RESUMEN
In the setting of an overall decline in living organ donation and new questions about long-term safety, a better understanding of outcomes after living donation has become imperative. Adequate information on outcomes important to donors may take many years to ascertain and may be evident only by comparing large numbers of donors with suitable controls. Previous studies have been unable to fully answer critical questions, primarily due to lack of appropriate controls, inadequate sample size, and/or follow-up duration that is too short to allow detection of important risks attributable to donation. The Organ Procurement and Transplantation Network does not follow donors long term and has no prospective control group with which to compare postdonation outcomes. There is a need to establish a national living donor registry and to prospectively follow donors over their lifetimes. In addition, there is a need to better understand the reasons many potential donors who volunteer to donate do not donate and whether the reasons are justified. Therefore, the US Health Resources and Services Administration asked the Scientific Registry of Transplant Recipients to establish a national registry to address these important questions. Here, we discuss the efforts, challenges, and opportunities inherent in establishing the Living Donor Collective.
Asunto(s)
Donadores Vivos , Trasplante de Órganos , Sistema de Registros , Obtención de Tejidos y Órganos , Atención a la Salud , HumanosRESUMEN
We studied whether the use of sirolimus with reduced-dose tacrolimus, as compared to standard-dose tacrolimus, after liver transplantation is safe, tolerated and efficacious. In an international multicenter, open-label, active-controlled randomized trial (2000-2003), adult primary liver transplant recipients (n=222) were randomly assigned immediately after transplantation to conventional-dose tacrolimus (trough: 7-15 ng/mL) or sirolimus (loading dose: 15 mg, initial dose: 5 mg titrated to a trough of 4-11 ng/mL) and reduced-dose tacrolimus (trough: 3-7 ng/mL). The study was terminated after 21 months due to imbalance in adverse events. The 24-month cumulative incidence of graft loss (26.4% vs. 12.5%, p=0.009) and patient death (20% vs. 8%, p=0.010) was higher in subjects receiving sirolimus. A numerically higher rate of hepatic artery thrombosis/portal vein thrombosis was observed in the sirolimus arm (8% vs. 3%, p=0.065). The incidence of sepsis was higher in the sirolimus arm (20.4% vs. 7.2%, p=0.006). Rates of acute cellular rejection were similar between the two groups. Early use of sirolimus using a loading dose followed by maintenance doses and reduced-dose tacrolimus in de novo liver transplant recipients is associated with higher rates of graft loss, death and sepsis when compared to the use of conventional-dose tacrolimus alone.
Asunto(s)
Rechazo de Injerto/tratamiento farmacológico , Supervivencia de Injerto/efectos de los fármacos , Inmunosupresores/uso terapéutico , Hepatopatías/cirugía , Trasplante de Hígado , Sirolimus/uso terapéutico , Tacrolimus/uso terapéutico , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Rechazo de Injerto/mortalidad , Humanos , Agencias Internacionales , Hepatopatías/complicaciones , Hepatopatías/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Factores de Tiempo , Inmunología del TrasplanteRESUMEN
BACKGROUND: The role of interleukin 2 (IL-2) receptor antibodies to avoid the nephrotoxic effects of calcineurin inhibitors in the early post-liver transplant (LT) period is not well defined. AIM: To examine the use of daclizumab induction in LT recipients with renal insufficiency. METHODS: Between 2002 and 2005, 62 patients (median pre-LT creatinine 2.4 mg/dL, IQR 1.9-3.7) received daclizumab induction with tacrolimus being administered when serum creatinine was <2.0 mg/dL. A concurrent comparison group (n = 221, 2002-2005) received tacrolimus-based immunosuppression without daclizumab (median pre-LT creatinine 1.1 mg/dL, IQR 0.9-1.4). A second historical comparison group (n = 103, 1995-2005) not receiving daclizumab was matched to the daclizumab patients by pre-LT serum creatinine (2.2 mg/dL, IQR 1.8-3.1). All patients received mycophenolate mofetil and steroids. RESULTS: Serum creatinine improved in the daclizumab group (-1.0 mg/dL, IQR -2.2 to -0.4) and worsened in the concurrent comparison group (+0.2 mg/dL, IQR 0-0.5) from pre-LT to 4 months. However, there was no difference when daclizumab group was compared with the historical comparison group matched on pre-LT creatinine (median change: -0.8 mg/dL vs. -0.7 mg/dL). Daclizumab induction was not associated with improvement in renal function at 4 months (P = 0.34) after adjusting for pre-LT creatinine, age, gender, hepatitis C status and simultaneous liver kidney transplantation. CONCLUSION: The incremental benefit offered by induction therapy with IL-2 receptor antibodies to preserve renal function is questionable.