RESUMEN
OBJECTIVE: The purpose of this study was to analyze the clinical, pathological, prognostic features and treatment response of the coexistence of focal segmental glomerulosclerosis lesions with idiopathic membranous nephropathy. METHODS: This is a two-center retrospective cohort study. Patients of idiopathic membranous nephropathy were enrolled and divided into two groups with or without focal segmental glomerulosclerosis lesions according to the renal biopsy. Laboratory data and pathological manifestation were compared. Renal phospholipase A2 receptor was detected by immunofluorescence. During the follow-up, the effects of different therapies and renal function were estimated. RESULTS: A total of 236 patients were finally enrolled in this study, of which 60 and 176 idiopathic membranous nephropathy patients were enrolled in the FSGS+ and FSGS- groups, respectively. The FSGS+ group showed a higher percentage of hypertension history (38.3 vs. 20.0%, p=0.004), with a significantly higher level of systolic pressure [137 (120, 160) mmHg vs. 130 (120, 140) mmHg, p=0.009]. Main laboratory findings, including serial albumin (20.4±7.8 g/L vs. 24.5±6.7 g/L, p<0.001), 24-h proteinuria [5.61 (3.10, 7.87) g/day vs. 3.82 (2.31, 5.79) g/day, p=0.002], serial creatinine [80.8 (65.8, 97.9) µmol/L vs. 72.0 (58.7, 84.9) µmol/L, p=0.003], and estimated glomerular filtration rate [86 (66, 101) mL/min/1.73 m2 vs. 95 (81, 108) mL/min/1.73 m2, p=0.007] showed significant differences between the two groups. Pathologically, patients with focal segmental glomerulosclerosis lesions appeared with a higher percentage of crescents, a more severe degree of interstitial fibrosis, and a higher level of membranous nephropathy stage. Renal phospholipase A2 receptor showed a relatively lower positive rate of only 75.0% in the FSGS+ group in comparison with the positive rate of 90.3% in the FSGS- group (p=0.031). The prognosis was generally similar between the two groups. Among patients who were given non-immunosuppression treatment, those with focal segmental glomerulosclerosis lesions took a relatively longer period of time to achieve complete remission (29.3±7.0 m vs. 15.4±8.9 m, p=0.025) and experienced a higher rate of renal function deterioration (37.5 vs. 5.4%, p=0.033) compared with the other ones. While among those receiving immunosuppression treatment, both groups received similar remission rates. CONCLUSION: Compared with FSGS- group, idiopathic membranous nephropathy with focal segmental glomerulosclerosis lesions represented more severe nephrotic syndrome and worse renal function. In view of the renal function decline during the follow-up, more aggressive treatment with the use of immunosuppressants should be considered for idiopathic membranous nephropathy patients with focal segmental glomerulosclerosis lesions.
Asunto(s)
Glomerulonefritis Membranosa , Glomeruloesclerosis Focal y Segmentaria , Inmunosupresores , Humanos , Glomerulonefritis Membranosa/patología , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis Membranosa/fisiopatología , Femenino , Masculino , Glomeruloesclerosis Focal y Segmentaria/patología , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Inmunosupresores/uso terapéutico , Biopsia , Tasa de Filtración Glomerular , Proteinuria/etiología , Receptores de Fosfolipasa A2/inmunología , Pronóstico , Resultado del Tratamiento , Riñón/patología , Riñón/fisiopatologíaRESUMEN
INTRODUCTION: The use of Rituximab (RTX) in glomerular diseases (GD) has increased in the past years, although it is still only used in a small fraction of patients. METHODS: A single center retrospective study of adult patients with membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), lupus nephritis (LN), and vasculitis treated with RTX as first or second-line therapy was conducted at our center from 2010 to 2020. RESULTS: We identified 19 patients; 36.8% had MN and 25.0% each had FSGS, LN, and vasculitis. RTX was first-line therapy in 26.3% of patients and in 73.7% it was second-line therapy. Mean follow-up time was 7.7 ± 7.2 years. In MN, 2 patients (28.6%) had complete remission (CR), 2 patients (28.6%) had partial remission (PR), and 3 patients (42.9%) had no response (NR). In FSGS, 2 patients (50.0%) presented CR, 1 patient (25.0%) had no response, and 1 patient had renal deterioration. Two patients (50.0%) had a LN class IV with a CR after RTX, 1 patient with LN class IIIC/V had no response, and 1 patient with LN class II had renal deterioration. In vasculitis, 3 patients (75.0%) presented CR and 1 patient had PR. Infusion reactions were present in 2 patients (10.5%) and one patient had multiple infectious complications. CONCLUSIONS: The efficacy of RTX in treating different types of immune-mediated GD has been demonstrated with different response rates, but an overall safe profile. In our case series, the results are also encouraging. Longitudinal studies are needed to better understand the effect of RTX in GD.
