Patterns of Clinical Response to Eculizumab in Patients With C3 Glomerulopathy

Quintrec, Moglie Le; Lapeyraque, Anne-Laure; Lionet, Arnaud; Sellier‐Leclerc, Anne‐Laure; Delmas, Yahsou; Baudouin, Véronique; Daugas, Éric; Decramer, Stéphane; Tricot, L.; Cailliez, Mathilde; Dubot, P.; Servais, Aude; Mourey-Epron, Catherine; Pourcine, Franck; Loirat, Chantal; Frémeaux‐Bacchi, Véronique; Fakhouri, Fádi

doi:10.1053/j.ajkd.2017.11.019

Cited by 107 publications

(80 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To summarize, the results of different studies with eculizumab in C3G revealed that this therapy may only be appropriate in certain cases. Currently, its main clinical Nephron 2020;144:272-280 DOI: 10.1159/000507254 indication is in those cases with crescentic rapidly progressive disease, although the evidence is still limited and subject to controversy [48]. Currently, there are several ongoing or planned clinical trials using new complement inhibitors targeting early components of the complement cascade, such as factor D (ACH-0144471) and FB (LNP023).…”

Section: Anticomplement Therapymentioning

confidence: 99%

Update on C3 Glomerulopathy: A Complement-Mediated Disease

Caravaca-Fontán

Lucientes

Cavero

et al. 2020

Nephron

View full text Add to dashboard Cite

C3 glomerulopathy (C3G) is a clinicopathologic entity secondary to dysregulation of the alternative complement pathway in plasma and the glomerular microenvironment. The current consensus definition of C3G relies on immunofluorescence staining criteria. However, due to its high clinical variability, these criteria may not be accurate enough in some clinical scenarios. Thus, a new pathogenic classification based on a cluster analysis of clinical, histologic, and genetic data has recently been proposed, which could also help identify patients at higher risk of progression. Several pathogenic abnormalities in complement genes have been described, and the role of autoantibodies in the disease is increasingly recognized, but still the genotype-phenotype correlations in C3G are poorly understood. C3G may be diagnosed in both children and adults. The spectrum of clinical manifestations is wide, although one of the most common clinical presentations is proteinuria with relatively preserved kidney function. In order to standardize the evaluation of kidney biopsies from these patients, a histopathologic index was recently proposed, including both parameters of activity and chronicity. However, this index has not yet been val-idated in independent cohorts. Currently, no targeted therapies are available in clinical settings for the treatment of C3G, although several new molecules are under investigation. Treatment with corticosteroids plus mycophenolate mofetil has been shown to be associated with improved renal outcomes, as compared to other immunosuppressive regimens. Yet, the main determinants of treatment response with this regimen and the influence of the underlying pathogenic drivers have not been extensively studied. The therapeutic response to eculizumab, an anti-C5 monoclonal antibody, has been shown to be highly heterogeneous. Thus, its current clinical indication in C3G is restricted to rapidly progressive forms of the disease. To summarize, in recent years, several important advances have taken place in the understanding of C3G, but still further studies are warranted to elucidate the best therapeutic strategies that could improve prognosis of this entity.

show abstract

Section: Anticomplement Therapymentioning

confidence: 99%

Update on C3 Glomerulopathy: A Complement-Mediated Disease

Caravaca-Fontán

Lucientes

Cavero

et al. 2020

Nephron

View full text Add to dashboard Cite

show abstract

“…Only 3/6 children in the Bomback trial and 3/4 in the Labreton one improved after treatment. The same is true with so far the largest observational study conducted by Le Quintrec et al, 21 which included 26 children and adults with C3GP. Six patients (23%) had global clinical response, 6 (23%) had partial and 14 had (54%) NR.…”

Section: Discussionmentioning

confidence: 52%

“…In the majority of case reports published, clinical improvement with eculizumab was, however, reported, but can be said to be biased by reporting mostly positive results. On the other hand, a closer look at, though very few (especially in children), large series of eculizumab‐treated C3GP patients describe various results …”

mentioning

confidence: 99%

See 1 more Smart Citation

C3 glomerulopathy in children: Is there still a place for anti‐cellular immunosuppression?

