Concentration-controlled use of sirolimus associated with reduced exposure of cyclosporine in black recipients of primarily living renal allograft donors: 12-month results.
OBJECTIVE
This study was designed to identify optimal therapeutic sirolimus (SRL) concentrations in black kidney transplant recipients on reduced cyclosporine (CsA) exposure and prednisone.


METHODS
Seventy patients (64 living/six deceased) received CsA (8-10 mg/kg/d), prednisone, and 15 mg loading dose followed by 5-mg fixed doses of SRL till day 7 when they were randomized to maintain SRL trough concentrations (high-performance liquid chromatography) of 8-12 (GI = 34) or 15-20 (GII = 36) ng/mL.


RESULTS
Mean CsA concentrations were 109 +/- 53 vs. 89 +/- 41 ng/mL and 75 +/- 54 vs. 60 +/- 35 ng/mL (ns) at 2 and 6 months. Accordingly, mean SRL trough concentrations were 12.4 +/- 6.1 vs. 20.0 +/- 9.5 ng/mL (p < 0.001) and 10.8 +/- 5.8 vs. 18.0 +/- 6.1 ng/mL (p < 0.001). The incidence of biopsy-proven acute rejection [13% (GI: 18% vs. GII: 8%, ns)], graft loss or death was 16% (GI: 21% vs. GII: 11%, ns]. There were no deaths and three graft losses (GI = 1; GII = 2). Creatinine clearance was higher in GI (64.5 +/- 17 vs. 54.4 +/- 14.7 mL/min, p = 0.011). The incidence of post-transplant diabetes mellitus was 13% and no CMV disease was observed.


CONCLUSIONS
In black recipients of primarily living renal allograft donors reduced CsA exposure and SRL concentration-controlled regimens produced low incidences of acute rejection, post-transplant diabetes mellitus and CMV disease, with no significant impairment in graft function.
Ferreira
Alexandra N
AN
Nephrology Division, Hospital do Rim e Hipertensão, Sao Paulo, SP, Brazil.
Machado
Paula G
PG
Felipe
Cláudia R
CR
Motegi
Sofia A
SA
Hosaka
Beatriz H
BH
Tanaka
Márcia K
MK
Kamura
Luciana A
LA
Park
Sung I
SI
Garcia
Riberto
R
Franco
Marcello
M
Alfieri
Fernando
F
Casarini
Dulci E
DE
Tedesco-Silva
Hélio
H
Medina-Pestana
José O
JO
D000328:Adult; D001741:Black or African American; D001706:Biopsy; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics; D006084:Graft Rejection / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007676:Kidney Failure, Chronic / Q000208:ethnology / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D011241:Prednisone / Q000008:administration & dosage / Q000493:pharmacokinetics; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011241:Prednisone; D020123:Sirolimus