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Efectivid= ad del tratamiento y manejo de la glomerulonefritis membranosa en pacientes adultos

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Effectiveness of treatment and management of membranous glomerulonephritis in adult patients

 


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Mónica Lizbeth Gahona Bravo=

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https://orcid.org/0009-0006-1135-3583

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Egresada de la carrera de medicina, Universidad Católica de Cuenca, Cuenca, Ecuado= r.

mlgahonab2= 0@est.ucacue.edu.ec=

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Andrés Santiago Bueno

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https://orcid.org/0009-0008-7581-4312

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Docente en la universidad Católica de cuenca- Nefrólogo en el Hospital Monte Sina= í, Cuenca, Ecuador.

andresmedico2012@hotmail.com<= /a>=

 

 

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Artículo de Investigación Científica y Tecnológica

Env= iado: 18/07/2023

Rev= isado: 16/08/2023

Ace= ptado: 01/09/2023

Pub= licado:05/10/2023

DOI: https://doi.org/10.33262= /concienciadigital.v6i4.2699                   <= /o:p>

 

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Cítese:

 

 

Gahona Bravo, M. L., & Santiago Bueno, A. (2023). Efectividad del tratamiento y manejo de la glomerulonefritis membranosa en pacientes adultos. ConcienciaDigital, 6(4= ), 145-175. https://doi.org/10.33262/concienciadigital.v6i4.2699=

 

 

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CONCIENCIA DIGITAL, es una revista multidisciplinar, trimestral,<= /b> que se publicará en soporte electrónico tiene como misión contribu= ir a la   formación de profesionales competentes con visión humaníst= ica y crítica que sean capaces de exponer sus resultados investigativos y científicos en la misma medida que se promueva mediante su intervención cambios positivos en la sociedad. https://concienciadigital.org  

La revista es editada por la Editorial Ciencia Digital (Editorial de prestigio registrada en la Cámara Ecuatoriana de Li= bro con No de Afiliación 663) www.celibro.org.ec<= /o:p>

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Esta revista está protegida bajo una licencia Creative Commons Attribution Non Commercial No Derivatives 4.0 International. Copia de la licencia: http://creativecommons.org/license= s/by-nc-nd/4.0/

 

Palabras claves:=

Glomerulonefr= itis membranosa, nefropatía membranosa primaria, síndrome nefrótico, terapia inmunosupresora

 

Resumen =

Introducción. La Glomerulonefritis Membranosa (GNM) es una patología renal crónica que afecta a los glomérulos, que son las estructu= ras encargadas de filtrar la sangre en los riñones. El tratamiento oportuno y= el manejo adecuado de la nefropatía membranosa en pacientes adultos es fundamental para mejorar la calidad de vida de los pacientes. Objetivo= . Describir los enfoques terapéuticos más efectivos y los factores que pueden influir= en la respuesta al tratamiento para un diagnóstico y manejo temprano de la glomerulonefritis membranosa. Metodología. Estudio descriptivo tipo narrativo realizado mediante la recopilación sistemática de datos, en el = cual se seleccionó una muestra representativa de investigaciones científicas relevantes para el tratamiento y manejo de la enfermedad durante el perio= do 2019 hasta 2023. Resultados. El tratamiento de la glomerulonefritis membranosa en pacientes de bajo riesgo se basa en la utilización de los A= RA II o IECA para controlar la presión arterial y reducir la proteinuria con= el objetivo de disminuir en un 20% la tasa de recaídas de la enfermedad, si = no existe respuesta a la terapéutica se consideran opciones más agresivas co= mo el tratamiento inmunosupresor mismo que aumenta la remisión total en un 7= 3% y reduce el riesgo de presentar enfermedad renal terminal en un 22%. Con= clusión. La eficacia de la terapéutica para la glomerulonefritis membranosa se basa en la combinación de una terapia inmunosupresora a base de esteroides más agentes alquilantes para evitar una mala tolerancia al tratamiento por parte del paciente nefrótico y disminuir las recaídas de la nefropatía membranosa. Área de estudio general: medicina. Área de estudio específica: medicina general.

 

Keywords:=

Membranous glomerulonephritis, Primary membranous nephropathy, Nephrotic syndrome,<= /o:p>

 

Abstract=

Introduction. Membranous glomerulonephritis (MGN) is a chronic renal pathology that affects the gl= omeruli, which are the structures responsible for filtering the blood in the kidne= ys. Timely treatment and proper management of membranous nephropathy in adult patients are essential to improve the quality of life of patients. Obj= ective. To describe the most effective therapeutic approaches and the factors that can influence the response to treatment for early diagnosis and management of membranous glomerulonephritis. Methodology. A descriptive narrative study was conducted through systematic data collect= ion, in which a representative sample of scientific research relevant to the treatment and management of the disease was selected during the period 2019-2023. Results.  Treat= ment of membranous glomerulonephritis in low-risk patients is based on the use= of ARA II or IECA to control blood pressure and reduce proteinuria, with the aim= of reducing by 20% the rate of recurrence of the disease. If there is not a response to therapy, more aggressive options are available, such as the immunosuppressive treatment itself, which increases total remission by 73% and reduces the risk of developing terminal kidney disease by 22%. Con= clusion.  The effectiveness of therapy for membranous glomerulonephritis is based on the combination of steroid-based immunosuppressive therapy with chlorambucil or cyclophosphamide to prevent poor treatment tolerance by the nephrotic patient and decrease the relaps= es of membrane nephropathy.

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Introducción

La glomerulonefritis membranosa (GNM) es una patología renal en la que se prod= uce una acumulación anormal de sustancias dentro de la membrana glomerular, lo = que lleva a la inflamación del glomérulo y daño en los riñones y esto a su vez puede conducir a un síndrome nefrótico, condición caracterizada por proteinuria, hipoproteinemia, edema e hiperlipidemia (elevación del coleste= rol) (Berchíd Débdi, 2019).

En los pacientes adultos, la GNM idiopática (sin causa conocida) es la forma m= ás común de la glomerulonefritis membranosa, sin embargo, de acuerdo con Carra= cedo et al. (Carracedo J, 2020) en un bajo porcentaje del 12%, esta patología es secundaria a enfermedades autoinmunes como la enfermedad de Hashimoto, cirrosis biliar primaria y la artritis reumatoidea, infecciones por estreptococos o parásitos, virus de la hepatitis B, sífilis congénita, diabetes y al lupus eritematoso sistémico, y según Von Groote et= al. (2021) en 1 % se debe a neoplasias.

El tratamiento y el manejo de la glomerulonefritis membranosa en pacientes adu= ltos tienen como objetivo controlar los síntomas, reducir la progresión de la enfermedad y preservar la función renal. Existen diferentes enfoques de tratamiento que pueden ser utilizados, y la elección del mejor enfoque depe= nde de varios factores, como la gravedad de los síntomas, la presencia de complicaciones y la respuesta individual del paciente (Kidney Disease: Improving Global Outcomes Glomerular Disease Work Group, 2021).

El uso de medicamentos inmunosupresores como los corticoides y la ciclofosfami= da, es uno de los enfoques de tratamiento más comunes. Estos medicamentos disminuyen la inflamación y detienen la respuesta inmunitaria que invade los glomérulos. En algunos casos de glomerulonefritis membranosa, también se ha utilizado con éxito el rituximab, medicamento que se dirige específicamente= a las células B del sistema inmunológico (D. Rodríguez Puyol y P. Martínez Miguel, 2019). Según los estudios = de Gordón, el uso de estos inmunosupresores puede causar remisiones parciales o completas en el 70-80% de los casos (Gordón, 2019).

Además del tratamiento farmacológico, es importante controlar y tratar las complicaciones asociadas con la glomerulonefritis membranosa como la hipertensión arterial y la proteinuria. Esto se puede lograr mediante cambi= os en la dieta, control de la presión arterial, uso de medicamentos para reduc= ir la proteinuria, control de los niveles de colesterol y la prevención de la formación de coágulos sanguíneos (Pertuz A, 2022; Cueto, 2019).

En algunos casos, cuando la función renal está deteriorada o las complicaciones son severas, puede ser necesario considerar opciones de tratamiento más invasivas, como la diálisis o el trasplante de riñón (Maifata, 2019).

Es importante enfatizar que el tratamiento y manejo de la glomerulonefritis membranosa en pacientes adultos debe ser individualizado y adaptado a las necesidades y características de cada paciente, siempre con un seguimiento a largo plazo y manejo de las complicaciones para lograr resultados exitosos = (Rivera F, 2020).

Por lo tanto, este estudio se basa en la recolección y análisis de datos clínic= os disponibles para evaluar la eficacia del régimen terapéutico de la glomerul= onefritis membranosa con la finalidad de mejorar la atención y los resultados clínico= s en esta enfermedad, proporcionando información científica sólida y recomendaci= ones basadas en los hallazgos del estudio.

Justificación

Este proyecto se fundamenta en la necesidad de abordar de manera integral la nefropatía membranosa (NM), una enfermedad renal crónica que afecta a los pacientes adultos en todo el mundo. Esta enfermedad representa la alteración más frecuente de síndrome nefrótico en pacientes adultos y ancianos, lo que resalta la importancia de desarrollar estrategias de tratamiento y manejo eficaces para mejorar la calidad de vida de estos individuos.

En el contexto específico de Ecuador, de acuerdo con el estudio de Gordón (Gordón, 2019) la glomerulonefritis membranosa ocupa el segundo lugar como diagnóstico histopatológico más común después de la nefritis lúpica. Sin embargo, resulta preocupante la falta de sistemas de bases de datos publicadas que brinden información precisa y actualizada sobre la distribución, frecuencia y su manejo en el Ecuador.

Esta carencia de datos detallados y actualizados dificulta la identificación de estrategias terapéuticas para abordar la nefropatía membranosa de manera óptima. Por lo tanto, es imperativo realizar un esfuerzo sistemático para recopilar y analizar la información disponible sobre el tratamiento y manej= o de la glomerulonefritis membranosa en pacientes adultos.

El objetivo principal de este estudio es identificar los enfoques terapéuticos= más efectivos para el manejo de la nefropatía membranosa, al tiempo que se expl= oran los factores que pueden influir en la respuesta de los pacientes al tratamiento. Además, se busca evaluar la viabilidad y efectividad de nuevas tecnologías y herramientas diagnósticas, tales como la detección de biomarcadores específicos y la secuenciación genética, con el fin de mejora= r el diagnóstico y seguimiento de la glomerulonefritis membranosa. Estas innovaciones pueden facilitar una mejor caracterización de la enfermedad, identificar subtipos y factores de riesgo, y permitir una evaluación objeti= va de la respuesta al tratamiento.

Al mejorar el conocimiento sobre el tratamiento y manejo efectivo de la NM, se pueden establecer pautas y recomendaciones claras para los profesionales de= la salud, lo que contribuirá a mejorar la estandarización de la atención y garantizar un acceso equitativo a un tratamiento óptimo para todos los pacientes, sin importar su origen socioeconómico o ubicación geográfica.

Además, al mejorar los resultados clínicos y la calidad de vida de las personas con glomerulonefritis membranosa, se puede reducir la carga de la enfermedad en= la sociedad. Un control más efectivo de esta patología puede disminuir la necesidad de tratamientos costosos, como la diálisis o el trasplante renal, aliviando así la carga económica en los sistemas de salud y mejorando la productividad laboral de los pacientes afectados.<= /p>

Planteamiento del problema

Según el estudio de Cueto (Cueto, 2019) la glomerulonefritis membranosa es una enfermedad renal crónica que afecta a una proporción significativa del 25% de pacientes adultos en todo el mundo. A pesar de los avances en la comprensión de su fisiopatología y el desarrollo de enfoques terapéuticos, aún existen interrogantes sobre la efectividad del tratamient= o y manejo de esta enfermedad.

El problema radica en la necesidad de determinar la verdadera efectividad de l= os diferentes enfoques terapéuticos utilizados en el tratamiento de la glomerulonefritis membranosa en pacientes adultos. Si bien la falta de información precisa y actualizada sobre las enfermedades crónicas que afect= an a Ecuador ha generado una insuficiente atención y prevención por parte de las autoridades. Aunque sabemos de la existencia de estos problemas, desconocem= os su verdadero alcance. Por tanto, resulta crucial contar con una base de dat= os que proporcione un conocimiento detallado de la magnitud de estas enfermeda= des y permita brindar atención oportuna a los pacientes afectados.

Maifata et al. (Maifata, 2019) demostraron que la nefropatía membranosa (NM) es un trastorno renal crónica que constituye una= de las causas más comunes de síndrome nefrótico en adultos y ancianos en un 21-35%, en comparación con un 1,5-9% en niños y adolescentes. La incidencia= de la nefropatía membranosa es de aproximadamente cinco a diez casos por milló= n de habitantes al año.

A lo largo de los años, se han logrado avances significativos en el tratamien= to de la glomerulonefritis membranosa gracias a una mejor comprensión de su origen. Sin embargo, en nuestro país carecemos de un sistema de datos publicados que brinde información exacta sobre la distribución, frecuencia y tratamiento actual de la NM. Es fundamental analizar esta enfermedad para conocer nuestra realidad en comparación con otras regiones.

Este estudio tiene como objetivo proporcionar información científica sólida que oriente la toma de decisiones clínicas y mejore los resultados en el tratamiento y manejo de la nefropatía membranosa en nuestra población. Al obtener una comprensión más profunda de la enfermedad y su abordaje, podrem= os implementar estrategias de prevención y tratamiento más efectivas.

En resumen, la falta de información precisa sobre la nefropatía membranosa y su manejo en nuestra población resalta la necesidad de realizar un análisis exhaustivo de la enfermedad. A través de la recopilación y el análisis de d= atos de pacientes, este estudio busca proporcionar una visión clara de la magnit= ud y evolución de la enfermedad en nuestra población, así como identificar facto= res que puedan influir en la respuesta al tratamiento. Los resultados de este estudio serán de gran utilidad para implementar estrategias efectivas que logren mejorar la atención y los resultados clínicos en pacientes con nefropatía membranosa en nuestro país, consiguiendo mejorar la calidad de v= ida de los pacientes y reducir la carga de la enfermedad en nuestra sociedad.

Formulación del problema

¿Cuál es la efectividad del tratamiento y manejo de la Glomerulonefritis membrano= sa en pacientes adultos?

Marco teórico

Glomerulopatías<= /o:p>

El término glomerulopatía o glomerulonefritis se refiere a un conjunto de enfermedades caracterizado por alteración de la membrana de filtración glomerular en el riñón. Esto conduce a la presencia de elementos sanguíneos= y moléculas grandes en la orina, como las proteínas, junto con una disminución variable en la capacidad de filtración del riñón. Estas enfermedades englob= an diversas entidades clínicas como el síndrome nefrítico, el síndrome nefróti= co, la hematuria recurrente y cambios en el sedimento urinario. En muchos casos, pueden causar insuficiencia renal aguda, aunque en algunos casos la función= de filtración glomerular puede permanecer normal (Kidney Disease: Improving Global Outcomes Glomerular Disease Work Group, 2021). Los estudios anatomopatológicos son fundamentales para clasificar estas enfermedades y determinar el curso clínico, el pronóstico y la terapéutica idónea para cada entidad. El estudio histopatológico renal es el método definitivo para su diagnóstico, basándose en la sospecha clínica y los resultados de los análi= sis de laboratorio. Según Rodriguez et al. (D. Rodríguez Puyol y P. Martínez Miguel, 2019) las glomerulopatías representan un importante desafío en el campo de la nefrología y son la ter= cera causa más común de enfermedad renal crónica después de la diabetes mellitus= y la hipertensión arterial.

Glomerulonefritis membranosa

Las patologías que afectan la función y estructura de los glomérulos renales se denominan glomerulopatías o glomerulonefritis. Aunque estas enfermedades ti= enen diferentes etiologías, patogenia, alteraciones funcionales y pronóstico, comparten los hallazgos histológicos de inflamación en los glomérulos y est= án relacionadas con el desarrollo de los mecanismos inmunológicos. Para un tratamiento adecuado y efectivo de la enfermedad glomerular, identificar rápidamente la causa es esencial para un mejor enfoque terapéutico. Esto pu= ede tener un efecto significativo en la conservación de la función renal. La glomerulonefritis membranosa idiopática es la causa más frecuente de enferm= edad renal en etapa terminal a nivel mundial, después de la glomerulonefritis membranosa por diabetes (Kidney Disease: Improving Global Outcomes Glomerular Disease Work Group, 2021).

La acumulación de depósitos inmunitarios subepiteliales densos y la formación = de espigas en la membrana son los síntomas de la enfermedad conocida como nefropatía membranosa. Estos depósitos inmunes están compuestos por inmunoglobulina G (IgG), antígenos relevantes y el complejo de ataque a la membrana del sistema de complemento. A diferencia de otras enfermedades glomerulares, no se evidencia infiltrado celular inflamatorio en el gloméru= lo, lo cual sugiere que el conflicto inmunológico ocurre fuera de la membrana b= asal glomerular (D. Rodríguez Puyol y P. Martínez Miguel, 2019).

La glomerulonefritis membranosa puede ocurrir de forma primaria, es decir, sin= una enfermedad subyacente asociada (80% de los casos), o secundaria, en asociac= ión con condiciones clínicas como infecciones (como la hepatitis B), lupus eritematoso sistémico, cáncer o intoxicación por drogas. Además, esta enfermedad presenta una variabilidad en su evolución clínica, con aproximadamente el 40% de los pacientes logrando una remisión espontánea, mientras que alrededor del 20% experimentará una progresión hacia una insuficiencia renal grave que requerirá tratamiento a base de reemplazo ren= al (Gordón, 2019).

La glomerulonefritis membranosa puede manifestarse en cualquier etapa de la vi= da, aunque es más común en adultos. Aproximadamente el 80% al 90% de los pacien= tes son diagnosticados después de los 30 años. La enfermedad suele comenzar ent= re los 50 y 60 años, y se presenta con síntomas de síndrome nefrótico, como ed= ema, proteinuria, hipoalbuminemia e hiperlipidemia. La función renal suele ser normal al inicio. La progresión de la enfermedad es gradual y, ocasionalmen= te, puede complicarse con eventos tromboembólicos. En algunos casos, puede haber hematuria, hipertensión arterial y disminución de la tasa de filtración glomerular desde el inicio o a lo largo del curso de la enfermedad. Un terc= io de las personas pueden desarrollar enfermedad renal terminal (ERT) aproximadamente 10 años posterior al inicio de la enfermedad<= w:Sdt Citation=3D"t" ID=3D"528219822">=  (Pertuz A, 2022).

En América Latina, la enfermedad renal es muy común, con 650 casos por cada mi= llón de habitantes y un aumento anual estimado del 10%. En el 2019, se calculó q= ue alrededor de 11.460 pacientes en Ecuador, con una población de 16.278.844 personas, padecían de glomerulonefritis membranosa. De acuerdo con el estud= io de Cueto (Cueto, 2019) la tercera causa más importante de enfermedad renal terminal en adultos es la nefropatía membran= osa, que representa entre el siete y el diez por ciento de los casos diagnostica= dos mediante biopsia renal. Se ha observado que esta patología se presenta entr= e el 35% y 40% de personas diagnosticadas con glomerulonefritis mayores de 50 añ= os. Este tipo de nefropatía se caracteriza frecuentemente por un síndrome nefró= tico completo.

Causas

La nefropatía membranosa ocurre cuando los pequeños vasos sanguíneos del riñón= que filtran los desechos de la sangre, glomérulos, sufren daño y se vuelven más gruesos. Como resultado, las proteínas se filtran de estos glomérulos alter= ados y son eliminados a través de la orina, lo que se conoce como proteinuria. C= on el tiempo, la pérdida de estas proteínas puede provocar síntomas y signos q= ue se conocen como "síndrome nefrótico".

La glomerulonefritis membranosa generalmente no requiere de tratamiento alguno, pero conforme la filtración de proteínas aumenta, también incrementa el rie= sgo de presentar alteraciones renales y esto a su vez puede causar insuficiencia renal en muchos pacientes. Aunque no existe un tratamiento definitivo para = la nefropatía membranosa, un manejo efectivo puede revertir la proteinuria y lograr una evolución positiva del paciente (Maifata, 2019).

Las complicaciones asociadas a la nefropatía membranosa:

·      =      Hiperlipidemia: las personas con nefropatía membranosa a menudo presentan niveles altos de colesterol y triglicéridos, lo que increm= enta considerablemente el riesgo de presentar patologías cardíacas.

·      =      Formación de trombos: la pérdida de proteínas que inhiben= la coagulación sanguínea a través de la orina, proteinuria, incrementa la propensión de los pacientes nefróticos a presentar tromboembolismo pulmonar= o trombosis venosa profunda, ya que existe una disminución de los factores procoagulantes.

·      =      Hipertensión arterial: la presión arterial puede aumentar debido a la retención de líquidos por un exceso de sodio y por la uremia

·      =      Infección: la proteinuria puede debilitar el sistema inmunológico, al perder las proteínas (anticuerpos) que protegen contra las infecciones, lo que aumenta la vulnerabilidad a las mismas.

·      =      Síndrome nefrótico: se caracteriza por presentar edema que puede llegar a la anasarca, hipoalbuminemia, hiperlipidemia y en especial proteinuria.=

·      =      Insuficiencia renal aguda: se da por un deterioro abrupto= y potencialmente reversible de la función renal, en la que se produce retenci= ón de la urea y productos nitrogenados con desregulación del volumen extracelu= lar y de electrolitos.<= /span>

·      =      Enfermedad renal crónica: por la presencia de edema intersticial e hipovolemia, lo que causa que el paciente requiera en la may= oría de los casos de trasplante renal o diálisis <= span style=3D'mso-bookmark:_Hlk81985521'>(Maifata, 2019)= .

Diagnóstico clínico

La glomerulonefritis membranosa suele manifestarse con un síndrome nefrótico completo, lo que facilita su diagnóstico debido a los síntomas visibles com= o el edema. Sin embargo, en algunos casos puede presentarse con proteinuria no nefrótica, lo que dificulta el diagnóstico al no haber síntomas evidentes. A pesar de que la microhematuria es común y la macrohematuria es poco frecuen= te, esta última puede indicar complicaciones asociadas a la nefropatía membrano= sa como tumores urológicos o trombosis venosa profunda=  (Gordón, 2019).

Para diagnosticar la glomerulonefritis membranosa se deben realizar una serie de pruebas diagnósticas como análisis de sangre y orina para evaluar la función renal, cultivos de garganta (hisopos faríngeos) para confirmar o descartar infecciones estreptocócicas, electrocardiograma para detectar cualquier anomalía en la actividad eléctrica del corazón o alteración en el músculo cardiaco, ultrasonido renal para evidenciar obstrucciones, masas, cálculos renales o quistes, radiografía de tórax y en algunos casos, una biopsia ren= al en la que se extrae una pequeña muestra de tejido renal para analizarla e identificar la enfermedad (Rivera F, 2020).

De acuerdo con algunos estudios, la presencia de anti-PLA2R positivos en pacie= ntes con síndrome nefrótico y proteinuria, permite diagnosticar de nefropatía membranosa sin el requerimiento de la realización de una biopsia renal. Exc= epto cuando se encuentran lesiones tubulointersticiales en etapa crónica que no responden a la terapia inmunosupresora, la clasificación histológica en cua= tro estadios de la glomerulonefritis membranosa tiene poca importancia pronosti= ca. Por lo tanto, en la actualidad, el diagnóstico se puede realizar sin biopsia renal en pacientes con resultados positivos de anti-PLA2R y que presenten cuadros clínicos compatibles con la enfermedad. Esta regla puede ser excepcionada en casos de síndrome nefrótico persistente a pesar del anti-PL= A2R negativo, resultados analíticos sugerentes de otras enfermedades, presentac= ión clínica atípica y disminución del filtrado glomerular=  (Sethi S, 2019).

Estadios anatomopatológicos

La glomerulonefritis membranosa se clasifica en cuatro estadios anatomopatológ= icos distintos. En el primer estadio, se pueden observar depósitos de inmunocomplejos sin alteraciones visibles en el espesor de las paredes capilares glomerulares. En el segundo estadio, la presencia de "púas&q= uot; o "spikes" y el engrosamiento de las paredes capilares solo se evidencian a base de tinciones con plata. En el tercer estadio, los inmunocomplejos están rodeados por prolongaciones de la membrana basal, lo = que demuestra una desestructuración y engrosamiento de la pared capilar. Por último, en el cuarto estadio, se evidencia el tubulointersticial y múltiples glomérulos con una esclerosis avanzada (Taherkhani A, 2019).

Biopsia renal

La biopsia renal es un procedimiento en el que se extrae una pequeña muestra de tejido renal para examinarla bajo el microscópico en busca de posibles lesi= ones o detectar cualquier enfermedad. Este procedimiento se recomienda para diagnosticar trastornos renales, evaluar la gravedad de una enfermedad rena= l o controlar el tratamiento. En casos de disfunción del trasplante de riñón, también puede ser necesario realizar una biopsia renal. Esto generalmente, = se realiza insertando una aguja delgada a través de la piel bajo la guía de imágenes de diagnóstico para obtener el tejido necesario=  (Rojas-Rivera, 2022).

Enfoque y manejo de la nefropatía membranosa

El primer método para tratar la glomerulonefritis membranosa consiste en reali= zar una biopsia renal para identificar el patrón histológico, identificar estud= ios pertinentes basados en el patrón ilustrativo de inmunofluorescencia y finalmente, dirigir el tratamiento adecuado. Las nefropatías pueden ser ocasionadas por causas primarias/idiopáticas o secundarias, siendo la prima= ria la más común. Antes de identificar una etiología principal y basándose en la relación en la patogénesis del complemento, es importante considerar entida= des relacionadas con la formación de inmunocomplejos. Por lo tanto, si no hay evidencia de C3 en la inmunofluorescencia, es necesario descartar la presen= cia de abscesos o infecciones por hepatitis B y C, y parásitos (Krishna CK, 2019)= .

En pacientes con nefropatía membranosa, es importante tomar precauciones al iniciar una terapia inmunosupresora debido a la posibilidad de remisión espontánea de proteinuria. Antes de considerar la inmunosupresión, se recomienda esperar al menos seis meses de tratamiento anti proteinúrico. Se= ha observado que hasta el 45% de los pacientes experimentan una remisión espontánea de proteinuria mayor a 4 g/d durante este período, el 35% con proteinurias superiores a 8 g/d dentro de los 6 meses de terapia de soporte= y el 20% con niveles de anticuerpos anti-PLA2R superiores a 275 RU/ml. Estos hallazgos respaldan la importancia de evaluar cuidadosamente la necesidad de iniciar la terapia inmunosupresora en pacientes con nefropatía membranosa, considerando el potencial de remisión espontánea de la enfermedad (Torres R, 2021).

La remisión espontánea es un fenómeno frecuente en la nefropatía membranosa y, debido a los posibles efectos negativos de la terapia inmunosupresora, es esencial determinar el estadio en el que se encuentra la alteración renal, = ya sea a nivel funcional o estructural, antes de comenzar el tratamiento. Se d= ebe reconsiderar el inicio del tratamiento antes de los seis meses en pacientes= con proteinuria de bajo peso molecular y anticuerpos anti-PLA2R positivos. Por = otro lado, en aquellos pacientes con síndrome nefrótico que no responden al tratamiento anti proteinúrico o presentan deterioro de la función renal, se= debe comenzar inmediatamente el tratamiento inmunosupresor, ya que la enfermedad continúa progresando pesar del tratamiento anti proteinúrico<= w:Sdt Citation=3D"t" ID=3D"911580574">=  (Kidney Disease: Improving Global Outcomes Glomerular Disease Work Group, 2021).

Los factores que predicen una remisión espontánea incluyen una reducción significativa de la proteinuria durante el primer año, el uso de tratamiento antiproteinúrico (IECA-ARB), el nivel de proteinuria al momento del diagnóstico y una función renal conservada, los cuales evidencian que el paciente tendrá un pronóstico favorable, con una t= asa de supervivencia renal del 100%. Sin embargo, en un 6% los pacientes con remisión espontánea presentan recaídas de la enfermedad, cursando con cuadr= os clínicos agresivos y una rápida disminución de la función renal en los prim= eros meses de la nefropatía= (Kidney Disease: Improving Global Outcomes Glomerular Disease Work Group, 2021; Torres R, 2021).

 

Tratamiento inmunosupresor en casos de bajo riesgo y remisión parcial espontánea <= /o:p>

Mantener el uso de antagonistas de los receptores de angiotensina II (ARAII) o inhibidores de la enzima convertidora de angiotensina (IECA) es crucial en estos casos para mantener la presión arterial en valores normales y reducir= la proteinuria. Sin embargo, en los últimos años se ha demostrado que el uso de nuevos fármacos antialbuminúricos y renoprotectores, como los inhibidores d= el cotransportador de sodio y glucosa tipo 2 (Empagliflozina), desempeñan un r= ol importante en el tratamiento de la nefropatía membranosa, en los casos de b= ajo riesgo, los cuales no solo disminuyen los niveles de proteinuria residual s= ino también ayudan a aumentar la protección renal proporcionada por el sistema renina angiotensina aldosterona. Además, es fundamental tomar medidas para reducir el riesgo cardiovascular, como mantener una dieta balanceada, reali= zar actividad física y controlar la presión arterial (Von Groote T, 2021; Coronel G, 2023).

Regímenes terapéutico= s en pacientes con enfermedad renal

La selección del régimen de tratamiento a seguir se basará en diversos aspecto= s, que incluyen las características individuales del paciente, la disponibilid= ad de los fármacos necesarios, la eficacia farmacológica de cada uno y su perf= il de efectos secundarios. Estos factores serán considerados para determinar la opción terapéutica más adecuada para cada paciente en particular. Es posible comenzar un tratamiento con inhibidores de la enzima convertidora de angiot= ensina (IECA) o antagonistas del receptor de angiotensina II (ARA-II) durante algu= nas semanas, con el objetivo de alcanzar una presión arterial objetivo de ≤125/75 mm Hg. Esto puede resultar en una disminución de la proteinur= ia en aproximadamente el 40-50% de los pacientes (Coronel G, 2023; Ponticelli C, 2021).

Se puede seguir un régimen de tratamiento que incluye la administración de glucocorticoides y citostáticos de la siguiente manera: se administra metil= prednisolona por vía intravenosa a dosis de 0,5-1,0 g al día durante 3 días, luego se continúa con prednisona por vía oral a dosis de 0,5 mg/kg al día durante 30 días. Durante los siguientes 30 días, se utiliza clorambucilo por vía oral a dosis de 0,15-0,2 mg/kg al día o ciclofosfamida por vía oral a dosis de 2 m= g/kg al día. Este ciclo de tratamiento (prednisona durante 30 días y citostáticos durante los siguientes 30 días) se repite tres veces en un período de 6 mes= es. Como alternativa, se puede considerar el uso de ciclosporina por vía oral a dosis de 3,5-5 mg/kg al día (junto con prednisona a dosis de 0,15-1,0 mg/kg= al día) o tacrolimus por vía oral a dosis de 0,05-0,075 mg/kg al día durante 6 meses. Se puede disminuir en un 50% la dosis del inhibidor de la calcineuri= na cada 4 a 8 semanas después de lograr una remisión sostenida y se debe conti= nuar la terapia durante al menos doce meses. Se recomienda suspender el tratamie= nto si no se logra la remisión durante los 6 meses (Fervenza F, 2019; SanMartin C, 2022).

En pacientes con hipertensión, incluso en casos de hipertensión leve (130/80 mm Hg) y con proteinuria, se recomienda el uso de inhibidores de la angiotensi= na como inhibidores de la enzima convertidora de angiotensina (IECA) o bloquea= ntes de los receptores de angiotensina II (BRA) en la nefritis lúpica. También, = es importante abordar de manera agresiva la dislipidemia y los factores de rie= sgo para la aterosclerosis (Chávez A, 2019).

En los casos de nefritis activa potencialmente reversible, se suele utilizar u= na combinación de ciclofosfamida y prednisona como tratamiento. Estos medicame= ntos tienen como objetivo reducir la inflamación y controlar la actividad de la enfermedad en los riñones (Goździk M, 2019).

Para pacientes con enfermedad renal en etapa terminal, el trasplante renal es una opción de tratamiento importante. El trasplante renal puede ofrecer una mej= or calidad de vida y una mayor supervivencia en comparación con la diálisis a largo plazo. Sin embargo, es necesario realizar una evaluación exhaustiva p= ara determinar la idoneidad del paciente para el trasplante y para encontrar un donante compatible (Chávez A, 2019; Goździk M, 2019).

La hormona adrenocorticotrópica (ACTH) tiene múltiples mecanismos de acción. S= us efectos protectores sobre los riñones engloban la supresión del sistema inmunológico y la reducción de la inflamación mediante la producción de esteroides, la modulación de los receptores MCR antiinflamatorios (MCR 1, 3= , 5) y la regulación de los niveles de lípidos en la sangre. Su capacidad para restaurar la expresión de una proteína llamada clusterina en los glomérulos, misma que protege contra el daño causado por el complejo de ataque C5b-9, destaca su efecto protector sobre las células de los podocitos=  (Wu Lianzhong, 2021).

En un estudio piloto con ratas que presentaban nefritis pasiva, se encontró el receptor MCR 1 en las células epiteliales especializadas adheridas a la membrana basal glomerular, lo que demostró que la administración de agonist= as como la hormona adrenocorticotrópica normalizan a las células renales y con ello reduce la proteinuria. Sin embargo, los efectos adversos como la apari= ción transitoria de edema relacionado con el uso de fármacos y el incremento del= IMC en algunos pacientes han demostrado que es necesaria una supervisión cuidad= osa del paciente (Krishna CK, 2019; Wu Lianzhong, 2021).

Avances en el manejo = de la nefropatía membranosa

La guía de práctica clínica para el manejo de enfermedades glomerulares KDIGO 2012, recomendó una terapia de apoyo con inhibidores del sistema renina-angiotensina-aldosterona durante al menos seis meses antes de inicia= r la terapia inmunosupresora en pMN nefrótica sin complicaciones graves. Esta estrategia de manejo uniforme ha sido motivo de controversia, dada la evolu= ción muy variable de la enfermedad. Mientras que la guía clínica KDIGO 2021 para= el tratamiento de enfermedades glomerulares se ha modificado teniendo en cuenta los numerosos avances en el campo de las pMN desde la edición anterior de 2= 012. Se han realizado importantes avances, sobre todo en la identificación de marcadores pronósticos. Así, la nueva guía propone categorizar a los pacien= tes con pMN y síndrome nefrótico según su riesgo de progresión de la enfermedad renal con el fin de proporcionar un manejo personalizado. Sin embargo, vari= os marcadores adicionales pueden ayudar a estratificar la severidad de la enfermedad, así como la respuesta a la terapia (Kidney Disease: Improving Global Outcomes Glomerular Disease Work Group, 2021; Wu Lianzhong, 2021). <= /span>

Aunque hasta el momento, la combinación de corticosteroides y agentes alquilantes = ha sido la única terapia que ha demostrado preservar la función renal a largo plazo, el uso de bioterapia anti-CD20, específicamente rituximab, se ha vue= lto cada vez más popular como tratamiento de primera línea. Esto se debe a la toxicidad asociada con los agentes alquilantes, la toxicidad renal a largo plazo de los inhibidores de la calcineurina (ICN) y el alto riesgo de recaí= da cuando se utilizan como monoterapia con o sin prednisona (Moroni G, 2020; S., 2021).

Un ensayo clínico aleatorizado multicéntrico llamado GEMRITUX se llevó a cabo = en Francia para evaluar el uso de rituximab en el tratamiento de la nefropatía membranosa. En este ensayo, 77 pacientes con función renal normal fueron asignados aleatoriamente a recibir rituximab (375 mg/  en los días uno y ocho) o continuar con = el tratamiento antiproteinúrico no inmunosupresor después de un período de preinclusión de seis meses de tratamiento antiproteinúrico en cada grupo. D= urante el período de seguimiento después de los primeros seis meses, la tasa de remisión de la proteinuria fue del 65% en el grupo de rituximab, en compara= ción con el 34% en el grupo de control, aunque la diferencia no fue estadísticam= ente significativa. Se observó una reducción significativa en los títulos de anticuerpos anti-PLA2R a los tres meses en el grupo tratado con rituximab, = lo que sugiere que la reducción en los títulos de anticuerpos puede preceder a= la disminución de la proteinuria y podría ser utilizado como un indicador para repetir la infusión de rituximab. Sin embargo, hasta hace poco, no se había realizado una comparación directa entre agentes alquilantes, inhibidores de= la calcineurina y rituximab en ensayos clínicos aleatorizados (Ronco P B. L., 2021; Alsharhan Loulwa, 2021).

El ensayo STARMEN es un ECA europeo que comparó la eficacia de un tratamiento secuencial a base de rituximab y tacrólimus con la de un tratamiento cíclico alternante con un protocolo Ponticelli modificado para inducir una remisión clínica persistente. Este ensayo controlado abierto se realizó en 86 person= as con síndrome nefrótico persistente y glomerulonefritis membranosa idiopática después de un período de preinclusión de seis meses. Los pacientes tenían al menos 4 g/día de proteinuria y una tasa de filtración glomerular estimada &= gt; 45 ml/min. /1,73 . Cuarenta y tres pacientes de cada grupo fueron asignados para recibir tratamientos cíclicos de seis meses con corticosteroides (dosis total acumu= lada de metilprednisolona oral, 3,4+/-0,9 g y de metilprednisolona intravenosa, 8,2+/-1,4 g) y ciclofosfamida (dosis total acumulada, 10+/−3,5 g) o terapia secuencial con rituximab (un gramo en el sexto mes) y tacrólimus (d= osis completa durante seis meses y disminución gradual durante otros tres meses)= . El 77% de los pacientes fueron PLA2R positivos (Rojas J, 2021; Thompson A, 2019).

Actualmente, se encuentra en desarrollo una nueva modalidad terapéutica conocida como anticuerpos de barrido, la cual permite la eliminación activa de antígenos solubles presentes en la circulación. Esta modalidad combina dos tecnología= s de ingeniería de anticuerpos: la ingeniería de región variable que permite que= el anticuerpo se una al antígeno en el plasma y luego se disocie del antígeno = en la endosoma y la ingeniería de región constante que aumenta la captación celular del complejo formado por el anticuerpo y el antígeno en la endosoma. Como resultado, el anticuerpo de barrido terapéutico recircula y contribuye= a una mayor eliminación de los antígenos de la circulación=  (Caravaca-Fontán, 2023).

Los estudios en modelos animales han demostrado que el método de barrido de anticuerpos puede utilizarse con éxito para eliminar específicamente los anticuerpos dirigidos a antígenos. Basándose en esta experiencia, se ha planteado la hipótesis de que el concepto de anticuerpos de barrido también podría aplicarse en pacientes con nefropatía membranosa= (Caravaca-Fontán, 2023; Teisseyre M, 2022)= .

El ensayo MENTOR fue el primer ensayo controlado aleatorizado realizado en América del Norte que comparó la eficacia de rituximab con ciclosporina en pacientes con nefropatía membranosa (MN). Este ensayo reclu= tó a 130 pacientes que presentaban al menos 5 g/día de proteinuria y un aclarami= ento de creatinina superior a 40 ml/min/1,73 . Los pacientes fueron asignados aleatoriamente a recibir rituximab (dos infusiones de 1000 mg cada una con un intervalo de 14 días, y se repetían a= los seis meses en caso de respuesta parcial) o ciclosporina (a una dosis de 3,5= mg por kilogramo de peso corporal por día durante 12 meses, con una reducción gradual posteriormente) (Rojas-Rivera, 2022; Ponticelli C, 2021).

A los 12 meses, el 60% de los pacientes en el grupo de rituximab (39 de 65 pacientes) y el 52% en el grupo de ciclosporina (34 de 65 pacientes) lograr= on una remisión parcial o completa. Sin embargo, a los 24 meses, el 60% de los pacientes en el grupo de rituximab (39 pacientes) aún se encontraba en remisión, mientras que la tasa de remisión en el grupo de ciclosporina se redujo al 20% (13 de 65 pacientes) debido a un gran número de recaídas desp= ués de suspender el tratamiento con ciclosporina de forma gradual y discontinua= rlo por completo. Además, el 35% de los pacientes en el grupo de rituximab alca= nzó una remisión completa, en comparación con los pacientes que recibieron ciclosporina. Por lo tanto, aunque el rituximab demostró ser inferior a la ciclosporina en términos de inducción de remisión a los doce meses, se enco= ntró estadísticamente superior a los 24 meses en cuanto al mantenimiento de la remisión a largo plazo y entre el 74% de los pacientes con nefropatía membranosa asociada a anti-PLA2R, se observó una disminución más rápida e intensa de los títulos de autoanticuerpos anti-PLA2R en el equipo de rituxi= mab a diferencia de los que recibieron ciclosporina. Al final del estudio, un m= ayor número de pacientes tratados con ciclosporina experimentaron una disminución del aclaramiento de creatinina ≥ 50% en comparación con el grupo de rituximab. Ambos tratamientos fueron comparables en términos de seguridad y tolerabilidad (Caravaca-Fontán, 2023; Teisseyre M, 2022)= .

En la actualidad, se han desarrollado nuevos anticuerpos humanizados dirigidos contra CD20 que presentan diversas ventajas en comparación con el rituximab. Estas ventajas incluyen un menor riesgo de generar una respuesta inmunológi= ca contra el anticuerpo monoclonal y una mayor duración del agotamiento de las células B. Se han reportado varios casos y series de casos en los cuales es= tos nuevos anticuerpos, como el ofatumumab, obinutuzumab y ocrelizumab, han demostrado ser efectivos en pacientes con nefropatía membranosa refractaria= o recurrente, así como en aquellos tratados previamente con rituximab y que desarrollaron la enfermedad del suero (Teisseyre M, 2022).

Dado que alrededor del 30% al 40% de los pacientes no logran una remisión de la nefropatía membranosa con el uso de rituximab y las recaídas son frecuentes= , es probable que estas nuevas bioterapias más potentes desempeñen un papel importante en el tratamiento de las formas graves de la enfermedad en un fu= turo cercano (Alsharhan Loulwa, 2021)<= /span>.

Además de estos nuevos anticuerpos, se han propuesto otros enfoques terapéuticos, = como la terapia anti-BAFF (belimumab), la terapia anti-células plasmáticas, la inmunoadsorción y la terapia anti-complemento. Estos tratamientos se justif= ican debido a la tasa de éxito relativamente baja, alrededor del 60% a los 24 me= ses, de las terapias basadas en rituximab en comparación con el 84% de la terapia basada en ciclofosfamida, aunque esto conlleva un mayor riesgo de eventos adversos graves (SAE), según los estudios MENTOR y STARMEN (Alsharhan Loulwa, 2021; Teissey= re M, 2022).

Objetivos

Objetivo General:

Describir la efectividad del tratamiento y manejo de la glomerulonefritis membranosa = en pacientes adultos.

 

Objetivos Específicos= :

1.      =    Recopilar y analizar datos de investigaciones y tratamien= tos disponibles sobre el manejo de la glomerulonefritis membranosa en pacientes adultos.

2.      =    Evaluar la evolución clínica de la nefropatía membranosa = con diferentes enfoques terapéuticos y determinar la efectividad de dichos tratamientos.

<= ![if !supportLists]>3.      =    Identificar factores que puedan influir en la respuesta al tratamiento de la nefropatía membranosa en pacientes adultos.

Metodología

La metodología que se utilizó para este proyecto de evaluación de la efectivid= ad del tratamiento y manejo de la glomerulonefritis membranosa en pacientes adultos se basó en el método de revisión bibliográfica de tipo narrativo, e= n el cual se analizó distintos tipos de artículos científicos relacionados al problema planteado en el presente trabajo, utilizando los criterios de inclusión y exclusión como requisitos para descartar datos irrelevantes y a= sí obtener mejores resultados.

La investigación en una primera fase empezó con un detallado marco teórico sob= re la efectividad del tratamiento y manejo de la glomerulonefritis membranosa = en pacientes adultos. En una segunda fase se realizó una búsqueda de artículos científicos en distintas bases de datos de reconocimiento como: PubMed, Schoolar Google, SciELO, Dialnet y Redalyc, con el objetivo de obtener información de calidad y tener confiabilidad en los resultados de la investigación.

Los artículos se seleccionaron en un rango de descripción de las siguientes palabras claves: Glomerulonefritis membranosa, Nefropatía membranosa primar= ia, Síndrome nefrótico, Terapia inmunosupresora

Diseño del estudio

Este proyecto se llevó a cabo como un estudio descriptivo tipo narrativo, utiliz= ando un enfoque histórico basado en documentos. La metodología de este estudio implicó la recolección y análisis sistemático de datos clínicos relevantes. Para lograrlo, se seleccionó una muestra representativa de casos y se recopilaron datos detallados que abarquen el periodo de tiempo comprendido entre 2019 y 2023.

La recopilación sistemática de datos se llevó a cabo utilizando fuentes confia= bles y especializadas, como registros médicos, informes clínicos y estudios prev= ios. Se dio prioridad a la calidad y la accesibilidad de los datos, asegurando q= ue sean completos y estén disponibles para su análisis.

Una vez recopilados los datos, se procedió a realizar un análisis detallado de = los mismos. Esto implicó la aplicación de técnicas estadísticas y métodos de investigación adecuados para obtener conclusiones válidas y confiables. Los resultados obtenidos fueron interpretados cuidadosamente, considerando la literatura científica existente y comparándolos con estudios previos realiz= ados en otras regiones.

A partir de los hallazgos del estudio, se elaboraron conclusiones sólidas y se proporcionaron recomendaciones basadas en la evidencia encontrada. Estas conclusiones y recomendaciones fueron de gran relevancia para mejorar el conocimiento y manejo de la glomerulonefritis membranosa en la población estudiada, así como para informar y guiar la práctica clínica.

Material y métodos

Como primer paso se desarrolló el capítulo uno del esquema tentativo. Como segun= do paso se elaboró la metodología para la cual se utilizó como principales bas= es de datos PubMed, SciELO, Dialnet y Redalyc, así mismo, se consultó en Schoo= lar Google los artículos científicos que se desarrollaron a lo largo de la investigación con las palabras claves. En el tercer paso, se realizó la selección de los artículos de la metodología descrita, que cumplían con los criterios requeridos. Como cuarto paso, se procedió a la revisión de artícu= los científicos sobre la efectividad del tratamiento y manejo de la glomerulonefritis membranosa en pacientes adultos, en los últimos 5 años. P= or último, se obtuvo conclusiones y se elaboraron las recomendaciones en base = a la información que se recolecto de las referencias seleccionadas. <= /span>

Selección de artículos

En las páginas anteriormente indicadas se obtuvo 50 artículos en español e ing= lés relacionados con el tema propuesto, posterior a eso se descartó los artícul= os que no cumplían con los criterios de inclusión para la investigación, de los cuales quedaron 35 artículos, mismos que se destacan por el tipo de informa= ción contenida en los artículos.

En la base de datos PubMed se obtuvo 20 artículos, en Google academic (Science Direct) 4 artículos y en Redalyc 11 artículos, dando un total de 35 artícul= os, 13 en español y 22 en inglés.

Criterios de inclusió= n

1.      =    Tipo de estudio: se incluirán investigaciones científicas, estudios clínicos, revisiones sistemáticas y guías de práctica clínica relacionados con el tratamiento y manejo de la glomerulonefritis membranosa= en pacientes adultos.

2.      =    Relevancia temática: se priorizarán los estudios y datos clínicos que aborden específicamente el tratamiento y manejo de la glomerulonefritis membranosa en pacientes adultos. Esto puede incluir intervenciones terapéuticas, seguimiento clínico, resultados de laboratorio, análisis histopatológicos y cualquier otro aspecto relacionado con la efectividad del tratamiento.

3.      =    Calidad y disponibilidad de los datos: se seleccionarán estudios y datos clínicos de calidad, provenientes de fuentes confiables y publicaciones científicas reconocidas. Además, se dará preferencia a aquell= os datos que estén completos y sean accesibles para su análisis.

Criterios de exclusió= n

1.      =    Estudios y datos clínicos que no estén relacionados directamente con la glomerulonefritis membranosa en pacientes adultos. Esto podría incluir estudios sobre otras enfermedades renales o en poblaciones diferentes a la adulta.

2.      =    Estudios y datos clínicos con una calidad deficiente o qu= e no cumplan con los estándares de investigación establecidos. Esto podría inclu= ir estudios con un diseño metodológico débil, falta de información relevante o resultados poco confiables.

3.      =    Datos clínicos incompletos o inaccesibles que no permitan= un análisis adecuado. Es importante contar con datos completos y disponibles p= ara garantizar la integridad de los resultados.

<= ![if !supportLists]>4.      =    Estudios y datos clínicos que no estén publicados en fuen= tes confiables, como revistas científicas revisadas por pares o documentos científicos reconocidos. Se busca asegurar la calidad y fiabilidad de la información recopilada.

Resultados

La glomerulopatía membranosa es el fenotipo histológico m= ás frecuentemente asociado con el síndrome nefrótico en adultos, y aunque la supervivencia renal a 10 años es del 70% a nivel global, el riesgo de progresi= ón de la enfermedad renal depende del nivel de proteinuria, presencia de hipertensión arterial y lesiones tubulointerstici= ales o glomerulares, y del estadio de la afectación a nivel renal = (Taherkhani A, 2019).

De acuerdo con el estudio de Rojas et al. (Rojas-Rivera, 2022) para el tratamiento = de la glomerulonefritis membranosa en pacientes de bajo riesgo, se sigue un enfoque conservador que incluye cambios en la dieta para reducir la ingesta= de sodio y proteínas, el uso de estatinas para tratar la dislipidemia, diuréti= cos para controlar los edemas, y medicamentos como antagonistas de los receptor= es de angiotensina II (ARA II) o inhibidores de la enzima convertidora de angiotensina (IECA) para el control de la presión arterial y la reducción d= e la proteinuria con el objetivo de disminuir en un 20% la tasa de recaídas de la enfermedad.

Según Krishna et al. (Krishna CK, 2019)= el tratamiento de la nefropatía membranosa en pacientes con riesgo moderado o alto se basa en opciones más agresivas como corticosteroi= des, agentes alquilantes o medicamentos inmunosupresores porque su uso no solo incrementa en un 50% la tasa de remisión parcial o completa de la patología sino también disminuyen en un 30% el riesgo de presentar insuficiencia renal aguda a largo plazo.

En el estudio de Von Groote et al. (Von Groote T, 2021) se ha demostrado que= el uso de corticosteroides y agentes alquilantes como ciclofosfamida o clorambucilo en ciclos con diferencia de 14 días por 6 meses puede lograr r= emisiones parciales o completas en aproximadamente el 70-80% de los pacientes nefróti= cos. Sin embargo, el uso de estos fármacos por un tiempo prolongado causa efectos secundarios graves, como riesgo de malignidad.

Los esquemas de administración no cíclica y paralela de ciclofosfamida y corticosteroides e= n el estudio de Coronel et al. (Coronel G, 2023)<= span style=3D'mso-bookmark:_Hlk81985521'> han evidenciado resultados generalmente positivos, logrando disminuir en un 30% el riesgo de diálisis y muerte del paciente con nefropatía membranosa, pero es importante tener en cuenta los efectos adversos asociados con el uso de dosis acumulad= as de ciclofosfamida extremadamente altas, debido a que causan perdida de su eficacia y aumento de la tasa de recaídas de la enfermedad renal.

Por otra parte, en el estudio de Ponticelli et al. (Ponticelli C, 2021) se pudo observar que tanto la administración del tacrólimus (0.05-0.075 mg/kg/día) como de la ciclosporina (3.5-5.0 mg/kg/día) durante un periodo de doce a dieciocho mes= es han demostrado ser efectivos en el tratamiento de la nefropatía membranosa, logrando una remisión parcial o completa de la enfermedad en un 85% de los pacientes, pero debido a que presentan una tasa de recaída del 50% se sigue considerando su uso en pacientes con niveles altos de proteinuria.

Un estudio prospectivo y aleatorizado llamado GEMRITUX comparó dos dosis diferentes de rituximab, en el cual la dosis de 375 mg/  separados por 7 días ha demostrado ser e= ficaz en el tratamiento de la glomerulonefritis membranosa, logrando una buena tolerancia a la terapéutica y remisión parcial o completa en aproximadament= e el 50-60% de los pacientes, debido a que mejora los parámetros renales y con e= llo un rápido retorno de la diuresis. Sin embargo, se necesita más investigación para comprender completamente su efecto y determinar la dosis óptima, ya qu= e en dosis altas causa neutropenia, lo que incrementa el riesgo de que presente infecciones (Fervenza F, 2019)= .

En el estudio de SanMartin et al.<= w:Sdt Citation=3D"t" ID=3D"-942843996"> (SanMartin C, 2022) se pudo observar que el micofenolato tanto en combinación con corticosteroi= des como en monoterapia ha demostrado resultados alentadores, consiguiendo una reducción en la proteinuria y mejoras en los marcadores de función renal, aunque se necesita más evidencia antes de que se pueda recomendar ampliamen= te el uso de micofenolato en el tratamiento de la nefropatía membranosa.<= /o:p>

Discusión  

El objetivo de este estudio fue determinar la efectividad del tratamiento y ma= nejo de la glomerulonefritis membranosa en pacientes adultos. Para lograr este objetivo, se recopilaron datos disponibles de investigaciones y tratamiento= s de la enfermedad, con el fin de examinar la evolución clínica y la terapéutica= de la nefropatía membranosa en la población de estudio.

La efectividad del tratamiento y manejo de la glomerulonefritis membranosa en adultos puede variar dependiendo de diferentes factores, incluyendo la severidad de la enfermedad, la respuesta individual al tratamiento y la adherencia al mismo. Según algunos estudios, el tratamiento inmunosupresor puede mejorar la función renal y disminuir los síntomas en algunos pacientes con nefropatía membranosa. Sin embargo, la respuesta al tratamiento puede variar y no todos los pacientes mejorarán significativamente debido a que la glomerulonefritis membranosa es una enfermedad compleja (Dhaouadi T, 2020)= .

En cuanto a los principales hallazgos de este estudio, se observó que la nefropatía membranosa es una patología renal crónica que afecta primordialm= ente a los adultos, este fenómeno se observó en el modelo de nefritis de Heymann, que es un modelo de nefropatía membranosa en ratas. En este modelo, las rat= as que fueron inmunizadas solo con el epítopo dominante de megalina desarrolla= ron gradualmente una respuesta inmunológica contra otros epítopos de megalina, = lo que se asoció con un empeoramiento de la enfermedad. Un proceso similar pue= de ocurrir en humanos con PLA2R1, el cual está compuesto por varios dominios, incluyendo ocho dominios de lectina tipo C (CTLD1 a CTLD8), un dominio de fibronectina tipo II y un dominio rico en cisteína <= /span>(Rojas J, 2021; Dhaouadi T, 2020= ).

En cuanto al significado de estos hallazgos, es importante destacar que la nefropatía membranosa representa una carga significativa para la salud de la población adulta. Los resultados de este estudio proporcionan información relevante sobre la evolución clínica y el tratamiento de la enfermedad en la población estudiada, lo que permitirá una mejor comprensión de la enfermeda= d y su abordaje. Estos hallazgos son especialmente relevantes para mejorar la atención y los resultados clínicos en pacientes con nefropatía membranosa e= n el país, ya que brindan una base científica sólida para orientar la toma de decisiones clínicas (Pertuz A, 2022).

En el ensayo multicéntrico, aleatorizado y controlado GEMRITUX, se comparó rituximab (2 infusiones de 375 mg/m 2 el día 1 y 8) combinado con un tratamiento antiproteinúrico no inmunosupresor con NIAT solo. A los seis me= ses, no hubo diferencias significativas entre los grupos en la tasa de remisión = clínica. Sin embargo, en el seguimiento prolongado (17 meses), se notificó una diferencia significativa con remisión clínica en el 65 % del grupo NIAT-rituximab, pero solo en el 34 % del grupo NIAT solo (p < 0,01). Ade= más, las tasas de depleción de anticuerpos anti-PLA2R1 fueron superiores en el g= rupo NIAT-rituximab que en el equipo NIAT solo en el tercer mes (56 % y 4 %, respectivamente, p < 0,001) y al sexto mes (50% y 12%, respectivamente, = p =3D 0,004). Por lo tanto, el retraso en la eficacia de rituximab en el estudio GEMRITUX podría explicarse por el hecho de que la remisión inmunológica pre= cede a la remisión clínica en varios meses (Teisseyre M, 2022; Ronco P P. E., 2021).

En un gran estudio de cohorte observacional retrospectivo, VAN DEN BRAND, analizó los resultados de 100 pacientes tratados con rituxim= ab en comparación con 103 pacientes tratados con glucocorticoides más ciclofosfamida oral. Durante una mediana de seguimiento de 40 meses, el gru= po de rituximab tuvo significativamente menos eventos adversos que el grupo de ciclofosfamida/glucocorticoide. Aunque la incidencia acumulada de remisión parcial fue menor en el grupo de rituximab, las tasas de remisión completa = y un criterio de valoración compuesto de duplicación de la creatinina sérica, enfermedad renal en etapa terminal o muerte no difirieron significativamente entre los grupos (Rojas-Rivera, 2022).

La investigación sobre la fisiopatología de la nefropatía membranosa ha avanza= do considerablemente en las últimas décadas, lo que ha llevado al descubrimien= to de proteínas implicadas y su valor pronóstico en esta enfermedad. Los estud= ios han utilizado modelos en ratas para identificar proteínas como la megalina,= que produce síndrome nefrótico en ratas cuando se daña a nivel de los podocitos. Sin embargo, esta proteína no se ha encontrado en humanos. En 2002, se descubrió la importancia de la inmunidad contra la endopeptidasa neutral en= la nefropatía membranosa, observando esta enfermedad en fetos de madres con deficiencia de esta proteína. Esto sugiere que la inmunidad contra la endopeptidasa neutral puede estar implicada en la patogénesis de la enferme= dad (Ronco P P. E., 2021).

En 2009, se descubrió que el antígeno responsable de la mayoría de los casos de nefropatía membranosa en humanos es el receptor 1 de la fosfolipasa A2 tipo= M (PLA2R1). Debido a su valor pronóstico, los anticuerpos contra PLA2R1, especialmente los del isotipo IgG 4, han despertado interés. Un rasgo distintivo de la glomerulonefritis membranosa primaria es la presencia de tinción positiva de PLA2R1 y depósitos de IgG en el tejido renal (Rojas J, 2021).

Además del PLA2R1, se ha estudiado otro anticuerpo llamado anti trombospondina 1 (THSD7A), presente en un pequeño porcentaje de pacientes con anticuerpos anti-PLA2R negativos. Estos avances en la identificación de proteínas y anticuerpos asociados a la nefropatía membranosa han mejorado nuestra comprensión de la enfermedad y pueden tener implicaciones en el diagnóstico= y pronóstico (Rojas J, 2021; Akiyama S, 2019).

Recientemente, se han realizado avances en el descubrimiento de nuevos biomarcadores y antígenos en la nefropatía membranosa utilizando técnicas avanzadas como la microdisección láser del glomérulo y la espectrometría de masas. Se han identificado cuatro nuevos biomarcadores/antígenos, incluyendo el exostosin= -1 y el NCAM-1 asociados a la nefritis lúpica clase V, el NELL1 relacionado con = la nefropatía membranosa primaria y con el cáncer y el Semaphorin-3b asociado = a la nefropatía membranosa temprana en la infancia. Estos descubrimientos pueden tener implicaciones en la clasificación y manejo de la enfermedad (Caravaca-Fontán, 2023; Ronco P P. E., 2021).

Se ha establecido que el examen histopatológico del tejido renal mediante técn= icas de inmunofluorescencia y microscopía electrónica es el método estándar para evaluar la nefropatía membranosa. En las primeras fases de la enfermedad, l= os cambios pueden no ser detectables a través del uso de un microscopio óptico, pero en estadios más avanzados, se pueden ver alteraciones distintivas. Con= la tinción de ácido periódico de Schiff se observa el engrosamiento de la pared capilar y con la tinción de plata metenamina se evidencia en la membrana ba= sal un incremento de los depósitos de complejos inmunes, mismos que forman "púas" o "spikes", lo que demuestra que la membrana glo= merular basal no presenta inflamación ni disrupción (Coronel G, 2023; Akiyama S, 201= 9).

El análisis de inmunohistoquímica también es útil para identificar la presenci= a de depósitos de IgG, especialmente de la subclase IgG 4 y la presencia de PLA2= R en el tejido renal. Estas características histológicas y de tinción pueden ayu= dar en el diagnóstico diferencial de la nefropatía membranosa idiopática y secundaria (Thompson A, 2019)= .

En cuanto al tratamiento de la nefropatía membranosa, el enfoque terapéutico se determina según diversos factores, como la edad, el estado de salud general= , la gravedad de la enfermedad, la tolerancia a los medicamentos, las expectativ= as de evolución de la enfermedad y las preferencias individuales. En casos de nefropatía membranosa causada por infección estreptocócica, el tratamiento = se centra en tratar la infección subyacente y aliviar los síntomas para retras= ar la progresión de la nefropatía membranosa y prevenir posibles complicacione= s (Ottati D, 2022; Yang, 2019).

El tratamiento de la nefropatía membranosa puede incluir medidas como el mante= ner una dieta saludable y equilibrada, regulación en el consumo de líquidos y u= so de fármacos como agentes inmunosupresores, diuréticos y antihipertensivos p= ara controlar la hiperfosfatemia, proteinuria y la presión arterial, y en casos graves, la necesidad de trasplante renal o diálisis. La selección del tratamiento se realiza de forma personalizada, considerando los factores individuales de cada paciente.

-      = En los casos de bajo = riesgo y aquellos que experimentan una remisión parcial espontánea después de recibir terapia inmunosupresora:

·      =      Controlar la presión arterial mediante antihipertensivos = como los IECA o los ARA-II y mantenerla en niveles objetivos (≤125/75 mm H= g).

·      =      Restricción de sodio en la dieta y la reducción de la ing= esta de proteínas

·      =      Control del perfil lipídico y el peso corporal=

<= ![if !supportLists]>·      =      Evitar el consumo de tabaco y el sedentarismo.

<= ![if !supportLists]>-      =       Tratamiento de casos de bajo riesgo y remisiones espontán= eas después del tratamiento antiproteinúrico:

<= ![if !supportLists]>·      =      Antagonistas de los receptores de angiotensina II (ARA-II= ) o inhibidores de la enzima convertidora de angiotensina (IECA)

<= ![if !supportLists]>·      =      Inhibidores de SGLT2

<= ![if !supportLists]>·      =      Antialdosterónicos de tercera generación

<= ![if !supportLists]>·      =      Anti-endotelina

<= ![if !supportLists]>-      =       Tratamiento en casos de riesgo moderado o alto: En estos casos, se han utilizado diferentes enfoques terapéuticos.

·      =      Corticosteroides más ciclofosfamida

·      =      Anticalcineurínicos

·      =      Rituximab

<= span style=3D'mso-bookmark:_Hlk142320839'>·      =      Micofenolato

Es importante tener en cuenta que el tratamiento de la nefropatía membranosa es individualizado y los beneficios y riesgos de cada enfoque terapéutico deben sopesarse cuidadosamente, considerando las características individuales del paciente, la gravedad de la enfermedad, la presencia de factores de riesgo cardiovascular y otros factores relevantes. Además, se recomienda el seguimiento regular y estrecho del paciente para evaluar la respuesta al tratamiento y realizar ajustes si es necesario (Ottati D, 2022; Yang, 2019).

Conclusiones

·      =    El tratamiento y manejo de la glomerulonefritis membranos= a en pacientes adultos puede ser variado y depende de varios factores, como la gravedad de la enfermedad, la presencia de síntomas y la función renal, por= lo que el uso de medicamentos inmunosupresores como los corticoides, ciclofosfamida, tacrólimus y el rituximab, aunque ayudan a controlar la enfermedad deben ser cuidadosamente evaluados, ya que pueden tener efectos secundarios y riesgos asociados, por ello el tratamiento debe ser un proceso individualizado que debe adaptarse al perfil de riesgo de cada paciente.

·      =    La implementación de pruebas de diagnóstico, como la detección de anticuerpos específicos, y el seguimiento personalizado son herramientas fundamentales en la atención de los pacientes con glomerulonef= ritis membranosa porque no solo permiten identificar y optimizar el manejo de la enfermedad primaria, sino también establecer un diagnóstico más preciso y ayudan a guiar el tratamiento adecuado para cada paciente a través de una combinación de enfoques conservadores y terapias más agresivas para consegu= ir la remisión de la enfermedad y mejorar los resultados a largo plazo. <= /o:p>

·      =    Aunque solo un pequeño porcentaje de pacientes desarrolla enfermedad renal crónica avanzada, es fundamental seguir un enfoque de tratamiento adecuado y personalizado de acuerdo con el grado de progresión = de la enfermedad. Esto permitirá mejorar los resultados a largo plazo en los pacientes con glomerulonefritis membranosa y reducir la carga de la enferme= dad en la sociedad.

·      =    En resumen, el abanico de opciones terapéuticas para la nefropatía membranosa (MN) idiopática está en constante expansión, aunque todavía existen aspectos por explorar. Si bien rituximab se considera actualmente la terapia de elección para la mayoría de los pacientes, el tratamiento cíclico aún ejerce un papel fundamental en el manejo de esta patología, especialmente en aquellos con alto riesgo, deterioro de la funci= ón renal o síndrome nefrótico grave, así como en casos resistentes a rituximab. Los primeros informes sobre enfoques de combinación de una terapia inmunosupresora a base de esteroides más clorambucilo o ciclofosfamida con fármacos nefroprotectores son muy prometedores y demuestran que la utilizac= ión de medicamentos con mecanismos de acción sinérgicos puede lograr tasas de remisión inmunológica muy altas. Sin embargo, a pesar de los datos alentado= res, la seguridad de estos regímenes combinados sigue siendo una preocupación importante, sobre todo considerando el curso recurrente que a menudo presen= ta la glomerulonefritis membranosa.

·      =    En el futuro, se requieren estudios adicionales para identificar endotipos moleculares clínicamente relevantes y descubrir biomarcadores predictivos de la respuesta al tratamiento. Esto implicará enfrentar los desafíos de desarrollar un enfoque de medicina de precisión e= n el manejo de la nefropatía membranosa.

Recomendaciones

1.      =    Se sugiere optimizar el uso de pruebas inmunológicas en el diagnóstico y manejo de pacientes con glomerulonefritis membranosa. Esto implica una mejor utilización de los recursos diagnósticos disponibles, alineándose con las prácticas actuales. Al implementar enfoques diagnósticos más precisos y eficientes, se podrían agilizar los procesos de detección y tratamiento, lo que resultaría en una atención más oportuna y efectiva para= los pacientes afectados.

2.      =    Asimismo, se resalta la importancia de brindar a cada paciente un seguimiento personalizado de su enfermedad. Esto garantizaría u= na adecuada adherencia al tratamiento prescrito, así como la detección tempran= a de posibles complicaciones. Un enfoque individualizado permitiría ajustar las estrategias terapéuticas según las necesidades específicas de cada paciente, mejorando así los resultados a largo plazo y promoviendo una mejor calidad = de vida

3.      =    En el contexto de los recursos sanitarios, resulta impera= tivo asegurar la disponibilidad de los medios diagnósticos necesarios en los cen= tros de atención médica. Esto evitaría retrasos en el diagnóstico y el manejo de= los pacientes, brindando una atención más oportuna y evitando desenlaces desfavorables. Es fundamental contar con la infraestructura y los equipos adecuados, así como con personal capacitado para realizar y analizar los estudios pertinentes, garantizando así la prontitud y precisión en el diagnóstico.

<= ![if !supportLists]>4.      =    Por último, se destaca la necesidad de promover trabajos = de investigación que analicen la evolución del manejo de pacientes con glomerulonefritis en nuestro entorno, en comparación con reportes regionale= s y globales. Esto permitiría identificar brechas en la atención, compartir conocimientos y experiencias, e impulsar la mejora continua de los protocol= os de manejo. Al comprender mejor el panorama local y su relación con el conte= xto global, se podrían implementar estrategias más eficaces y adaptadas a nuest= ra realidad, mejorando así la atención y los resultados para los pacientes afectados por estas enfermedades.

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= ISSN: 2600-5859

= Vol. 6 No. 4, pp. 145 – 175, oc= tubre – diciembre 2023

www= .concienciadigital.org

 

 

 

 

 

                                      Perspectiva Científica        Página 145 | 175

 

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