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Glomerulonefritis Membranosa , Glomeruloesclerosis Focal y Segmentaria , Nefritis Lúpica , Vasculitis , Adulto , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Rituximab/uso terapéutico , Resultado del TratamientoRESUMEN
Abstract Introduction: Some cases of membranous nephropathy (MGN) present focal segmental glomerulosclerosis (FSGS) typically associated with disease progression. However, we report a case of a patient who seemed to have MGN and FSGS, both primary. Case presentation: A 17-year-old female, Caucasian, presenting lower extremity edema associated with episodes of foamy urine and high blood pressure, had physical and laboratorial exams indicating nephrotic syndrome. A renal biopsy was performed and focal and segmental glomerulosclerosis were observed under light microscopy in some glomeruli presented as tip lesion, and in others it was accompanied by podocyte hypertrophy and podocyte detachment in urinary space, compatible with podocytopathy FSGS. Besides, there were thickened capillary loops with basement membrane irregularities due to "spikes" compatible with MGN stage II. Immunofluorescence showed finely granular IgG, IgG4, and PLA2R deposits in capillary loops and, in electron microscopy, subepithelial deposits and foot process effacement. These morphological findings are compatible with FSGS and MGN stage II. Conclusions: In the present case, clinical and morphological characteristics showed a possible overlap of primary FSGS and MGN as focal and segmental glomerulosclerosis does not seem to be related with MGN progression but with the podocytopathy FSGS.
Resumo Introdução: Alguns casos de nefropatia membranosa (NM) apresentam glomeruloesclerose segmentar e focal (GESF) tipicamente associada a progressão da doença. Contudo, relatamos o caso de uma paciente que parece ter NM e GESF, ambas primárias. Apresentação do caso: Uma jovem branca de 17 anos de idade com edema de membros inferiores associado a episódios de urina espumosa e hipertensão apresentou-se com achados físicos e laboratoriais sugestivos de síndrome nefrótica. Foi realizada biópsia renal. GESF foi observada por microscopia de luz em alguns glomérulos que apresentavam lesões de ponta, enquanto em outros o achado era acompanhado por hipertrofia podocitária e descolamento de podócitos no espaço urinário, compatíveis com podocitopatia GESF. Além disso, as alças capilares estavam espessadas com irregularidades na membrana basal devido a "espículas" compatíveis com NM estágio II. Imunofluorescência revelou depósitos finamente granulares de IgG, IgG4 e PLA2R nas alças capilares. Microscopia eletrônica exibiu depósitos subepiteliais e apagamento de pedicelos. Tais achados morfológicos são compatíveis com GESF e NM estágio II. Conclusões: No presente caso, as características clínicas e morfológicas revelaram uma possível sobreposição de GESF primária e NM, uma vez que a glomeruloesclerose segmentar e focal não parece estar relacionada com a progressão da NM, mas com a podocitopatia GESF.
Asunto(s)
Humanos , Femenino , Adolescente , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Glomeruloesclerosis Focal y Segmentaria/diagnóstico , Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis Membranosa/diagnóstico , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/diagnóstico , Biopsia , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Glomeruloesclerosis Focal y Segmentaria/patología , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glomerulonefritis Membranosa/patología , Glomerulonefritis Membranosa/tratamiento farmacológico , Resultado del Tratamiento , Riñón/patología , Síndrome Nefrótico/tratamiento farmacológicoRESUMEN
INTRODUCTION: Some cases of membranous nephropathy (MGN) present focal segmental glomerulosclerosis (FSGS) typically associated with disease progression. However, we report a case of a patient who seemed to have MGN and FSGS, both primary. CASE PRESENTATION: A 17-year-old female, Caucasian, presenting lower extremity edema associated with episodes of foamy urine and high blood pressure, had physical and laboratorial exams indicating nephrotic syndrome. A renal biopsy was performed and focal and segmental glomerulosclerosis were observed under light microscopy in some glomeruli presented as tip lesion, and in others it was accompanied by podocyte hypertrophy and podocyte detachment in urinary space, compatible with podocytopathy FSGS. Besides, there were thickened capillary loops with basement membrane irregularities due to "spikes" compatible with MGN stage II. Immunofluorescence showed finely granular IgG, IgG4, and PLA2R deposits in capillary loops and, in electron microscopy, subepithelial deposits and foot process effacement. These morphological findings are compatible with FSGS and MGN stage II. CONCLUSIONS: In the present case, clinical and morphological characteristics showed a possible overlap of primary FSGS and MGN as focal and segmental glomerulosclerosis does not seem to be related with MGN progression but with the podocytopathy FSGS.
