RESUMEN
Regulatory T cells (Tregs), defined as CD4+CD25+highFoxP3+CD127- cells, could promote tolerance in renal transplantation (Tx). In an open-label, randomized, controlled trial 62 de-novo Tx recipients received induction with basiliximab and cyclosporine A (CsA) for the first month after Tx and then were assigned to treatment with sirolimus (SRL) or CsA and followed up for 2 years. The primary endpoint was to evaluate the effects of induction and maintenance treatments on circulating Tregs, while the secondary endpoint was the assessment of Treg renal infiltration and the relationship between Treg count and clinical outcomes. There were no significant differences in either circulating or tissue Treg number between the two groups. At 1 month post-Tx, all patients presented a profound Treg depletion, followed by a significant increase in Tregs that resulted stable during the follow-up. The same trend was also observed for non-activated Tregs (CD69-) and for other immunocompetent cells (CD4+ and CD8+ T cells, B cells and NK cells). Moreover, the Treg count did not correlate either with renal function or with acute rejection and graft loss. Initial immunosuppression is crucial to regulate circulating Tregs, regardless of subsequent immunosuppressive maintenance regimens. Strategies aiming to promote tolerance should consider the effects of different induction regimens.
Asunto(s)
Ciclosporina/administración & dosificación , Rechazo de Injerto/prevención & control , Trasplante de Riñón , Sirolimus/administración & dosificación , Linfocitos T Reguladores/efectos de los fármacos , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Antígenos CD/metabolismo , Basiliximab , Proliferación Celular/efectos de los fármacos , Ciclosporina/efectos adversos , Estudios de Seguimiento , Factores de Transcripción Forkhead/metabolismo , Rechazo de Injerto/inmunología , Humanos , Terapia de Inmunosupresión , Quimioterapia de Inducción , Quimioterapia de Mantención , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Sirolimus/efectos adversos , Linfocitos T Reguladores/inmunología , Tolerancia al TrasplanteAsunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Riñón/patología , Leucemia Linfocítica Crónica de Células B/patología , Infiltración Leucémica/patología , Compuestos de Mostaza Nitrogenada/uso terapéutico , Tomografía Computarizada por Rayos X , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Clorhidrato de Bendamustina , Biopsia , Humanos , Riñón/diagnóstico por imagen , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Infiltración Leucémica/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Inducción de Remisión , Diálisis RenalRESUMEN
Heparin has remained the most commonly used anticoagulant in hemodialysis patients (HD). Its use is usually safe but, in some cases, important adverse effects can occur. Heparin-induced thrombocytopenia (HIT) is an immuno-mediated condition due to the formation of PF4/heparin/IgG complex leading to the activation of platelets and coagulative cascade. The consequent prothrombotic hypercoagulable state may cause venous or arterial thrombosis, skin gangrene and acute platelet activation syndrome. Clinical and laboratory findings may be suggestive for HIT, but formal diagnosis requires the demonstration of the presence of circulating antibodies. Clinical management is complex including the withdrawal of any form of heparin and the administration of anticoagulants. In addition, since anticoagulation is routinely required to prevent clotting of the dialysis lines and membranes, in HD patients presenting HIT it is mandatory to establish heparin-free anticoagulation strategies. Thus, the use of citrate, direct thrombin inhibitors or eparinods have been proposed as alternative anticoagulation approaches in HIT. Here, we review the most important pathogenic factors and clinical features of HIT occurring in HD patients.