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      High serum IgA/C3 ratio better predicts a diagnosis of IgA nephropathy among primary glomerular nephropathy patients with proteinuria ≤ 1 g/d: an observational cross-sectional study

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          Abstract

          Background

          The serum immunoglobulin A (IgA)/C3 ratio is considered to be an effective predictor of IgA nephropathy (IgAN). This study sought to explore the diagnostic value of the IgA/C3 ratio in IgAN among primary glomerular nephropathy patients in China.

          Methods

          We recruited 1095 biopsy-diagnosed primary glomerular nephropathy patients, including 757 IgAN patients and 338 non-IgAN patients. Patient demographics, serum immunological indices, and other clinical examinations were measured. IgAN cases were propensity score matched (PSM) to non-IgAN cases on the logit of the propensity score using nearest neighbor matching in a 1:1 fashion, with a caliper of 0.02 with no replacements, according to age, gender, BMI, proteinuria level, and estimated glomerular filtration rate (eGFR).

          Results

          We found that in both the full cohort and PSM cohort, the IgA/C3 ratio in the IgAN group was significantly higher than that of the non-IgAN group. The same results were also obtained with stratification by different levels of proteinuria and renal function. In the PSM cohort, there was no difference in IgA/C3 ratio in patients with IgAN between different proteinuria groups and different chronic kidney disease (CKD) groups. The area under the ROC curve (AUROC) of the IgA/C3 ratio in distinguishing IgAN among primary glomerular disease was 0.767 in the full cohort, and 0.734 in the PSM cohort. The highest AUROC of the IgA/C3 ratio was in the ≤1 g/d proteinuria group (0.801 in the full cohort, and 0.803 in the PSM cohort); however, there was no difference between all CKD groups. Meanwhile, the diagnostic accordance rate for the diagnosis of IgAN among all patients with an IgA/C3 ratio > 3.5304 was as high as 92.02% in the full cohort. IgAN was independently correlated with IgA/C3 ratio in the full cohort by multivariate logistic regression analysis.

          Conclusions

          The present study provides clear evidence that the IgA/C3 ratio is an effective predictor of IgA diagnosis, especially in patients with proteinuria ≤1 g/d. In order to study the effectiveness of this biomarker, and to determine a standardized cut-off value, additional multicenter large-scale studies are needed.

          Electronic supplementary material

          The online version of this article (10.1186/s12882-019-1331-0) contains supplementary material, which is available to authorized users.

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          Most cited references33

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          A critical appraisal of propensity-score matching in the medical literature between 1996 and 2003.

          Propensity-score methods are increasingly being used to reduce the impact of treatment-selection bias in the estimation of treatment effects using observational data. Commonly used propensity-score methods include covariate adjustment using the propensity score, stratification on the propensity score, and propensity-score matching. Empirical and theoretical research has demonstrated that matching on the propensity score eliminates a greater proportion of baseline differences between treated and untreated subjects than does stratification on the propensity score. However, the analysis of propensity-score-matched samples requires statistical methods appropriate for matched-pairs data. We critically evaluated 47 articles that were published between 1996 and 2003 in the medical literature and that employed propensity-score matching. We found that only two of the articles reported the balance of baseline characteristics between treated and untreated subjects in the matched sample and used correct statistical methods to assess the degree of imbalance. Thirteen (28 per cent) of the articles explicitly used statistical methods appropriate for the analysis of matched data when estimating the treatment effect and its statistical significance. Common errors included using the log-rank test to compare Kaplan-Meier survival curves in the matched sample, using Cox regression, logistic regression, chi-squared tests, t-tests, and Wilcoxon rank sum tests in the matched sample, thereby failing to account for the matched nature of the data. We provide guidelines for the analysis and reporting of studies that employ propensity-score matching. Copyright (c) 2007 John Wiley & Sons, Ltd.
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            The incidence of primary glomerulonephritis worldwide: a systematic review of the literature.

