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      Serum levels of galactose-deficient immunoglobulin (Ig) A1 and related immune complex are associated with disease activity of IgA nephropathy

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          Abstract

          Background

          The primary abnormal manifestation in immunoglobulin A nephropathy (IgAN) is recurring bouts of hematuria with or without proteinuria. Although immunohistochemical analysis of renal biopsy tissue remains the gold standard not only for diagnosis but also for evaluating the activity of IgAN, new sensitive and reasonably specific noninvasive tests are emerging to guide therapeutic strategy applicable to all stages of IgAN. The present study examined serum levels of galactose-deficient IgA1 (Gd-IgA1) and its immune complex (IgA/IgG-IC) as noninvasive markers for the disease activity.

          Methods

          We enrolled 50 IgAN patients (male 40 %, median age 37 years) showing complete or partial clinical remission after steroid pulse therapy with tonsillectomy (TSP) whose clinical data and serum could be followed up for 3–5 years.

          Results

          Cross-sectional analysis revealed that the degree of hematuria and proteinuria were significantly associated with levels of Gd-IgA1 and levels of IgA/IgG-IC. Longitudinal analysis further showed that from the group of 44 patients with heavy hematuria before TSP, 31 patients showed complete disappearance of hematuria (group A), but the remaining patients did not (group B). Although the levels of Gd-IgA1 and IgA/IgG-IC in the two groups before TSP were similar, percentage decrease of Gd-IgA1 and IgA/IgG-IC levels in group A was significantly higher than in group B.

          Conclusion

          Disease activity of IgAN assessed by hematuria and proteinuria correlated with serum levels and changes of Gd-IgA1 and IgA/IgG-IC. These new noninvasive disease activity markers can be useful for future activity scoring system and guiding therapeutic approaches.

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          Most cited references30

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          IgA nephropathy.

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            The commonest glomerulonephritis in the world: IgA nephropathy.

            G D'Amico (1987)
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              Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors.

              G D'Amico (2000)
              Idiopathic immunoglobulin A nephropathy is characterized by an extreme variability in clinical course and sometimes by the unpredictability of the ultimate outcome. Among the numerous studies published in the last 15 years that have calculated the actuarial renal survival and tried to individuate the prognostic role of the clinical and histological features present at the onset of the disease or the time of biopsy, we chose to analyze critically the results of the most valid (30 studies). Actuarial renal survival at 10 years in adults was between 80% and 85% in most of the European and Asian studies, but it was less in studies from the United States and exceeded 90% in the few studies of children. Concordance existed in this selected literature that impairment of renal function, severe proteinuria, and arterial hypertension are the strongest and more reliable clinical predictors of an unfavorable outcome. However, analysis of the prognostic value of morphological lesions was more difficult because they have been characterized in some studies using an overall score or histological classes of progressively more severe involvement and, in others, using a semiquantitative grading of individual glomerular, tubular, interstitial, and vascular changes. In adult patients, a high score of glomerular and tubulointerstitial lesions, corresponding to classes IV and V of the Lee or Haas classifications, predicted a more rapid progression. When single lesions were analyzed separately, glomerulosclerosis and interstitial fibrosis appeared to be the strongest, most reliable predictors of unfavorable prognosis. More controversial was the role of crescents and capsular adhesions. None of the immunohistological features was found to be a risk factor for progression in the more accurate statistical analyses. The same histological features predicted outcome in children, although the severity of lesions at the time of biopsy was usually less than that in adults. However, in the single patient, even the evaluation of these prognostic markers sometimes fails to correctly predict outcome, probably because of the heterogeneity of the disease and the discontinuous activity of some injuring mechanisms during its course.
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                Author and article information

                Contributors
                +81-3-58021065 , +81-3-58021065 , yasu@juntendo.ac.jp
                Journal
                Clin Exp Nephrol
                Clin. Exp. Nephrol
                Clinical and Experimental Nephrology
                Springer Japan (Tokyo )
                1342-1751
                1437-7799
                30 January 2014
                30 January 2014
                2014
                : 18
                : 5
                : 770-777
                Affiliations
                [ ]Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, Japan
                [ ]Department of Nephrology, Sendai Shakaihoken Hospital, Tutumi-cho 3-16-1, Aoba-ku, Sendai, Miyagi Japan
                [ ]Hotta Osamu Clinic, Rokuchonome Minami-cho 2-39, Wakabayashi-ku, Sendai, Miyagi Japan
                [ ]Faculty of Medicine, Clinical Research Center, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo, Japan
                [ ]Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL USA
                Article
                921
                10.1007/s10157-013-0921-6
                4194014
                24477513
                b02822c8-b070-41cc-b06b-e09f076f172b
                © The Author(s) 2014

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 29 November 2012
                : 27 November 2013
                Categories
                Original Article
                Custom metadata
                © Japanese Society of Nephrology 2014

                Nephrology
                iga nephropathy,disease activity,underglycosylated iga,immune complex,biomarker
                Nephrology
                iga nephropathy, disease activity, underglycosylated iga, immune complex, biomarker

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