Randomized controlled study comparing reduced calcineurin inhibitors exposure versus standard cyclosporine-based immunosuppression.
BACKGROUND
Immunosuppressive regimens based on low doses of cyclosporine A (CsA) or tacrolimus (TAC) may improve short-term outcome after kidney transplantation (KT), but the optimal immunosuppressive protocol is currently unknown.


METHODS
This study compared the 24-month efficacy and safety of two immunosuppressive regimens using reduced calcineurin inhibitors (CNIs) exposure with standard dosage of CsA in 240 patients who were randomized into three groups: group A (n=80): Thymoglobulin, CsA (4 mg/kg twice daily) plus azathioprine (1.5 mg/kg once daily); group B (n=80): basiliximab, CsA (2 mg/kg/ twice daily) plus mycophenolate mofetil (MMF; 1 g twice daily); and group C (n=80): basiliximab, TAC (0.05 mg/kg/ twice daily) plus MMF (1 g twice daily). Steroid administration was identical for all groups.


RESULTS
A significantly better creatinine clearance at 12 months, estimated by Cockcroft-Gault (57+/-12, 65.2+/-20, 73.5+/-27 ml/min, P=0.044), the Jelliffe-2 (51.5+/-16, 56+/-19, 59.4+/-19 ml/min/1.73 m2, P=0.041) and the Modification of Diet in Renal Disease equations (53+/-17, 58.5+/-20, 61.6+/-22 ml/min/1.73 m2, P=0.035), was observed in group C compared with group A. No significant differences were observed between groups B and C. The incidence of biopsy-proven acute rejection was similar between groups (15%, 13.8%, and 16.3%). In addition, patient and graft survival at 24 months were not different between groups. Adverse effects were similar among groups, but cytomegalovirus infections was significantly higher in group A (41% vs. 20% vs. 25%; P=0.008).


CONCLUSIONS
Immunosuppressive regimens with reduced CNI exposure provide similar preservation of renal function compared with standard dose of CsA after KT and do not lead to underimmunosuppression.
Hernández
Domingo
D
Nephrology Section and Research Unit, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain. domingohernandez@gmail.com
Miquel
Rosa
R
Porrini
Esteban
E
Fernández
Ana
A
González-Posada
José Manuel
JM
Hortal
Luis
L
Checa
María Dolores
MD
Rodríguez
Aurelio
A
García
José Javier
JJ
Rufino
Margarita
M
Torres
Armando
A
D000328:Adult; D065095:Calcineurin Inhibitors; D002318:Cardiovascular Diseases / Q000453:epidemiology; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015994:Incidence; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D007674:Kidney Diseases / Q000139:chemically induced / Q000453:epidemiology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000453:epidemiology; D016019:Survival Analysis; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus