Randomized trial of mycophenolate mofetil versus enteric-coated mycophenolate sodium in primary renal transplantation with tacrolimus and steroid avoidance: four-year analysis.
BACKGROUND
Our single-center, open-labeled randomized trial of 150 adult, primary kidney transplant recipients receiving 2 g mycophenolate mofetil (group A, n=75) versus 1.440 g enteric-coated mycophenolate sodium (group B, n=75), with reduced maintenance tacrolimus dosing, steroid elimination at 1 week, and combined rabbit antithymocyte globulin/daclizumab induction, previously showed at 1 year posttransplant low biopsy-proven acute rejection (BPAR), acceptably high renal function, and no differences in incidence of symptomatic gastrointestinal (GI) side effects between the two groups. This report includes 3 additional years of follow-up with similar endpoints as in the original study.


METHODS
Rates of developing first BPAR, graft failure (death censored and uncensored), death, and adverse events (GI toxicity, infections requiring hospitalization, and new onset diabetes mellitus after transplantation) during the first 48 months posttransplant were compared between the two groups using an intent-to-treat approach.


RESULTS
At 48 months posttransplant, patient/graft survival in groups A and B was 97%/90% vs. 96%/86%, respectively (not significant [NS]). Twenty-seven patients experienced BPAR (including borderline), with actuarial 19% (14/75) vs. 18% (13/75) in groups A and B, respectively (NS). Geometric mean*/standard error serum creatinine level and arithmetic mean calculated glomerular filtration rate (±standard error) at 48 months in groups A and B, respectively, were 1.25*/1.06 and 69.2±3.9 vs. 1.20*/1.05 and 71.2±3.2 (NS). Incidence of new onset diabetes mellitus after transplantation (22% vs. 15%), infections requiring hospitalization (31% vs. 39%), and GI side effects (45% vs. 52%) seemed equivalent.


CONCLUSIONS
This is the first long-term, randomized trial comparing enteric-coated mycophenolate sodium versus mycophenolate mofetil along with reduced maintenance tacrolimus dosing and steroid avoidance, which resulted in similarly low-BPAR rates, acceptably high renal function at 48 months, and an equivalent side effect profile.
The Lillian Jean Kaplan Renal Transplant Center of the Division of Transplantation, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33101, USA. gciancio@med.miami.edu
Gaetano
G
Ciancio
Jeffrey J
JJ
Gaynor
Alberto
A
Zarak
Junichiro
J
Sageshima
Giselle
G
Guerra
David
D
Roth
Randolph
R
Brown
Warren
W
Kupin
Linda
L
Chen
Lissett
L
Tueros
Lois
L
Hanson
Phillip
P
Ruiz
George W
GW
Burke
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D013608:Tablets, Enteric-Coated; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D009173:Mycophenolic Acid; D016559:Tacrolimus