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      A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy

      research-article
      1 , 2 , 1 , 1 , 3 , 1 , 4 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 5 , 6 , 6 , 7 , 3 , 3 , 8 , 9 , 10 , 11 , 12 , 12 , 13 , 14 , 15 , 16 , 6 , The Special IgA Nephropathy Study Group
      Nephrology Dialysis Transplantation
      Oxford University Press
      clinical remission, estimated glomerular filtration rate, hematuria, proteinuria

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          Abstract

          Background

          The study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN).

          Methods

          Patients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria.

          Results

          During 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent factor contributing to the disappearance of proteinuria (odds ratio 2.98, 95% CI 1.01–8.83, P = 0.049), but did not identify an independent factor in achieving the disappearance of hematuria or clinical remission.

          Conclusions

          The results indicate tonsillectomy combined with steroid pulse therapy has no beneficial effect over steroid pulses alone to attenuate hematuria and to increase the incidence of clinical remission. Although the antiproteinuric effect was significantly greater in combined therapy, the difference was marginal, and its impact on the renal functional outcome remains to be clarified.

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          Most cited references27

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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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            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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              Predicting progression in IgA nephropathy.

              Immunoglobulin A (IgA) nephropathy is one of the most common primary types of glomerulonephritis to progress to end-stage renal disease. Its variable and often long natural history makes it difficult to predict outcome. We investigated the association of the rate of renal function decline based on the slope of creatinine clearance over time with demographic, clinical, laboratory, and histological data from 298 patients with biopsy-proven IgA nephropathy with a mean follow-up of 70 months. Using univariate analysis, urinary protein excretion at baseline and Lee pathological grading, as well as mean arterial pressure (MAP) and urinary protein excretion during follow-up, were associated with the rate of deterioration in renal function. Of these, only MAP and urinary protein excretion during follow-up were identified as independent factors by multiple linear regression analysis. The combination of best accuracy of prediction and shortest observation time using these two parameters was reached between the second and third years of follow-up. A semiquantitative method of estimating the rate of progression by using these factors was developed. These results indicate that MAP and severity of proteinuria over time are the most important prognostic indicators of IgA nephropathy. The potential relevance of the algorithm in patient management is shown.
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                Author and article information

                Journal
                Nephrol Dial Transplant
                Nephrol. Dial. Transplant
                ndt
                ndt
                Nephrology Dialysis Transplantation
                Oxford University Press
                0931-0509
                1460-2385
                August 2014
                03 March 2014
                03 March 2014
                : 29
                : 8
                : 1546-1553
                Affiliations
                [1 ]Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine , Tokyo, Japan
                [2 ]Department of Internal Medicine, Kanazawa Medical Centre , Kanazawa, Japan
                [3 ]Division of Kidney and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine , Kawasaki, Japan
                [4 ]Division of Clinical Epidemiology, Research Center for Medical Science, Jikei University School of Medicine , Tokyo, Japan
                [5 ]Second Department of Internal Medicine, Nagasaki University Hospital of Medicine and Dentistry , Nagasaki, Japan
                [6 ]Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine , Tokyo, Japan
                [7 ]Division of Nephrology, Department of Medicine, Showa University School of Medicine , Tokyo, Japan
                [8 ]Department of Internal Medicine, Chiba-East Hospital , Chiba, Japan
                [9 ]Division of Kidney and Hypertension, Department of Internal Medicine, Saitama University Medical Centre , Saitama, Japan
                [10 ]Department of Internal Medicine, National Hospital Organization, Osaka National Hospital , Osaka, Japan
                [11 ]Department of Internal Medicine, Teine Keijinkai Hospital , Sapporo, Japan
                [12 ]Division of Nephrology and Rheumatology, Department of Internal Medicine, Aichi Medical University School of Medicine , Nagakute, Aichi, Japan
                [13 ]Department of Internal Medicine, Fuji City Central Hospital , Fuji, Japan
                [14 ]Department of Internal Medicine, Iwate Prefectural Central Hospital , Morioka, Japan
                [15 ]Department of Internal Medicine, Faculty of Medicine, University of Miyazaki , Miyazaki, Japan
                [16 ]Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Nagoya , Nagoya, Japan
                Author notes
                Correspondence and offprint requests to: Tetsuya Kawamura; E-mail: kawatetu@ 123456coral.ocn.ne.jp
                Article
                gfu020
                10.1093/ndt/gfu020
                4106640
                24596084
                440e3ca5-2442-4632-b3c3-01b6fbc05e07
                © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 25 October 2013
                : 17 January 2014
                Categories
                CLINICAL SCIENCE
                Chronic Kidney Disease

                Nephrology
                clinical remission,estimated glomerular filtration rate,hematuria,proteinuria
                Nephrology
                clinical remission, estimated glomerular filtration rate, hematuria, proteinuria

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