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Pharmacotherapy: Pharmacokinetics and Pharmacodynamics (including: ADE, TDM, DUE)
Delayed introduction at reduced doses of prolonged-release tacrolimus in kidney transplants treated with quadruple immunosupressive therapy
  1. M. Castaño,
  2. F.J. Gainza,
  3. E. Alvarez,
  4. U. González,
  5. B. San José
  1. 1Hospital de Cruces, Pharmacy, Barakaldo, Spain
  2. 2Hospital de Cruces, Nephrology, Barakaldo, Spain

Abstract

Background The transplantation of organs from expanded criteria donors (ECDs) increases the risk of delayed graft function. In our hospital, when such kidneys are transplanted quadruple treatment is used: basiliximab, mycophenolate, corticosteroids and tacrolimus in deferred introduction at half dose (0.1 mg/kg/day).

Purpose To evaluate the progress of patients who have followed this immunosuppression regimen.

Materials and methods The authors assessed all kidney transplants from ECDs treated with quadruple immunosuppressive therapy from March 2009 to March 2010. The following data was obtained: donor and recipient age, incidence of delayed graft function and acute rejection, creatinine and glomerular filtration rate (GFR) at discharge and length of hospital stay. About the treatment with prolonged-release tacrolimus (PRT) The authors obtained: day of treatment initiation post-transplant, initial dose, dose at discharge and plasma levels. The PRT dose was adjusted to achieve target levels of 8 ng/ml.

Results The authors assessed 40 kidney transplants from ECD: mean age of donors was 60 +/- 13 years, recipients mean age was 58 +/- 11 years, 47% of recipients were male. PRT began on post-transplant day +4 +/- 1.5; the initial dose was 0.11 +/- 0.03 mg/kg/day and dose at discharge 0.15 +/- 0.08 mg/kg/day. Tacrolimus levels were: in the first determination 6.9 +/-4.5 ng/ml, at 14 days 7.7 +/- 2.3 ng/ml and at discharge 8.0 +/- 2.3 ng/ml. In 26 patients (65%) the initial dose of PRT was increased. 13 patients (32%) had delayed graft function, one episode of acute rejection presented and the average hospital stay was 22 +/- 9 days. Creatinine at discharge was 2.15 +/- 0.93 mg/dl, creatinine clearance (Cockroft-Gault 43.4 +/- 17 ml/min) and GFR (MDRD 33.9 ml/min/1.73m2, 3 patients with GFR> 60).

Conclusions With the delayed introduction at half-dose of PRT it was possible to achieve the target plasma levels, although moderate increases of doses were frequent. The clinical results were favourable, so it could be a valid strategy to avoid the nephrotoxicity of calcineurin inhibitors. These are introduced later and at lower doses due to the coverage provided by the immunosuppression induced with basiliximab (approximate duration 4-6 weeks).

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