Urinary excretion of soluble tumour necrosis factor receptor 1 as a marker of increased risk of progressive kidney function deterioration in patients with primary chronic glomerulonephritis

Idasiak-Piechocka, Ilona; Oko, Andrzej; Pawliczak, Elżbieta; Kaczmarek, Elżbieta; Czekalski, Stanisław

doi:10.1093/ndt/gfq310

Cited by 33 publications

(46 citation statements)

References 27 publications

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“…Whereas, TNFR1, but not TNFR2, is expressed in the glomeruli in healthy subjects [25], TNFR1 and TNFR2 are expressed in glomerular and tubular cells after renal injury [20]. A large body of evidence explicates the association of TNFRs with inflammatory kidney disease [17], [18], [26], [27], [28], but there is a paucity of data on the correlation between clinical manifestations and cTNFRs levels in patients with iMN.…”

Section: Discussionmentioning

confidence: 99%

Circulating TNF Receptors Are Significant Prognostic Biomarkers for Idiopathic Membranous Nephropathy

et al. 2014

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Idiopathic membranous nephropathy (iMN) is a common cause of nephrotic syndrome in adults. A biomarker to accurately indicate the severity of iMN and predict long-term prognosis is insufficient. Here, we evaluated the clinical significance of circulating tumor necrosis factor receptors (cTNFRs) as prognostic biomarkers of iMN with nephrotic syndrome. A total of 113 patients with biopsy-proven iMN and 43 healthy volunteers were enrolled in this study. Ninety patients with iMN had nephrotic range proteinuria. Levels of cTNFRs were measured by using serum samples collected at the time of initial diagnosis. Levels of cTNFRs were higher in the patients with nephrotic syndrome than in those with subnephrotic range proteinuria or in the healthy volunteers (P for trend <0.001). Estimated glomerular filtration rate and proteinuria tended to worsen as the cTNFRs levels increased. Having a cTNFR1 level within the highest tertile was a significant risk factor for renal progression after adjustment, in comparison with the other tertiles (hazard ratio [HR], 3.39; 95% confidence interval [95% CI], 1.48–7.78; P = 0.004). The cTNFR2 level within the highest tertile also significantly increased the risk of renal progression (HR, 3.29; 95% CI, 1.43–7.54; P = 0.005). Renal tubular TNFRs expression was associated with cTNFRs level. However, the cTNFRs levels were not associated with autoantibody against phospholipase A2 receptor reactivity/levels or treatment response. This study demonstrated that cTNFRs levels at the time of initial diagnosis could predict renal progression in patients with iMN.

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Section: Discussionmentioning

confidence: 99%

Circulating TNF Receptors Are Significant Prognostic Biomarkers for Idiopathic Membranous Nephropathy

et al. 2014

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“…87 In addition, elevated urinary TNFR1 predicted progression of renal function impairment and advanced renal interstitial fibrosis in patients with newly diagnosed primary GNs. 88 ANCA-induced nephritis. Crescentic GN is prevalent in forms of small-vessel vasculitis that are strongly associated with autoantibodies against lysosomal components of neutrophils and monocytes such as myeloperoxidase and proteinase 3 (anti-neutrophil cytoplasmic autoantibodies) (ANCAs).…”

Section: Biological Responses Of Tnfrs In Renal Dysfunction Crescentimentioning

confidence: 99%

“…The protective effect is associated with a marked reduction in tubulointerstitial macrophage infiltration. 27,29 TNFR1 and TNFR2 in endothelial cells promotes Type I IFNb production and subsequent autocrine signaling through the IFNa/b receptor to induce the transcription of mononuclear chemokines, such as Cxcl9, Cxcl10 and Urinary levels of soluble TNFR1 and TNFR2 were effective in predicting a favorable response to immunosuppressive treatments in patients with primary GN 87 Elevated urinary TNFR1 predicted progression of renal function impairment and advanced renal interstitial fibrosis in newly diagnosed primary GNs 88 ANCA In a murine model of ANCA mediated NCGN, anti-TNF antibody prior to induction of disease, reduced glomerular crescent formation and macrophage influx but did not improve renal function (Reference 87) 89 In a rat model of MPO-ANCA associated NCGN, anti-TNF antibody markedly reduced albuminuria and crescent formation even when administered after GN was established (Ref 88) 90 TNF and soluble TNFRs may serve as prognostic indicators of disease in patients (Refs 89-93) [91][92][93][94][95] LN No association between TNFR2-196M/R polymorphisms and SLE in Caucasians is detected using the transmission disequilibrium test. 102 Circulating levels of both TNFRs are significantly higher in SLE than in rheumatoid arthritis, and spondyloarthropathies.…”

