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      Distinct characteristics and outcomes in elderly-onset IgA vasculitis (Henoch-Schönlein purpura) with nephritis: Nationwide cohort study of data from the Japan Renal Biopsy Registry (J-RBR)

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          Abstract

          Background

          The clinical presentation and prognosis of adult and elderly patients with IgA vasculitis (Henoch-Schönlein purpura) accompanied by nephritis (IgAV-N) have not been investigated in detail. We therefore surveyed the features and outcomes of IgAV-N based on nationwide data derived from the Japan Renal Biopsy Registry (J-RBR).

          Methods

          This multi-center cohort study compared the clinicopathological parameters at diagnosis, initial therapies and outcomes between 106 adult (age 19–64 years) and 46 elderly (≥65 years) patients with IgAV-N who were registered in the J-RBR between 2007 and 2012. The primary end-points comprised a 50% increase in serum creatinine (sCr) values or end-stage kidney disease. Factors affecting a decrease in renal function were assessed using Cox proportional hazards models.

          Results

          Rates of hypertension, impaired renal function, hypoalbuminemia and crescentic glomerulonephritis were significantly higher among the elderly, than the adult patients. About 80% and 60% of the patients in both groups were respectively treated with corticosteroid and a renin-angiotensin system (RAS) blockade. Both groups had favorable renal survival rates for nine years (93.6% and 91.4% of the adult and elderly patients, respectively). Significantly more elderly than adult patients developed a 50% increase in sCr during a mean observation period of 3.9 years (21.7% vs. 4.7%, p = 0.012), and significantly fewer elderly, than adult patients achieved clinical remission (23.9% vs. 46.2%, p = 0.016). Multivariate analysis selected advanced age (≥65 years) and lower serum albumin values as independent prognostic factors for a decline in renal function, whereas steroid pulse therapy helped to preserve renal function.

          Conclusions

          The renal prognosis of adult and elderly patients with IgAV-N was favorable when treated aggressively with corticosteroid and RAS blockade. However, the course of renal function should be carefully monitored in patients aged over 65 years and those with hypoalbuminemia.

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          Most cited references24

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          Henoch-Schönlein Purpura in adults: outcome and prognostic factors.

          Henoch-Schönlein Purpura nephritis (HSPN) has been extensively studied in children but, its natural history in adults is much less known. A cohort of 250 adults suffering HSP was retrospectively analyzed for a median follow-up period of 14.8 yr. All patients had biopsies consistent with HSP (predominant IgA mesangial deposits) associated with purpura, bowel angina, and/or abdominal pain. At presentation, palpable purpura was present in 96% of patients, and arthritis was reported in 61%, and gastrointestinal involvement in 48%. Thirty-two percent of the patients showed renal insufficiency (Creatinine clearance [CrCl] <50 ml/min), usually associated with proteinuria (99%) and/or hematuria (93%). Endocapillary glomerulonephritis was the most frequent lesion on renal biopsy (61%). At the end of follow-up, patient survival was only 74%. The first cause of death was carcinoma (most of them of respiratory or digestive tract). Regarding renal function, 11% of patients reached end-stage renal failure, 13% exhibited severe renal failure (CrCl <30 ml/min), and 14% moderate renal insufficiency (CrCl <50 ml/min). Clinical remission defined as the absence of proteinuria, hematuria, and a normal renal function was achieved in only 20%. This is a retrospective study; therefore, it is not possible to demonstrate any steroid and/or cyclophosphamide efficacy in diminishing the incidence of renal insufficiency. Multivariate analysis demonstrated that renal function impairment and proteinuria level at presentation and, on renal biopsy, the degree of interstitial fibrosis, percentage of sclerotic glomeruli, and presence of glomeruli with fibrinoid necrosis were associated with a poor renal prognosis. The data indicate that clinical presentation of HSPN in adults is severe and its outcome relatively poor, worse than in children. Identification of clinical and histologic prognostic factors may permit the design of appropriate therapeutic prospective studies.
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            IgA nephropathy and IgA vasculitis with nephritis have a shared feature involving galactose-deficient IgA1-oriented pathogenesis

            Galactose-deficient IgA1 has been proposed as an important effector molecule in IgA nephropathy (IgAN). We previously showed that the galactose-deficient IgA1-specific monoclonal antibody KM55 can detect circulating galactose-deficient IgA1 in patients with IgAN, enabling us to study the molecular roles of galactose-deficient IgA1. Herein, we further examined the pathophysiological significance of galactose-deficient IgA1 in glomerular deposits of patients with IgAN by immunohistochemistry using KM55. Immunostaining of galactose-deficient IgA1 with KM55 was performed in paraffin-embedded sections of renal biopsy specimens from 48 patients with IgAN and 49 patients with other renal diseases such as lupus nephritis, HCV-related nephropathy, IgA vasculitis with nephritis (IgA-VN), and membranous nephropathy. Glomerular galactose-deficient IgA1 was specifically detected in IgAN and IgA-VN but not in the other renal diseases. Galactose-deficient IgA1 was localized predominantly in the mesangial region as IgA deposition. However, galactose-deficient IgA1 was not detected in patients with lupus nephritis accompanied by glomerular IgA deposition. Thus, our study strongly suggests that IgAN and IgA-VN have a shared feature regarding galactose-deficient IgA1-oriented pathogenesis.
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              IgA vasculitis (Henoch-Shönlein purpura) in adults: Diagnostic and therapeutic aspects.

