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Study 2: comparison of tacrolimus and sirolimus combination with tacrolimus and mycophenolate mofetil in kidney transplant recipients with steroid avoidance
Study 2: Comparison of Tacrolimus and Sirolimus Combination With Tacrolimus and Mycophenolate Mofetil in Kidney Transplant Recipients With Steroid Avoidance Aparna Kumar, Daniel Lee, Sheng G. Xiao, Michael J. Moritz, Billie Fyfe, Michael Heifets, Debra Sierka, and Mysore S. Anil Kumar
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ong-term steroid therapy is toxic and may accentuate the side effects of tacrolimus (TAC) and sirolimus (SRL) (ie, diabetes mellitus and dyslipidemia). A prospective, randomized, steroid-free therapy study was carried out with TAC–mycophenolate mofetil (MMF) (group 1) and tacrolimussirolimus (TAC-SRL) (group 2) to determine the efficacy, safety, and advantages of these 2 combinations while the steroid-related side effects are avoided. Forty-nine primary kidney recipients with low panel reactive antibody (PRA) were randomized into 2 groups with comparable demographic characteristics. All received basiliximab and were given 2 doses of methylprednisolone (250 mg on day 0, 125 mg on day 1, and then totally discontinued). Group 1 was given MMF 2 g/d, and in group 2, the SRL dose was adjusted to maintain blood levels of around 10 to 15 ng/mL. Blood TAC levels in both groups were maintained at 10 to 15 ng/mL. Acute rejections (ARs) were diagnosed by biopsy and treated with pulse doses of steroids, 500 mg/d for 4 days. Maintenance steroids were not initiated in these patients with AR. Protocol biopsies were completed at 1, 6, and 12 months to diagnose chronic allograft nephropathy (CAN) and subclinical acute rejection (SCAR). SCAR in this study was defined as stable serum From the Departments of Surgery/Transplant, Drexel University College of Medicine; Pathology, Drexel University College of Medicine; Transplant, Hahnemann University Hospital; and Medicine/Nephrology, Drexel University College of Medicine, Philadelphia, PA. © 2003 Elsevier Inc. All rights reserved. 0955-470X/03/1704-0000$30.00/0 doi:10.1016/j.trre.2003.10.013
creatinine level and rejection of Banff grade 1A or more in protocol biopsies. CAN was graded according to standard Banff criteria. Kidney function was assessed by serum creatinine level and creatinine clearance. Twenty-nine recipients were in group 1 and 20 in group 2. AR was seen in 14% of MMF and 5% of SRL (P ⫽ NS). SCAR was seen in 14% of MMF and 15% of SRL groups. In the MMF group, CAN was absent in 47%, mild in 28%, and moderate in 25%, and in the SRL group, CAN was absent in 50%, mild in 30%, and moderate in 20%. Serum creatinine levels were 1.7 and 1.8 mg/dL, and creatinine clearance values were 74 and 59 mL/min in MMF and SRL groups, respectively. One-year patient survival rates were 100% in group 1 and 95% in group 2, and the graft survival rate was 95% in both groups 1 and 2. The incidence of bone marrow depression, gastrointestinal side effects, and hyperlipidemia was similar in the 2 groups. However, more recipients required lipid-lowering agents in the SRL groups compared with the MMF group. There was no incidence of delayed wound healing in the SRL groups, but lymphoceles were seen in 10% of them compared with 0% in the MMF group. In the TAC-MMF group, posttransplant diabetes mellitus (PTDM) developed in 1 African American recipient (3%), and in the TAC-SRL group, none had PTDM. Conclusion: Our data indicate that steroid-free combinations of TAC-MMF and TAC-SRL provide comparable patient and graft survival with a similar incidence of graft function, CAN, and acute rejection. Incidence of TAC-associated PTDM was significantly reduced in both groups compared with previous reports in the literature.
Transplantation Reviews, Vol 17, No 4 (October), 2003: p S45
S45
L
ong-term steroid therapy is toxic and may accentuate the side effects of tacrolimus (TAC) and sirolimus (SRL) (ie, diabetes mellitus and dyslipidemia). A prospective, randomized, steroid-free therapy study was carried out with TAC–mycophenolate mofetil (MMF) (group 1) and tacrolimussirolimus (TAC-SRL) (group 2) to determine the efficacy, safety, and advantages of these 2 combinations while the steroid-related side effects are avoided. Forty-nine primary kidney recipients with low panel reactive antibody (PRA) were randomized into 2 groups with comparable demographic characteristics. All received basiliximab and were given 2 doses of methylprednisolone (250 mg on day 0, 125 mg on day 1, and then totally discontinued). Group 1 was given MMF 2 g/d, and in group 2, the SRL dose was adjusted to maintain blood levels of around 10 to 15 ng/mL. Blood TAC levels in both groups were maintained at 10 to 15 ng/mL. Acute rejections (ARs) were diagnosed by biopsy and treated with pulse doses of steroids, 500 mg/d for 4 days. Maintenance steroids were not initiated in these patients with AR. Protocol biopsies were completed at 1, 6, and 12 months to diagnose chronic allograft nephropathy (CAN) and subclinical acute rejection (SCAR). SCAR in this study was defined as stable serum From the Departments of Surgery/Transplant, Drexel University College of Medicine; Pathology, Drexel University College of Medicine; Transplant, Hahnemann University Hospital; and Medicine/Nephrology, Drexel University College of Medicine, Philadelphia, PA. © 2003 Elsevier Inc. All rights reserved. 0955-470X/03/1704-0000$30.00/0 doi:10.1016/j.trre.2003.10.013
creatinine level and rejection of Banff grade 1A or more in protocol biopsies. CAN was graded according to standard Banff criteria. Kidney function was assessed by serum creatinine level and creatinine clearance. Twenty-nine recipients were in group 1 and 20 in group 2. AR was seen in 14% of MMF and 5% of SRL (P ⫽ NS). SCAR was seen in 14% of MMF and 15% of SRL groups. In the MMF group, CAN was absent in 47%, mild in 28%, and moderate in 25%, and in the SRL group, CAN was absent in 50%, mild in 30%, and moderate in 20%. Serum creatinine levels were 1.7 and 1.8 mg/dL, and creatinine clearance values were 74 and 59 mL/min in MMF and SRL groups, respectively. One-year patient survival rates were 100% in group 1 and 95% in group 2, and the graft survival rate was 95% in both groups 1 and 2. The incidence of bone marrow depression, gastrointestinal side effects, and hyperlipidemia was similar in the 2 groups. However, more recipients required lipid-lowering agents in the SRL groups compared with the MMF group. There was no incidence of delayed wound healing in the SRL groups, but lymphoceles were seen in 10% of them compared with 0% in the MMF group. In the TAC-MMF group, posttransplant diabetes mellitus (PTDM) developed in 1 African American recipient (3%), and in the TAC-SRL group, none had PTDM. Conclusion: Our data indicate that steroid-free combinations of TAC-MMF and TAC-SRL provide comparable patient and graft survival with a similar incidence of graft function, CAN, and acute rejection. Incidence of TAC-associated PTDM was significantly reduced in both groups compared with previous reports in the literature.
Transplantation Reviews, Vol 17, No 4 (October), 2003: p S45
S45