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      Factors affecting the long-term outcomes of idiopathic membranous nephropathy

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          Abstract

          Background

          We attempted to describe the clinical features and determine the factors associated with renal survival in idiopathic membranous nephropathy (iMN) patients with nephrotic syndrome (NS) and to determine the factors associated with spontaneous complete remission (sCR) and progression to NS in iMN patients with subnephrotic proteinuria.

          Methods

          This retrospective study involved 166 iMN patients with NS and 65 patients with subnephrotic proteinuria. The primary end point was a doubling of serum creatinine or initiation of dialysis. In patients with subnephrotic proteinuria, we determined the factors associated with sCR and factors associated with progression to NS.

          Results

          Remission of NS was achieved in 125 out of 166 patients (75.3%). Of those who reached remission, 26 patients (20.8%) experienced relapse that was followed by second remission. The relapse or persistence of proteinuria was associated with the primary end points (hazard ratio [HR] = 12.40, P = 0.037, HR = 173, P < 0.001, respectively). In patients with subnephrotic proteinuria, sCR occurred in 35.4% of the patients. The patients with sCR had lower proteinuria and serum creatinine levels and higher serum albumin concentrations at baseline. The serum albumin level at diagnosis was a prognostic factor for progression to NS (Odds ratio [OR] = 0.015, P < 0.001).

          Conclusions

          The occurrence of relapse or persistence of proteinuria had negative effects on renal survival in iMN patients with NS, and low serum albumin levels at baseline were associated with non-achievement of sCR and progression to NS.

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          Most cited references14

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          The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient.

          The KDIGO guideline for glomerulonephritis is designed to assist health-care providers in treating patients with glomerular diseases. A guideline is not a set of rules but is intended to allow the practitioner to make an informed decision based on the available evidence. Due to its general nature and the variability of strength of the available studies, it is often difficult to directly apply a guideline to the care of an individual patient. This commonly relates to the limited generalizability of the evidence, i.e., does not cover every clinical scenario. To underscore this point, we have introduced within the context of the glomerulonephritis guideline cases with specific features to illustrate the constant need for clinical judgment. These vignettes are intended to demonstrate how the best treatment plans should be individualized and take into account patient preference and clinical acumen, as well as the best available evidence.
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            A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy.

            To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy, we compared two regimens based on a 6-mo treatment, alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide. Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were randomized to be given methylprednisolone (1 g intravenously for 3 consecutive days followed by oral methylprednisolone, 0.4 mg/kg per d for 27 d) alternated every other month either with chlorambucil (0.2 mg/kg per d for 30 d) or cyclophosphamide (2.5 mg/kg per d for 30 d). The whole treatment lasted 6 mo; 3 mo with corticosteroids and 3 mo with one cytotoxic drug. Among 87 patients followed for at least 1 yr, 36 of 44 (82%; 95% confidence interval [CI], 67.3 to 91.8%) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome, versus 40 of 43 (93%; 95% CI, 80.9 to 98.5%) assigned to methylprednisolone and cyclophosphamide (P = 0.116). Of patients who attained remission of the nephrotic syndrome, 11 of 36 in the chlorambucil group (30.5%) and 10 of 40 in the cyclophosphamide group (25%) had a relapse of the nephrotic syndrome between 6 and 30 mo. The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups (P < 0.01) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr. Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects. Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster. One patient per group developed cancer. It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr.
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              Glomerular diseases: membranous nephropathy--a modern view.

              Membranous nephropathy (MN) is an autoimmune disease usually associated with a nephrotic syndrome and it may progress to ESRD in the long term. Its etiology is often unknown (idiopathic MN), whereas other cases have a recognizable etiology (secondary MN). In idiopathic MN, the glomerular lesions are mainly caused by autoantibodies against a podocyte membrane protein, the M-type of phospholipase A2 receptor 1. The natural course of idiopathic MN is quite varied with spontaneous complete or partial remissions a relatively common occurrence. Patients with asymptomatic non-nephrotic proteinuria seldom progress and need only conservative management. Those with persistent full-blown nephrotic syndrome and those with declining renal function are candidates for specific treatment with any of several regimens. Cyclical therapy with alternating monthly intravenous and oral glucocorticoids combined with a cytotoxic agent can induce remission and preserve renal function in the long term. Cyclosporine or tacrolimus can induce remission, but relapses are frequent after the drug withdrawal. Mycophenolate mofetil monotherapy seems to be ineffective, but may be beneficial when administered together with steroids. The experience with adrenocorticotropic hormone, natural or synthetic, is limited to a few studies with short-term follow-up, but high rates of remission can be seen after prolonged treatment. A high rate of remission and good tolerance have also been reported with rituximab. Patients with moderate renal insufficiency may also benefit from treatment, but at a price of frequent and serious side effects. With these limitations in mind, idiopathic MN may be considered a treatable disease in many patients.
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                Author and article information

                Contributors
                hh820616@hanmail.net
                dewyhj@hanmail.net
                nephrolee@gmail.com
                dkkim73@gmail.com
                oh.sohee@gmail.com
                yoonkyuoh@gmail.com
                yonsukim@snu.ac.kr
                +82-2-870-2215 , cslimjy@snu.ac.kr
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                27 March 2017
                27 March 2017
                2017
                : 18
                : 104
                Affiliations
                [1 ]ISNI 0000 0001 0302 820X, GRID grid.412484.f, Department of Internal Medicine, , Seoul National University Hospital, ; Seoul, Republic of Korea
                [2 ]GRID grid.412479.d, Department of Internal Medicine, , Seoul National University Boramae Medical Center, ; 20 Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061 Republic of Korea
                [3 ]ISNI 0000 0004 0470 5905, GRID grid.31501.36, Department of Internal Medicine, , Seoul National University College of Medicine, ; Seoul, Republic of Korea
                [4 ]GRID grid.412479.d, Department of Biostatistics, , Seoul National University Boramae Medical Center, ; Seoul, Republic of Korea
                Article
                525
                10.1186/s12882-017-0525-6
                5369217
                28347297
                e90c5ef7-2b23-4908-809d-fe16d08973ad
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 18 January 2016
                : 23 March 2017
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Nephrology
                idiopathic membranous nephropathy,nephrotic syndrome,prognosis,proteinuria,renal survival

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