RESUMO
BACKGROUND: This study aimed to compare the efficacy and safety of basiliximab (BAS) versus a single dose of anti-thymocyte globulin (r-ATG) induction therapy in pediatric kidney transplant recipients (KTRs). METHODS: This single-center retrospective comparative cohort study included all pediatric KTRs from May 2013 to April 2018 and followed up to 12 months. In the first period, all recipients received BAS, while from May 2016, a single 3 mg/kg dose of r-ATG was instituted. Maintenance therapy consisted of a calcineurin inhibitor plus prednisone plus azathioprine or mycophenolate. RESULTS: A total of 227 patients were included (BAS, n = 113; r-ATG, n = 114). The main combination of immunosuppressive drugs was tacrolimus, prednisone, and azathioprine in both groups (87% vs. 88%, p = .718). Patients receiving r-ATG showed superior survival-free of the composite endpoint (acute rejection, graft loss, or death; 76% vs. 61%, p = .003; HR 2.08, 1.29-3.34, p = .003) and lower incidence of biopsy-proven acute rejection (10% vs. 21%, p = .015). There was no difference in the overall incidence of CMV infection (33% vs. 37%, p = .457), PTLD (1% vs. 3%, p = .309), 30-day hospital readmissions (24% vs. 23%, p = .847), and kidney function at 12 months (86 ± 29 vs. 84 ± 30 mL/min/1.73m2, p = .614). CONCLUSIONS: These data suggest that induction therapy with a single 3 mg/kg dose of r-ATG is associated with higher efficacy for preventing acute rejection and similar safety profile compared to BAS.
Assuntos
Soro Antilinfocitário , Transplante de Rim , Humanos , Criança , Basiliximab/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Prednisona/uso terapêutico , Estudos Retrospectivos , Estudos de Coortes , Azatioprina , Quimioterapia de Indução , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/epidemiologia , Imunossupressores/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , TransplantadosRESUMO
Previous studies have shown that immunosuppressive drugs impair the airway mucociliary clearance of rats. However, considering the high specificity of basiliximab (BSX) and the absence of studies reporting its side effects, our aim was to investigate whether BSX, associated or not with triple therapy, impairs the mucociliary system. Forty rats were divided into 4 groups: Control, BSX, Triple, and BSX + Triple. After 15 days of treatment, animals were euthanized and the ciliary beating frequency (CBF), mucociliary transport velocity (MCTV), neutral and acid mucin production, Muc5ac and Muc5b gene expression, inflammatory cell number, and interleukin (IL)-6 concentration were analyzed. CBF and MCTV were lower in Triple and BSX + Triple groups (p < 0.05). Neutral mucin percentage was higher in Triple group (p < 0.05), and acid mucin percentage was higher in Triple and BSX + Triple groups (p < 0.05). The Muc5ac and Muc5b gene expression was higher in Triple and BSX + Triple groups (p < 0.05). Animals from Triple and BSX + Triple groups presented fewer mononuclear cells (p < 0.05). The number of polymorphonuclear cells was higher in the Triple group (p < 0.05). In the analysis of inflammatory cells in the blood, there was a decrease in lymphocytes and an increase in neutrophils in the Triple and BSX + Triple groups (p < 0.05). The concentration of IL-6 significantly increased in the animals of the Triple and BSX + Triple groups (p < 0.05). BSX did not change the mucociliary apparatus of rats.
Assuntos
Basiliximab , Imunossupressores , Mucina-5AC , Depuração Mucociliar , Animais , Ratos , Basiliximab/farmacologia , Imunossupressores/farmacologia , Mucina-5AC/genéticaRESUMO
INTRODUCTION AND AIM: The interleukin-2 receptor antagonist; basiliximab is used to allow delayed introduction of Calcineurin inhibitors (CNI) after liver transplantation and thus delay their renal insult. However, there is only little evidence for the safety and the efficacy of this regimen. This study aimed to evaluate the effectiveness and safety of basiliximab induction in liver transplantation. MATERIALS AND METHODS: This study included 89 patients who were classified into two groups: standard triple immunosuppression (IS) regimen of steroid, tacrolimus (TAC) and mycophenolate mofetil (MMF) (n = 47) and induction IS regimen of basiliximab, low dose steroids and MMF with delayed introduction of CNI (n = 42). All patients were followed after liver transplantation for at least six months or until death. RESULTS: There were no significant differences in patient survival, graft dysfunction, infection rate or type, or wound healing between both groups. The acute rejection rate was equivalent in both groups. Renal dysfunction in the first six months post-transplant was less in the basiliximab group in comparison to the other group (7.1% and 19.1% respectively). CONCLUSION: Basiliximab-induced IS protocol is a safe regimen that reduces medium-term renal dysfunction and achieves similar survival without increasing the acute rejection or infection rate in liver transplantation recipients.
