Complement and kidney disease

Cook, H. Terence

doi:10.1097/mnh.0b013e32835ff9cb

Cited by 19 publications

(14 citation statements)

References 51 publications

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“…29,30 Hence, the IgG galactosylation pattern observed in our population supports the theory that complement activation/dysregulation is crucial in renal damage. 31 It is not clear whether IgG galactosylation is a consequence or an individual predisposition for a disease. The heritability of galactosylated glycans was very high, 24 indicating that galactosylation could partly be genetically predetermined.…”

Section: Galactosylation Of Iggmentioning

confidence: 99%

Glycosylation Profile of IgG in Moderate Kidney Dysfunction

Barrios

Zierer

Gudelj

et al. 2016

Journal of the American Society of Nephrology

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Glycans constitute the most abundant and diverse form of the post-translational modifications, and animal studies have suggested the involvement of IgG glycosylation in mechanisms of renal damage. Here, we explored the associations between IgG glycans and renal function in 3274 individuals from the TwinsUK registry. We analyzed the correlation between renal function measured as eGFR and 76 N-glycan traits using linear regressions adjusted for covariates and multiple testing in the larger population. We replicated our results in 31 monozygotic twin pairs discordant for renal function. Results from both analyses were then meta-analyzed. Fourteen glycan traits were associated with renal function in the discovery sample (P,6.5310 24 ) and remained significant after validation. Those glycan traits belong to three main glycosylation features: galactosylation, sialylation, and level of bisecting N-acetylglucosamine of the IgG glycans. These results show the role of IgG glycosylation in kidney function and provide novel insight into the pathophysiology of CKD and potential diagnostic and therapeutic targets.

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Section: Galactosylation Of Iggmentioning

confidence: 99%

Glycosylation Profile of IgG in Moderate Kidney Dysfunction

Barrios

Zierer

Gudelj

et al. 2016

Journal of the American Society of Nephrology

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“…There is growing evidence to show that IgAN is an immune-complex-mediated renal disease [3,4]. In addition to the well-known multihit pathogenesis [2], a variety of factors, such as complement activation and autophagy, are involved in its occurrence and development [5,6,7,8]. …”

Section: Introductionmentioning

confidence: 99%

Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy

Liu

Chen

et al. 2017

Am J Nephrol

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Background: IgA nephropathy (IgAN) has been considered to be the most frequent form of primary glomerulonephritis that occurs worldwide with a variety of factors involved in its occurrence and development. The impact of autophagy in IgAN, however, remains partially unclear. This study was designed to investigate the effects of rapamycin in an IgAN model. Method: After establishing an IgAN rat model, SD rats were divided into 4 groups: control, control + rapamycin, IgAN, IgAN + rapamycin. Proteinuria and the pathological changes and the level of autophagy of kidney were texted. Identify the expression of phosphorylation and total mammalian target of rapamycin (mTOR) and s6k1 as well as cyclin D1 in the kidney of rats through Western blot and immunohistochemistry. Results: With rapamycin treatment, we observed a significant reduction in the progression of proteinuria as well as alleviation of pathological lesions in IgAN rats. Besides, autophagy was inhibited, while the mTOR/S6k1 pathway was activated and expression of cyclin D1 was increased in IgAN. Rapamycin treatment increased autophagy and decreased the expression of cyclin D1. Conclusion: These results may suggest that mTOR-mediated autophagy inhibition may result in mesangial cell proliferation in IgAN.

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“…Under physiologic conditions, it is highly regulated by several plasmatic and membrane-bound molecules to avoid damage to self-tissues [1]. In recent years, dysregulation of the complement system has been involved in a myriad of kidney diseases, and C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome represent the two main complement-driven glomerular diseases [5].…”

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confidence: 99%

Update on C3 Glomerulopathy: A Complement-Mediated Disease

Caravaca-Fontán

Lucientes

Cavero

et al. 2020

Nephron

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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.

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Complement and kidney disease

Abstract: Complement activation or dysregulation is important in a range of renal pathology and new therapeutic strategies are being developed which may allow rational therapy for these diseases.

Cited by 19 publications

References 51 publications

Glycosylation Profile of IgG in Moderate Kidney Dysfunction

Glycosylation Profile of IgG in Moderate Kidney Dysfunction

Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy

Update on C3 Glomerulopathy: A Complement-Mediated Disease

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