C3 Glomerulopathy: Ten Years' Experience at Mayo Clinic

Ravindran, Aishwarya; Fervenza, Fernando C.; Smith, Richard J.H.; Vriese, An S. De; Sethi, Sanjeev

doi:10.1016/j.mayocp.2018.05.019

Cited by 86 publications

(102 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Complement genetic abnormalities may be found in about 25% of patients [10,15,17,22], mostly affecting the C3 gene, CFB, CFH, CFI, and CFHR, which encode complement component C3, factor B (FB), factor H (FH), factor I (FI), and FH-related (FHR) proteins, respectively [6,18]. Most pathogenic variants in C3 affect the recognition sites for the binding of FH and FI, leading to an improper cleavage of the molecule [23].…”

Section: Pathogenesismentioning

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: Pathogenesismentioning

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

“…Meanwhile, studies comparing the two appeared in the literature and concluded that DDD was a more severe form of C3G presenting at an early age, with poor response to treatment and worse outcome [17]. However, newer studies with a larger sample size and longer follow-up have shown no major difference between these 2 subgroups [8,9]. Two large cohorts of C3G which deserve special mention were published in 2018 from North America.…”

Section: Discussionmentioning

confidence: 99%

“…Although these series primarily studied the EM subdivisions of C3G, the EM subgroups did not predict ESRD. Only the markers of chronicity at the time of diagnosis, either clinical (i.e., elevated creatinine, reduced GFR, and advanced age) or LM (i.e., interstitial fibrosis and glomerulosclerosis), were the strongest predictors of outcome [8,9]. An alternative classification system that would relate better to the clinicopathological profile, treatment response, and renal outcome of C3G was timely and necessary.…”

Section: Discussionmentioning

confidence: 99%

“…Recently published C3G studies in the USA have found no significant differences in outcomes between C3GN and DDD subgroups. Even in these studies, the predictors of progression to end-stage renal disease (ESRD) were LM findings of chronicity (i.e., interstitial fibrosis or glomerulosclerosis) and not the EM findings (i.e., C3GN or DDD) [8,9]. These studies have set up a debate about the use of classifying C3G on the basis of EM findings.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinicopathological Significance and Renal Outcomes of Light Microscopic Patterns in Complement Component 3 Glomerulopathy

Wani

Zahir

Gupta

et al. 2020

Nephron

View full text Add to dashboard Cite

Background: Complement component 3 glomerulopathy (C3G) is a disease diagnosed based on the predominance of C3 immunostaining in glomeruli. The popular electron microscopic subtyping of C3G into dense deposit disease and C3 glomerulonephritis (GN) is not without limitations. We aimed to study the light microscopic (LM) patterns of C3G along with their clinicopathological correlation and treatment outcome. Methods: C3G biopsies were classified into 4 LM patterns (membranoproliferative GN [MPGN], mesangial proliferative GN [MesPGN], diffuse proliferative GN [DPGN], and crescentic GN [CrGN]). These patterns were compared for clinicopathological profile, treatment outcome, and renal survival. Further, predictors of end-stage renal disease (ESRD) were determined using the Cox proportional hazards model. Results: Of 162 biopsies, there were 83 MPGN, 36 DPGN, 22 MesPGN, and 21 CrGN. Majority of the patients were young, with males being more than females.About half (48%) of the patients received immunosuppression, steroids alone (29%) or steroids with other immunosuppressants (19%). The overall remission rate was 32.7% (median follow-up = 14 months). CKD developed in 46 patients and 31 patients progressed to ESRD. Predictors of progression to ESRD were older age (hazard ratio [HR] = 1.04, p < 0.01), advanced renal failure at presentation (HR = 3.73, p < 0.01), glomerulosclerosis (HR = 5.07, p < 0.01), and severity of interstitial fibrosis and tubular atrophy (HR = 8.25, p = 0.01). Conclusions: The LM patterns differed in their clinicopathological profiles, without any significant difference in their renal outcomes. Glomerulosclerosis and interstitial fibrosis portend a poor prognosis. Besides CrGN, MesPGN pattern of C3G presented as a severe form of disease.

show abstract

“…C4 nephritic factors (C4NeFs) stabilize the C3 convertase (C4bC2a) of classical and lectin pathways. There is evidence of sporadic C4NeF positivity in patients with C3GN, although the recorded prevalence varies 28,29) . The functions of these nephritic factors often require the presence of properdin 17,26,27) .…”

Section: Autoantibodies To Alternative Pathway Regulatorsmentioning

confidence: 99%

Pathology of C3 Glomerulopathy

Shin¹,

Seong²,

Lim³

2019

Child Kidney Dis

View full text Add to dashboard Cite

Pathology of C3 Glomerulopathy C3 glomerulopathy is a renal disorder involving dysregulation of alternative pathway complement activation. In most instances, a membranoproliferative pattern of glomerular injury with a prevalence of C3 deposition is observed by immunofluorescence microscopy. Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are subclasses of C3 glomerulopathy that are distinguishable by electron microscopy. Highly electron-dense transformation of glomerular basement membrane is characteristic of DDD. C3GN should be differentiated from post-infectious glomerulonephritis and other immune complex-mediated glomerulonephritides showing C3 deposits.

show abstract

C3 Glomerulopathy: Ten Years' Experience at Mayo Clinic

Abstract: C3 glomerulopathy is a heterogeneous disease entity with complex triggering events and abnormalities of the alternative pathway of complement. The disease tends to be progressive and exhibits a variable response to immunosuppressive therapy.

Cited by 86 publications

References 42 publications

Update on C3 Glomerulopathy: A Complement-Mediated Disease

Update on C3 Glomerulopathy: A Complement-Mediated Disease

Clinicopathological Significance and Renal Outcomes of Light Microscopic Patterns in Complement Component 3 Glomerulopathy

Pathology of C3 Glomerulopathy

Contact Info

Product

Resources

About