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      Seasonal proteinuria changes in IgA nephropathy patients after proteinuria remission

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          Abstract

          Background

          Proteinuria is a powerful prognostic factor for end-stage renal disease in IgA nephropathy (IgAN) patients. However, it is not known whether proteinuria exacerbations are related to seasonal changes.

          Methods

          We retrospectively enrolled consecutive patients diagnosed with IgAN by kidney biopsy at our hospital between 2002 and 2014. Proteinuria remission was defined as urinary protein <0.3 g/gCr in two consecutive outpatient urinalyses and exacerbation as urinary protein ≥0.75 g/gCr. Four seasons were defined: spring (March–May), summer (June–August), autumn (September–November), and winter (December–February). We performed a multivariate analysis to identify factors associated with the second remission following a proteinuria exacerbation.

          Results

          We analyzed 116 patients. Proteinuria remission and exacerbation occurred in 77, and 43 patients, respectively. The incidence of proteinuria exacerbation was significantly higher in autumn and winter than in spring and summer (p = 0.040). The cumulative second remission rate was significantly higher in patients with autumn and winter proteinuria exacerbation than in patients with spring and summer exacerbations (p = 0.0091). In multivariate analyses, exacerbation onset in autumn and winter (hazard ratio [HR], 3.51; 95% confidence interval [CI], 1.41–8.74) and intensive therapy (HR, 2.26; 95% CI, 1.05–4.88) were significantly associated with a second proteinuria remission.

          Conclusion

          In IgAN patients in proteinuria remission, proteinuria exacerbation frequently occurred in autumn and winter. Exacerbations occurring in autumn and winter tended to remit early.

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          Most cited references20

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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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            The commonest glomerulonephritis in the world: IgA nephropathy.

            G D'Amico (1987)
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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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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draft
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – review & editing
                Role: Formal analysisRole: Writing – review & editing
                Role: Project administrationRole: Writing – review & editing
                Role: Project administration
                Role: Project administration
                Role: Project administration
                Role: Formal analysisRole: Project administration
                Role: Project administration
                Role: Project administration
                Role: Project administration
                Role: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2 November 2017
                2017
                : 12
                : 11
                : e0187607
                Affiliations
                [1 ] Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
                [2 ] Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan
                Kawasaki Ika Daigaku, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ These authors also contributed equally to this work.

                Author information
                http://orcid.org/0000-0001-7366-0868
                Article
                PONE-D-17-25441
                10.1371/journal.pone.0187607
                5667876
                29095887
                189edcb1-9330-44be-bec2-ccf84e2f4ac7
                © 2017 Inagaki et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 6 July 2017
                : 23 October 2017
                Page count
                Figures: 1, Tables: 3, Pages: 11
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004948, Astellas Pharma;
                Funded by: funder-id http://dx.doi.org/10.13039/100006396, Alexion Pharmaceuticals;
                Funded by: funder-id http://dx.doi.org/10.13039/501100007132, Otsuka Pharmaceutical;
                Funded by: funder-id http://dx.doi.org/10.13039/501100004095, Kyowa Hakko Kirin;
                Funded by: funder-id http://dx.doi.org/10.13039/501100002973, Daiichi-Sankyo;
                Funded by: funder-id http://dx.doi.org/10.13039/100008373, Takeda Pharmaceutical Company;
                Funded by: funder-id http://dx.doi.org/10.13039/100010795, Chugai Pharmaceutical;
                Funded by: funder-id http://dx.doi.org/10.13039/501100002975, Dainippon Sumitomo Pharma;
                Funded by: funder-id http://dx.doi.org/10.13039/100010793, Pfizer Japan;
                Funded by: funder-id http://dx.doi.org/10.13039/100009947, Merck Sharp and Dohme;
                Funded by: funder-id http://dx.doi.org/10.13039/501100004820, Mochida Pharmaceutical Company;
                Funded by: Torii Pharmaceutical Co., Ltd
                Funded by: Kissei Pharmaceutical Co
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100008792, Novartis Pharma;
                Award Recipient :
                Funded by: Kowa Pharmaceutical
                Award Recipient :
                Funded by: Nippon Boehringer Ingelheim
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100002491, Bristol-Myers Squibb;
                Award Recipient :
                Funded by: Mitsubishi Tanabe Pharma Corporation
                Award Recipient :
                Funded by: Teijin Pharma Limited
                Award Recipient :
                Nagoya university nephrology is supported by the following funders; Astellas Pharma, Alexion Pharmaceuticals, Otsuka Pharmaceutical, Kyowa Hakko Kirin, Daiichi-Sankyo, Takeda Pharmaceutical Company, Chugai Pharmaceutical, Dainippon Sumitomo Pharma, Pfizer Japan, Merck Sharp and Dohme, Mochida Pharmaceutical Company, Torii Pharmaceutical, Kissei Pharmaceutical, Novartis Pharma, Kowa Pharmaceutical, Nippon Boehringer Ingelheim, Bristol-Myers Squibb, Mitsubishi Tanabe Pharma Corporation, and Teijin Pharma Limited. However, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Proteinuria
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Proteinuria
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Biopsy
                Biology and Life Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Otolaryngological Procedures
                Tonsillectomy
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Hypertension
                Biology and Life Sciences
                Anatomy
                Histology
                Medicine and Health Sciences
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                Earth Sciences
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                Meteorology
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