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Sent with Reeder
Transplantation - Published Ahead-of-Print Comparison of Pharmacokinetics and Pathology for Low-Dose Tacrolimus Once-Daily and Twice-Daily in Living Kidney Transplantation: Prospective Trial in Once-Daily Versus Twice-Daily TacrolimusBackground: A prolonged-release formulation of tacrolimus (Tacrolimus QD) was developed to allow once-daily dosing and to have similar safety and efficacy profiles to twice-daily tacrolimus (Tacrolimus BID). This study compared the pharmacokinetics (PK) and renal pathology by protocol biopsy in de novo living kidney transplant recipients treated with either low-dose Tacrolimus QD or Tacrolimus BID. Methods: Between November 2009 and January 2011, 102 consecutive adult patients were randomized to receive either low-dose Tacrolimus QD or Tacrolimus BID. All patients underwent PK study and protocol biopsy on postoperative day 14. Additional protocol biopsies were performed between 6 and 12 months after renal transplantation. Results: During the 1-year follow up, the incidence of biopsy-proven acute rejection and toxic tubulopathy was low and similar in both groups. Twenty-four hours area under the curve (AUC0-24) was not different in both groups (285+/-78.7 and 281+/-62.4 ng hr/mL in Tacrolimus QD and Tacrolimus BID, respectively). C0 was well correlated with AUC0-24 in both groups and AUC0-24 between 260 and 280 in the Tacrolimus QD group was achieved by 6 to 8 ng/mL of C0. Acute nephrotoxicity was less than 10% in both groups without any clinical manifestation. Conclusion: Clinical efficacy, safety, and PK profile of Tacrolimus QD is same as those of Tacrolimus BID. (C) 2013 Lippincott Williams & Wilkins, Inc.
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Cost-effectiveness analysis of the early conversion of tacrolimus to mammalian
target of rapamycin inhibitors in patients with renal transplantation.
Gamboa O, Montero C, Mesa L, Benavides C, Reino A, Torres RE, Castillo JS.
Fundaci�n Esensa, Bogot�, Colombia. email@example.com
BACKGROUND: Renal replacement therapies which consist of renal transplantation
and dialysis are the only treatment options for patients with terminal renal
failure. These therapies have changed the outcome from being fatal to being a
chronic disease. Kidney transplantation involves the use of immunosuppressive
agents to prevent rejection. Currently, several immunosuppressive agents have
shown efficacy, safety, and different costs.
OBJECTIVE: The aim was to evaluate the cost-effectiveness of early conversion
from tacrolimus to mammalian target of rapamycin inhibitors sirolimus or
everolimus versus continuous treatment with tacrolimus among renal transplantat
patients in Colombia.
METHODS: We performed systematic literature review to extract data for clinical
effectiveness and safety of tacrolimus replacement schemes for immunosuppressive
therapy in renal transplantation in adults. A Markov model in TreeAge was
developed, simulating the patient's natural history with renal transplantation.
The perspective of the Colombian Health System was used, including only direct
costs. The cost-effectiveness ratio and incremental cost-effectiveness ratio were
estimated. Deterministic and probabilistic sensitivity analyses were performed. A
5% discount rate was applied in costs and health results.
RESULTS: Results for the replacement of tacrolimus to sirolimus are provided. The
cost per year of additional life gained for sirolimus was Col$2,441,171.43; the
cost for avoided loss was Col$4,014,152.84. The acceptability curve shows that a
strategy with sirolimus is the most cost-effective one.
CONCLUSIONS: This study suggested that the sirolimus strategy is cost-effective
in Colombia for patients with renal transplantation using as threshold less than
three times the gross domestic product (GDP) per capita of Colombia per life of
Copyright � 2011 Elsevier Inc. All rights reserved.
PMID: 22099798 [PubMed - in process]
There are limited published data concerning the effects of different immunosuppressive regimens on the development of polyomavirus (BKV) viremia. We examined the risk of developing BKV viremia in kidney transplant recipients receiving everolimus (EVR) or mycophenolic acid (MPA) as maintenance therapy.
We observationally analyzed 296 patients who underwent renal transplantation at our center between 2005 and 2010: 58 were treated with EVR and low-dose cyclosporine (LD-CyA) (group 1) and 238 with MPA and standard-dose CyA (group 2). All of the patients received induction therapy with basiliximab and maintenance steroids. BKV viremia (a whole-blood viral load of >850 copies/mL) was measured by means of real-time polymerase chain reaction at least once a month during a 12-month follow-up period.
BKV viremia was detected in 57 patients (19%), five (9%) in group 1 and 52 (22%) in group 2. Kaplan–Meier analyses showed that freedom from BKV viremia was significantly more frequent in group 1. The mean time of onset of BKV viremia was about four months after transplantation in both groups. The median viral load was greater in group 2 (12.5 ± 6.1 vs. 2.5 ± 1.8 × 104 copies/mL; p = 0.01). After the onset of BKV viremia, graft function significantly declined in group 2: 11 patients developed polyomavirus-associated nephropathy (PVAN) and four presumptive PVAN; nine experienced an acute rejection after the discontinuation of MPA, and 11 (21%) lost their graft. There was no graft loss in group 1.
These findings suggest that in comparison with MPA and Cya, an EVR and LD-CyA regimen lowers the risk of BKV viremia after kidney transplantation and favorably alters outcomes.
Memory T cells play a central role in mediating allograft rejection and are a rational target for immunosuppressive therapy. Alefacept is a recombinant LFA3/IgG1 fusion protein that reduces the number of memory T cells in both psoriatic lesions and the peripheral circulation of psoriasis patients. This study evaluated the efficacy and safety of alefacept compared with placebo when combined with tacrolimus, mycophenolate mofetil and corticosteroids in de novo renal transplant recipients. Between December 2007 and March 2009 patients were randomized in a double-blind fashion to receive alefacept (n = 105) or placebo (n = 107) for 3 months and were then followed for a further 3 months. The primary efficacy endpoint was the incidence of biopsy-confirmed acute T cell mediated rejection (Banff grade ≥1) through Month 6. Memory T cell counts were significantly reduced in the alefacept group from Week 3 to study end compared with placebo. However, there was no significant difference between the alefacept and placebo groups for the primary efficacy endpoint (alefacept, 11.0% vs. placebo, 7.0%, p = 0.3). Patient and graft survival as well as renal function was similar between treatment groups. Safety and tolerability were generally similar between the treatment arms. Malignancy was higher in the alefacept treatment arm.