study 2: comparison of tacrolimus and sirolimus combination with tacrolimus and mycophenolate...

Study 2: Comparison of Tacrolimus andSirolimus Combination With Tacrolimus andMycophenolate Mofetil in Kidney TransplantRecipients With Steroid AvoidanceAparna Kumar, Daniel Lee, Sheng G. Xiao, Michael J. Moritz, Billie Fyfe, MichaelHeifets, Debra Sierka, and Mysore S. Anil Kumar

L ong-term steroid therapy is toxic and may ac-centuate the side effects of tacrolimus (TAC)

and sirolimus (SRL) (ie, diabetes mellitus and dys-lipidemia). A prospective, randomized, steroid-freetherapy study was carried out with TAC–mycophe-nolate mofetil (MMF) (group 1) and tacrolimus-sirolimus (TAC-SRL) (group 2) to determine theefficacy, safety, and advantages of these 2 combina-tions while the steroid-related side effects areavoided.

Forty-nine primary kidney recipients with lowpanel reactive antibody (PRA) were randomized into2 groups with comparable demographic characteris-tics. All received basiliximab and were given 2 dosesof methylprednisolone (250 mg on day 0, 125 mg onday 1, and then totally discontinued). Group 1 wasgiven MMF 2 g/d, and in group 2, the SRL dose wasadjusted to maintain blood levels of around 10 to 15ng/mL. Blood TAC levels in both groups were main-tained at 10 to 15 ng/mL. Acute rejections (ARs)were diagnosed by biopsy and treated with pulsedoses of steroids, 500 mg/d for 4 days. Maintenancesteroids were not initiated in these patients with AR.Protocol biopsies were completed at 1, 6, and 12months to diagnose chronic allograft nephropathy(CAN) and subclinical acute rejection (SCAR).SCAR in this study was defined as stable serum

creatinine level and rejection of Banff grade 1A ormore in protocol biopsies. CAN was graded accord-ing to standard Banff criteria. Kidney function wasassessed by serum creatinine level and creatinineclearance. Twenty-nine recipients were in group 1and 20 in group 2. AR was seen in 14% of MMF and5% of SRL (P � NS). SCAR was seen in 14% of MMFand 15% of SRL groups. In the MMF group, CANwas absent in 47%, mild in 28%, and moderate in25%, and in the SRL group, CAN was absent in 50%,mild in 30%, and moderate in 20%. Serum creatininelevels were 1.7 and 1.8 mg/dL, and creatinine clear-ance values were 74 and 59 mL/min in MMF andSRL groups, respectively. One-year patient survivalrates were 100% in group 1 and 95% in group 2, andthe graft survival rate was 95% in both groups 1 and2. The incidence of bone marrow depression, gastro-intestinal side effects, and hyperlipidemia was simi-lar in the 2 groups. However, more recipients re-quired lipid-lowering agents in the SRL groupscompared with the MMF group. There was no inci-dence of delayed wound healing in the SRL groups,but lymphoceles were seen in 10% of them comparedwith 0% in the MMF group. In the TAC-MMF group,posttransplant diabetes mellitus (PTDM) developedin 1 African American recipient (3%), and in theTAC-SRL group, none had PTDM.

Conclusion: Our data indicate that steroid-freecombinations of TAC-MMF and TAC-SRL providecomparable patient and graft survival with a similarincidence of graft function, CAN, and acute rejec-tion. Incidence of TAC-associated PTDM was signif-icantly reduced in both groups compared with previ-ous reports in the literature.

From the Departments of Surgery/Transplant, Drexel University Collegeof Medicine; Pathology, Drexel University College of Medicine; Transplant,Hahnemann University Hospital; and Medicine/Nephrology, Drexel Uni-versity College of Medicine, Philadelphia, PA.

© 2003 Elsevier Inc. All rights reserved.0955-470X/03/1704-0000$30.00/0doi:10.1016/j.trre.2003.10.013

Transplantation Reviews, Vol 17, No 4 (October), 2003: p S45 S45