Treatment of Atypical Hemolytic Uremic Syndrome and Thrombotic Microangiopathies: A Focus on Eculizumab

Schmidtko, Jan; Peine, Sven; El-Housseini, Youssef; Pascual, Manuel; Meier, Pascal

doi:10.1053/j.ajkd.2012.07.028

Cited by 78 publications

(65 citation statements)

References 73 publications

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“…Eculizumab (Soliris; Alexion Pharmaceuticals, Cheshire, CT) was given for at least 3 months and according to the dosing regimen established for atypical HUS (22). Eculizumab treatment beyond this time was at the physician's discretion.…”

Section: Methodsmentioning

confidence: 99%

Eculizumab in Pediatric Dense Deposit Disease

Oosterveld¹,

Garrelfs²,

Höppe

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare disease affecting mostly children. Treatment options are limited. Debate exists whether eculizumab, a monoclonal antibody against complement factor C5, is effective in DDD. Reported data are scarce, especially in children.Design, setting, participants, & measurements The authors analyzed clinical and histologic data of five pediatric patients with a native kidney biopsy diagnosis of DDD. Patients received eculizumab as therapy of last resort for severe nephritic or nephrotic syndrome with alternative pathway complement activation; this therapy was given only when the patients had not or only marginally responded to immunosuppressive therapy. Outcome measures were kidney function, proteinuria, and urine analysis.Results In all, seven disease episodes were treated with eculizumab (six episodes of severe nephritic syndrome [two of which required dialysis] and one nephrotic syndrome episode). Median age at treatment start was 8.4 (range, 5.9-13) years. For three treatment episodes, eculizumab was the sole immunosuppressive treatment. In all patients, both proteinuria and renal function improved significantly within 12 weeks of treatment (median urinary protein-to-creatinine ratio of 8.5 [range, 2.2-17] versus 1.1 [range, 0.2-2.0] g/g, P,0.005, and eGFR of 58 [range, 17-114] versus 77 [range, 50-129] ml/min per 1.73 m 2 , P,0.01). A striking finding was the disappearance of leukocyturia within 1 week after the first eculizumab dose in all five episodes with leukocyturia at treatment initiation.Conclusions In this case series of pediatric patients with DDD, eculizumab treatment was associated with reduction in proteinuria and increase in eGFR. Leukocyturia resolved within 1 week of initiation of eculizumab treatment. These results underscore the need for a randomized trial of eculizumab in DDD.

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Section: Methodsmentioning

confidence: 99%

Eculizumab in Pediatric Dense Deposit Disease

Oosterveld¹,

Garrelfs²,

Höppe

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…Adicionalmente, las infecciones gripales, la gestación u otras condiciones y tratamientos médicos, pueden estimular aún más la actividad del complemento, generando una amplificación significativa del mismo. En los individuos sanos, las células propias se protegen de la actividad y amplificación permanente del complemento a través de un conjunto regulado de inhibidores 3,15,16 . Los pacientes con SHUa carecen intrínsecamente de los reguladores del complemento (activadores e inhibidores de las proteínas) que protegen las células y los tejidos, lo cual induce los efectos crónicos nocivos de un sistema del complemento hiperactivo 1,3,14,15 .…”

Section: Disregulación Del Complementounclassified

Síndrome hemolítico urémico atípico, revisión de la literatura y documento de consenso. Enfoque diagnóstico y tratamiento

Córdoba¹,

Contreras²,

Larrarte³

et al. 2015

Rev. Colomb. Nefrol.

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ResumenEl Síndrome Hemolítico Urémico atípico (SHUa) es una enfermedad ultra-huérfana; más del 50% de los pacientes muere, necesita terapia de remplazo renal o sufre insuficiencia renal terminal dentro del primer año de diagnóstico. Con el tratamiento de soporte actual (plasmaféresis o infusión deplasma) 9-15% de los pacientes de SHUa mueren dentro del lapso de 1 año, después de una manifestación clínica de hemólisis. Las consecuencias severas de esta enfermedad refuerzan la importancia del diagnóstico y tratamiento temprano. Las manifestaciones clínicas incluyen la triada clásica de anemia microangiopática, trombocitopenia y daño a otros órganos, donde la insuficiencia renal es la manifestación más común, frecuentemente asociada a otras complicaciones tales como neurológicas, cardíacas y gastrointestinales. Las mutaciones en las proteínas reguladoras del sistema del complemento son reconocidas como las causas de este síndrome; sin embargo, no se identifican en todos los pacientes con diagnóstico de SHUa. Existe una alta tasa de pérdida del injerto postrasplante renal, en aproximadamente 60% de los casos.La plasmaféresis, considerada como terapia de primera línea, no ha demostrado resultados satisfactorios a largo plazo. Desde el año 2011 está disponible en Colombia un anticuerpo monoclonal recombinante dirigido contra el complemento a nivel C5 (eculizumab), medicamento único aprobado para el tratamiento del SHUa. Este tratamiento ha demostrado mejorar, de manera significativa, el pronóstico y la progresión de la enfermedad, y es considerado la primera línea de terapia hoy en día.

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“…6 Two doses of eculizumab improved the serum levels of LDH, FDP and Hb (Figure 2). However, serum levels of LDH rebounded before the third eculizumab administration (Figure 2).…”

mentioning

confidence: 95%

“…Eculizumab, a humanized moAb against the complement component C5 that prevents tissue damage by blocking the formation of the membrane attack complex, has been successful in the treatment of paroxysmal nocturnal hemoglobinuria or atypical hemolytic uremic syndrome (aHUS). 5,6 Thus, if uncontrolled activation of the complement system has an important role in the development of TA-TMA, eculizmab could be a targeted therapy for TA-TMA.…”

mentioning

confidence: 99%

“…We administered eculizumab with 600 mg as the initial dose according to recommendations for children with aHUS because the patient's weight was 23 kg. 6 However, we should have increased the dose to 900 mg, suggesting that a much higher dose of eculizumab may be required for the treatment of TA-TMA compared with the dose required for the treatment of aHUS. After four doses of eculizumab every week, the hematological parameters associated with TA-TMA began to improve with other complications, including neuropsychiatric symptoms and respiratory distress.…”

mentioning

confidence: 99%

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