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      A case of membranous nephropathy diagnosed with lupus nephritis 11 years after onset

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          Abstract

          A 34-year-old female patient presented to our hospital with lower extremity edema and proteinuria during pregnancy. Renal biopsy was performed and the patient was diagnosed with nephrotic syndrome due to lupus-like membranous nephropathy. This diagnosis was reached upon as laboratory findings upon admission, wherein both anti-nuclear and anti-double-stranded DNA antibodies revealed negative, did not fulfill the criteria for systemic lupus erythematosus (SLE) proposed by the American College of Rheumatology (ACR) and the patient did not reveal any typical physical manifestations of SLE. Methylprednisolone pulse therapy was started followed by oral administration of prednisolone. Urinary protein excretion diminished after 1 year of treatment. Eleven years later, the same patient was admitted to our hospital again with relapse of nephrotic syndrome. Laboratory findings upon second admission, wherein both anti-nuclear and anti-double-stranded DNA antibodies revealed positive, fulfilled the ACR criteria. Renal biopsy was performed again, resulting in a diagnosis of lupus nephritis. Steroid therapy combined with administration of mycophenolate mofetil led to an incomplete remission. Immunofluorescence studies confirmed the presence of IgG, IgM, C3, and C1q in renal biopsy specimens both at first and second admissions. Furthermore, immunofluorescence studies confirmed the presence of IgG1–4 in the first biopsy and tubuloreticular inclusions (TRIs) were revealed using electron microscopy. The present case represents the possibility that characteristic pathological findings of lupus nephritis, including TRIs, can reveal themselves before a diagnosis of SLE.

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          A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis.

          Studies of the impact of systemic lupus erythematosus (SLE) and its pregnancy complications have yielded conflicting results. Major limitations of these studies relate to their small numbers of patients and retrospective designs. The aim of this study was to perform a systematic literature review of pregnancy outcomes in women with SLE and a meta-analysis of the association of lupus nephritis with adverse pregnancy outcomes. We searched electronic databases from 1980 to 2009 and reviewed papers with validity criteria. Random-effects analytical methods were used to evaluate pregnancy complications rates. Thirty-seven studies with 1842 patients and 2751 pregnancies were included. Maternal complications included lupus flare (25.6%), hypertension (16.3%), nephritis (16.1%), pre-eclampsia (7.6%), and eclampsia (0.8%). The induced abortion rate was 5.9%, and when excluded, fetal complications included spontaneous abortion (16.0%), stillbirth (3.6%), neonatal deaths (2.5%), and intrauterine growth retardation (12.7%). The unsuccessful pregnancy rate was 23.4%, and the premature birth rate was 39.4%. Meta-regression analysis showed statistically significant positive associations between premature birth rate and active nephritis and increased hypertension rates in subjects with active nephritis or a history of nephritis. History of nephritis was also associated with pre-eclampsia. Anti-phospholipid antibodies were associated with hypertension, premature birth, and an increased rate of induced abortion. In patients with SLE, both lupus nephritis and anti-phospholipid antibodies increase the risks for maternal hypertension and premature births. The presented evidence further supports timing of pregnancy relative to SLE activity and multispecialty care of these patients.
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            Pregnancy in lupus nephritis.

            Fetal and maternal outcomes of 70 pregnancies in 48 women with lupus nephritis were retrospectively analyzed. In 13 women, lupus nephritis developed during pregnancy (group A). In 38 patients with known lupus nephritis (including 3 patients in group A who had another pregnancy), 57 pregnancies occurred. In 6 patients, a therapeutic abortion was performed. The remaining 51 pregnancies were considered pregnancies in lupus nephritis (group B). Fetal loss was 36% (38%, group A; 35%, group B); it decreased from 46% in the 1970s to 30% in the last decade. Among 41 live births, there were 13 preterm deliveries and 28 full-term deliveries. At multivariate analysis, proteinuria (P = 0.025), arterial hypertension (P = 0.05), and antiphospholipid antibodies (P = 0.01) were independent predictors of fetal loss. In group A, 3 patients developed acute renal failure, irreversible in 1 patient (7.7%); all other patients recovered after steroid and immunosuppressive therapy. In group B, 12 renal flares and 1 extrarenal flare developed during pregnancy or the postpartum period. Two patients progressed to irreversible renal failure (3.9%), and 1 of the 2 patients died. All other patients recovered. The incidence of renal flares before or during pregnancy was not different (P = 0.51). Renal quiescence at the onset of pregnancy was the only predictor of favorable maternal outcome. Proteinuria, hypertension, and positivity of antiphospholipid antibodies are independent predictors of adverse fetal outcome. Quiescence of renal disease is the only predictor of favorable maternal outcome. Copyright 2002 by the National Kidney Foundation, Inc.
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              Pathologic differentiation between lupus and nonlupus membranous glomerulopathy.

