A randomized long-term trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus cyclosporine (NEORAL)/sirolimus in renal transplantation. II. Survival, function, and protocol compliance at 1 year.
BACKGROUND
In an attempt to reduce chronic calcineurin inhibitor induced allograft nephropathy in first cadaver and human leukocyte antigen non-identical living-donor renal transplantation, sirolimus (Siro) or mycophenolate mofetil (MMF) was tested as adjunctive therapy, with planned dose reductions of tacrolimus (Tacro) over the first year postoperatively. Adjunctive Siro therapy with a similar dose reduction algorithm for Neoral (Neo) was included for comparison.


METHODS
The detailed dose reduction plan (Tacro and Siro, group A; Tacro and MMF, group B; Neo and Siro, group C) is described in our companion report in this issue of Transplantation. The present report documents function, patient and graft survival, protocol compliance, and adverse events.


RESULTS
As mentioned (in companion report), group demographics were similar. The present study shows no significant differences in 1-year patient and graft survival but does show a trend that points to more difficulties in group C by way of a rising slope of serum creatinine concentration (P=0.02) and decreasing creatinine clearance (P=0.04). There were more patients who discontinued the protocol plan in group C. Thus far, no posttransplant lymphomas have appeared, and infectious complications have not differed among the groups. However, a greater percentage of patients in group C were placed on antihyperlipidemia therapy, with an (unexpected) trend toward a higher incidence of posttransplant diabetes mellitus in this group. Group A required fewer, and group B the fewest, antihyperlipidemia therapeutic interventions (P<0.00001).


CONCLUSIONS
This 1-year interim analysis of a long-term, prospective, randomized renal-transplant study indicates that decreasing maintenance dosage of Tacro with adjunctive Siro or MMF appears to point to improved long-term function, with reasonably few adverse events.
Ciancio
Gaetano
G
Department of Surgery, Division of Transplantation, University of Miami School of Medicine, Miami, FL 33101, USA. gciancio@med.miami.edu
Burke
George W
GW
Gaynor
Jeffrey J
JJ
Mattiazzi
Adela
A
Roth
David
D
Kupin
Warren
W
Nicolas
Maud
M
Ruiz
Phillip
P
Rosen
Anne
A
Miller
Joshua
J
D003404:Creatinine / Q000097:blood / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology* / Q000523:psychology; D008210:Lymphocele / Q000453:epidemiology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010349:Patient Compliance; D011183:Postoperative Complications / Q000145:classification / Q000453:epidemiology; D020123:Sirolimus / Q000627:therapeutic use*; D013530:Surgical Wound Infection / Q000453:epidemiology; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors
D016572:Cyclosporine; D003404:Creatinine; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus