be followed until the end of the study in all cases. All failed patients will be followed until the end of the last follow up visit (36 months) unless consent is withdrawn. The proportion of patients experiencing any opportunistic infections will be summarized up to 6, 12, 24 ,and 36 months after randomization.