Assuntos
Basiliximab/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Fígado , Adulto , Basiliximab/efeitos adversos , Inibidores de Calcineurina/uso terapêutico , Quimioterapia Combinada , Egito , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Humanos , Imunossupressores/efeitos adversos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Esteroides/uso terapêutico , Tacrolimo/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
Resumen Introducción: identificar los factores asociados con pérdida de la función del injerto puede ser un paso importante hacia la prolongación de la sobrevida del injerto renal. Objetivo: determinar la asociación entre los cambios histológicos presentes en las biopsias por protocolo, en el primer año postrasplante en receptores de bajo riesgo inmunológico, recibiendo inducción con basiliximab y pérdida en la función del injerto 12 meses postrasplante. Métodos: se incluyeron pacientes receptores de riñones de donante cadavérico (95 %) o donante vivo (5 %) trasplantados entre agosto de 2007 y julio de 2012. El desenlace primario fue pérdida en la tasa de filtración glomerular calculada (Cockroft & Gault) mayor a 5ml/min 12 meses postrasplante, en comparación con la función renal previa a la biopsia por protocolo. Resultados: la cohorte de estudio estuvo conformada por 114 pacientes, de los cuales 25 presentaron el desenlace principal. Los hallazgos asociados con pérdida de función fueron glomerulitis (p=0,024), inflamación intersticial (p=0,001), tubulitis (p=0,001), capilaritis (p=0,001), glomerulitis + capilaritis (p=0,001), nefropatía por polioma virus (p=0,04) y la presencia de rechazo subclínico (p=0,015). Por análisis de regresión logística la presencia de inflamación intersticial (OR = 2,11; IC 95 %: 1,13-3,95) y capilaritis (0R=7,12; IC 95 %:1,57-32,27) fueron las variables asociadas con pérdida de función del injerto renal 12 meses postrasplante renal. Conclusión: la inflamación intersticial y capilaritis son variables histológicas asociadas con pérdida de función del injerto renal, 12 meses postrasplante, independiente de otras variables.
Abstract Introduction: Identifying factors that are associated of allograft function loss might be an important step toward prolonging kidney allograft survival. Purpose: In this study we found to determine the association between histologic changes on 1-year surveillance biopsies and changes in graft function. Methods: Recipients of kidneys from deceased donors (95%) or living donors (5%) trasplanted between 2007 and 2012. The primary end point was reduction in calculated glomerular filtration rate (Cockroft anf Gault) higher 5ml/min 12 months post transplant vs calculated glomerular filtration rate previous surveillance biopsie. Results: This analysis included 114 adults, recipients of kidneys with low immunological risk receiving basiliximab induction from deceased donors (95%) or living donors (5%), transplanted between august 2007 and july 2012. The primary end point was reduction in calculated glomerular filtration rate (Cockroft & Gault) higher 5ml/min 12 months post trasplant. 25 of 114 patientes showing reduction; The histologic changes associated with renal function reduction were glomerulitis (p=0,024), interstitial inflamation (p=0,001), tubulitis (p=0,001), capilaritis (p=0,001), glomerulitis + capilaritis (p=0,001), polyoma virus nephropathy (p=0,04) and subclinical rejection (p=0,015). By regression analyses, interstitial inflamation (OR = 2,11; IC 95%: 1,13-3,95) and capilaritis (0R=7,12; IC 95%: 1,57-32,27) were associated with renal function reduction 12 month post-transplant. Conclusion: inflammation and capilaritis in protocol biopsies in first year post-transplant predict loss of graft function and independently of other variables.
Assuntos
Humanos , Masculino , Feminino , Transplante de Rim , Basiliximab , Nefropatias , Biópsia , ColômbiaRESUMO
The history of Immunosuppresslon is a long one. From the utilization of steroids and azathloptlne In the 50's to the design of humanized molecules that specifically block cell surface receptors. Liver transplantation is one of the procedures that benefit the most with the development of new immunosuppressors and is also one of the reasons to create a new branch in research and clinical practice: transplant medicine. It also set the standards for research in the "immunologic tolerance" field. The cornerstone in the post-liver transplant stage is the utilization of calcineurin inhibitors combined with new anti-metabolites and monoclonal antibodies. All these settings conforms a promising field in the research of new and better immunosuppressing agents.
Se ha recorrido mucho camino desde el diseño de la inmunosupresión en la década de los 50's. Desde la utilización de los esteroides y la azatioprina hasta el desarrollo de moléculas humanizadas, que bloquean específicamente receptores de superficie celular para inducir tolerancia del injerto, ha transcurrido medio siglo. El trasplante hepático ha sido uno de los procedimientos más beneficiados con el desarrollo de las nuevas drogas inmunosupresoras y ha dado origen a una nueva rama de la medicina: la medicina de trasplantes. También ha sentado las bases de investigación tendiente a lograr la "tolerancia inmunológica" del órgano trasplantado. La piedra angular en la inmunosupresión postrasplante hepático es la utilización de los inhibidores de calcineurina que, en combinación con nuevos antimetabolitos y anticuerpos monoclonales, dibujan un futuro promisorio en la búsqueda de mejores agentes.