Belimumabe comparado à terapia padrão do Sistema Único de Saúde no tratamento da nefrite lúpica nos estágios III, IV e V: revisão rápida / Belimumab compared to standard therapy of the Brazilian Public Health System in the treatment of lupus nephritis in stage III, IV, and V: rapid review

Belimumabe, rituximabe, terapia imunossupressora. Indicação: Nefrite lúpica nos estágios III, IV, V, refratária à terapia imunossupressora. Pergunta: Belimumabe é eficaz (remissão da nefrite, normalização da perda da função renal, qualidade de vida) e seguro (descontinuação devido a eventos adversos totais e eventos adversos graves) para o tratamento de pacientes com nefrite lúpica refratária nos estágios III, IV, V em comparação aos medicamentos disponíveis no Sistema Único de Saúde? Objetivo: Avaliar a segurança e eficácia do belimumabe em comparação com os medicamentos disponíveis no Sistema Único de Saúde em pacientes adultos com nefrite lúpica. Métodos: Revisão rápida de revisões sistemáticas. Levantamento bibliográfico foi realizado nas bases de dados PUBMED, EMBASE, SCOPUS, BVS, EPISTEMONIKOS, Cochrane Library e em registros de revisões sistemáticas e ensaios clínicos. Seguiu estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica dos estudos incluídos através da ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Resultados: Foram selecionadas duas revisões sistemáticas que atendiam aos critérios de elegibilidade, mas nenhum ensaio clínico foi escolhido, pois não atendiam aos critérios de inclusão. Conclusão: a terapia combinada de belimumabe, ou de rituximabe, com tratamento imunossupressor padrão é mais eficaz que o tratamento padrão para alcançar remissão clínica da nefrite lúpica. A terapia combinada é tão segura quanto o tratamento padrão. Belimumabe e rituximabe tem eficácia similar entre si

Belimumab, rituximab, and immunosuppressive therapy. Indication: Refractory lupus nephritis to immunosuppressive therapy in stages III, IV, V. Question: Is belimumab effective (for remission of nephritis, normalization of loss of renal function, quality of life) and safe (for discontinuation due to total adverse events and serious adverse events) in the treatment of patients with refractory lupus nephritis in stages III, IV, V compared to the drugs available in the Brazilian Public Health System? Objective: To evaluate the safety and efficacy of belimumab compared to drugs available in the Brazilian Public Health System in adult patients with lupus nephritis. Methods: Rapid review of systematic reviews. A bibliographic search was done in the PUBMED, EMBASE, SCOPUS, BVS, EPISTEMONIKOS, Cochrane Library databases and in records of systematic reviews and clinical trials. It has followed predefined search strategies. The methodological quality of the included studies was evaluated using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews Version 2). Results: Two systematic reviews were selected, which met the eligibility criteria, but no clinical trials were chosen, as they did not meet the inclusion criteria. Conclusion: Combination therapy of belimumab or rituximab with standard immunosuppressive treatment is more effective than standard treatment in achieving clinical remission of lupus nephritis. Combination therapy is as safe as standard treatment. Belimumab and rituximab have similar efficacy to each other

Nefritis como debut lúpico en el embarazo: reporte de dos casos y revisión de la literatura / Nephritis as a lupic debut in pregnancy: report of two cases and review of the literature

ANTECEDENTES: El lupus eritematoso sistémico es una enfermedad autoinmunitaria multisistémica que afecta principalmente a mujeres en edad fértil. La nefritis lúpica es la manifestación clínica más frecuente durante la gestación y constituye un factor de riesgo para la pérdida del embarazo, en especial en pacientes con insuficiencia renal. Además, presenta mayor riesgo de pérdida fetal, restricción del crecimiento intrauterino e hipertensión. CASOS CLÍNICOS: El primer caso se trata de una gestante de 28 + 2 semanas con daño renal grave y anticuerpos anti-DNA en título elevado. En el segundo caso destaca el debut con sintomatología de dificultad respiratoria y edemas como manifestaciones clínicas de nefropatía lúpica tipo V a las 23 semanas de gestación. En ambas pacientes destaca la prematuridad como complicación perinatal, así como el crecimiento intrauterino retardado en el primer caso. Por último, se describen los resultados clínico-analíticos tras el inicio terapéutico específico en ambos casos. CONCLUSIONES: El diagnóstico diferencial del debut de nefritis lúpica durante la gestación continúa siendo un desafío, a pesar de los avances en cuanto a marcadores angiogénicos. La valoración clínica continúa siendo la piedra angular de este proceso diagnóstico y de sus implicaciones en cuanto a complicaciones del embarazo actuales y futuras.