              The following clinical and pathologic features were evaluated in 170 patients with electron microscopically documented membranous glomerulopathy: age, sex, race, American Rheumatism Association lupus criteria, serum ANA, serum complement, glomerular hypercellularity, stage of subepithelial dense deposits, endothelial tubuloreticular inclusions, tubular basement membrane deposits, tissue ANA, glomerular deposition of IgG, IgM, IgA, C3, C4, and Clq. At the time of biopsy 148 patients had no clinical evidence for lupus, and 22 had a clinical diagnosis of lupus. Six additional patients eventually developed overt lupus after an average of 12 months. Incidences of serologic and pathologic features in lupus as compared with nonlupus membranous glomerulopathy were determined. These data were used to calculate sensitivity, specificity, positive and negative predictive values, and overall efficiency of each parameter in differentiating between lupus and nonlupus membranous glomerulopathy. In general, serologic, morphologic and immunohistopathologic features are more accurate at ruling out lupus than making the diagnosis of lupus. However, a number of features are significantly more frequent in lupus membranous glomerulopathy. Therefore, identification of these features, especially more than one, warrants a high suspicion of lupus rather than nonlupus membranous glomerulopathy even in patients without clinically overt systemic lupus erythematosus. The positive/negative predictive values of some of the pathologic features studied are as follows: mesangial dense deposits 63/99, subendothelial dense deposits 77/93, tubuloreticular inclusions 61/96, intense C1q deposition 47/95, tubular basement membrane deposits 100/87, and glomerular hypercelularity 26/86.
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                Author and article information

                Contributors
                0476-99-1111 , t-yamada@nms.ac.jp
                Journal
                CEN Case Rep
                CEN Case Rep
                CEN Case Reports
                Springer Singapore (Singapore )
                2192-4449
                9 August 2019
                9 August 2019
                November 2019
                : 8
                : 4
                : 301-307
                Affiliations
                [1 ]GRID grid.416273.5, ISNI 0000 0004 0596 7077, Department of Nephrology, , Nippon Medical School Chiba Hokusoh Hospital, ; 1715, Kamagari, Inzai, Chiba 270-1694 Japan
                [2 ]GRID grid.459842.6, ISNI 0000 0004 0406 9101, Department of Nephrology, , Nippon Medical School Musashi Kosugi Hospital, ; 1-396, Kosugimachi, Nakahara-ku, Kawasaki, Kanagawa 211-8533 Japan
                [3 ]GRID grid.410821.e, ISNI 0000 0001 2173 8328, Department of Nephrology, , Nippon Medical School, ; 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
                [4 ]GRID grid.410821.e, ISNI 0000 0001 2173 8328, Department of Analytic Human Pathology, , Nippon Medical School, ; 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
                Author information
                http://orcid.org/0000-0001-9474-1341
                Article
                412
                10.1007/s13730-019-00412-5
                6820642
                31399881
                ec625ca7-38ae-4709-b864-b76e7eb82784
                © The Author(s) 2019

                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.

                History
                : 26 November 2018
                : 31 July 2019
                Categories
                Case Report
                Custom metadata
                © Japanese Society of Nephrology 2019

                membranous lupus nephritis,lupus-like membranous nephropathy,tubuloreticular inclusion,igg subclass

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