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      Corticosteroids in Patients with IgA Nephropathy and Severe Chronic Renal Damage

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          Abstract

          Little is known about the utility of treating patients with advanced IgA nephropathy (IgAN). From 2001 to 2005, four patients came to our observation because of serum creatinine higher than 3 mg/dL, proteinuria ranging from 1.8 to 5.1 g/day, and a histological picture of diffuse sclerotic lesions. A corticosteroid course of 12 months was given. Patients were observed for a mean follow up of 84 months. At the end of the steroid course, proteinuria lowered quickly below 1 g/day in two patients, whereas the other two experienced a slower and less persistent decrease of proteinuria. Despite similar lesion severity at renal biopsy, renal function stabilized only in these two ones. In conclusion, these preliminary observations suggest a possible efficacy of corticosteroids in slowing down the progression of renal disease and in postponing the need of dialysis in IgAN patients with stage IV CKD and severe chronic histological lesions.

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          Most cited references 32

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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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            Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases.

            IgA nephropathy (IgAN) may present with a wide variety of histologic patterns on renal biopsy, ranging from a minimal lesion to a diffuse proliferative glomerulonephritis (GN). The histologic features of 244 cases of IgAN (not including Schönlein-Hanoch nephritis) diagnosed between 1980 and 1994 were reviewed, and each case was subclassified using the following, relatively simple histologic classification scheme: subclass I (39 cases): minimal or no mesangial hypercellularity, without glomerular sclerosis; subclass II (18 cases): focal and segmental glomerular sclerosis without active cellular proliferation; subclass III (110 cases): focal proliferative GN; and subclass IV (42 cases): diffuse proliferative GN; and subclass V (35 cases): any biopsy showing > or = 40% globally sclerotic glomeruli and/or > or = 40% estimated cortical tubular atrophy or loss. Subsequent analysis of renal survival in 109 patients who underwent biopsy before or during 1992 for whom such data were available showed a strong, statistically significant correlation between histologic subclass and renal survival, with an order I, II (greatest survival) > III > IV, V. Crescents were a significant negative prognostic indicator for renal survival in subclass III (but not in subclass IV), and interstitial expansion was a negative prognostic indicator in subclasses III and IV, although the statistical significance of these were not maintained after controlling for serum creatinine at the time of biopsy. The presence of peripheral glomerular capillary deposits ultrastructurally had no prognostic significance. With respect to clinical presentation, hypertension (systolic blood pressure > or = 130 mm Hg and diastolic blood pressure > or = 90 mm Hg) and proteinuria of > or = 2.0 g/24 hr were significant negative prognostic indicators for renal survival, even when controlling for serum creatinine at the time of renal biopsy. The presence of gross hematuria correlated significantly with increased renal survival by univariate analysis, but not when controlling for serum creatinine at the time of renal biopsy. The findings of this study confirm the wide variety of clinical and histopathologic presentations of IgAN, and indicate the utility of the proposed histologic classification schema in assessing a patient's likelihood of ultimately developing end-stage renal disease.
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              Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy.

              Immunoglobulin A nephropathy (IgAN) is the most common cause of chronic renal failure among primary glomerulonephritis patients. The best treatment for IgAN remains poorly defined. We planned a long-term, prospective, open-label, multicentre, centrally randomized controlled trial to assess whether the combination of prednisone and ramipril was more effective than ramipril alone in patients with proteinuric IgAN. Ninety-seven biopsy-proven IgAN patients with moderate histologic lesions, 24-h proteinuria > or =1.0 g and estimated glomerular filtration rate (eGFR) > or = 50 ml/min/ 1.73 m(2) were randomly allocated to receive a 6-month course of oral prednisone plus ramipril (combination therapy group) or ramipril alone (monotherapy group) for the total duration of follow-up. The primary outcome was the progression of renal disease defined as the combination of doubling of baseline serum creatinine or end-stage kidney disease (ESKD). The secondary outcomes were the rate of renal function decline defined as the eGFR slope over time, and the reduction of 24-h proteinuria. After a follow-up of up to 96 months, 13/49 (26.5%) patients in the monotherapy group reached the primary outcome compared with 2/48 (4.2%) in the combination therapy group. The Kaplan-Meier analysis showed a significantly higher probability of not reaching the combined outcome in the combination therapy group than in the monotherapy group (85.2% versus 52.1%; log-rank test P = 0.003). In the multivariate analysis, baseline serum creatinine and 24-h proteinuria were independent predictors of the risk of primary outcome; treatment with prednisone plus ramipril significantly reduced the risk of renal disease progression (hazard ratio 0.13; 95% confidence interval 0.03-0.61; P = 0.01). The mean rate of eGFR decline was higher in the monotherapy group than in the combination therapy group (-6.17 +/- 13.3 versus -0.56 +/- 7.62 ml/min/ 1.73 m(2)/year; P = 0.013). Moreover, the combined treatment reduced 24-h proteinuria more than ramipril alone during the first 2 years. Our results suggest that the combination of corticosteroids and ramipril may provide additional benefits compared with ramipril alone in preventing the progression of renal disease in proteinuric IgAN patients in the long-term follow-up.
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                Author and article information

                Journal
                Case Rep Nephrol
                Case Rep Nephrol
                CRIM.NEPHROLOGY
                Case reports in nephrology
                Hindawi Publishing Corporation
                2090-6641
                2090-665X
                2012
                10 October 2012
                : 2012
                Affiliations
                1Department of Nephrology and Dialysis, “Bassini” Hospital, Via Gorki 50, 20092 Cinisello Balsamo, Italy
                2Department of Nephrology, Dialysis, and Renal Transplant, Alessandro Manzoni Hospital, Via dell'Eremo 9, 23900 Lecco, Italy
                Author notes

                Academic Editors: K. C. Siamopoulos and L. Zuo

                Article
                10.1155/2012/180691
                3914212
                Copyright © 2012 Claudio Pozzi et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Case Report

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