Serum IL-18 Is Closely Associated with Renal Tubulointerstitial Injury and Predicts Renal Prognosis in IgA Nephropathy

Shi, Beili; Ni, Zhaohui; Cao, Liou; Zhou, Minjie; Mou, Shan; Wang, Qin; Zhang, Minfang; Fang, Wei; Yan, Yucheng; Qian, Jiaqi

doi:10.1155/2012/728417

Cited by 34 publications

(26 citation statements)

References 34 publications

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“…In addition, in both patients [39]–[41] and animal models [42], [43], IL-1β plays a pathogenic role in the evolution of IgAN, while patients with IgAN have been shown to have increased IL-18 levels in urine [44] and serum [45] and this is considered as a prognostic factor in these patients [45]. Mature IL-1β and IL-18 are generated from their respective precursors, pro-IL-1β and pro-IL-18, by active caspase-1 produced by the NLRP3 inflammasome [32], [46].…”

Section: Discussionmentioning

confidence: 99%

Osthole Mitigates Progressive IgA Nephropathy by Inhibiting Reactive Oxygen Species Generation and NF-κB/NLRP3 Pathway

et al. 2013

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Renal reactive oxygen species (ROS) and mononuclear leukocyte infiltration are involved in the progressive stage (exacerbation) of IgA nephropathy (IgAN), which is characterized by glomerular proliferation and renal inflammation. The identification of the mechanism responsible for this critical stage of IgAN and the development of a therapeutic strategy remain a challenge. Osthole is a pure compound isolated from Cnidiummonnieri (L.) Cusson seeds, which are used as a traditional Chinese medicine, and is anti-inflammatory, anti-apoptotic, and anti-fibrotic both in vitro and in vivo. Recently, we showed that osthole acts as an anti-inflammatory agent by reducing nuclear factor-kappa B (NF-κB) activation in and ROS release by activated macrophages. In this study, we examined whether osthole could prevent the progression of IgAN using a progressive IgAN (Prg-IgAN) model in mice. Our results showed that osthole administration resulted in prevention of albuminuria, improved renal function, and blocking of renal progressive lesions, including glomerular proliferation, glomerular sclerosis, and periglomerular mononuclear leukocyte infiltration. These findings were associated with (1) reduced renal superoxide anion levels and increased Nrf2 nuclear translocation, (2) inhibited renal activation of NF-κB and the NLRP3 inflammasome, (3) decreased renal MCP-1 expression and mononuclear leukocyte infiltration, (4) inhibited ROS production and NLRP3 inflammasome activation in cultured, activated macrophages, and (5) inhibited ROS production and MCP-1 protein levels in cultured, activated mesangial cells. The results suggest that osthole exerts its reno-protective effects on the progression of IgAN by inhibiting ROS production and activation of NF-κB and the NLRP3 inflammasome in the kidney. Our data also confirm that ROS generation and activation of NF-κB and the NLRP3 inflammasome are crucial mechanistic events involved in the progression of the renal disorder.

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Section: Discussionmentioning

confidence: 99%

Osthole Mitigates Progressive IgA Nephropathy by Inhibiting Reactive Oxygen Species Generation and NF-κB/NLRP3 Pathway

et al. 2013

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“…Levels of advanced oxidative protein products in 292 patients with IgA nephropathy from the USA and Italy correlated with the rate of decline in renal function (r = −0.33, p = 0.008) measured by eGFR [32]. An increased serum level of interleukin-18, a cytokine associated with renal injury in ischemia-reperfusion models, was significantly correlated with the rate of loss of renal function (r = 0.242, p = 0.021), also measured by eGFR, in a cohort of 76 Chinese patients with IgA nephropathy with moderate to severe histologic changes on kidney biopsy (greater than 25% of glomeruli with crescents, segmental sclerosis, or global sclerosis) [93]. …”

