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DOI: 10.1016/j.medcle.2021.02.004
Primary membranous nephropathy in the era of autoantibodies and biological therapies
Nefropatía membranosa primaria en la era de los autoanticuerpos y de las terapias biológicas
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Jorge Enrique Rojas-Riveraa,b,c,d,
Corresponding author
jerori2003@yahoo.com

Corresponding author.
, Alberto Ortiz Arduánb,c,d
a Unidad de Enfermedades Glomerulares y Autoinmunes
b Servicio de Nefrología e Hipertensión, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
c Grupo Español de Estudio en Enfermedades Glomerulares (GLOSEN), Spain
d Departamento de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
Received 23 November 2020. Accepted 03 February 2021
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Table 1. Diseases associated with membranous nephropathy.
Table 2. Key histopathological findings to differentiate primary from secondary membranous nephropathy.
Table 3. Comparative findings of the main randomized clinical trials of rituximab in primary membranous nephropathy.
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Abstract

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.

Keywords:
Membranous nephropathy
Nephrotic syndrome
Anti-PLA2R antibodies
Immunosuppressive therapy
Anti-CD20 treatment
Resumen

La nefropatía membranosa primaria es una enfermedad renal autoinmune y la causa más frecuente de síndrome nefrótico en el adulto. El 70 a 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 claves 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 seguridad de los tratamientos actualmente disponibles, incluyendo el rituximab y nuevas terapias biológicas, e identificamos necesidades clínicas no cubiertas.

Palabras clave:
Nefropatía membranosa primaria
Síndrome nefrótico
Anticuerpos anti-PLA2R
Terapia inmunosupresora
Tratamiento anti-CD20

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