No abstract

This multicenter, 1:1-randomized, parallel-group, noninferiority study compared the efficacy and safety of twice-daily tacrolimus (Tacrolimus BID; Prograf) and once-daily tacrolimus prolonged release (Tacrolimus QD; Advagraf), combined with steroids and low-dose mycophenolate mofetil without antibody induction, in 667 de novo kidney transplant recipients. A doubleblind, double-dummy 24-week period was followed by an open extension of up to 12 months posttransplant. Biopsy-proven acute rejection rate at 24 weeks (primary endpoint, per-protocol analysis) was 15.8% for Tacrolimus BID versus 20.4% for Tacrolimus QD (p = 0.182; treatment difference 4.5%, 95% confidence interval--1.8%, 10.9%, just outside the prespecified 10% noninferiority margin). Kaplan-Meier 12-month patient and graft survival rates were 97.5% and 92.8% for Tacrolimus BID and 96.9% and 91.5% for QD. Both treatment groups showed equally wellmaintained renal function at 12 months (mean creatinine clearance approximately 67 mL/min) and similar adverse event profiles. Overall results obtained with either Tacrolimus QD or BID, without antibody induction, were good, supporting use of the once-daily formulation as an effective alternative to the established twice-daily formulation.

These data indicate that the capacities to clear 5-FU are lower in women compared with men and are not influenced by age. It would be of interest to know whether this sex-related difference in 5-FU Cl may be clinically relevant by considering both toxicity and tumor response to 5-FU treatment.

In certain patients, inflammatory microenvironment provides BAFF-dependent paracrine survival signal to B-cells in TLOs, allowing them to escape rituximab-induced apoptosis, thereby thwarting therapeutic efficiency.

Retrospective studies suggest that chronic allograft nephropathy might progress more rapidly in patients with post-transplant anemia, but whether correction of anemia improves renal outcomes is unknown. An open-label, multicenter, randomized controlled trial investigated the effect of epoetin-b to normalize hemoglobin values (13.0-15.0 g/dl, n=63) compared with partial correction of anemia (10.5-11.5 g/dl, n=62) on progression of nephropathy in transplant recipients with hemoglobin ,11.5 g/dl and an estimated creatinine clearance (eCrCl) ,50 ml/min per 1.73 m 2 . After 2 years, the mean hemoglobin was 12.9 and 11.3 g/dl in the normalization and partial correction groups, respectively (P,0.001). From baseline to year 2, the eCrCl decreased by a mean 2.4 ml/min per 1.73 m 2 in the normalization group compared with 5.9 ml/min per 1.73 m 2 in the partial correction group (P=0.03). Furthermore, fewer patients in the normalization group progressed to ESRD (3 versus 13, P,0.01). Cumulative death-censored graft survival was 95% and 80% in the normalization and partial correction groups, respectively (P,0.01). Complete correction was associated with a significant improvement in quality of life at 6 and 12 months. The number of cardiovascular events was low and similar between groups. In conclusion, this prospective study suggests that targeting hemoglobin values $13 g/dl reduces progression of chronic allograft nephropathy in kidney transplant recipients.