Eculizumab deposits in vessel walls in thrombotic microangiopathy

Cassol, Clarissa; Brodsky, Sergey V.; Satoskar, Anjali A.; Blissett, Angela R.; Cataland, Spero R.; Nádasdy, Tibor

doi:10.1016/j.kint.2019.05.008

Cited by 12 publications

(12 citation statements)

References 26 publications

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“…C5b-9 stained moderately in the mesangium and capillary wall in one case, weakly in only the mesangium in another case, and strongly in the vascular wall in both cases. Similar staining was found before and after treatment with eculizumab in one of them ( 100 ).…”

Section: Kidney Diseases Due To Alternative Pathway Activationsupporting

confidence: 82%

“…It was present in biopsies taken both shorter and longer than twenty weeks after the onset of IgA vasculitis, whereas C3 and MBL were present in only the former ( 99 ). It remained present with unchanged intensity in patients with C3 glomerulopathy or thrombotic microangiopathy after one or two weeks ( 100 ), after three months ( 101 ), after four months ( 102 ), and after a year ( 103 ) of treatment with eculizumab. Yet, in other reports on various kidney diseases, its staining resolved within three days after administration of eculizumab ( 104 ), after three months to 3 years of treatment with eculizumab ( 105 – 108 ), and after half a year of treatment with other immunosuppressive medication ( 18 , 109 ), as illustrated in Figure 3C .…”

Section: Staining Techniquesmentioning

confidence: 99%

“…Glomerular, but not tubular, staining of C5b-9 was more intense in more severe classes, increasing from I and II to III and V and being strongest in class IV ( 18 , 95 , 111 , 119 , 139 , 171 , 174 ). In lupus nephritis with thrombotic microangiopathy, staining intensity was variable in the glomerulus and strong in the vascular wall ( 100 , 130 , 175 ).…”

Section: Kidney Diseases Due To Immune Complex Depositionmentioning

confidence: 99%

“…An example is shown in Figure 2B . In a late-stage case, staining was weak in the mesangium, absent from the capillary wall, and intense in the vascular wall ( 100 ). Staining in recurrent aHUS after transplantation was similar to that in native kidneys ( 130 ).…”

Section: Kidney Diseases Due To Alternative Pathway Activationmentioning

confidence: 99%

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Deposition of the Membrane Attack Complex in Healthy and Diseased Human Kidneys

et al. 2021

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The membrane attack complex—also known as C5b-9—is the end-product of the classical, lectin, and alternative complement pathways. It is thought to play an important role in the pathogenesis of various kidney diseases by causing cellular injury and tissue inflammation, resulting in sclerosis and fibrosis. These deleterious effects are, consequently, targeted in the development of novel therapies that inhibit the formation of C5b-9, such as eculizumab. To clarify how C5b-9 contributes to kidney disease and to predict which patients benefit from such therapy, knowledge on deposition of C5b-9 in the kidney is essential. Because immunohistochemical staining of C5b-9 has not been routinely conducted and never been compared across studies, we provide a review of studies on deposition of C5b-9 in healthy and diseased human kidneys. We describe techniques to stain deposits and compare the occurrence of deposits in healthy kidneys and in a wide spectrum of kidney diseases, including hypertensive nephropathy, diabetic nephropathy, membranous nephropathy, IgA nephropathy, lupus nephritis, C3 glomerulopathy, and thrombotic microangiopathies such as the atypical hemolytic uremic syndrome, vasculitis, interstitial nephritis, acute tubular necrosis, kidney tumors, and rejection of kidney transplants. We summarize how these deposits are related with other histological lesions and clinical characteristics. We evaluate the prognostic relevance of these deposits in the light of possible treatment with complement inhibitors.

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Section: Kidney Diseases Due To Alternative Pathway Activationsupporting

confidence: 82%

Section: Staining Techniquesmentioning

confidence: 99%

Section: Kidney Diseases Due To Immune Complex Depositionmentioning

confidence: 99%

Section: Kidney Diseases Due To Alternative Pathway Activationmentioning

confidence: 99%

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Deposition of the Membrane Attack Complex in Healthy and Diseased Human Kidneys

et al. 2021

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“… 11 Furthermore, deposition of eculizumab has been reported in individuals with C3 glomerulopathy or cTMA and its significance is currently unknown. 12 , 13 …”

Section: Discussionmentioning

confidence: 99%

Successful Pregnancies During Ongoing Eculizumab Therapy in Two Patients With Complement-Mediated Thrombotic Microangiopathy

et al. 2020

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In patients with pregnancy-associated complement gene variant–mediated thrombotic microangiopathy (cTMA), terminal complement blockade is used for treatment of cTMA flares during pregnancy or following delivery. We report pregnancy and delivery outcomes of 2 genetically high-risk patients with cTMA, including 1 kidney transplant recipient, during ongoing eculizumab therapy. In both patients, the first manifestation of cTMA occurred independent from pregnancy. One patient has a history of 2 uneventful pregnancies with prophylactic plasma infusions, and the other has a history of early abortion during long-term eculizumab therapy following kidney transplantation. Overall, pregnancy and delivery outcomes under ongoing eculizumab therapy in our 2 patients with preserved kidney function were excellent as compared with other patients reported in the literature. Eculizumab plasma concentrations were maintained in the therapeutic range during pregnancy and were also detectable in cord blood. Results of cord blood analysis showed deficient complement activity, with low factor and regulator levels, most likely reflecting the age of the neonates and presence of eculizumab in cord blood. In conclusion, pregnancy during ongoing eculizumab treatment appeared to be safe in 2 women with a history of high-risk genetic cTMA and excellent kidney function, even following kidney transplantation.

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