THE SIGNIFICANCE OF PROTOCOL BIOPSY IN IMMUNOMINIMIZATION PROTOCOL: A PROSPECTIVE STUDY OF STEROID WITHDRAWAL

Abstract

O229 Aims: In the current immunosuppression era the emergence of new immunosuppression agents has allowed avoidance or withdrawal of steroid or calcineurin inhibitors (CNI) in many transplant centres, so called “Immunominimization Protocols” (IMP). The safety and efficacy of previously published IMP’s rely upon acute graft rejection (AGR) rates and/or serum creatinine. The impact of these IMP’s on long term graft survival and chronic allograft nephropathy (CAN) have not been well established. The goal of this randomized prospective study is to evaluate the effect of steroid withdrawal on the progression of CAN using protocol biopsies. Methods: From 7/01 to 12/03, 201 kidney transplants were performed in our transplant centre. 78 patients were consented for enrolment in this study. 39 patients were randomised to steroid withdrawal (SW) group and 39 continued to receive steroid indefinitely (SC). Baseline characteristics of both groups were similar. All pts. Received thymoglobulin (3-4 mg/kg/total) and solumedrol (250 mg POD 0 and 125 mg POD 1) with FK506 and MMF maintenance therapy. The SC group received prednisone 30mg on POD2, tapered to 5mg by POD 30 and continued indefinitely. The SW group received prednisone only for 7 days. All pt. underwent protocol biopsy at 1, 6 and 12 months. Results: Average follow-up was 387 ± 164 days. All patients underwent at least one protocol biopsy. 21% of the SC and 26% of the SW group could not complete one year of study due to persistent FK toxicity on biopsy or clinical adverse effects. Only 8% in each group experienced AGR. 96% of the SC and 78% of SW protocol biopsies were normal at one-month. Only 4% of biopsies in the SC group showed borderline subclinical rejection (BLSCR) whereas in the SW group 11% showed BLSCR and 11% had unsuspected FK toxicity at one month. At 6 months, 75% of SC and 87% of the SW biopsies were normal; 25% of the SC biopsies showed BLSCR and 13% of the SW biopsies revealed FK toxicity. At one year, 58% of the SC biopsies and 86% of the SW biopsies were normal; 28% of the SC biopsies showed BLSCR and 14% of the SW biopsies had FK toxicity. Protocol biopsies showed absent or minimal CAN in the vast majority of pts. Absent or minimal CAN was noted in 19 of 21, 10 of 11 and 4 of 5 biopsies in SC patients and 19 of 19, 8 of 11 and 3 of 5 of the biopsies in the SW group at 1, 6 and 12 months respectively. Renal function was also well maintained with creatinine clearance of 78.6 ± 32.2 ml/min in SC and 81.5 ± 36.4 ml/min in the SW pts at 1 year (P=NS). The immunosuppression therapy was adjusted in 11% of the pts in both groups based on protocol biopsies. Conclusions: This randomized prospective study showed that withdrawal of steroid does not significantly effect the progression of CAN. Although CAN was more common in later biopsies, steroid therapy did not affect the frequency or severity of CAN. Protocol biopsy is a very informative tool to assure the safety and efficacy of immunosuppression therapy particularly if immunominimization therapy is considered.