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      Clinical Presentation, Outcomes, and Treatment of Membranous Nephropathy after Transplantation

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          Abstract

          There are scarce data about clinical presentation and outcomes of posttransplant membranous nephropathy (MN), and few reports include a large number of patients. This was a retrospective cohort including adult patients with posttransplant MN transplanted between 1983 and 2015 in a single center (n=41). Only patients with histological diagnosis of MN in kidney grafts were included. Clinical and laboratory presentation, histological findings, treatment, and outcomes were detailed. Patients were predominantly male (58.5%), with a mean age of 49.4 ± 13.2 years; 15 were considered as recurrent primary MN; 3 were class V lupus nephritis; 14 were considered as de novo cases, 7 secondary and 7 primary MN; and 9 cases were considered primary but it was not possible to distinguish between de novo MN and recurrence. Main clinical presentations were proteinuria (75.6%) and graft dysfunction (34.1%). Most patients with primary recurrent and de novo primary MN were submitted to changes in maintenance immunosuppressive regimen, but no standard strategy was identified; 31 patients presented partial or complete remission, and glomerulopathy appeared not to impact graft and patient survival.

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          The pathogenesis of idiopathic membranous nephropathy: a 50-year odyssey.

          Ever since its first delineation as a distinct clinicopathologic entity in 1957, idiopathic membranous nephropathy (MN) has been the subject of intense laboratory and clinical investigation. The availability of laboratory models (particularly active and passive Heymann nephritis) of this disorder has been a boon to investigators. Concepts regarding the fundamental mechanisms of immune deposit formation, a sine qua non of idiopathic MN, have evolved and now are firmly established. Circulating autoantibodies (immunoglobulin G4 and immunoglobulin G1 subclasses) interacting with antigens native to or planted in the glomerular capillary wall at the podocyte cell membrane-basement membrane interface generally are regarded as the fundamental pathobiological mechanism. Thus, MN now is regarded as a podocytopathy. The immune deposits evoke an alteration in glomerular capillary permeability, probably through complement-mediated injury of the podocyte and its slit-pore membrane; however, cell-mediated immunity also may have a role, and the physical presence of immune deposits and basement membrane alterations also may participate. The exact nature of the autoantibody systems operative in human idiopathic MN is being uncovered rapidly. It is hoped that this 50-year odyssey will culminate in real progress in the diagnosis, prognosis, and therapy for the human disease.
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            Recent advances in our understanding of recurrent primary glomerulonephritis after kidney transplantation.

            Recurrent glomerulonephritis (GN) is an important cause of kidney allograft failure, particularly in younger recipients. Approximately 15% of death-censored graft failures are due to recurrent GN, but this incidence is likely an underestimation of the magnitude of the problem. Overall, 18% to 22% of kidney allografts are lost due to GN, either recurrent or presumed de novo. The impact of recurrent GN on allograft survival was recognized from the earliest times in kidney transplantation. However, progress in this area has been slow, and our understanding of GN recurrence remains limited, in large part due to incomplete understanding of the pathogenesis of these diseases. This review focuses on recent advances in our general understanding of the pathophysiology of primary GN, the risk of recurrence in the allograft, and the consequences for kidney graft survival. We focus specifically on the most common forms of primary GN, including focal segmental glomerulosclerosis, membranous nephropathy, membranoproliferative glomerulonephritis, and IgA nephropathy. New understanding of the pathogenesis of these diseases has had direct clinical implications for transplantation, allowing better identification of candidates at high risk of recurrence and earlier diagnoses, and it is expected to lead to significance improvements in the therapy and perhaps even prevention of GN recurrence. More than ever, it is essential to fully characterize GN before transplantation as this information will direct our management posttransplantation. Further, the relative rarity of recurrent GN dictates the need for multicenter studies in order to evaluate, test, and validate recent advances and therapies.
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              Autoantibodies specific for the phospholipase A2 receptor in recurrent and De Novo membranous nephropathy.

              Recent findings in idiopathic membranous nephropathy (MN) suggest that in most patients, the disease is because of anti-phospholipase A(2) receptor (PLA(2) R1) autoantibodies. Our aim was to analyze the prevalence and significance of anti-PLA(2) R1 antibodies in recurrent and de novo MN after transplantation. We assessed circulating PLA(2) R1 autoantibodies by a direct immunofluorescence assay based on human embryonic kidney cells transfected with a PLA(2) R1 cDNA, and the presence of PLA(2) R1 antigen in immune deposits. We showed that PLA(2) R1 was involved in 5 of 10 patients with recurrent MN, but in none of the 9 patients with de novo MN. We also showed a marked heterogeneity in the kinetics and titers of anti-PLA(2) R1, which may relate to different pathogenic potential. We provide evidence that some patients with PLA(2) R1-related idiopathic MN and anti-PLA(2) R1 antibodies at the time of transplantation will not develop recurrence. Because PLA(2) R1 autoantibody was not always associated with recurrence, its predictive value should be carefully analyzed in prospective studies. No claim to original US government works Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.
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                Author and article information

                Contributors
                Journal
                Int J Nephrol
                Int J Nephrol
                IJN
                International Journal of Nephrology
                Hindawi
                2090-214X
                2090-2158
                2018
                5 July 2018
                : 2018
                : 3720591
                Affiliations
                1Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil
                2Federal University of Ceará (UFC), Fortaleza, CE, Brazil
                Author notes

                Academic Editor: Franca Anglani

                Author information
                http://orcid.org/0000-0001-9262-6403
                http://orcid.org/0000-0002-4435-0614
                http://orcid.org/0000-0003-1317-4109
                Article
                10.1155/2018/3720591
                6077578
                1f68ad07-1a3d-4737-864b-4f20825b3beb
                Copyright © 2018 Artur Q. B. da Silva et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 December 2017
                : 20 May 2018
                : 12 June 2018
                Funding
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico
                Categories
                Research Article

                Nephrology
                Nephrology

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