            Little is known about the worldwide variation in incidence of primary glomerulonephritis (GN). The objective of this review was to critically appraise studies of incidence published in 1980-2010 so that an overall view of trends of these diseases can be found. This would provide important information for determining changes in rates and understanding variations between countries. All relevant papers found through searches of Medline, Embase and ScienceDirect were critically appraised and an assessment was made of the reliability of the reported incidence data. This review includes 40 studies of incidence of primary GN from Europe, North and South America, Canada, Australasia and the Middle East. Rates for the individual types of disease were found to be in adults, 0.2/100,000/year for membrano-proliferative GN, 0.2/100,000/year for mesangio-proliferative GN, 0.6/100,000/year for minimal change disease, 0.8/100,000/year for focal segmental glomerulosclerosis, 1.2/100,000/year for membranous nephropathy and 2.5/100,000/year for IgA nephropathy. Rates were lower in children at around 0.1/100,000/year with the exception of minimal change disease where incidence was reported to be 2.0/100,000/year in Caucasian children with higher rates in Arabian children (9.2/100,000/year) and Asian children (6.2-15.6/100,000/year). This study found that incidence rates of primary GN vary between 0.2/100,000/year and 2.5/100,000/year. The incidence of IgA nephropathy is at least 2.5/100,000/year in adults; this disease can exist subclinically and is therefore only detected by chance in some patients. In addition, referral policies for diagnostic biopsy vary between countries. This will affect the incidence rates found.
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              Remission of proteinuria improves prognosis in IgA nephropathy.

              Proteinuria has been shown to be an adverse prognostic factor in IgA nephropathy. The benefit of achieving a partial remission of proteinuria, however, has not been well described. We studied 542 patients with biopsy-proven primary IgA nephropathy in the Toronto Glomerulonephritis Registry and found that glomerular filtration rate (GFR) declined at -0.38 +/- 0.61 ml/min per 1.73 m2/mo overall, with 30% of subjects reaching end-stage renal disease. Multivariate analysis revealed that proteinuria during follow-up was the most important predictor of the rate of GFR decline. Among the 171 patients with 3 g/d (n = 121) lost renal function 25-fold faster than those with or =3 g/d who achieved a partial remission (<1 g/d) had a similar course to patients who had < or =1 g/d throughout, and fared far better than patients who never achieved remission. These results underscore the relationship between proteinuria and prognosis in IgA nephropathy and establish the importance of remission.
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                Author and article information

                Contributors
                gongwenyugz@qq.com
                liumanjx@163.com
                luodan72@qq.com
                13560421216@126.com
                medicalyinlh@126.com
                106544760@qq.com
                zj_ncjx@163.com
                pengh@mail.sysu.edu.cn
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                30 April 2019
                30 April 2019
                2019
                : 20
                : 150
                Affiliations
                [1 ]ISNI 0000 0004 1790 3548, GRID grid.258164.c, Division of Nephrology, Department of medicine, the First Affiliated Hospital, , Jinan University, ; Guangzhou, 510630 Guangdong China
                [2 ]GRID grid.412615.5, Division of Gastroenterology and Hepatology, , The First Affiliated Hospital of Sun Yat-sen University, ; Guangzhou, Guangdong China
                [3 ]ISNI 0000 0004 1762 1794, GRID grid.412558.f, Division of Nephrology, Department of medicine, , Third Affiliated Hospital of Sun Yat-Sen University, ; Guangzhou, 510630 Guangdong China
                Article
                1331
                10.1186/s12882-019-1331-0
                6492345
                31039758
                ce226ace-3fcb-4505-afa5-680f3fad1e48
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 5 January 2019
                : 8 April 2019
                Funding
                Funded by: the project of cultivating young teachers in Sun Yat-sen University
                Award ID: No. 17kypy56
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Nephrology
                immunoglobulin a nephropathy,serum immunoglobulin a/c3 ratio,diagnosis
                Nephrology
                immunoglobulin a nephropathy, serum immunoglobulin a/c3 ratio, diagnosis

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