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      Avaliação de 100 pacientes com nefrite lúpica acompanhados por dois anos Translated title: Analysis of 100 patients with lupus nephritis followed up for 2 years

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          Abstract

          OBJETIVOS: Determinar a frequência de remissão total e parcial no tratamento da nefrite lúpica aos 12 e 24 meses de seguimento. Comparar esses subgrupos aos 12 meses, correlacionando as variáveis renais iniciais com a resposta ao tratamento. Analisar e comparar os resultados terapêuticos do subgrupo com glomerulonefrite proliferativa difusa por correlação clínico-patológica ("classe IV clínica") com aqueles de "classe IV histológica", isto é, com biópsia renal comprovada pela Organização Mundial da Saúde. MATERIAL E MÉTODOS: Foram estudados 100 pacientes consecutivos com diagnóstico de lúpus eritematoso sistêmico (LES) e nefrite, atendidos no Serviço de Reumatologia da Santa Casa de Misericórdia de São Paulo e acompanhados por dois anos. Os portadores de comorbidades que comprometem os rins foram excluídos. Foram analisadas as variáveis demográficas, clínicas, laboratoriais e o índice de atividade da doença (SLEDAI). Os pacientes com classe histológica III, IV ou V receberam corticosteroide e ciclofosfamida como tratamento de indução da nefrite lúpica e aqueles com classe II receberam apenas corticosteroide. RESULTADOS: A idade média ao diagnóstico de LES foi de 24,71 ± 10,14 anos, com predomínio do sexo feminino (88%). O SLEDAI calculado ao diagnóstico foi de 16,09 ± 6,48. Em relação às variáveis renais iniciais, a creatinina média foi de 1,02 ± 0,49 mg/dL, a proteinúria de 24 horas média foi de 2,57 ± 2,39 g e o anticorpo anti-dsDNA foi encontrado em 66% dos casos. Todos os pacientes receberam corticosteroide e 75% utilizaram a ciclofosfamida. Cinquenta e seis pacientes foram submetidos à biópsia renal. Os subtipos II e IV foram os mais prevalentes (33,9% e 32,2%, respectivamente). Após 12 meses de acompanhamento, todos os pacientes apresentaram redução significativa da proteinúria de 24 horas, melhora do sedimento urinário e dos valores das frações do complemento (C3, C4, CH50). A frequência de remissão total aos 12 meses foi 72,7% e, aos 24 meses, 85,7% (p = 0,013). A remissão parcial ocorreu em 27,3% dos doentes aos 12 meses e em 14,3% aos 24 meses. O sexo masculino apresentou menor frequência de remissão total comparado ao feminino aos 12 meses de acompanhamento (45,5% versus 81,6%, p = 0,007). Dentre as diferentes variáveis estudadas, nenhuma se correlacionou com remissão total ou parcial aos 12 meses. O subgrupo "classe IV clínica" apresentou maior frequência de remissão total que o subgrupo "classe IV histológica". CONCLUSÃO: Com o esquema terapêutico usado em nosso serviço, verificou-se um excelente desfecho em dois anos. Não foram observadas correlações entre variáveis clínico-laboratoriais e remissão total ou parcial. O sexo masculino apresentou menores taxas de remissão total comparado ao feminino. Apesar do pequeno número de pacientes estudados e das controvérsias quanto à biópsia renal, a taxa de remissão total foi maior nos pacientes com "classe IV clínica" em relação àqueles com "classe IV histológica".

          Translated abstract

          OBJECTIVES: To assess the frequency of total and partial remission in the treatment of lupus nephritis at 12 months and 24 months. To compare these subgroups at 12 months and correlate the initial renal variables with the therapeutic response. To analyze and to compare the therapeutic results of the subgroup with diffuse proliferative glomerulonephritis by clinicopathological correlation ("clinical class IV") with those with biopsy-proven WHO class IV ("histological class IV"). PATIENTS AND METHODS: One hundred consecutive patients with diagnosis of systemic lupus erythematosus (SLE) and nephritis who attended to the department of rheumatology of a tertiary referral center were studied. The length of the follow up was 2 years. Patients with comorbidities that compromise the kidneys had been excluded. The demographic, clinical and laboratory variables and the disease activity index (SLEDAI) were analyzed. Patients with lupus nephritis WHO class III, IV or V received glucocorticoid and cyclophosphamide for induction of remission and those with class II received only glucocorticoid. RESULTS: The average age at SLE diagnosis was of 24.71 + 10.14 years, with a predominance of female gender (88%). The initial SLEDAI was 16.09 ± 6.48. At the time of the diagnosis of nephritis, mean serum creatinine was 1.02 ± 0.49 mg/dL, mean 24-hour urinary protein level was of 2.57 ± 2.39g and the antibody anti-dsDNA was found in 66% of the cases. All the patients had received glucocorticoids and 75% had used cyclophosphamide. Fifty-six patients had been submitted to renal biopsy. The most prevalent subtypes were class II and IV (33.9% and 32.2%, respectively). After 12 months, all the patients had significant reduction in the 24-hour urinary protein level, improvement in the urinary sediment and increase in the fractional values of the complement (C3, C4, CH50). The frequency of total remission at 12 months was 72.7% and, at 24 months, 85.7% (p =0.013). Partial remission occurred in 27.3% at 12 months and, in 14.3%, at 24 months. Male gender presented a lower rate of total remission compared with women at 12 months (45.5% versus 81.6%, p = 0.007). Among several factors studied, none was correlated with total or partial remission at 12 months. The subgroup "clinical class IV" presented a higher frequency of total remission than the subgroup "histological class IV". CONCLUSION: Our therapeutic approach achieved an excellent outcome in two years. Correlations between clinical and laboratory variables and total or partial remission were not observed. Male gender presented a lower rate of total remission compared with women. Despite the small number of patients studied and the controversies of renal biopsy, the rate of total remission was higher in patients with "clinical class IV" than in those with "histological class IV".