BACKGROUND: Systemic lupus erythematosus is a multisystem autoimmune disease that mainly affects women of childbearing age. Lupus nephritis represents the most frequent clinical manifestation in pregnancy, constituting a risk factor for pregnancy loss, especially in patients with kidney damage. It also has a higher risk of fetal loss, intrauterine growth restriction, and gestational hypertension. CLINICAL CASES: The first case is a 28 + 2-week pregnant woman with severe kidney damage and high-titles anti-DNA antibodies. In the second case, we highlight the debut with symptoms of respiratory distress and edema as clinical manifestations of type V lupus nephropathy in a 23-week gestation. In both cases, prematurity stands out as a perinatal complication, as well as delayed intrauterine growth in the former. Finally, the clinical-analytical results are described, after the specific therapeutic initiation in both cases. CONCLUSIONS: The differential diagnosis of the onset of lupus nephritis during pregnancy continues to be a challenge, despite the advances in angiogenic markers; clinical assessment continues to be the cornerstone of this diagnostic process and its implications for current and future pregnancy complications.

Guía de práctica clínica para el tratamiento farmacológico de nefritis lúpica / Clinical practice guideline for the pharmacological treatment of lupus nephritis

La nefritis lúpica (NL) es un tipo de glomerulonefritis que se desarrolla como consecuencia del lupus eritematoso sistémico (LES), una enfermedad autoinmune sistémica de presentación clínica variable (1, 2). La NL se clasifica histológicamente en seis clases(I-VI) (3), las cuales poseen diferentes manifestaciones clínicas y expresan diferentes grados de gravedad del daño renal (1). En este documento no se abordará a pacientes con clase VI pues solo son tributarios a terapia de reemplazo renal. La NL se presenta aproximadamente en el 50 a 60% de las personas con LES, en quienes es una de las principales causas de morbimortalidad puesto que progresa a falla renal o muerte (1, 2). En suma, la prevalencia, gravedad y mortalidad de la NL son mayores en hispanos, afroamericanos, y asiáticos (4). El tratamiento farmacológico de la NL consta de las fases de inducción y mantenimiento (1). Entre los fármacos principalmente utilizados durante estas fases, se encuentran los antimaláricos, glucocorticoides (GC), inmunosupresores como micofenolato mofetilo (MMF) y ciclofosfamida (CYC) endovenosa, entre otros (1, 2). Sin embargo, la incidencia de respuesta renal completa suele ser baja (~20 a 30%) (1, 5, 6), y tanto las recaídas como los eventos adversos pueden ser frecuentes con estas terapias (1). Por ello, actualmente se ha propuesto el uso de diferentes dosis de dichos fármacos y otros inmunosupresores ya sea solos o en combinación. La evaluación de los beneficios y daños de estos fármacos permitirá conocer cuáles son las opciones más eficaces y seguras que logren inducir la remisión de la enfermedad, prevenir las recaídas, prevenir la progresión a falla renal y disminuir la mortalidad de los adultos con diagnóstico reciente de NL. Por ello, el Seguro Social de Salud (EsSalud) priorizó la realización de la presente guía de práctica clínica (GPC) para establecer lineamientos basados en evidencia con el fin de gestionar de la mejor manera los procesos y procedimientos asistenciales de la presente condición. Esta GPC fue realizada por la Dirección de Guías de Práctica Clínica, Farmacovigilancia y Tecnovigilancia del Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) de EsSalud.