Section: Renal Dysfunctionmentioning

confidence: 99%

TNF receptors: signaling pathways and contribution to renal dysfunction

Al‐Lamki

Mayadas

2015

Kidney International

175

126

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Tumor necrosis factor (TNF), initially reported to induce tumor cell apoptosis and cachexia, is now considered a central mediator of a broad range of biological activities from cell proliferation, cell death and differentiation to induction of inflammation and immune modulation. TNF exerts its biological responses via interaction with two cell surface receptors: TNFR1 and TNFR2. (TNFRs). These receptors trigger shared and distinct signaling pathways upon TNF binding, which in turn result in cellular outputs that may promote tissue injury on one hand but may also induce protective, beneficial responses. Yet the role of TNF and its receptors specifically in renal disease is still not well understood. This review describes the expression of the TNFRs, the signaling pathways induced by them and the biological responses of TNF and its receptors in various animal models of renal diseases, and discusses the current outcomes from use of TNF biologics and TNF biomarkers in renal disorders.

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“…At low concentrations, sTNFRs enhance the actions of TNF-α, but at higher sTNFR concentrations the effects of TNF-α are abrogated [25]. Also in urine, increased TNFR1 excretion reflects increased TNFR shedding from the cell membranes and may be interpreted as a marker of increased TNF-α expression in activated renal cells [29]. Another possibility is that the shedding of receptors represents a mechanism for desensitizing the cells that shed the receptors from the effects of TNF-α [30].…”

Section: General Characteristicsmentioning

confidence: 99%

Tumor Necrosis Factor Receptors: Biology and Therapeutic Potential in Kidney Diseases

Speeckaert

Laute³

et al. 2012

Am J Nephrol

105

101

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The major evolutionary advance represented in the human immune system is a mechanism of antigen-directed immunity in which tumor necrosis factor (TNF)-α and TNF receptors (TNFRs) play essential roles. Binding of TNF-α to the 55-kDa type I TNFR (TNFR1, TNFRSF1A, CD120a, p55) or the 75-kDa type II TNFR (TNFR2, TNFRSF1B, CD120b, p75) activates signaling pathways controlling inflammatory, immune and stress responses, as well as host defense and apoptosis. Multiple studies have investigated the role of TNFRs in the development of early and late renal failure (diabetic nephropathy, nephroangiosclerosis, acute kidney transplant rejection, renal cell carcinoma, glomerulonephritis, sepsis and obstructive renal injury). This article reviews the general characteristics, the analytical aspects and the biology of TNFRs in this domain. In addition, the potential therapeutic application of specific TNFR blockers is discussed.

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Urinary excretion of soluble tumour necrosis factor receptor 1 as a marker of increased risk of progressive kidney function deterioration in patients with primary chronic glomerulonephritis

Abstract: Markedly elevated urinary TNFR1 excretion may be considered as a good marker of an activated TNFα-pathway in patients with newly diagnosed GN and as a potentially modifiable risk factor of progressive kidney function impairment.

Cited by 33 publications

References 27 publications

Circulating TNF Receptors Are Significant Prognostic Biomarkers for Idiopathic Membranous Nephropathy

Circulating TNF Receptors Are Significant Prognostic Biomarkers for Idiopathic Membranous Nephropathy

TNF receptors: signaling pathways and contribution to renal dysfunction

Tumor Necrosis Factor Receptors: Biology and Therapeutic Potential in Kidney Diseases

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