Asunto(s)
Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis Membranosa/diagnóstico , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Glomeruloesclerosis Focal y Segmentaria/diagnóstico , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/diagnóstico , Adolescente , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Biopsia , Femenino , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/patología , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Riñón/patología , Síndrome Nefrótico/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is considered one of the most severe glomerular diseases and around 80% of cases are resistant to steroid treatment. Since a large proportion of steroid-resistant (SR) FSGS patients progress to end-stage renal disease, other therapeutic strategies may benefit this population. However, identification of non-invasive biomarkers to predict this high-risk population is needed. OBJECTIVE: We aimed to identify the biomarker candidates to distinguish SR from steroid-sensitive (SS) patients using metabolomics approach and to identify the possible molecular mechanism of resistance. METHODS: Urine was collected from biopsy-proven FSGS patients eligible for monotherapy with prednisolone. Patients were followed for 6-8 weeks and categorized as SS or SR. Metabolite profile of urine samples was analyzed by one-dimensional 1H-nuclear magnetic resonance (1H-NMR). Predictive biomarker candidates and their diagnostic importance impaired molecular pathways in SR patients, and the common target molecules between biomarker candidates and drug were predicted. RESULTS: Homovanillic acid, 4-methylcatechol, and tyrosine were suggested as the significant predictive biomarker candidates, while L-3,4-dihydroxyphenylalanine, norepinephrine, and gentisic acid had high accuracy as well. Tyrosine metabolism was the most important pathway that is perturbed in SR patients. Common targets of the action of biomarker candidates and prednisolone were molecules that contributed in apoptosis. CONCLUSION: Urine metabolites including homovanillic acid, 4-methylcatechol, and tyrosine may serve as potential non-invasive predictive biomarkers for evaluating the responsiveness of FSGS patients.
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Metabolómica/métodos , Prednisolona/uso terapéutico , Adulto , Biomarcadores/metabolismo , Femenino , Glomeruloesclerosis Focal y Segmentaria/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del Tratamiento , Adulto JovenRESUMEN
Abstract Background Focal segmental glomerulosclerosis (FSGS) is considered one of the most severe glomerular diseases and around 80% of cases are resistant to steroid treatment. Since a large proportion of steroid-resistant (SR) FSGS patients progress to end-stage renal disease, other therapeutic strategies may benefit this population. However, identification of non-invasive biomarkers to predict this high-risk population is needed. Objective We aimed to identify the biomarker candidates to distinguish SR from steroid-sensitive (SS) patients using metabolomics approach and to identify the possible molecular mechanism of resistance. Methods Urine was collected from biopsy-proven FSGS patients eligible for monotherapy with prednisolone. Patients were followed for 6-8 weeks and categorized as SS or SR. Metabolite profile of urine samples was analyzed by one-dimensional 1H-nuclear magnetic resonance (1H-NMR). Predictive biomarker candidates and their diagnostic importance impaired molecular pathways in SR patients, and the common target molecules between biomarker candidates and drug were predicted. Results Homovanillic acid, 4-methylcatechol, and tyrosine were suggested as the significant predictive biomarker candidates, while L-3,4-dihydroxyphenylalanine, norepinephrine, and gentisic acid had high accuracy as well. Tyrosine metabolism was the most important pathway that is perturbed in SR patients. Common targets of the action of biomarker candidates and prednisolone were molecules that contributed in apoptosis. Conclusion Urine metabolites including homovanillic acid, 4-methylcatechol, and tyrosine may serve as potential non-invasive predictive biomarkers for evaluating the responsiveness of FSGS patients.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Prednisolona/uso terapéutico , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Metabolómica/métodos , Glucocorticoides/uso terapéutico , Glomeruloesclerosis Focal y Segmentaria/fisiopatología , Biomarcadores/metabolismo , Proyectos Piloto , Resultado del TratamientoRESUMEN
