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      A comparison of the effectiveness of cyclophosphamide, leflunomide, corticosteroids, or conservative management alone in patients with IgA nephropathy: a retrospective observational study

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          Abstract

          To compare the long-term efficacy of corticosteroids (P) alone or in combination with cyclophosphamide (CTX), leflunomide (LEF), or Angiotensin-convertase inhibitors or angiotensin II receptor blockers (ACEI/ARB) in treatment for IgA nephropathy (IgAN), 311 patients with IgAN were identified. Therapeutic effectiveness (including progression, partial remission, complete remission) and combined renal endpoint (defined as 30% reduction in eGFR or ESRD) were compared based on different therapies. After immunosuppressive and ACEI/ARB treatment, the levels of eGFR, proteinuria and albumin were significantly improved at the last follow-up, the extent of improvement of eGFR, proteinuria, and albumin was more notable in P + CTX group and P + LEF group. 41%, 52.2%, 55.3% and 55.2% in P + CTX, P + LEF, P and ACEI/ARB group achieved complete remission, respectively. Multivariate regression analysis indicated that only proteinuria (Relative risk (RR) 0.82(0.72–0.94), P = 0.004) and tubular atrophy/interstitial fibrosis (RR 0.26(0.13–0.57), P = 0.001) were predictors for complete remission. The optimal cutoffs of eGFR was 47.085 ml/min/1.73 m 2 predicting renal function recovery in P + CTX therapy. In conclusion, tubular atrophy/interstitial fibrosis and massive proteinuria were poor predictors for complete remission in IgAN, it appears as though patients may have benefited from immunosuppressive treatment but that comparison to a well-matched contemporary control group or, ideally, a randomized controlled clinical trial, would be required to show this.

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          Most cited references39

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          IgA nephropathy.

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            Long-term renal survival and related risk factors in patients with IgA nephropathy: results from a cohort of 1155 cases in a Chinese adult population.

            We sought to identify the long-term renal survival rate and related risk factors of progression to renal failure in Chinese adult patients with IgA nephropathy (IgAN) and to quantify the effects of proteinuria during the follow-up on outcome in patients with IgAN. Patients with biopsy-proven primary IgAN in the Nanjing Glomerulonephritis Registry were studied. Renal survival and the relationships between clinical parameters and renal outcomes were assessed. One thousand one hundred and fifty-five patients were enrolled in this study. The 10-, 15- and 20-year cumulative renal survival rates, calculated by Kaplan-Meier method, were 83, 74 and 64%, respectively. At the time of biopsy, proteinuria>1.0 g/day [hazard ratio (HR) 3.2, P 1.0 g/day were associated with a 9.4-fold risk than patients with TA-P<1.0 g/day (P<0.001) and 46.5-fold risk than those with TA-P<0.5 g/day (P<0.001). Moreover, patients who achieved TA-P<0.5 g/day benefit much more than those with TA-P between 0.5 and 1.0 g/day (HR 13.1, P<0.001). Thirty-six percent of Chinese adult patients with IgAN progress to end stage renal disease within 20 years. Five clinical features-higher proteinuria, hypertension, impaired renal function, hypoproteinemia and hyperuricemia-are independent predictors of an unfavorable renal outcome. The basic goal of anti-proteinuric therapy for Chinese patients is to lower proteinuria<1.0 g/day and the optimal goal is to lower proteinuria to <0.5 g/day.
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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
                guisenli@163.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                12 September 2018
                12 September 2018
                2018
                : 8
                : 13662
                Affiliations
                ISNI 0000 0004 0369 4060, GRID grid.54549.39, Renal Division and Institute of Nephrology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, , Medical School of University of Electronic Science and Technology of China, ; Chengdu, 610072 China
                Author information
                http://orcid.org/0000-0003-1970-9979
                Article
                31727
                10.1038/s41598-018-31727-5
                6135814
                30209279
                0c51a260-69af-4a07-9e3c-58c343851a32
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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                : 12 July 2017
                : 6 August 2018
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