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      Outcome of Patients with Primary Immune-Complex Type Mesangiocapillary Glomerulonephritis (MCGN) in Cape Town South Africa

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          Abstract

          Background and Aim

          Mesangiocapillary glomerulonephritis (MCGN) is a common cause of chronic kidney disease in developing countries. Data on the renal outcome of patients with idiopathic MCGN is limited. The aim of this study is to investigate the outcome of patients with idiopathic MCGN presenting to the Groote Schuur Hospital (GSH) Renal Unit in Cape Town.

          Materials and Methods

          A retrospective study of patients with idiopathic MCGN followed up at our clinic. Seventy-nine patients with no identifiable cause of MCGN were included for analysis. A composite renal outcome of persistent doubling of serum creatinine or end stage renal disease (ESRD) was used. Kaplan Meier survival and Cox regression analysis were used to assess survival and identify factors predicting the outcome.

          Results

          The mean age at biopsy was 33.9±13.6 years and 41.8% were black. Mean duration of follow up was 13.5±18.8 months. Twenty-three patients (34.2%) reached the composite endpoint. Overall, median renal survival was 38.7±11.7 months (95% CI 15.7–61.8) with 2-year and 5-year renal survival of 61% and 40.3% respectively. No significant difference was found for renal survival between males and females, treatment or non-treatment with immunosuppression, presence or absence of crescents or histological type of MCGN (p>0.05). On univariate Cox-regression analysis, factors found to be associated with the outcome were the estimated glomerular filtration rate at biopsy (OR 0.97 [95%CI: 0.95–0.99], p<0.0001), black race (OR 3.03 [95%CI: 1.27–7.21], p = 0.012) and presence of interstitial fibrosis in the biopsy (OR 2.64 [95%CI: 1.07–6.48], p = 0.034). Age, systolic blood pressure and attaining complete or partial remission approached significant values with the endpoint.

          Conclusions

          The outcome of idiopathic MCGN in Cape Town is poor and requires further prospective studies to improve our understanding of this common disease.

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          Most cited references32

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          The timing of specialist evaluation in chronic kidney disease and mortality.

          Care for chronic renal failure involves management of complications and preparation for possible dialysis. Patients often are not evaluated by nephrologists in a timely manner. To identify factors associated with late evaluation by a nephrologist and to assess whether late evaluation is associated with worse survival once patients develop end-stage renal disease (ESRD). National prospective cohort study. 81 dialysis facilities throughout the United States. 828 patients with new-onset ESRD. Time from first evaluation by a nephrologist to initiation of dialysis, classified as late ( 12 months); rate of death, from initiation of dialysis to an average of 2.2 years of follow-up; and demographic, clinical, and laboratory characteristics. After adjustment for potential confounders, late evaluation was more common among black men than white men (44.8% vs. 24.5%; P < 0.05), uninsured patients than insured patients (56.7% vs. 29.0%; P < 0.05) and patients with severe comorbid disease than those with mild comorbid disease (35.0% vs. 23.0%; P < 0.05). Compared with patients who had early evaluation, the risk for death was greater among patients evaluated late and was graded (hazard ratio, 1.3 [95% CI, 0.87 to 2.06] for patients with intermediate evaluation and 1.8 [CI, 1.21 to 2.61] for those with late evaluation) after adjustment for dialysis method, demographic characteristics, and socioeconomic status in Cox proportional hazards regression analysis. After additional adjustment for such factors as the presence and severity of comorbid conditions, the association remained graded (hazard ratio, 1.2 [CI, 0.73 to 1.82] for patients evaluated at an intermediate point and 1.6 [CI, 1.04 to 2.39] for those evaluated late). Late evaluation of patients with chronic renal failure by a nephrologist is associated with greater burden and severity of comorbid disease, black ethnicity, lack of health insurance, and shorter duration of survival.
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            The American College of Rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials.

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              C3 glomerulonephritis associated with monoclonal gammopathy: a case series.

              C3 glomerulonephritis (GN) is a proliferative GN resulting from glomerular deposition of complement factors due to dysregulation of the alternative pathway of complement. Dysregulation of the alternative pathway of complement may occur as a result of mutations or functional inhibition of complement-regulating proteins. Functional inhibition of the complement-regulating proteins may result from a monoclonal gammopathy. Case series. 32 Mayo Clinic patients with C3 GN, 10 (31%) of whom had evidence of a monoclonal immunoglobulin in serum. Clinical features, hematologic and bone marrow biopsy findings, kidney biopsy findings, kidney measures, complement pathway abnormalities, treatment, and follow-up of patients with C3 GN that was associated with a monoclonal gammopathy. Mean age of patients with C3 GN associated with monoclonal gammopathy was 54.5 years. Bone marrow biopsy done in 9 patients revealed monoclonal gammopathy of undetermined significance in 5 patients, small lymphocytic lymphoma/chronic lymphocytic leukemia in one patient, and no abnormal clones in the other 3 patients. Kidney biopsy showed membranoproliferative GN with bright capillary wall C3 staining in all 10 patients. Evaluation of the alternative pathway of complement showed abnormalities in 7 of 9 patients tested. No mutation in complement-regulating proteins was detected in any patient. As an index case, one patient with C3 GN and chronic lymphocytic leukemia was treated with rituximab, cyclophosphamide, vincristine, and prednisone, and one patient with C3 GN and monoclonal gammopathy of undetermined significance was treated with dexamethasone and bortezomib. Both patients showed significant decreases in hematuria and proteinuria and stabilization of kidney function. Studies to show evidence of direct activation of the alternative pathway by monoclonal immunoglobulin were not done. The study highlights the association of C3 GN and monoclonal gammopathy, in particular in the older population, and the importance of targeting the underlying hematologic malignancy as an approach to treating C3 GN. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                20 November 2014
                : 9
                : 11
                : e113302
                Affiliations
                [1 ]Division of Nephrology and Hypertension, Groote Schuur Hospital and University of Cape Town, South Africa
                [2 ]Division of Anatomical Pathology, National Health and Laboratory Services (NHLS), University of Cape Town, South Africa
                [3 ]Department of Medicine, Aga Khan University Hospital, Nairobi, Kenya
                Mario Negri Institute for Pharmacological Research and Azienda Ospedaliera Ospedali Riuniti di Bergamo, Italy
                Author notes

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

                Conceived and designed the experiments: IGO TALD MD BLR GM CRS. Performed the experiments: IGO TALD MD BLR GM CRS. Analyzed the data: IGO TALD MD BLR GM CRS. Contributed reagents/materials/analysis tools: IGO TALD MD BLR GM CRS. Wrote the paper: IGO TALD MD BLR GM CRS.

                Article
                PONE-D-13-53730
                10.1371/journal.pone.0113302
                4239048
                25411791
                8984e448-4498-4653-a980-133507f5f980
                Copyright @ 2014

                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
                : 20 December 2013
                : 27 October 2014
                Page count
                Pages: 10
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Hypertension
                Nephrology
                Chronic Kidney Disease
                Medical Dialysis
                Tubulointerstitial Disease

                Uncategorized
                Uncategorized

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