Optimizing tacrolimus therapy in the maintenance of renal allografts: 12-month results.
BACKGROUND
The determination of optimal tacrolimus (TAC) trough levels is needed to prevent adverse effects of calcineurin inhibitors.


METHODS
Stable transplant recipients currently receiving cyclosporine (CsA) were assigned randomly (1:1:1) to continue CsA (target trough level of 50-250 ng/mL); or convert to "reduced" TAC (target trough level 3.0-5.9 ng/mL) or "standard" TAC (target trough level 6.0-8.9 ng/mL).


RESULTS
At 12 months, there was a significant improvement in renal function in the reduced TAC versus CsA group with lower serum creatinine (P=0.004) and cystatin C (P<0.001), and higher estimated creatinine clearance (P=0.017). However, there were no statistically significant differences in any renal parameter in the standard TAC versus CsA group. Total and low-density lipoprotein cholesterol were significantly reduced in both TAC groups versus the CsA group (P<0.001). Patient and graft survival and episodes of biopsy-confirmed acute rejection were similar for all treatment groups, and no statistically significant differences were observed between groups in the incidence of new-onset diabetes or cardiac conditions, or in the prevalence of hyperglycemia, hypertension, or hyperlipidemia among patients who did not have these conditions at baseline. Alopecia developed more commonly among TAC-treated patients than CsA-treated patients (P<0.001).


CONCLUSIONS
Compared with CsA continuation, conversion to reduced TAC target trough concentrations resulted in significantly improved renal function without increasing the risk of rejection. Conversion to TAC, regardless of target concentration, resulted in improved serum lipid profiles in kidney transplant recipients at 12 months.
Bolin
Paul
P
Division of Nephrology, Department of Medicine, East Carolina University, Greenville, NC, USA.
Shihab
Fuad S
FS
Mulloy
Laura
L
Henning
Alice K
AK
Gao
Jeff
J
Bartucci
Marilyn
M
Holman
John
J
First
M Roy
MR
D000328:Adult; D002318:Cardiovascular Diseases / Q000209:etiology; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D006084:Graft Rejection / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D012307:Risk Factors; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D007166:Immunosuppressive Agents; D008055:Lipids; D016572:Cyclosporine; D016559:Tacrolimus