ABSTRACT
La nefropatía membranosa primaria es una enfermedad renal autoinmune y la causa más frecuente de síndrome nefrótico en el adulto. Del 70 al 80% de los casos están causados por anticuerpos anti-PLA2R y en menor porcentaje por anticuerpos anti-THSD7A y otros autoanticuerpos recientemente descubiertos, cuya confirmación y validación clínica están pendientes. Estudios piloto y ensayos clínicos recientes han mostrado que diversos agentes biológicos dirigidos frente a las células productoras de autoanticuerpos son eficaces en el control de la enfermedad con un mejor perfil de seguridad que los inmunosupresores inespecíficos clásicos.En esta revisión narrativa actualizamos conceptos clave sobre la patogenia y el diagnóstico mediante autoanticuerpos y biopsia renal de la nefropatía membranosa primaria. Además, proponemos un algoritmo diagnóstico, terapéutico y de seguimiento de la respuesta al tratamiento, comparamos la eficacia y la seguridad de los tratamientos actualmente disponibles, incluyendo el rituximab y nuevas terapias biológicas, e identificamos necesidades clínicas no cubiertas. (AU)
Primary membranous nephropathy is an autoimmune kidney disease and the most common cause of nephrotic syndrome in adults. About 70%-80% of cases are caused by anti-PLA2R antibodies. Its association with anti-THSD7A antibodies and other autoantibodies has also been described. Recent pilot studies and clinical trials have shown that several biological agents targeting autoantibody-producing cells are effective in controlling the disease with an acceptable safety profile.In this narrative review, we update key concepts about the pathogenesis, autoantibody-based diagnosis, and kidney biopsy findings in primary membranous nephropathy. In addition, we propose a diagnostic and therapeutic algorithm, including guidance on monitoring the response to therapy. We compare the efficacy and safety of currently available treatments, including rituximab and new biological agents, and identify unmet clinical needs. (AU)
Subject(s)
Humans , Autoantibodies , Biological Therapy , Glomerulonephritis, Membranous/diagnosis , Glomerulonephritis, Membranous/drug therapy , Kidney , ThrombospondinsABSTRACT
Primary membranous nephropathy is an autoimmune kidney disease and the most common cause of nephrotic syndrome in adults. About 70%-80% of cases are caused by anti-PLA2R antibodies. Its association with anti-THSD7A antibodies and other autoantibodies has also been described. Recent pilot studies and clinical trials have shown that several biological agents targeting autoantibody-producing cells are effective in controlling the disease with an acceptable safety profile. In this narrative review, we update key concepts about the pathogenesis, autoantibody-based diagnosis, and kidney biopsy findings in primary membranous nephropathy. In addition, we propose a diagnostic and therapeutic algorithm, including guidance on monitoring the response to therapy. We compare the efficacy and safety of currently available treatments, including rituximab and new biological agents, and identify unmet clinical needs.
Subject(s)
Glomerulonephritis, Membranous , Adult , Autoantibodies , Biological Therapy , Glomerulonephritis, Membranous/diagnosis , Glomerulonephritis, Membranous/drug therapy , Humans , Kidney , ThrombospondinsABSTRACT
The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines for glomerulonephritis shed light on the complex world of glomerulonephritis therapy. However, they may no longer apply to idiopathic membranous nephropathy, as recently concluded by the KDIGO 2019 Working Group. This is due to the discovery of autoantibodies such as anti-phospholipase A2 receptor (anti-PLA2R) that allow disease monitoring as well as to results from recent clinical trials, comparative cohort studies and meta-analyses. Perhaps the most disruptive of them is the Membranous Nephropathy Trial of Rituximab (MENTOR) trial comparing rituximab with cyclosporine A, which supports the superiority of rituximab in efficacy and safety. Furthermore, rituximab results compared favourably with the short-term results of classical clinical trials that supported the KDIGO 2012 recommendation of immunosuppressive cyclophosphamide-based regimens as first choice for active treatment of idiopathic membranous nephropathy. Thus, the KDIGO recommendations for cyclophosphamide-based regimens or calcineurin inhibitors as the first line of active treatment regimens for idiopathic membranous nephropathy with nephrotic syndrome may no longer apply. By contrast, rituximab-based regimens or other B-cell-targeted therapies appear to represent the present and future of membranous nephropathy therapy.
