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Does the renal expression of Toll-like receptors play a role in patients with IgA nephropathy?

ABSTRACT: The onset of IgA nephropathy (IgAN), characterized by glomerular deposition of IgA-containing immune complexes, is often associated with synpharyngitic hematuria. Innate immune responses mediated by Toll-like receptors (TLR) may play a role in IgAN onset and/or progression. Here, we assessed the expression of TLR 4, 7, 8, and 9 in renal-biopsy specimens from patients with IgAN, with different degree of proteinuria and eGFR, compared with normal-kidney and disease-control tissues (ANCA-associated vasculitis). Renal-biopsy specimens from 34 patients with IgAN and 7 patients with ANCA-associated vasculitis were used. In addition, we used 15 healthy portions of renal-tissue specimens from kidneys after nephrectomy for cancer as control specimens. Expression of TLR 4, 7, 8, and 9 was assessed using immunohistochemical staining of paraffin-embedded renal-biopsy tissue specimens with specific antibodies and evaluated semiquantitatively by light microscopy. Linear discriminant analysis (LDA) was used to test whether intrarenal staining of TLR 4, 7, 8, and 9 distinguished patients with IgAN from controls or correlated with eGFR and/or proteinuria. eGFR was calculated using the creatinine-based formula. Moreover, the biopsies from patients with IgAN were scored according to the Oxford Classification. LDA showed that staining for TLR 4, 7, 8, and 9 was more intense in specimens from IgAN patients compared to normal kidney tissues. The intensity of intrarenal staining of TLRs discriminated four groups of IgAN patients with different eGFR and proteinuria and MEST scoring.

SUBMITTER: Ciferska H

PROVIDER: S-EPMC7170228 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Does the renal expression of Toll-like receptors play a role in patients with IgA nephropathy?

Ciferska Hana H Honsova Eva E Lodererova Alena A Hruskova Zdenka Z Neprasova Michaela M Vachek Jan J Suchanek Miloslav M Zima Tomas T Coppo Rosanna R Tesar Vladimir V Novak Jan J Maixnerova Dita D

Journal of nephrology 20190905 2

The onset of IgA nephropathy (IgAN), characterized by glomerular deposition of IgA-containing immune complexes, is often associated with synpharyngitic hematuria. Innate immune responses mediated by Toll-like receptors (TLR) may play a role in IgAN onset and/or progression. Here, we assessed the expression of TLR 4, 7, 8, and 9 in renal-biopsy specimens from patients with IgAN, with different degree of proteinuria and eGFR, compared with normal-kidney and disease-control tissues (ANCA-associated ...[more]

PMID: 31489594

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Project description:Many studies have shown that chronic changes are strong predictors of renal outcomes in various kidney diseases, including IgA nephropathy. The Mayo Clinic/Renal Pathology Society suggested a glomerulonephritis reporting system with a proposal for standardized grading of chronic changes. The purpose of this study was to predict renal outcomes in patients with IgA nephropathy using chronicity grading in comparison to the Oxford classification which did not include global sclerosis. A total of 4,151 patients with IgA nephropathy were enrolled from the Korean GlomeruloNephritis Study Group registry. Chronicity grading was categorized into minimal, mild, moderate, and severe according to the extent of chronic changes. The Oxford T and S scores were considered as chronic lesions. Three prediction models were constructed: the Oxford classification model (Oxford S plus T), chronicity grading model A (chronicity grading), and chronicity grading model B (chronicity grading plus Oxford S). Using these three prediction models, the primary renal outcome (end-stage renal disease) was evaluated using Cox regression analysis and prediction performance. During the median follow-up of 6.1 (2.7-9.9) years, 304 (7.3%) patients progressed to end-stage renal disease with a cumulative incidence rate of 1.02 events per 100 person-years. In a fully adjusted multivariable model, chronicity grading was independently associated with the primary renal outcome in both models A and B. Compared to the Oxford model, both models A and B showed improvements in model fit, but not in discrimination (ΔC 0.001; 95% CI, -0.010 to 0.013 and ΔC 0.002; 95% CI, -0.005 to 0.008, respectively). Model B demonstrated improvements in integrated discrimination improvement (0.01; 95% CI, 0-0.03) and continuous net reclassification improvement (0.49; 95% CI, 0.02-0.72). The severity of chronicity grading is closely related to adverse renal outcomes in patients with IgA nephropathy, and chronicity grading could provide additional information in clinical practice alongside the Oxford classification.

Project description:Background and objectivesSome studies suggest that the incidence of IgA nephropathy is increasing in older adults, but there is a lack of information about the epidemiology and behavior of the disease in that age group.Design, setting, participants, & measurementsIn this retrospective multicentric study, we analyzed the incidence, forms of presentation, clinical and histologic characteristics, treatments received, and outcomes in a cohort of 151 patients ≥65 years old with biopsy-proven IgA nephropathy diagnosed between 1990 and 2015. The main outcome was a composite end point of kidney replacement therapy or death before kidney replacement therapy.ResultsWe found a significant increase in the diagnosis of IgA nephropathy over time from six patients in 1990-1995 to 62 in 2011-2015 (P value for trend =0.03). After asymptomatic urinary abnormalities (84 patients; 55%), AKI was the most common form of presentation (61 patients; 40%). Within the latter, 53 (86%) patients presented with hematuria-related AKI (gross hematuria and tubular necrosis associated with erythrocyte casts as the most important lesions in kidney biopsy), and eight patients presented with crescentic IgA nephropathy. Six (4%) patients presented with nephrotic syndrome. Among hematuria-related AKI, 18 (34%) patients were receiving oral anticoagulants, and this proportion rose to 42% among the 34 patients older than 72 years old who presented with hematuria-related AKI. For the whole cohort, survival rates without the composite end point were 74%, 48%, and 26% at 1, 2, and 5 years, respectively. Age, serum creatinine at presentation, and the degree of interstitial fibrosis in kidney biopsy were risk factors significantly associated with the outcome, whereas treatment with renin-angiotensin-aldosterone blockers was associated with a lower risk. Immunosuppressive treatments were not significantly associated with the outcome.ConclusionsThe diagnosis of IgA nephropathy among older adults in Spain has progressively increased in recent years, and anticoagulant therapy may be partially responsible for this trend. Prognosis was poor.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_07_16_CJASNPodcast_19_08_.mp3.

Dataset Information

Does the renal expression of Toll-like receptors play a role in patients with IgA nephropathy?

Publications

Does the renal expression of Toll-like receptors play a role in patients with IgA nephropathy?

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