Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus.
DIRECT (Diabetes Incidence after Renal Transplantation: Neoral C(2) Monitoring Versus Tacrolimus) was a 6-month, open-label, randomized, multicenter study which used American Diabetes Association/World Health Organization criteria to define glucose abnormalities. De novo renal transplant patients were randomized to cyclosporine microemulsion (CsA-ME, using C(2) monitoring) or tacrolimus, with mycophenolic acid, steroids and basiliximab. The intent-to-treat population comprised 682 patients (336 CsA-ME, 346 tacrolimus): 567 were nondiabetic at baseline. Demographics, diabetes risk factors and steroid doses were similar between treatment groups. The primary safety endpoint, new-onset diabetes after transplant (NODAT) or impaired fasting glucose (IFG) at 6 months, occurred in 73 CsA-ME patients (26.0%) and 96 tacrolimus patients (33.6%, p = 0.046). The primary efficacy endpoint, biopsy-proven acute rejection, graft loss or death at 6 months, occurred in 43 CsA-ME patients (12.8%) and 34 tacrolimus patients (9.8%, p = 0.211). Mean glomerular filtration rate (Cockcroft-Gault) was 63.6 +/- 20.7 mL/min/1.73 m(2) in the CsA-ME cohort and 65.9 +/- 23.1 mL/min/1.73 m(2) with tacrolimus (p = 0.285); mean serum creatinine was 139 +/- 58 and 133 +/- 57 mumol/L, respectively (p = 0.005). Blood pressure was similar between treatment groups at month 6, but total cholesterol, LDL-cholesterol and triglyceride levels were significantly higher with CsA than with tacrolimus (total cholesterol:HDL remained unchanged). The profile and incidence of adverse events were similar between treatments. The incidence of NODAT or IFG at 6 months post-transplant is significantly lower with CsA-ME than with tacrolimus without a significant difference in short-term outcome.
Vincenti
F
F
University of California San Francisco Kidney Transplant Service, San Francisco, CA, USA. VincentiF@surgery.ucsf.edu
Friman
S
S
Scheuermann
E
E
Rostaing
L
L
Jenssen
T
T
Campistol
J M
JM
Uchida
K
K
Pescovitz
M D
MD
Marchetti
P
P
Tuncer
M
M
Citterio
F
F
Wiecek
A
A
Chadban
S
S
El-Shahawy
M
M
Budde
K
K
Goto
N
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000276:immunology; D004359:Drug Therapy, Combination; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D008659:Metabolic Diseases / Q000453:epidemiology / Q000276:immunology*; D008875:Middle Aged; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D005947:Glucose; D016559:Tacrolimus