              Immunoglobulin A (IgA) vasculitis, formerly called Henoch-Schönlein purpura, is an immune complex vasculitis affecting small vessels with dominant IgA deposits. Clinical manifestations mainly involve cutaneous purpura, arthralgias and/or arthritis, acute enteritis and glomerulonephritis. IgA vasculitis is more common among children than adults, with more severe disease in adults. Gastrointestinal and renal involvements represent the principal causes of morbidity and mortality in adults. Factors associated with long-term end-stage renal disease (ESRD) include baseline renal function impairment and baseline proteinuria >1 or 1.5 g/day, and on renal biopsy degree of interstitial fibrosis, sclerotic glomeruli and fibrinoid necrosis. Management of IgA vasculitis in adults is rendered difficult for clinicians because of the absence of correlation between initial presentation and long-term renal outcome, and the possible occurrence of spontaneous remission in patients with severe presentation or, in contrast, possible evolution to ESRD in patients with mild symptoms. Treatment is often symptomatic because disease course is usually benign. Treatment of severe involvement, including severe gastrointestinal complications or proliferative glomerulonephritis, remains controversial, with no evidence that corticosteroids or immunosuppressive agents improved long-term outcome. Prospective, randomized, controlled trials are thus needed to analyze the benefit-risk ratio of such treatments.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: Validation
                Role: ConceptualizationRole: MethodologyRole: Project administrationRole: Supervision
                Role: Data curationRole: Investigation
                Role: Data curationRole: Investigation
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Supervision
                Role: Data curationRole: Investigation
                Role: Data curationRole: InvestigationRole: Supervision
                Role: Data curationRole: Investigation
                Role: Data curationRole: Investigation
                Role: Data curationRole: Investigation
                Role: Data curationRole: Investigation
                Role: Data curationRole: Investigation
                Role: Data curationRole: Investigation
                Role: Data curationRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Validation
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                8 May 2018
                2018
                : 13
                : 5
                : e0196955
                Affiliations
                [1 ] Department of Nephrology, University of Miyazaki Hospital, Miyazaki, Japan
                [2 ] Department of Hemovascular Medicine and Artificial Organs, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
                [3 ] Department of Nephrology, Nagoya University Graduate School of Medicine, Aichi, Japan
                [4 ] Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
                [5 ] Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama, Japan
                [6 ] Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
                [7 ] Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan
                [8 ] Department of Nephrology and Rheumatology, Iwate Prefectural Central Hospital, Iwate, Japan
                [9 ] Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan
                [10 ] Division of Nephrology and Hypertension, Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan
                [11 ] Department of Nephrology, Nagasaki University Hospital, Nagasaki, Japan
                [12 ] Department of Nephrology, Sendai Shakai Hoken Hospital, Sendai, Japan
                [13 ] Division of Clinical Nephrology and Rheumatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
                [14 ] Division of Nephrology, Kanazawa Medical University School of Medicine, Ishikawa, Japan
                INSERM1163, FRANCE
                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/0000-0001-7557-2204
                http://orcid.org/0000-0002-4127-6471
                Article
                PONE-D-18-06625
                10.1371/journal.pone.0196955
                5940189
                29738576
                7fea810f-911b-4cbf-be2c-6ed2561fae1a
                © 2018 Komatsu 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 March 2018
                : 23 April 2018
                Page count
                Figures: 3, Tables: 4, Pages: 14
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100005123, Japanese Society of Nephrology;
                Award ID: JRBR-20
                Award Recipient :
                This study was supported in part by the Japanese Society of Nephrology, by a Grant-in-Aid for Intractable Renal Diseases Research, Research on Rare and Intractable Diseases, and by Health and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare of Japan.
                Categories
                Research Article
                Medicine and Health Sciences
                Geriatrics
                People and Places
                Population Groupings
                Age Groups
                Elderly
                Biology and Life Sciences
                Anatomy
                Renal System
                Medicine and Health Sciences
                Anatomy
                Renal System
                Medicine and Health Sciences
                Geriatrics
                Geriatric Nephrology
                Medicine and Health Sciences
                Nephrology
                Geriatric Nephrology
                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
                Pharmaceutics
                Drug Therapy
                Steroid Therapy
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Steroid Therapy
                Corticosteroid Therapy
                Biology and Life Sciences
                Biochemistry
                Proteins
                Albumins
                Serum Albumin
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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