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          Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide.

          Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a remission-maintaining treatment. In this multicenter, prospective clinical trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent-to-treat analyses were performed. Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group. Sixteen percent of those in the low-dose group and 20% of those in the high-dose group experienced treatment failure (not statistically significant by Kaplan-Meier analysis). Levels of serum creatinine, albumin, C3, 24-hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low-dose group and 54% of the high-dose group (not statistically significant). Renal flares were noted in 27% of the low-dose group and 29% of the high-dose group. Although episodes of severe infection were more than twice as frequent in the high-dose group, the difference was not statistically significant. The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission-inducing regimen of low-dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen.
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            Prognostic factors in lupus nephritis. Contribution of renal histologic data.

            The predictive value of laboratory results and renal histologic data was examined in 102 patients upon entry into prospective, randomized, therapeutic trials of lupus nephritis. Three clinical features at the time of entry into the study were individually associated with increased rates of renal failure: age less than 24 years, male gender, and an elevated serum creatinine level. Subjects with diffuse proliferative or membranoproliferative glomerulonephritis were at a modest but significantly increased risk for the development of end-stage renal disease compared with patients with other classes of lupus nephritis. Semiquantitative scores of histologic features (specified by activity and chronicity indexes) identified subgroups of patients with comparatively high renal failure rates. To address the controversial issue of whether renal histologic data significantly improve the outcome predictions in patients with lupus nephritis, multivariate survival models were generated, permitting simultaneous consideration of multiple prognostic factors. Outcome predictions based on the strongest clinical predictors (age, sex, and serum creatinine level) were significantly enhanced by the addition of activity and chronicity indexes. Only age and chronicity index contributed significantly to the five-variable model and together constituted a two-variable model, the predictions of which were similar to observed outcomes. In the context of the highly significant prognostic indicators (age and chronicity index), immunosuppressive agents appeared to provide a slight therapeutic advantage over oral corticosteroids alone.
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              Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only.

              The purpose of this study was to assess long-term preservation of renal function in 111 patients with systemic lupus erythematosus and active glomerulonephritis who participated in a randomized treatment trial. Four different drug treatment programs, each of which allowed the use of low-dose oral prednisone in addition to the study drug(s), were compared with a regimen consisting solely of high-dose oral prednisone. Patients randomized to receive intravenous cyclophosphamide, oral cyclophosphamide, or oral azathioprine plus cyclophosphamide had significantly better preservation of renal function than did patients who were randomized to receive prednisone only. Results in the azathioprine group did not differ from those in the prednisone-only group. Cyclophosphamide appears to have long-term benefit in the delay or prevention of end-stage renal disease in patients with lupus nephritis.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                rbr
                Revista Brasileira de Reumatologia
                Rev. Bras. Reumatol.
                Sociedade Brasileira de Reumatologia (São Paulo, SP, Brazil )
                0482-5004
                1809-4570
                February 2009
                : 49
                : 1
                : 8-19
                Affiliations
                [02] orgnameIrmandade da Santa Casa de Misericórdia de São Paulo orgdiv1Serviço de Reumatologia
                [01] orgnameSanta Casa de Misericórdia de São Paulo orgdiv1Faculdade de Ciências Médicas
                Article
                S0482-50042009000100002
                10.1590/S0482-50042009000100002
                17ecdbf1-ff57-48b3-8747-e900e49e772a

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 21 October 2008
                : 01 November 2007
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 19, Pages: 12
                Product

                SciELO Brazil

                Categories
                Artigo Original

                remissão total,biópsia renal,nefrite,lúpus eritematoso sistêmico,renal biopsy,complete remission,nephritis,systemic lupus erythematosus

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