Wound-healing complications after kidney transplantation: a prospective, randomized comparison of sirolimus and tacrolimus.
BACKGROUND
Sirolimus has been associated with an increased risk of wound-healing complications in several retrospective analyses. The authors compared the rates of wound-healing complications in renal allograft recipients in a prospective, randomized trial of sirolimus-mycophenolate mofetil-prednisone versus tacrolimus-mycophenolate mofetil-prednisone.


METHODS
All patients received antithymocyte globulin induction. In the first phase of the study, patients (n = 77) were included regardless of body mass index (BMI). In the second phase (n = 46 patients), the authors excluded patients with a BMI greater than 32 kg/m2, and the target trough sirolimus level was lowered to 10 to 15 ng/mL (previously 15-20 ng/mL). Multivariate logistic regression analyses were performed to identify predictors of wound complications.


RESULTS
Fifty-nine patients received tacrolimus and 64 received sirolimus and were included in subsequent analyses. The incidence of complications was 8% (5 of 59) in the tacrolimus group and 47% (30 of 64) in the sirolimus group (P < 0.0001). Rates of perigraft fluid collections, superficial wound infections, and incisional herniae were significantly higher in the sirolimus group. Multivariate logistic regression showed only sirolimus (P = 0.0001) and BMI (P = 0.0021) to independently correlate with complications. In the first phase of the study, the wound complication rate in the sirolimus group was 55% (21 of 38 patients). After excluding obese recipients and decreasing the target sirolimus level, the wound complication rate in the sirolimus group was 35% (9 of 26 patients; P = 0.1040).


CONCLUSIONS
The use of sirolimus-based immunosuppressive regimens leads to a higher incidence of wound-healing complications and will require new approaches to patient selection and management to decrease their incidence.
Dean
Patrick G
PG
Department of Surgery, Division of Transplant Surgery, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905, USA.
Lund
William J
WJ
Larson
Timothy S
TS
Prieto
Mikel
M
Nyberg
Scott L
SL
Ishitani
Michael B
MB
Kremers
Walter K
WK
Stegall
Mark D
MD
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015994:Incidence; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects*; D016019:Survival Analysis; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects*; D014945:Wound Healing / Q000187:drug effects*
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus