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Bloqueo del complemento: promesas terapéuticas y retos pendientes en la práctica clínica.

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Title: Bloqueo del complemento: promesas terapéuticas y retos pendientes en la práctica clínica.
Alternate Title: Complement blockade: Therapeutic promises and remaining challenges in clinical practice.
Authors: Fernández-Juárez, Gema1,2 Gema.fernandezjuarez@salud.madrid.org, Azores-Moreno, Javier1,2, León-Machado, Lina1,2, Vázquez-Raso, Irene1, Soriano-Guillén, María1, Mendoza, Ana2, Maldonado, María1,2, Becerra, Begoña Rivas1, Cabrera, Cristina Vega1, Shabaka, Amir1
Source: Nefrologia. Apr2026, Vol. 46 Issue 4, p1-7. 7p.
Subjects: COMPLEMENT inhibition, KIDNEY glomerulus diseases, PAROXYSMAL hemoglobinuria, INDIVIDUALIZED medicine, HEMOLYTIC-uremic syndrome, DISEASE complications, ECULIZUMAB, COMPLEMENT activation
Abstract (English): Understanding of the complement system in glomerulopathies has advanced significantly, revealing that this system —beyond its role in innate immunity— is a key mediator of kidney injury across a wide spectrum of nephropathies, from those driven by immune complexes to those caused by primary dysregulation of the alternative pathway. The introduction of complement inhibitors, such as C5 blockade with eculizumab, marked a milestone: in aHUS it significantly improved renal function and patient survival, and in paroxysmal nocturnal hemoglobinuria it reduced thrombotic complications, achieving survival rates comparable to the general population. These advances have spurred the extension of this approach to other nephropathies and the development of new anti-complement agents. However, the heterogeneity of complement dysregulation among glomerulopathies —and even among patients with the same disease— limits the application of a uniform therapeutic strategy. This scenario calls for a more precise characterization of the underlying pathophysiological mechanisms and the identification of critical points of intervention in each clinical context. Currently, inhibitors targeting both proximal and terminal steps of the cascade are being investigated to achieve more individualized therapies, although challenges remain, such as the lack of reliable biomarkers, uncertainty regarding optimal treatment duration, scarcity of disease-specific trials, high costs, and the integration of these agents with immunosuppressive regimens. The aim of this review is to analyze the role of the complement system in glomerulopathies and to summarize current and future therapeutic advances, with particular emphasis on the challenges and opportunities on the path toward more personalized medicine. [ABSTRACT FROM AUTHOR]
Abstract (Spanish): La comprensión del complemento en las glomerulopatías ha avanzado notablemente, mostrando que este sistema, más allá de la inmunidad innata, es un mediador clave del daño renal en un amplio espectro de nefropatías, desde las mediadas por inmunocomplejos hasta aquellas debidas a la desregulación primaria de la vía alternativa. La introducción de inhibidores del complemento, como el bloqueo de C5 con eculizumab, marcó un hito: en el SHUa mejoró de forma significativa la función renal y la supervivencia de los pacientes, y en la hemoglobinuria paroxística nocturna redujo las complicaciones trombóticas, logrando una supervivencia comparable a la población general. Estos avances impulsaron la extensión de este enfoque a otras nefropatías y el desarrollo de nuevos fármacos anti-complemento. Sin embargo, la heterogeneidad en la desregulación del complemento entre glomerulopatías, e incluso entre los pacientes de una misma enfermedad, limita la aplicación de una estrategia uniforme. Este escenario exige una caracterización más precisa de los mecanismos fisiopatológicos y la identificación de los puntos críticos de intervención en cada contexto clínico. Actualmente se investigan inhibidores en fases proximales y terminales de la cascada para alcanzar terapias más individualizadas, aunque persisten desafíos como la ausencia de biomarcadores fiables, la duración óptima del tratamiento, la escasez de ensayos específicos, el elevado coste y su integración con la inmunosupresión. El objetivo de esta revisión es analizar el papel del complemento en las glomerulopatías y revisar los avances terapéuticos actuales y futuros, con especial atención a los retos y oportunidades hacia una medicina más personalizada. [ABSTRACT FROM AUTHOR]
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Database: MedicLatina
Description
Abstract:Understanding of the complement system in glomerulopathies has advanced significantly, revealing that this system —beyond its role in innate immunity— is a key mediator of kidney injury across a wide spectrum of nephropathies, from those driven by immune complexes to those caused by primary dysregulation of the alternative pathway. The introduction of complement inhibitors, such as C5 blockade with eculizumab, marked a milestone: in aHUS it significantly improved renal function and patient survival, and in paroxysmal nocturnal hemoglobinuria it reduced thrombotic complications, achieving survival rates comparable to the general population. These advances have spurred the extension of this approach to other nephropathies and the development of new anti-complement agents. However, the heterogeneity of complement dysregulation among glomerulopathies —and even among patients with the same disease— limits the application of a uniform therapeutic strategy. This scenario calls for a more precise characterization of the underlying pathophysiological mechanisms and the identification of critical points of intervention in each clinical context. Currently, inhibitors targeting both proximal and terminal steps of the cascade are being investigated to achieve more individualized therapies, although challenges remain, such as the lack of reliable biomarkers, uncertainty regarding optimal treatment duration, scarcity of disease-specific trials, high costs, and the integration of these agents with immunosuppressive regimens. The aim of this review is to analyze the role of the complement system in glomerulopathies and to summarize current and future therapeutic advances, with particular emphasis on the challenges and opportunities on the path toward more personalized medicine. [ABSTRACT FROM AUTHOR]
ISSN:02116995
DOI:10.1016/j.nefro.2025.501464