Glucocorticoid-free induction regimen in severe ANCA-associated vasculitis using a combination of rituximab and eculizumab

Ribes, David; Béllière, Julie; Piedrafita, Alexis; Faguer, Stanislas

doi:10.1093/rheumatology/kez190

Cited by 17 publications

(12 citation statements)

References 6 publications

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“…C5a is produced by the cleavage of C5 under the catalysis of C5 invertase. The C5 inhibitor eculizumab has been used in the clinical practice of AAV, which could rapidly reverse AAV-related renal failure [37,38]. The preliminary results of phase 2 clinical study showed that CCX168 has successfully replaced GC in the treatment of AAV [38].…”

Section: Discussionmentioning

confidence: 99%

Relationship between Renal Damage and Serum Complement C3 in Children with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Zhang

Yang

et al. 2021

Nephron

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Background: Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) disease is a well-known antibody-induced autoimmune disease. The pathogenesis of AAV has not yet been completely clarified, but may be related to heredity, infection, environmental factors, cellular immunity, etc. In recent years, complement in AAV pathogenesis has become the latest research hotspot, and the decrease of serum complement C3 is associated with poor prognosis of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. In the current study, we investigated the associations between serum complement C3 and kidney injury in AAV children. Methods: Twenty-four children with AAV admitted to our hospital from June 2014 to June 2019 were divided into the low C3 group and the normal C3 group. All the children have undergone renal biopsy. The clinical manifestations, laboratory tests, renal pathology, treatment, and prognosis of the 2 groups were observed. The primary end point was end-stage renal disease (ESRD). Results: It was shown that kidney injury was more obvious in patients with low C3 than in patients with normal C3 serum. The values of ESR, Scr, and UA before treatment in the low C3 group were higher than those in the normal C3 group (p < 0.01); the values of RBC, Hb, PLT, ALB, LDH, and eGFR in the normal C3 group were higher than those in the low C3 group (p < 0.01). The values of urinary protein and NAG enzyme in the low C3 group were higher than those in the normal C3 group (p < 0.01). The area of glomerular abandonment, sclerosis, segmental sclerosis, crescent, cellular crescent, cellular fibrous crescent, fibrous crescent, segmental loop necrosis, and the number of cases with acute renal tubulointerstitial lesions in the low C3 group were bigger than those in the normal C3 group (p < 0.05 and < 0.01). The number of cases with C3 deposition in the low C3 group was higher than that in the normal C3 group (p < 0.05). The number of patients receiving CRRT and PE in the low C3 group was higher than that in the normal C3 group (p < 0.05 and < 0.01). In this study, 3 children entered the stage of ESRD and 1 died in the low C3 group. Conclusion: The kidney injury of AAV children with low complement C3 is serious, and the prognosis is poor. We should pay attention to the influence of decreased complement C3 on the condition and prognosis of AAV children.

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Section: Discussionmentioning

confidence: 99%

Relationship between Renal Damage and Serum Complement C3 in Children with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Zhang

Yang

et al. 2021

Nephron

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“…The possibility to block C5 by the use of a monoclonal antibody against C5 in atypical hemolytic uremic syndrome (HUS) has significantly improved clinical outcomes for this patient group ( 137 , 138 ). Preliminary data on other glomerular diseases are also promising pinpointing the importance of the complement system in glomerular disease onset and progression ( 139 ).…”

Section: Mesangial Cells and Complement Activationmentioning

confidence: 99%

The Glomerulus According to the Mesangium

2022

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The glomerulus is the functional unit for filtration of blood and formation of primary urine. This intricate structure is composed of the endothelium with its glycocalyx facing the blood, the glomerular basement membrane and the podocytes facing the urinary space of Bowman's capsule. The mesangial cells are the central hub connecting and supporting all these structures. The components as a unit ensure a high permselectivity hindering large plasma proteins from passing into the urine while readily filtering water and small solutes. There has been a long-standing interest and discussion regarding the functional contribution of the different cellular components but the mesangial cells have been somewhat overlooked in this context. The mesangium is situated in close proximity to all other cellular components of the glomerulus and should be considered important in pathophysiological events leading to glomerular disease. This review will highlight the role of the mesangium in both glomerular function and intra-glomerular crosstalk. It also aims to explain the role of the mesangium as a central component involved in disease onset and progression as well as signaling to maintain the functions of other glomerular cells to uphold permselectivity and glomerular health.

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“…Non-selective inhibition of complement with anti-C5 antibody (eculizumab) was shown in a case report to improve renal function in the patient with AAV ( 28 ) and was effective in a patient with severe AAV in combination with rituximab in corticosteroid-free regimen ( 29 ).…”

Section: Complement Inhibition In Aav—clinical Studiesmentioning

confidence: 99%

Complement Inhibition in ANCA-Associated Vasculitis

Tesař

Hrušková

2022

Front. Immunol.

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Efficacy of immunosuppressive treatment of Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is complicated by its toxicity. With the replacement of cyclophosphamide with rituximab, serious adverse events seem to be associated especially with high-dose corticosteroids. Activation of alternative complement pathway plays an important role in the pathogenesis of AAV. Avacopan (C5a receptor inhibitor) was demonstrated to have at least similar efficacy and better safety (in terms of corticosteroid-related adverse events) compared with high-dose corticosteroids in the induction treatment of AAV. Other modes of the inhibition of alternative complement pathway are currently tested in AAV or could be considered on the basis of the experience in other glomerular diseases.

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Glucocorticoid-free induction regimen in severe ANCA-associated vasculitis using a combination of rituximab and eculizumab

Cited by 17 publications

References 6 publications

Relationship between Renal Damage and Serum Complement C3 in Children with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Relationship between Renal Damage and Serum Complement C3 in Children with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

The Glomerulus According to the Mesangium

Complement Inhibition in ANCA-Associated Vasculitis

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