Nefritis lúpica: experiencia con dosis reducidas de glucocorticoides en una unidad de enfermedades autoinmunes sistémicas / Lupus nephritis: low-dose glucocorticoids in a systemic autoimmune diseases unit / Nefritis lúpica: experiência con doses reduzidas de glicocorticoides em uma unidade de doenças autoinmunes sistémicas

Resumen: Introducción: las recomendaciones actuales del tratamiento de la nefritis lúpica (NL) apuntan a dosis de glucocorticoides más bajas para lograr el control de la enfermedad y evitar el daño acumulado. Objetivo: conocer y comparar la respuesta al tratamiento de pacientes con NL proliferativa en su etapa de inducción con dos pautas de tratamiento con prednisona (PDN): dosis iniciales reducidas 30 mg/d. Método: se compararon variables clínicas, analíticas y terapéuticas de pacientes con NL proliferativa categorizados en dos grupos según la dosis inicial de prednisona (PDNi) estándar o reducida. Resultados: se estudiaron 21 pacientes con NL proliferativa (n=12 PDNi reducida vs. n=9 PDNi estándar). No hubo diferencias significativas en las variables clínicas y analíticas. Se observó una diferencia estadísticamente significativa en el número de pulsos de metilprednisolona (5 ± 2,95 PDNi 30 mg/d, p = 0,041) y en la dosis de prednisona acumulada a 6 meses (12,8 mg ± 4,9 PDNi 30 mg/d, p =0,008). No hubo diferencias significativas en la proporción de pacientes que alcanzaron la respuesta completa, en el tiempo hasta alcanzarla ni en los efectos adversos entre ambos grupos. Conclusiones: el esquema terapéutico del grupo PDNi <30 mg/d se asoció a una menor dosis acumulada de prednisona y una respuesta al tratamiento comparable, lo que hace presumir menor daño acumulado relacionado al uso de glucocorticoides.

Abstract: Introduction: current recommendations to treat lupus nephritis (LN) point to low-dose glucocorticoids to control the disease and avoid cumulativedamage. Objective: to learn about and compare the response of patients with proliferative LN who are treated following two prednisone therapy guidelines: reduced initial doses 30 mg/d during the induction stage. Method: clinical, analytical and therapeutic guidelines of patients with proliferative LN were compared and classified into two groups according to the standard or low-dose initial prednisone dose. Results: 21 patients with proliferative LN were studied (n=12 low-dose initial prednisonevs. n=9 standard initial prednisone). No significant differences were found between clinical and analytical variables, although a significantly different statistic difference was observed in the number of methylprednisone pulses (5 ± 2.95 initial prednisone 30 mg/d, p = 0.041) and in the prednisone dose accumulated in 6 months (12.8 mg ± 4.9 initial prednisone 30 mg/d, p =0.008). No significant differences were seen between both groups in the proportion of patients who achieved complete response, neither in terms of the time it took to achieve it or in the side effects. Conclusions: the treatment plan for the initial prednisone <30 mg/d was associated to a lower cumulative dose of response prednisone considering the comparable treatment, what suggests there being smaller cumulative harm as a consequence of the use of glucocorticoids.

Resumo: Introdução: as recomendações atuais para o tratamento da nefrite lúpica (NL) estão orientadas a doses de glicocorticoides mais baixas para controlar a enfermidade e evitar o dano acumulado. Objetivo: conhecer e comparar a resposta ao tratamento de pacientes com NL proliferativa na etapa de indução com duas pautas de tratamento com prednisona (PDN): doses iniciais reduzidas 30 mg/d. Método: foram comparadas variáveis clínicas, analíticas e terapêuticas de pacientes com NL proliferativa divididos em dois grupos segundo a dose inicial de prednisona (PDNi) padrão ou reduzida. Resultados: 21 pacientes com NL proliferativa (n=12 PDNi reduzida vs. n=9 PDNi estândar) foram estudados. Não foram observadas diferenças significativas nas variáveis clínicas e analíticas. Observou-se uma diferença estatisticamente significativa no número de pulsos de metilprednisolona (5 ± 2,95 PDNi 30 mg/d, p = 0,041) e nas doses de prednisona acumulada aos 6 meses (12,8 mg ± 4,9 PDNi 30 mg/d, p =0,008). Não foram observadas diferenças significativas na proporção de pacientes que alcançaram a resposta completa, no tempo até alcançá-la nem nos efeitos adversos entre ambos grupos. Conclusões: o esquema terapêutico do grupo PDNi <30 mg/d foi associado a uma menor dose acumulada de prednisona em resposta ao tratamento comparável, o que sugere menos dano cumulativo relacionado ao uso de glicocorticoides.

