Background:Acute allograft dysfunction due to IFTA is often attributed to cumulative exposure to tacrolimus. Can replacement of CNI with m-TOR inhibitor prevent progression in IF/TA and graft failure? Methods: We conducted a case-control study by linking our data set with UNOS and ESRD database.All patients were on maintenance tacrolimus and MMF without steroids.We studied treatment with sirolimus as the exposure group and continuation of tacrolimus as the comparator group between Jan 2003 to April 2006, with follow-up of 3 yrs.The primary outcome was a composite of graft loss and death with functioning graft. Secondary outcomes included graft loss, death with function, death after graft loss, and graft function at 1,2, & 3 yrs. Similar analysis was performed in different subgroups of IF/TA.Results: A total of 497 recipients had different grades of IF/TA at the time of index biopsy.221(45%) patients were changed to sirolimus & MMF without steroids. There were no systematic differences in the baseline characteristics between the two groups (table1).There were significant differences in the primary and secondary outcomes in the two groups (table 2).After adjusting for (age, race, gender, type of transplant, time to index biopsy and baseline creatinine), none of these had a significant impact on primary outcome and graft function on Cox analysis. Analysis of primary outcome in the three Banff subgroups of IF/TA had significantly increased risk of mortality following exposure to sirolimus. Conclusions: Sirolimus use increased all cause mortality and also death after graft loss. These marked differences in outcomes were similar across the groups of different degrees of IF/TA. Changing CNI to sirolimus based therapy in patients with threatened allograft needs more detailed studies.

« Back to 2013 American Transplant Congress