Once daily tacrolimus formulation: monitoring of plasma levels, graft function, and cardiovascular risk factors.

Background: Advagraf, an extended release formulation of tacrolimus, is administered once daily during the morning fast. Tacrolimus can be safely converted from the twice daily formulation (Prograf) to the same dose (1 mg:1 mg) of once daily dosing tacrolimus (m-Tac). The adverse effects of tacrolimus play important roles in posttransplant cardiovascular risk factors (CVR): hyperglycemia, posttransplant diabetes mellitus, dyslipidemia and hypertension. It has been suggested that avoiding high tacrolimus peak levels minimizes its diabetogenic effects leading to better glycemic control. The aim of our study was to observe the effects of conversion to m-Tac therapy on graft function and CVR among stable transplant kidney recipients. Methods: We selected 2 groups of 20 patients with stable kidney transplantation, who had been treated with Prograf for >6 months with a triple regimen. Group 1 were converted to once daily tacrolimus at the same dose (1 mg:1 mg); whereas in group 2, the therapy was maintained as a twice daily regimen. Blood pressure, creatinine and glomerular filtration rate levels evaluated by the Modification of Diet in Renal Disease formula, as well as urea, total, high- and low-density lipoprotein remained stable between the 2 groups as well as inside group 1 before and after conversion. Results: After conversion, glycemia and triglyceride values showed significant reductions in group 1 and between the 2 groups. These results were significant, as they may be associated with better long-term graft and patient survivals. © 2010 Elsevier Inc. All rights reserved

Polyomavirus BK Replication in Adult Polycystic Kidney Disease Post-Renal Transplant Patients and Possible Role of Cellular Permissivity

Cell division and differentiation but not proliferation seem to be necessary for BK virus (BKV) replication and reactivation of persistent infection. Only terminal differentiating cells are permissive to BKV replication. Renal tubular epithelial cells in human adult polycystic kidney disease (ADPKD) are characterized by increased proliferative activity leading to cyst growth with less cellular differentiation. The aim of this study was to evaluate the possibility of different BKV replication patterns in patients with polycystic kidney disease versus non-ADPKD patients. From May 2006 to April 2008, we performed renal transplantations in 47. Eleven patients were affected by ADPKD (Pc group) and 36 patients, non ADPKD (n-Pc group). BKV replication was evaluated by quantitative real-time polymerase chain reactions (PCR) on plasma and urine samples at 12 hours (T0/early) as well as 3 (T3) and 6 (T6) months after transplantation. BKV viremia occurred in 9%, 12.5%, and 20% among the Pc group versus 33.3%, 42.4%, and 50% among the n-Pc group at 12 hours as well as 3 and 6 months posttransplantation, respectively. A higher discordance (BKV-PCR blood -/urine +) was observed in plasma and urine BKV replication among Pc versus n-Pc groups. We hypothesized that the lower number of patients with active BKV plasma replication in the Pc group may be related to a lower cellular permissivity of the renal tubular epithelial cells in ADPKD

Improvement of Graft Function after Conversion to Once Daily Tacrolimus of Stable Kidney Transplant Patients

Background. Chronic renal dysfunction is present in about one quarter of kidney transplant patients at 1 year and in about 90% by 10 years. Nephrotoxicity caused by calcineurin inhibitors is among the most common factors. Elevated tacrolimus levels have been correlated with worse control of side effects including acute and/or chronic nephrotoxicity. The aim of this study was to observe the effects on graft function of conversion from the twice daily to the once daily extended release tacrolimus formulation in stable kidney transplant recipients within 5 years of grafting. Methods. Thirty-one stable kidney transplant patients were converted at the same dosage (1 mg:1 mg). Patients served as their own controls based on results before versus after conversion. Results. The trough levels of tacrolimus showed a slight albeit significant reduction after the conversion. Serum creatinine and glomerular filtration rate showed a significant improvement without an association with the tacrolimus trough levels. Conclusion. We suggest that the immunosuppression with once daily tacrolimus may be a good option for kidney transplant patients

Tacrolimus Trough Levels and Level-to-Dose Ratio in Stable Renal Transplant Patients Converted to a Once-Daily Regimen

Numerous evidence has been reported to support a safe 1:1 conversion from the twice-daily tacrolimus (Tac-T) to the once-daily tacrolimus regimen (Tac-O), but frequently there is a reduction in drug trough levels, which has been estimated by some authors to be about 20%. The relationship between Tac-O dosage and trough levels after conversion is not clear. The tacrolimus trough levels-to-dose ratio has been applied to better define the wide variability in doses and blood levels of tacrolimus. The aim of this study was to evaluate tacrolimus trough levels, tacrolimus daily dosage, and tacrolimus level-to-dose ratio during 1 year pre-postconversion follow-up in 31 stable kidney transplant patients who had received Tac-T therapy for over 6 months with stable renal function. They were converted to the same dosage of Tac-O. Patients before and after conversion were their own controls. The trough levels of tacrolimus showed a slight albeit significant reduction after conversion, remaining in the therapeutic range. Nineteen percent underwent an adjustment in total daily dosage after conversion versus 39% before conversion with no significant difference. No significant differences were detected in the total daily dose administered either by tacrolimus level-to-dose ratio before or after conversion. Kidney transplant recipients under Tac-O therapy were safely maintained using the same therapeutic monitoring as when receiving Tac-T