2019

View full text Add to dashboard Cite

Aim To contribute additional clinical experience to the paucity of reports on C3 glomerulopathy (C3GP) in children, we are reporting our cohort of 11 children with C3GP, emphasizing the therapeutic options in this peculiar entity. Methods We describe the incidence, manifestation, histopathology findings, follow‐up, treatment and outcome of C3GP in 11 children with C3GP by retrospectively analyzing their clinical charts and renal biopsy reports. Results Eleven C3GP patients were identified among 240 children who had undergone renal biopsy, accounting for a 4.6% incidence of C3GP. A light microscopy examination showed a membranoproliferative pattern (n = 8), mesangial proliferation (n = 1), a mesangial/membranoproliferative pattern (n = 1) and endocapillary proliferation (n = 1). All children presented with proteinuria of varying degrees, the majority of them with additional hematuria, three with full‐blown nephrotic‐nephritic syndrome, and two with renal insufficiency at presentation. Very diverse treatments were applied in our cohort of patients, from no specific treatment to different mono or combined anti‐cellular immunosuppression treatments, as well as a trial of plasma therapy or eculizumab. Our results are in to some extend in concordance with other studies revealing that an optimal therapy for C3GP is still unknown, but we believe that a trial of classical immunosuppression before eculizumab is still worth trying, while eculizumab can have a beneficial effect, but not in all patients. Conclusion A diverse histological pattern and clinical picture and no known optimal therapy are a hallmark of C3GP.

show abstract

“…Because of the low frequency of C3 GP, patient cohort studies are important and can provide valuable information regarding clinical presentation, pathological and laboratory features, and their correlation with disease outcomes. Table 1 shows the clinical and laboratory data of patients affected by C3 GP in different cohorts, as described by many investigators [23,25,29,[31][32][33][34][35][36]. C3 GP involves mainly children and young people and may develop after an infectious episode (i.e., streptococcal infection) of the upper respiratory tract.…”

Section: Clinical Manifestationsmentioning

confidence: 99%

A Narrative Review on C3 Glomerulopathy: A Rare Renal Disease

Schena

Esposito

Rossini

2020

IJMS

View full text Add to dashboard Cite

In April 2012, a group of nephrologists organized a consensus conference in Cambridge (UK) on type II membranoproliferative glomerulonephritis and decided to use a new terminology, “C3 glomerulopathy” (C3 GP). Further knowledge on the complement system and on kidney biopsy contributed toward distinguishing this disease into three subgroups: dense deposit disease (DDD), C3 glomerulonephritis (C3 GN), and the CFHR5 nephropathy. The persistent presence of microhematuria with or without light or heavy proteinuria after an infection episode suggests the potential onset of C3 GP. These nephritides are characterized by abnormal activation of the complement alternative pathway, abnormal deposition of C3 in the glomeruli, and progression of renal damage to end-stage kidney disease. The diagnosis is based on studying the complement system, relative genetics, and kidney biopsies. The treatment gap derives from the absence of a robust understanding of their natural outcome. Therefore, a specific treatment for the different types of C3 GP has not been established. Recommendations have been obtained from case series and observational studies because no randomized clinical trials have been conducted. Current treatment is based on corticosteroids and antiproliferative drugs (cyclophosphamide, mycophenolate mofetil), monoclonal antibodies (rituximab) or complement inhibitors (eculizumab). In some cases, it is suggested to include sessions of plasma exchange.

show abstract

Patterns of Clinical Response to Eculizumab in Patients With C3 Glomerulopathy

Cited by 107 publications

References 33 publications

Update on C3 Glomerulopathy: A Complement-Mediated Disease

Update on C3 Glomerulopathy: A Complement-Mediated Disease

C3 glomerulopathy in children: Is there still a place for anti‐cellular immunosuppression?

A Narrative Review on C3 Glomerulopathy: A Rare Renal Disease

Contact Info

Product

Resources

About