Analysis of the clinical effects of the combination of mycophenolate mofetil with either tacrolimus or cyclophosphamide

OBJECTIVES: Here, we aimed to compare the clinical effects of mycophenolate mofetil combined with either tacrolimus or with cyclophosphamide on lupus nephritis (LN) and to analyze their influence on the expression of cystatin C and on transforming growth factor-1 (TGF-β1). METHODS: A total of 234 patients were randomly divided into two groups: group A, for mycophenolate mofetil combined with tacrolimus (n=117) and group B, for mycophenolate mofetil combined with cyclophosphamide (n=117). The enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum TGF-β1 and cystatin C before and after treatment. RESULTS: The total effectiveness rate in group A was much higher than that in group B. The times of effectiveness and effect validity in group A were much lower than those in group B. The expression levels of serum TGF-β1 and cystatin C decreased slightly after treatment in the two groups, and those of group A were much lower than those of group B. CONCLUSIONS: The combination of mycophenolate mofetil and tacrolimus showed better clinical efficacy on LN and was safer than that of mycophenolate mofetil and cyclophosphamide. Moreover, the drug combination of mycophenolate mofetil and tacrolimus greatly reduced the expression levels of serum TGF-β1 and cystatin C.

Pediatric lupus nephritis / Nefrite lúpica em pediatria

Abstract Involvement of the kidneys by lupus nephritis (LN) is one of the most severe clinical manifestations seen in individuals with systemic lupus erythematosus (SLE). LN is more frequent and severe in pediatric patients and has been associated with higher morbidity and mortality rates. This narrative review aimed to describe the general aspects of LN and its particularities when affecting children and adolescents, while focusing on the disease's etiopathogenesis, clinical manifestations, renal tissue alterations, and treatment options.

Resumo A nefrite lúpica (NL) é caracterizada pelo acometimento dos rins no contexto das diversas manifestações clínicas do Lupus Eritematoso Sistêmico (LES), e representa uma das manifestações clínicas mais graves da doença. A NL é mais frequente e mais grave nos pacientes pediátricos, em comparação com os adultos, e causa maiores taxas de morbidade e mortalidade. O objetivo desta revisão narrativa foi descrever os aspectos gerais da NL e suas particularidades em crianças e adolescentes, com foco em sua etiopatogênese, nas manifestações clínicas, nas alterações histopatológicas renais e na abordagem terapêutica.

Mujer joven con nefritis lúpica y dengue / Young woman with lupus nephritis and dengue

Se reporta caso clínico de una mujer de 21 años con lupus eritematoso sistémico (LES) de diagnóstico reciente complicada con nefritis lúpica (NL) tratada en nuestro centro, con evolución favorable con inmunosupresores. Pero reingresa por dengue con signos de alarma del cual se recupera satisfactoriamente.

Clinical case of a 21 year old woman with complicated systemic lupus erythem atosus (SLE) recently diagnosed with lupus nephritis (LN) treated at our center, with favorable evolution immunosuppression reported. But readmitted because dengue of with warning signs, at present he is recovering satisfactorily

Tratamientos biológicos para nefropatía lúpica / Biological treatment and lupus nephritis

Renal involvement in patients with Systemic Lupus Erythematosus is frequent causing considerable morbidity and mortality. Conventional therapy consists of immunosuppressive medications administered in two stages, induction followed by a maintenance phase. Different drugs result in similar outcomes although with adverse events and relapses. Here we present a brief review of the published literature regarding new approaches in therapy with emphasis on biological treatment and lupus nephritis...

La afectación renal en pacientes con Lupus Eritematoso Sistémico es frecuente, causando un aumento tanto de la morbilidad como la mortalidad. El tratamiento convencional incluye inmunosupresores en una fase de inducción y otra de mantención, con una eficacia similar entre ellos, sin embargo pueden presentar efectos adversos graves y recaídas de la enfermedad. A continuación se presenta una breve revisión de la literatura publicada respecto a los nuevos tratamientos biológicos y nefritis lúpica...