Section: Biomarkers Of Iga Nephropathymentioning

confidence: 99%

Biomarkers in IgA nephropathy: relationship to pathogenetic hits

Hastings

Moldoveanu

Suzuki

et al. 2013

Expert Opinion on Medical Diagnostics

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Introduction IgA nephropathy, the most prevalent glomerular disease in the world, requires a renal biopsy for diagnosis. Reliable biomarkers are needed for the non-invasive diagnosis of this disease and to more fully delineate its natural history and risk for progression. Areas covered In this review, the authors examine serum levels of galactose-deficient IgA1 (Gd-IgA1) and glycan-specific IgG and IgA autoantibodies that are integral to pathogenesis of IgA nephropathy. They also explore biomarkers related to alternative and lectin pathways of complement activation and serum and urinary peptide biomarkers detected by mass spectrometric methods. The literature search included review of all publications having IgA nephropathy in the title that were cited in PubMed and Scopus over the past 10 years and a non-systematic review of abstracts published for the annual meetings of the American Society of Nephrology and the International Symposia on IgA Nephropathy. Expert opinion Serum Gd-IgA1 level and glycan-specific autoantibody levels are prime candidates to become diagnostic biomarkers for IgA nephropathy because of their central role in the earliest stages of disease pathogenesis. Assays for serum levels of complement proteins C3 and factor H are readily available in clinical practice and deserve continued study, either alone or in tandem with total serum IgA or serum Gd-IgA1 levels, as prognostic biomarkers for patients with IgA nephropathy. Urinary peptidomic data are also reviewed because this approach can successfully differentiate patients with IgA nephropathy from healthy controls and from patients with other forms of renal disease.

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“…A clinical study in Finland enrolled total of 174 patients with IgAN found that there was a marked increase in inflammatory markers such s‐albumin, high‐sensitivity C‐reactive protein, and white blood cells, which were suggested to be associated with the progression of IgAN 7. Moreover, increasing clinical evidences further demonstrated that the production of proinflammatory cytokines such IL‐18 and IL‐1β were dramatically upregulated in IgAN patients and this is considered as a prognostic factor in these patients 8, 9, 10. It has been documented that mature IL‐18 and IL‐1β are generated via the activation of Nlrp3 inflammasome 13, 27.…”

Section: Discussionmentioning

confidence: 99%

Icariin ameliorates IgA nephropathy by inhibition of nuclear factor kappa b/Nlrp3 pathway

Zhang

Wang

et al. 2016

FEBS Open Bio

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Immunoglobulin A nephropathy (IgAN) is the most frequent form of glomerulonephritis, which is characterized by glomerular proliferation and renal inflammation. Icariin is a flavonoid from the Chinese herb Epimedium, and its anti‐inflammatory effect has been reported. This study aimed to investigate the effects of icariin on the renal damage in IgAN rats and the mechanisms behind these effects. IgAN model was established in Sprague–Dawley rats by oral and intravenous immunization with bovine gamma‐globulin for 12 weeks, and rats were treated with icariin from 12 to 18 weeks. At the end of experimental period, kidneys, urine, and blood samples were collected for further analysis. Our results showed that icariin ameliorated the increase in the levels of proteinuria, serum creatinine, and urea nitrogen without severe side effects. IgAN rats exhibited significantly increased IgA deposition, mesangial matrix expansion, and glomerular fibrosis, while icariin treatment markedly attenuated these alterations. Moreover, treatment with icariin also dramatically blocked nuclear factor kappa b (NF‐κB) nuclear translocation and Nlrp3 inflammasome activation in IgAN rats, leading to reduced downstream proinflammatory cytokines production. Mechanistically, we found that icariin treatment inhibited IKKβ and IκBα phosphorylation and IκBα degradation in IgAN rats. Our data demonstrate that icariin ameliorates renal damage in IgAN rats via inhibition of NF‐κB‐mediated Nlrp3 inflammasome activation. These findings provide insight into an application of icariin for the treatment of IgAN disease, and represent a novel mechanism behind these effects.

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Serum IL-18 Is Closely Associated with Renal Tubulointerstitial Injury and Predicts Renal Prognosis in IgA Nephropathy

Cited by 34 publications

References 34 publications

Osthole Mitigates Progressive IgA Nephropathy by Inhibiting Reactive Oxygen Species Generation and NF-κB/NLRP3 Pathway

Osthole Mitigates Progressive IgA Nephropathy by Inhibiting Reactive Oxygen Species Generation and NF-κB/NLRP3 Pathway

Biomarkers in IgA nephropathy: relationship to pathogenetic hits

Icariin ameliorates IgA nephropathy by inhibition of nuclear factor kappa b/Nlrp3 pathway

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