RESUMO
BACKGROUND: Induction therapy is associated with excellent short-term kidney graft outcome. The aim of this study was to evaluate differences in the intragraft transcriptome after successful induction therapy using two rabbit antithymocyte globulins. METHODS: The expression of 376 target genes involved in tolerance, inflammation, T- and B-cell immune response, and apoptosis was evaluated using the quantitative real-time reverse-transcriptase polymerase chain reaction (2(-ΔΔCt)) method in kidney graft biopsies with normal histological findings and stable renal function, 3 months posttransplantation after induction therapy with Thymoglobulin, ATG-Fresenius S (ATG-F), and a control group without induction therapy. RESULTS: The transcriptional pattern induced by Thymoglobulin differed from ATG-F in 18 differentially expressed genes. Down-regulation of genes involved in the nuclear factor-κB pathway (TLR4, MYD88, and CD209), costimulation (CD80 and CTLA4), apoptosis (NLRP1), chemoattraction (CCR10), and dendritic cell function (CLEC4C) was observed in the biopsies from patients treated with Thymoglobulin. A hierarchical clustering analysis clearly separated the Thymoglobulin group from the ATG-F group, while the control group had a similar profile as the Thymoglobulin group. CONCLUSIONS: Despite normal morphology in graft biopsy taken 3 months posttransplantation, the intrarenal transcriptome differed in patients treated with induction therapy using different rATGs. In the Thymoglobulin high-risk group, the transcriptome profile was identical to the low-risk group. Therefore, the down-regulation of the nuclear factor-κB pathway after Thymoglobulin induction in vivo is likely to explain the clinical success of this biologic.
Assuntos
Soro Antilinfocitário/farmacologia , Terapia de Imunossupressão/métodos , Transplante de Rim/imunologia , Transplante de Rim/fisiologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Adulto , Idoso , Animais , Apoptose , Biópsia , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/imunologia , Regulação para Baixo/fisiologia , Feminino , Seguimentos , Perfilação da Expressão Gênica , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/prevenção & controle , Humanos , Rim/metabolismo , Rim/patologia , Transplante de Rim/patologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , RNA Mensageiro/metabolismo , Coelhos , Transdução de Sinais/imunologiaRESUMO
BACKGROUND: Kidney transplantation represents the method of choice of end stage renal disease. METHODS AND RESULTS: The program of kidney transplantation was established in 1966 in our centre. In recent years, roughly 200 patients have undergone kidney transplantation annually, and 20-30 of them have received a graft from the living donor. Triple immunosuppressive regimen based on tacrolimus, MMF and steroids is given to majority of patients, in a case of high rejection risk; patients have received the induction protocols with polyclonal or monoclonal antilymphocyte globulins. Acute rejection is not a frequent finding in recent years and has occurred in 15% of cases in the first 3 months, the use of induction immunosuppression has decreased the rejection risk. Valgancyclovir has been used as prophylactic agent to prevent and treat cytomegalovirus infection. The usage of this strategy reduced the incidence of CMV infection below 10%. Kidney transplant recipients suffer from similar comorbidities as other renal patients in the long term, as cardiovascular complications, infections and malignancies. Anemia is a frequent complication in patients with graft dysfunction and erythropoesis stimulating agents have been used in its therapy. The median kidney graft survival is 8 years. CONCLUSIONS: Kidney transplantation is associated with better long-term results when compared with dialysis therapy and thus this method should be offered to all of suitable end stage renal disease patients.