Are serum cystatin C levels influenced by steroid doses in lupus nephritis patients? / Os níveis séricos de cistatina C sofrem influência da dose de corticoide em pacientes com nefrite lúpica?

INTRODUÇÃO: A cistatina C é considerada como um teste promissor para avaliar a taxa de filtração glomerular, pois apresenta características de um marcador endógeno ideal, sendo similar ou até superior à creatinina sérica, segundo alguns estudos. No entanto, é possível que alguns fatores (como corticoterapia) influenciem os níveis séricos da cistatina C, independente da taxa de filtração glomerular. Procurouse investigar se diferentes doses de glicocorticoides afetariam os níveis do marcador em pacientes com nefrite lúpica. MÉTODOS:Foramavaliados42pacientescom nefrite lúpica, submetidos a 109 coletas de sangue diferentes; a idade média deles era de 37,7 ± 13,1 anos, e 88 por cento eram do sexo feminino; a taxa de filtração glomerular estimada média era de 61,9 ± 20,0 mL/min. Os pacientes foram divididos, de acordo com a dose de corticoide, em dois grupos: A - altas (pulsoterapia com metilprednisolona e prednisona > 0,5 mg/kg/dia, n = 14) versus B - baixas doses (prednisona ≤ 0,5 mg/kg/dia, n = 28). Os níveis de creatinina sérica foram usados como parâmetros de comparação em relação à função renal. A cistatina C foi determinadapor metodologia desenvolvida in-house, usando citometria de fluxo na plataforma Luminex. RESULTADOS: Considerando esses dois grupos, os níveis de cistatina C foram diferentes apenas nas amostras da segunda consulta (p = 0,106). Mas, quando considerados os níveis de creatinina sérica nos mesmos grupos, foi observada uma diferença marginalmente significante entre eles (p=0,070), sugerindo que a diferença nos níveis de cistatina C entre os grupos foi causada por suas respectivas taxas de filtração glomerular. Não houve diferença entre os que receberam, ou não, pulsoterapia. CONCLUSÕES: Embora alguns estudos tenham mostrado que os glicorticoides podem influenciar os níveis de cistatina C, não foi observada tal interferência nesta população de pacientes com nefrite lúpica submetidos à corticoterapia.

INTRODUCTION: Cystatin C is considered a promising test to evaluate glomerular filtration rate, since it has characteristics of an ideal endogenous marker, being similar or even superior to serum creatinine according to some studies. However, it is possible that some factors (as corticotherapy) could have an influence on serum cystatin C levels regardless of the glomerular filtration rate. The aim of this study was to investigate if different doses of glucocorticoid could have an influence on serum cystatin C levels in lupus nephritis patients. METHODS: We evaluated 42 patients with lupus nephritis that performed 109 different blood collections; their mean age was 37.7 ± 13.1 years old, and 88 percent were female; the mean estimated glomerular filtration rate was of 61.9 ± 20.0 mL/min. Patients were divided according to their glucocorticoid dose in two groups: A - high (pulse therapy with methylprednisolone and prednisone > 0.5 mg/kg/d, n = 14) versus B - low doses (prednisone ≤ 0.5 mg/kg/d, n = 28). Serum creatinine levels were used as parameters for renal function comparison. Cystatin C was determined by an in-house methodology, using Luminex system flow citometry. RESULTS: Considering these groups, cystatin C levels were different only in the second visit (p = 0.106). But, when the serum creatinine levels were considered in the same groups, a marginally significant difference among them (p = 0.070) was observed, which suggested that the difference in cystatin C levels between the groups was caused by their respective glomerular filtration rate. There was not any difference between those groups that received or did not receive pulse therapy. CONCLUSION: Although some previous studies have shown that glucocorticoid has an influence on serum cystatin C levels, we have not observed such interference in the lupus nephritis patients submitted to corticotherapy.

Nephrogenic systemic fibrosis following acute kidney injury and exposure to gadolinium.

Nephrogenic systemic fibrosis (NSF) is a scleroderma-like systemic fibrosing condition of unknown etiology described in patients with renal insufficiency. Gadolinium exposure has been strongly associated with the development of NSF though the mechanism of such injury is not known. There are only few reported cases of NSF in the setting of acute renal failure and fewer reported cases where skin lesions developed after kidney function had returned to normal. We report a case of NSF in a young Hispanic woman with lupus nephritis but normal creatinine, who received gadolinium during a brief episode of prerenal acute kidney injury not requiring dialysis, secondary to sepsis.

Factores predictores de la respuesta a la terapia de inducción con ciclofosfamida en nefritis lúpica proliferativa / Predictive factors of response to cyclophosphamide-based induction therapy for proliferative lupus nephritis

El daño renal adiciona significativa morbilidad y mortalidad a los pacientes afectados por lupus eritematoso sistémico (LES). Se estudiaron 38 enfermos con LES con nefritis lúpica proliferativa para determinar el porcentaje de ellos que logran buena respuesta con la terapia de inducción con ciclofosfamida endovenosa y los factores que permitan predecir la respuesta a la misma. Estos sujetos fueron atendidos entre enero de 1997 y diciembre del 2006, período durante el cual recibieron terapia de inducción con 6 dosis de pulsos mensuales de ciclofosfamida. Se realizó un estudio longitudinal de evaluación pronóstica. Se obtuvo respuesta con la terapia de inducción en 27 pacientes, el 71,1 por ciento: completa en 24 casos y parcial en 3. Las variables analizadas, tanto sociodemográficas como clínicas e histológicas, presentes antes de iniciar el tratamiento, no mostraron asociación significativa en predecir la respuesta al mismo, incluidas dentro de estas las pruebas de función renal y los índices de actividad y de cronicidad histológica. Se concluyó que la ciclofosfamida es eficaz en la terapia de inducción de la nefritis lúpica proliferativa, pero no se identificaron factores que permitan predecir los casos que no lograran respuesta con la misma.

Renal damage brings significant additional morbidity and mortality to patients with systemic erythematous lupus (SEL). Thirty eight patients with SEL and proliferative lupus nephritis were studied to determine what percentage of them has good response to intravenous cyclophosphamide-based induction therapy and the factors that allow predicting that response. These subjects were seen in the period from January 1997 to December 2006 and received induction therapy based on 6 doses of cyclophosphamide pulses every month. A longitudinal prognostic evaluation study was undertaken. Response to induction therapy was seen in 27 patients (71.1 percent) that was complete in 24 cases and partial in 3 patients. The analyzed variables comprising socio-demographic, clinical and histological ones, already existing before the treatment, were not significantly associated to response prediction including renal function test and renal activity, and histological chronicity indexes. It was concluded that cyclophosphamide is effective in induction therapy for proliferative lupus nephritis; however, the predictive factors for cases that will not respond to it remained unknown.

Terapia de rescate con micofenolato mofetil en pacientes con nefritis lúpica / Rescue therapy in lupus nephritis patients with micophenolato mofetil

La terapia a largo plazo con ciclofosfamida combinada con esteroides mejora la sobrevida renal en pacientes con Nefritis Lúpica Proliferativa, pero con efectos tóxicos considerables. En años recientes, el Micofenolato Mofetil (MMF) un inmunosupresor usado en trasplante, parece ser efectivo en casos selectos de Nefritis Lúpica. Métodos: Describiremos 6 pacientes con Nefritis Lúpica clase IV y V según OMS que por distintas razones debieron ser tratados con MMF como droga de rescate. El mismo estabilizó la función renal. Controló la actividad del LES y permitió la disminución o suspensión del corticoide. Resultados: En tres casos se logró remisión completa, dos presentaron remisión parcial y tuvimos un fracaso por plaquetopenia y leucopenia severa con sepsis grave a punto de partida de una neumopatía; en este paciente se suspendió el tratamiento. Uno de ellos presentó un herpes zóster que se trató con Aciclovir y la suspensión transitoria de MMF. Conclusión: EL MMF fue efectivo para conseguir remisiones en la NL y mantener inactivo el LES, por lo que se lo debiera considerar como terapia de rescate, o bien para tratamiento de mantenimiento luego de la inducción con ciclofosfamida, o directamente como terapia de inducción en aquellos pacientes donde la fertilidad es un factor importante. Seguimientos a largo plazo de las pacientes son necesarios para evaluar su efectividad en la sobreviva renal, como ya ha sido demostrado con la Ciclofosfamida.

Long term cyclophosfamide combinated steroids therapy improves renal survival in patients with Proliferate Lupus Nephritis, with considerable toxic effects. In lately years MMF, a immune suppressor used in transplant, seems to be effective in selected cases of Lupus Nephritis. Methods: We will describe six patients with Lupus Nephritis class IV and V (OMS Classification). that what different causes they must be treated with MMF like rescue drug. This stabilizes the renal function. controls LES activity and allows reductions or end of corticoids. Results: In tree cases we achievement total remission, two show partial remission and we had a fail because plaquetopenia and severe leucopenia with serious sepsis to give rise to neumopaty; this patient broke off the treatment. One presented Zoster...

Curso clínico de la nefropatía membranosa lúpica pura / Long-Term outcome of type V lupus membranous glomerulonephritis

Background: The long-term outcome of the pure form of WHO type V lupus membranous glomerulonephritis is apparently more benign than that of other forms of lupus glomerulonephritis. However 12percent of such patients progress to terminal renal failure. The presence of proteinuria may be an indication of cytotoxic agents. Aim: To study the clinical long-term outcome of WHO type V lupus membranous glomerulonephritis. Material and methods: A retrospective analysis of all kidney biopsies of a University Pathology Department, with the diagnosis of WHO type V lupus membranous glomerulonephritis. Review of medical records of patients with the disease and one clinical assessment of all living patients. Results: Between 1973 and 2000, 703 kidney biopsies were done to patients with systemic lupus erythematosus. Of these, 40 were membranous glomerulonephritis and in 33 patients (28 women, age range 6-71 years), data on the evolution and survival was obtained. Nineteen had type Va and the rest type Vb nephritis. Two presented with renal failure and 11 with proteinuria over 3.5 g/24h. The median follow-up since the renal biopsy was 63 months (range 1-316). At the end of follow-up, four had a creatinine clearance of less then 15 ml/h and four a clearance between 15 and 29 ml/h (one of these received a renal allograft). Eleven (33percent) patients had died, mostly due to infections. Life expectancy at five years with a creatinine clearance over 15 ml/h was 75percent. Bad prognostic factors were an elevated creatinine clearance over 15 ml/h was 75percent. Bad prognostic factors were an elevated creatinine and high blood pressure at the moment of the biopsy. Conclusions: The clinical outcome of these patients was bad. Twelve percent reached a stage of terminal renal failure. This is in contrast with the 3percent progression to a similar stage of proliferative glomerulonephritis treated with i.v. cyclophosphamide. New therapies for this condition must be sought.

Renal Involvement in Systemic Lupus Erythematosus in Pakistan

To find the prevalence of lupus nephritis, delineate its clinical, immunological and therapeutic characteristics and compare them with the data worldwide. Between 1985 and 2001, 198 patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatism Association [ARA] admitted to the hospital were studied by means of a retrospective review of their records. Renal involvement was found in 89 [45%] patients. Biopsy showed lupus nephritis in 42 patients; there were 9 male and 33 females. Mean age at initial presentation was 27 years and mean duration of follow-up was 2.3 years. The histological types [WHO Classification] were mainly class. 4 [n=27], class 3 [n=7] and class 5 [n=6]. Immunoflourescence showed a predominantly granular pattern of IgG, IgA and C3. Renal manifestations included renal failure [50%], microscopic hematuria [67%], active urine sediment [22%], and proteinuria [74%]. Proteinuria was nephrotic range in 45% patients. Treatment was with combinations of prednisolone and cyclophosphamide [n=13], prednisolone and azathioprine [n=27]. 19 patients received high dose methyl prednisolone [1 gm/day for 3 days]. There was no difference in mortality rate between prednisolone and cyclophosphamide and prednisolone and azathioprine treatment groups. The overall mortality rate was 17% [n=7]. Mortality was higher in WHO class 4 and 5 as compared to class 2 and 3 [p<0.001]. The prevalence of lupus nephritis in our population is an intermediate between Caucasians and other Asians. Certain clinical characteristics in our patients with lupus nephritis are different as compared to various other studies. Because of limited resources for treatment in developing countries, we believe that patients with lupus nephritis should be treated with improved ancillary medical therapies and more effective immunosuppressive regimens

