Renal function, efficacy, and safety of sirolimus and mycophenolate mofetil after short-term calcineurin inhibitor-based quadruple therapy in de novo renal transplant patients: one-year analysis of a randomized multicenter trial.
BACKGROUND
De novo sirolimus in calcineurin inhibitor-free regimens, although potentially useful to improve early renal function, are complicated by various drug-related side effects.


METHODS
We report a prospective open-label, multicenter, randomized trial to evaluate early conversion from a CsA-based to a sirolimus (SRL)-based regimen 10 to 24 days after renal transplantation. Of the 196 patients, 141 patients with a low-to-moderate immunological risk were eligible to be converted to SRL or to continue CsA. All patients received antithymocyte globulin-F single-bolus induction, mycophenolate mofetil, and steroids.


RESULTS
The primary endpoint, renal function determined by S-creatinine and estimated glomerular filtration rate calculated by Nankivell formula at 12 months was significantly better in the SRL group (1.51+/-0.59 vs. 1.87+/-0.98 mg/dL or 64.5+/-25.2 vs. 53.4+/-18.0 mL/min/1.73 m). Patient survival, graft survival, and incidence of biopsy-proven acute rejection after conversion were not statistically different. Drug discontinuations were significantly higher in the SRL group (36.2% vs. 19.7%). Significantly, more patients in the SRL group reported acne, aphtous, and temporary hyperlipidemia, whereas cytomegalovirus viremia was significantly decreased (7.3% vs. 28.2%).


CONCLUSIONS
Early conversion to a calcineurin inhibitor-free regimen with SRL in combination with mycophenolate mofetil may be a useful strategy to improve renal function. The identification of appropriate candidates and safe management of SRL-related adverse events will be a key to avoid the high rate of dropouts, which currently limit the broad applicability of this protocol.
Guba
Markus
M
Department of Surgery, Munich University Hospital, Campus Grosshadern, Munich, Germany. Markus.Guba@gmail.com
Pratschke
Johann
J
Hugo
Christian
C
Krämer
Bernhard K
BK
Nohr-Westphal
Constanze
C
Brockmann
Jens
J
Andrassy
Joachim
J
Reinke
Petra
P
Pressmar
Katharina
K
Hakenberg
Oliver
O
Fischereder
Michael
M
Pascher
Andreas
A
Illner
Wolf-Dieter
WD
Banas
Bernhard
B
Jauch
Karl-Walter
KW
D000152:Acne Vulgaris / Q000139:chemically induced; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D065095:Calcineurin Inhibitors; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018579:Patient Selection; D011446:Prospective Studies; D012449:Safety; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D014019:Tissue Donors / Q000706:statistics & numerical data
D000305:Adrenal Cortex Hormones; D000961:Antilymphocyte Serum; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D003404:Creatinine; D009173:Mycophenolic Acid; D020123:Sirolimus