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Vol. 34. Núm. 3.Mayo 2014
Páginas 273-424
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Vol. 34. Núm. 3.Mayo 2014
Páginas 273-424
DOI: 10.3265/Nefrologia.pre2014.Feb.12506
Acceso a texto completo
Papel de los anticuerpos monoclonales en el tratamiento de las enfermedades glomerulares autoinmunes
Role of monoclonal antibodies in the treatment of immune-mediated glomerular diseases
Visitas
...
Joaquín Manriquea, Paolo Cravedib
a Servicio de Nefrolog??a, Complejo Hospital de Navarra, Pamplona, Spain,
b 2Icahn School of Medicine at Mount Sinai, New York, USA,
Información del artículo

Los inmunosupresores no específicos han representado durante décadas las únicas terapias para pacientes con enfermedades glomerulares autoinmunes. Estos tratamientos, sin embargo, se asociaban con unas tasas muy elevadas de no respondedores y mucha toxicidad que contrarrestaba su efecto antiproteinúrico. Recientemente están disponibles anticuerpos monoclonales cuyo objetivo selectivo son poblaciones celulares o mediadores directamente implicados en la patofisiología de las enfermedades glomerulares. El rituximab es un anticuerpo monoclonal quimérico dirigido contra el antígeno CD20 en la superficie de los linfocitos B que reduce de manera eficaz y segura la proteinuria en pacientes con síndrome nefrótico secundario a nefropatía membranosa, enfermedad de cambios mínimos o glomeruloesclerosis segmentaria y focal. Su capacidad para reducir la formación de anticuerpos ha sido empleada también en las vasculitis ANCA positivas, nefropatía lúpica y crioglobulinemia mixta. Diversos trabajos han documentado la eficacia del anticuerpo monoclonal anti-factor C5, eculizumab, para el tratamiento del síndrome hemolítico urémico atípico, la nefropatía C3 o la glomerulonefritis membranoproliferativa. Con base en estos prometedores resultados, los anticuerpos monoclonales se han convertido en estrategias muy útiles en el tratamiento de pacientes con enfermedades glomerulares. Incluso, basado en su mecanismo de acción, estos y otros monoclonales han contribuido a mejorar el conocimiento de la patofisiología de la enfermedad glomerular. Sin embargo, su todavía elevado coste representa un hándicap en la generalización de su uso en todos aquellos pacientes que potencialmente podrían beneficiarse.

Palabras clave:
Anticuerpo monoclonal
Palabras clave:
Rituximab
Palabras clave:
Enfermedad glomerular
Palabras clave:
Fresolimumab
Palabras clave:
Eculizumab
Palabras clave:
Belimumab
Palabras clave:
Adalimumab
Palabras clave:
Abatacept

Non-specific immunosuppressants have represented for decades the only therapies for patients with immune-mediated glomerular diseases. These treatments, however, are associated with high rates of no-response and are burdened by toxicities that frequently offset the benefits of proteinuria reduction. Monoclonal antibodies targeting selective cell populations or mediators implicated in the pathophysiology of glomerular diseases have recently become available. Rituximab, a chimeric monoclonal antibody against the CD20 antigen on B cells, safely reduced proteinuria in patients with nephrotic syndrome secondary to membranous nephropathy, minimal change disease, or focal segmental glomerulosclerosis. Its ability to reduce auto-antibody formation has been instrumental to treat also ANCA-associated vasculitis, lupus nephritis, and mixed cryoglobulinemia. Many reports have also documented the efficacy of the anti-C5 humanized monoclonal antibody Eculizumab to treat atypical hemolytic uremic syndrome, C3 nephropathy, and membranoproliferative glomerulonephritis. Thanks to these encouraging findings, monoclonals are becoming very helpful tools to treat patients with glomerular diseases. Moreover, thanks to their specific mechanism of action, these and other monoclonal antibodies are important in improving our understanding of the pathophysiology of glomerular diseases. Their still high costs, however, might represent a major hurdle for their widespread implementation for all patients in need.

Keywords:
Monoclonal antibody
Keywords:
Rituximab
Keywords:
Glomerular disease
Keywords:
Fresolimumab
Keywords:
Eculizumab
Keywords:
Belimumab
Keywords:
Adalimumab
Keywords:
Abatacept
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