Análise dos indicadores de atividade da doença em pacientes com nefrite lúpica antes e após seis pulsos de ciclofosfamida / Analysis of disease activity indicators in patients with lupus nephritis before and after six pulses of cyclophosphamide

Introduçäo: A ciclofosfamida é atualmente uma das principais drogas citotóxicas para o tratamento da nefropatia lúpica, manifestaçäo clínica de grande morbidade e mortalidade. Objetivo: Avaliar os níveis da proteinúria de 24 horas em pacientes com Lupus Eritematoso Sistêmico, tratados com pulsos de ciclofosfamida, estabelecendo uma correlaçäo com a hemoglobina, a velocidade de hemossedimentaçäo, a creatinina e fraçöes C3 e C4 do complemento. Métodos: Foram analisados os prontuários de 29 pacientes antes e após seis pulsos mensais e consecutivos de ciclofosfamida, correlacionando os níveis da proteinúria de 24 horas, hemoglobina, velocidade de hemossedimentaçäo, creatinina, C3 e C4. Resultados: Observaram-se diminuiçäo na proteinúria de 24 horas (p<0,01), aumento da hemoglobina (p<0,01), diminuiçäo da velocidade de hemossedimentaçäo (p<0,05) e elevaçäo dos níveis de C3 (p<0,05) e C4 (p<0,05). Também foi encontrada correlaçäo entre hemoglobina e velocidade de hemossedimentaçäo (p<0,01), hemoglobina e C4 (p<0,05) e C3 e C4 (p<0,01). Conclusäo: Os parâmetros analisados e correlacionados apresentaram melhora significativa, sendo mais pronunciada na proteinúria e na hemoglobina. Este estudo retrospectivo demonstrou a açäo da ciclofosfamida nos indicadores de atividade da doença, no Lúpus Eritematoso Sistêmico, e a correlaçäo destes indicadores.

Tratamento da nefropatia lúpica severa: efeito da ciclofosfamida endovenosa prolongada intermitente / Treatment of severe lupus nephritis: effect of prolonged and intermittent intravenous cyclophosphamide

A ciclofosfamida intravenosa é amplamente usada no tratamento da nefrite lúpica. Para analisar os desfechos a longo prazo, estudamos 54 pacientes tratados com ciclofosfamida no período entre 1989/1999...

Uso de pentoxifilina en pacientes pediátricos con nefropatía lúpica grado IV (OMS) multitratados / Use of pentoxifilina in pediatrics patients with lupic nefrofatia degree IV the (WHO) multitred

Antecedentes: el lupus eritematoso sistémico es una enfermedad autoinmune; 90 por ciento de los niños que la padecen llega a sufrir nefropatía Material y método: se estudiaron seis pacientes con nefropatía lúpica grado IV (OMS), entre 0 y 16 años, multitratados, a quienes se administró pentoxifilina (PTX). Se tomaron exámenes antes, durante el inicio y cuatro meses posteriores al tratamiento; se evaluaron las funciones renal y hepática. Resultados: se estudió a seis pacientes (cuatro mujeres y dos hombres) con una media de edad 14.1 años, La proteinuria obtuvo una p=0.0012 que fue significativa; los complejos inmunes circulantes tuvieron una p=0.0050. La hematuria mostró disminución paulatina. La inversa de la creatinina mostró modificación en su pendiente. Conclusión: el uso de la pentoxifilina en pacientes con nefritis lúpica ayuda a frenar el deterioro habitual de la función renal. Si se incluyeran más pacientes y se trataran durante más tiempo, seguramente se obtendrían mejores resultados.