Premium
An open‐label randomized trial of the safety and efficacy of sirolimus vs. azathioprine in living related renal allograft recipients receiving cyclosporine and prednisone combination
Author(s) -
Machado Paula GP,
Felipe Cláudia R,
Hanzawa Nilva M,
Park Sung I,
Garcia Riberto,
Alfieri Fernando,
Franco Marcelo,
Silva Hélio T,
MedinaPestana José O
Publication year - 2004
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/j.1399-0012.2004.00113.x
Subject(s) - medicine , azathioprine , prednisone , sirolimus , gastroenterology , creatinine , transplantation , clinical endpoint , adverse effect , urology , surgery , randomized controlled trial , disease
Background: The ability of sirolimus (SRL), in combination with reduced exposure of cyclosporine, was investigated to prevent acute rejection and associated side effects. Methods: Between June 1999 and February 2000, 70 recipients of primary one‐haplotype living‐related donor renal allografts were randomized to receive SRL (2 mg/d) or azathioprine (AZA) (2 mg/kg/d) combined with cyclosporine and prednisone. The primary end‐point was a composite of first occurrence of biopsy‐confirmed acute rejection, graft loss, or death during the first 3 months after transplantation. Results: From week 4 to month 12, SRL patients received lower cyclosporine (week 4: 364 mg/d vs. 455 mg/d, p = 0.004; month 12: 195 mg/d vs. 255 mg/d, p = 0.038) doses and showed lower cyclosporine concentrations (week 4: 247 ng/mL vs. 309 ng/mL, p = 0.04; month 12: 143 ng/mL vs. 188 ng/mL, p = 0.045). Compared with AZA, SRL patients showed reduced 3‐month primary end point (0% vs. 17.1%, p = 0.025), and reduced incidence of biopsy‐confirmed acute rejection at 3 months (0% vs. 14.3%, p = 0.01) but not at 12 months (11.4% vs. 14.3%, NS). Mean creatinine at 12 months were not different (1.8 ± 0.6 vs. 1.6 ± 0.6, p = 0.23). Hyperlipidemia was the only adverse event more frequent among SRL patients (49% vs. 17%, p = 0.01). There were no differences in infections and no malignancies in both groups. Conclusions: The combination of 2 mg fixed doses of SRL, reduced cyclosporine exposure and prednisone was associated with a low incidence of acute rejection and did not result in significantly impaired graft function compared with patients receiving AZA, standard doses of cyclosporine and prednisone.