2011 - IPITA - Prague


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Parallel session 5 – Open mini-oral presentations Topic: Pancreas transplantation

5.3 - Protocol biopsies and early detection of rejection improve pancreas transplant outcomes in the preuremic diabetic recipient

Presenter: R.H., Lee, San Francisco, USA
Authors: R.H. Lee, A.M. Posselt, M. Tavakol, R. Hirose, S.M. Kang, S. Feng, B. Hynson, S. Gustafson, C.E. Freise, P.G. Stock


Protocol biopsies and early detection of rejection improve pancreas transplant outcomes in the preuremic diabetic recipient

R.H. Lee, A.M. Posselt, M. Tavakol, R. Hirose, S.M. Kang, S. Feng, B. Hynson, S. Gustafson, C.E. Freise, P.G. Stock
UCSF, San Francisco, USA

Objective: Overall graft survival in preuremic diabetics receiving pancreas transplants (PTA) is compromised by high rejection rates. Furthermore, high doses of calcineurin inhibitors (CNIs) required to prevent/treat rejection can cause significant deterioration in renal function. To address these issues, we adopted a strategy of aggressive, non-nephrotoxic immunosuppressive therapy with protocol biopsies to identify and treat early rejection.

Methods: Between 2001 and 2010, 24 PTAs were performed in preuremic type 1 diabetics with documented hypoglycemic unawareness. Induction immunotherapy consisted of Thymoglobulin (6mg/kg). Maintenance included low-dose tacrolimus (trough levels 7-10ng/ml for 3 months, then 3-5ng/ml), mycophenolate mofetil, sirolimus (trough levels 5-7ng/ml) and prednisone (5mg QD). Protocol biopsies were performed at 3-6 months or for clinical indication. Moderate-severe rejection was treated with a second course of Thymoglobulin, whereas mild rejection was managed with steroid recycling and dosage escalation of myfortic and tacrolimus. Graft failure was defined as return to insulin therapy. UCSF graft survival rates after PTA were compared to national data.

Results: Our 1, 3, and 5 year patient and graft survival were significantly better than the national average (figure). Creatinine remained stable during the average follow-up period of 46.6 ± 6.8 months. Rejection-free survival in our cohort was 34% at 5 years (95% CI 14.7%-54.6%, figure), with the majority of rejections occurring within the first 6 months. Out of the 12 protocol biopsies that were successfully performed, 7/12 (58%) pts had evidence of rejection. 4/5 (80%) of clinically indicated biopsies had rejection.

Conclusions: We demonstrate that aggressive immunosuppression and close monitoring with protocol biopsies improves graft survival in this PTA group. In addition, use of low-dose CNIs helps prevent deterioration of native renal function. Advances in immunosuppression and monitoring will continue to improve graft longevity and outcomes making PTA a viable treatment option for preuremic type 1 diabetes.


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