ABSTRACT
BACKGROUND: Mammalian target of rapamycin inhibitors (mTORi), sirolimus (SRL) and everolimus (EVR), have distinct pharmacokinetic/pharmacodynamics properties. There are no studies comparing the efficacy and safety of de novo use of SRL versus EVR in combination with reduced-dose calcineurin inhibitor. METHODS: This single-center prospective, randomized study included first kidney transplant recipients receiving a single 3 mg/kg antithymocyte globulin dose, tacrolimus, and prednisone, without cytomegalovirus (CMV) pharmacological prophylaxis. Patients were randomized into 3 groups: SRL, EVR, or mycophenolate sodium (MPS). Doses of SRL and EVR were adjusted to maintain whole blood concentrations between 4 and 8 ng/mL. The primary endpoint was the 12-mo incidence of the first CMV infection/disease. RESULTS: There were 266 patients (SRL, n = 86; EVR, n = 90; MPS, n = 90). The incidence of the first CMV event was lower in the mTORi versus MPS groups (10.5% versus 7.8% versus 43.3%, P < 0.0001). There were no differences in the incidence of BK polyomavirus viremia (8.2% versus 10.1% versus 15.1%, P = 0.360). There were no differences in survival-free from treatment failure (87.8% versus 88.8% versus 93.3%, P = 0.421) and incidence of donor-specific antibodies. At 12 mo, there were no differences in kidney function (75 ± 23 versus 78 ± 24 versus 77 ± 24 mL/min/1.73 m 2 , P = 0.736), proteinuria, and histology in protocol biopsies. Treatment discontinuation was higher among patients receiving SRL or EVR (18.6% versus 15.6% versus 6.7%, P = 0.054). CONCLUSIONS: De novo use of SRL or EVR, targeting similar therapeutic blood concentrations, shows comparable efficacy and safety. The reduced incidence of CMV infection/disease and distinct safety profile of mTORi versus mycophenolate were confirmed in this study.
Subject(s)
Cytomegalovirus Infections , Kidney Transplantation , Humans , Everolimus/adverse effects , Tacrolimus/adverse effects , Sirolimus/adverse effects , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Prospective Studies , Immunosuppressive Agents/adverse effects , Mycophenolic Acid/adverse effects , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/prevention & control , Cytomegalovirus Infections/drug therapy , Cytomegalovirus , Graft Rejection/epidemiology , Graft Rejection/prevention & control , Transplant RecipientsABSTRACT
The allele HLA-A*68:250 differs from HLA-A*68:27:01 by three nucleotides.
Subject(s)
Bone Marrow Transplantation , Bone Marrow , Alleles , Brazil , HLA-A Antigens , High-Throughput Nucleotide Sequencing , Humans , Tissue Donors , VolunteersABSTRACT
Resumo: O conhecimento do genoma humano, decorrente do grande avanço obtido pela genética clínica tem possibilitado o estudo da identificaçâo dos possíveis genes envolvidos com o fenótipo de várias doenças, sobretudo as alérgicas. Entre elas destaca- se a asma. Neste trabalho so apresentados conceitos básicos sobre genética clínica que nos permitirão compreender de modo mais adequado esta nova área do conhecimento, sobretudo o estudo dos polimorfismos. Os conceitos aqui apresentados foram obtidos por busca ativa em tratados específicos e levantamento nos bancos de dados MEDLINE e EMBASE.
