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      Demographic, clinical characteristics and treatment outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulonephritis in Japan: A retrospective analysis of data from the Japan Renal Biopsy Registry

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          Abstract

          The reclassification of membranoproliferative glomerulonephritis (MPGN) into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) based on immunofluorescence findings in kidney biopsies has provided insights into these two distinct diseases. C3G is further classified into dense deposit disease and C3 glomerulonephritis (C3GN) based on electron micrographic findings. Although these diseases have poor outcomes, limited Japanese literature confined to small, single-center cohorts exist on these diseases. We retrospectively analyzed 81 patients with MPGN type I and III from 15 hospitals in the Japan Renal Biopsy Registry to compare demographic, clinical characteristics and treatment outcomes of patients with IC-MPGN to those with C3GN. Of the 81 patients reviewed by immunofluorescence findings in kidney biopsies, 67 patients had IC-MPGN and 14 patients had C3GN. Age at diagnosis and systolic and diastolic pressure were higher and proteinuria and impaired renal function were significantly more prevalent in patients with IC-MPGN than those with C3GN. About 80% of the patients in both groups were treated with immunosuppressive therapy. At last follow-up (median 4.8 years), complete remission rate of proteinuria was significantly higher in patients with C3GN (64.3%) than in those with IC-MPGN (29.9%; P = 0.015). The renal survival rate was lower in patients with IC-MPGN when compared to C3GN (73.1% vs. 100%; log-rank, P = 0.031). Systolic blood pressure and renal function at baseline were independent predictors of progression to end-stage kidney disease. The overall prognosis of patients with C3GN is more favorable than for patients with IC-MPGN.

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          Revised equations for estimated GFR from serum creatinine in Japan.

          Estimation of glomerular filtration rate (GFR) is limited by differences in creatinine generation among ethnicities. Our previously reported GFR-estimating equations for Japanese had limitations because all participants had a GFR less than 90 mL/min/1.73 m2 and serum creatinine was assayed in different laboratories. Diagnostic test study using a prospective cross-sectional design. New equations were developed in 413 participants and validated in 350 participants. All samples were assayed in a central laboratory. Hospitalized Japanese patients in 80 medical centers. Patients had not participated in the previous study. Measured GFR (mGFR) computed from inulin clearance. Estimated GFR (eGFR) by using the modified isotope dilution mass spectrometry (IDMS)-traceable 4-variable Modification of Diet in Renal Disease (MDRD) Study equation using the previous Japanese Society of Nephrology Chronic Kidney Disease Initiative (JSN-CKDI) coefficient of 0.741 (equation 1), the previous JSN-CKDI equation (equation 2), and new equations derived in the development data set: modified MDRD Study using a new Japanese coefficient (equation 3), and a 3-variable Japanese equation (equation 4). Performance of equations was assessed by means of bias (eGFR - mGFR), accuracy (percentage of estimates within 15% or 30% of mGFR), root mean squared error, and correlation coefficient. In the development data set, the new Japanese coefficient was 0.808 (95% confidence interval, 0.728 to 0.829) for the IDMS-MDRD Study equation (equation 3), and the 3-variable Japanese equation (equation 4) was eGFR (mL/min/1.73 m2) = 194 x Serum creatinine(-1.094) x Age(-0.287) x 0.739 (if female). In the validation data set, bias was -1.3 +/- 19.4 versus -5.9 +/- 19.0 mL/min/1.73 m2 (P = 0.002), and accuracy within 30% of mGFR was 73% versus 72% (P = 0.6) for equation 3 versus equation 1 and -2.1 +/- 19.0 versus -7.9 +/- 18.7 mL/min/1.73 m(2) (P < 0.001) and 75% versus 73% (P = 0.06) for equation 4 versus equation 2 (P = 0.06), respectively. Most study participants had chronic kidney disease, and some may have had changing GFRs. The new Japanese coefficient for the modified IDMS-MDRD Study equation and the new Japanese equation are more accurate for the Japanese population than the previously reported equations.
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            Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference.

            In both atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) complement plays a primary role in disease pathogenesis. Herein we report the outcome of a 2015 Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference where key issues in the management of these 2 diseases were considered by a global panel of experts. Areas addressed included renal pathology, clinical phenotype and assessment, genetic drivers of disease, acquired drivers of disease, and treatment strategies. In order to help guide clinicians who are caring for such patients, recommendations for best treatment strategies were discussed at length, providing the evidence base underpinning current treatment options. Knowledge gaps were identified and a prioritized research agenda was proposed to resolve outstanding controversial issues.
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              C3 glomerulopathy: consensus report

              C3 glomerulopathy is a recently introduced pathological entity whose original definition was glomerular pathology characterized by C3 accumulation with absent or scanty immunoglobulin deposition. In August 2012, an invited group of experts (comprising the authors of this document) in renal pathology, nephrology, complement biology, and complement therapeutics met to discuss C3 glomerulopathy in the first C3 Glomerulopathy Meeting. The objectives were to reach a consensus on: the definition of C3 glomerulopathy, appropriate complement investigations that should be performed in these patients, and how complement therapeutics should be explored in the condition. This meeting report represents the current consensus view of the group.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Funding acquisitionRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 September 2021
                2021
                : 16
                : 9
                : e0257397
                Affiliations
                [1 ] Division of Cardiology, Nephrology, Pulmonology and Neurology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Japan
                [2 ] Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
                [3 ] Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya, Japan
                [4 ] Clinical Pharmacology and Therapeutics, Tohoku University, Graduate School of Pharmaceutical Sciences, Sendai, Japan
                [5 ] Department of Nephrology and Rheumatology, Iwate Prefectural Central Hospital, Morioka, Japan
                [6 ] Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
                [7 ] Faculty of Medicine, Department of Hemovascular Medicine and Artificial Organs, University of Miyazaki, Miyazaki, Japan
                [8 ] Department of Pediatric Nephrology, Tokyo Women’s Medical University, Tokyo, Japan
                [9 ] Department of Pediatrics, National Hospital Organization Chibahigashi National Hospital, Chiba, Japan
                [10 ] Department of Pediatric Nephrology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
                [11 ] Faculty of Medicine, Department of Nephrology, Juntendo University, Tokyo, Japan
                [12 ] Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
                [13 ] Department of Nephrology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
                [14 ] Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
                [15 ] Department of Nephrology and Rheumatology, Gunma University Graduate School of Medicine, Maebashi, Japan
                [16 ] Health and Counseling Center, Osaka University, Toyonaka, Japan
                [17 ] Department of Nephrology, Kanazawa Medical University School of Medicine, Uchinada, Japan
                [18 ] Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
                [19 ] Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan
                Shizuoka General Hospital: Shizuoka Kenritsu Sogo Byoin, JAPAN
                Author notes

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

                Author information
                https://orcid.org/0000-0002-5398-3667
                Article
                PONE-D-21-21696
                10.1371/journal.pone.0257397
                8439563
                34520493
                ce8877a1-bf4f-4784-be1a-1bbb27e90ad0
                © 2021 Nakagawa 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
                : 2 July 2021
                : 1 September 2021
                Page count
                Figures: 3, Tables: 5, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003478, ministry of health, labour and welfare;
                Award ID: 20FC1045
                Award Recipient :
                This study was supported in part by a Grant-in-Aid for Intractable Renal Diseases Research, Research on rare and intractable diseases, Health and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare of Japan (20FC1045). There was no additional external funding received for this study.
                Categories
                Research Article
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Steroid Therapy
                Medicine and Health Sciences
                Nephrology
                Renal Diseases
                Chronic Kidney Disease
                Biology and Life Sciences
                Anatomy
                Renal System
                Medicine and Health Sciences
                Anatomy
                Renal System
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Biopsy
                Medicine and Health Sciences
                Nephrology
                Glomerulonephritis
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
                Proteinuria
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Complement System
                Biology and Life Sciences
                Immunology
                Immune System
                Complement System
                Medicine and Health Sciences
                Immunology
                Immune System
                Complement System
                Biology and Life Sciences
                Immunology
                Immune System Proteins
                Complement System
                Medicine and Health Sciences
                Immunology
                Immune System Proteins
                Complement System
                Biology and Life Sciences
                Biochemistry
                Proteins
                Immune System Proteins
                Complement System
                Custom metadata
                All relevant data are within the manuscript and its Supporting information files.

                Uncategorized
                Uncategorized

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