CORRELATION OF CLINICAL OUTCOMES AFTER TACROLIMUS CONVERSION FOR RESISTANT KIDNEY REJECTION OR CYCLOSPORINE TOXICITY WITH PATHOLOGICAL STAGING BY THE BANFF CRITERIA

Background. Refractory rejection and cyclosporine (CsA)-induced nephro pathy remain important causes of renal allograft loss. Previous studie s demonstrated that 70-85% of the episodes of refractory acute rejecti on (AR) occurring in renal allograft recipients on a CsA-based immunos uppressive regimen could be salvaged by conversion to tacrolimus, No d ata are available regarding the correlation between allograft histolog y at the time of conversion and the response to tacrolimus. We examine d the response to tacrolimus conversion in relation to preconversion b iopsies stratified by the Banff criteria. Methods. Since May 1992, we have converted 22 patients from CsA to tacrolimus as part of a rescue protocol, We report on 18 patients in whom g-month follow-up was avail able after conversion for biopsy-proven AR (n = 13) or CsA toxicity (n = 5). Sixteen patients were recipients of renal allografts, including three second transplants, and two were recipients of kidney-pancreas transplants, All patients with AR were treated with one or more course s of methylprednisolone and OKT3 before conversion, Renal allograft bi opsies were interpreted by a transplant pathologist blinded to the cli nical history, and graded according to the Banff criteria, Responses t o tacrolimus were scored as improved (creatinine returned to within 15 0% of baseline), stabilized (creatinine rise arrested), or failed (ret urned to dialysis). Results. Mean follow-up was 17.3+/-8 months. Fourt een of 18 patients (78%) showed improvement or stabilization in renal function as assessed by creatinine at 6 months or 1 year (when availab le). Of the 13 patients with histological AR, nine (69%) improved, inc luding five of six with borderline AR, two of three with grade I AR, a nd two of four with grade II AR. Of the four other patients with AR, t wo stabilized and two failed, Three of five patients with severe clini cal rejection requiring dialysis (range 2-16 weeks) recovered renal fu nction after conversion. Of five patients with CsA toxicity, two (40%) improved. Seven of eight patients who were converted to tacrolimus le ss than 90 days after transplantation improved, compared with only 4 o f 10 who were converted more than 90 days after transplantation. No gr afts were lost in patients with a creatinine less than or equal to 3.0 mg/dl at the time of conversion versus two of seven grafts lost when the creatinine was 3.1-5.0 mg/dl and two of eight grafts lost when the creatinine was >5.0 mg/dl. Conclusion. The majority of steroid and an tilymphocyte antibody (OKT3 or ATGAM) unresponsive rejections in patie nts on CsA-based immunosuppression will improve or stabilize after con version to tacrolimus. There was no correlation with allograft histolo gy stratified by the Banff criteria and the response to tacrolimus. Al though there was a trend toward a poorer response with more severe his tological rejection, higher serum creatinine at the time of conversion , and longer time from transplantation to conversion, favorable respon ses were noted in all groups, This indicates that a trial of conversio n is warranted, irrespective of the histological severity of injury.