Rituximab is a chimeric anti-CD20 monoclonal protein used in various clinical scenarios in kidney transplant recipients. However, its evidence-based use there remains limited due to lack of controlled studies, limited sample size, short follow-up and poorly defined endpoints. Rituximab is indicated for CD20+ posttransplant lymphoproliferative disorder. It may be beneficial for treating recurrent membranous nephropathy and recurrent allograft antineutrophilic cytoplasmic antibody vasculitis and possibly for recurrent focal segmental glomerulosclerosis. Rituximab, in combination with IVIg/plasmapheresis, appears to decrease antibody level and increase the odds of transplantation in sensitized recipients. The role of Rituximab in ABOi transplant remains unclear, as similar outcomes are achieved without its use. Rituximab is not efficacious in antibody-mediated rejection/chronic antibody-mediated rejection. Strict randomized control trials are necessary to elucidate its true role in these settings.
Asunto(s)
Trasplante de Riñón , Rituximab/uso terapéutico , Sistema del Grupo Sanguíneo ABO/inmunología , Incompatibilidad de Grupos Sanguíneos , Desensibilización Inmunológica , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Rechazo de Injerto/inmunología , Rechazo de Injerto/terapia , Humanos , Trasplante de Riñón/efectos adversos , Trastornos Linfoproliferativos/tratamiento farmacológico , Rituximab/efectos adversos , Rituximab/farmacocinética , Rituximab/farmacologíaRESUMEN
INTRODUCTION: There is scarce data on the clinical profile of adult Brazilian patients with nephrotic syndrome caused by minimal change disease (MCD) and focal segmental glomerulosclerosis. OBJECTIVE: We evaluated the clinical characteristics and response to treatment in adult patients with nephrotic syndrome having a histological diagnosis of MCD or FSGS. METHODS: This is a retrospective analysis of 50 patients with MCD and 120 with FSGS. All patients were initially treated with steroids. The study outcomes were: steroid responsiveness, prevalence of total remission, progression to chronic renal failure and need of renal replacement therapy due to end-stage renal disease (ESRD). RESULTS: Initial serum creatinine level was 24% higher among patients with FSGS (p = 0.02), and proteinuria levels were 36% higher in MCD (p < 0.001). Patients with MCD were sensitive to steroid therapy in 80% of the cases, with total remission in 74%, while patients with FSGS were sensitive in 58% (p = 0.01), with total remission in 30% (p = 0.002). Patients with FSGS had an acute renal failure prevalence of 39% (vs. 12%, p = 0.013) and ESRD of 10% (vs. 0%, p < 0.001). Steroid responsiveness reduced in 83% the risk of ESRD (p < 0.001), while total remission was associated to a reduction in risk of 89% (p < 0.001). CONCLUSION: A positive response to steroid therapy was the most important factor related with preservation of renal function and FSGS was related with less steroid responsiveness.
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Nefrosis Lipoidea/tratamiento farmacológico , Síndrome Nefrótico/etiología , Esteroides/uso terapéutico , Adulto , Brasil , Creatinina/sangre , Femenino , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Humanos , Estudios Longitudinales , Masculino , Nefrosis Lipoidea/complicaciones , Síndrome Nefrótico/tratamiento farmacológico , Proteinuria/diagnóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
Resumo Introdução: O perfil clínico de pacientes brasileiros adultos com síndrome nefrótica por doença de lesões mínimas (LM) e glomeruloesclerose segmentar e focal (GESF) é pouco conhecido. Objetivo: Avaliamos as características clínico-laboratoriais e resposta a tratamento em pacientes adultos com síndrome nefrótica e diagnósticos histológicos de LM ou GESF. Métodos: Fez-se a análise retrospectiva de 50 pacientes adultos com LM e 120 com GESF. Todos os pacientes foram inicialmente tratados com corticosteroide. Os desfechos do estudo foram: resposta a corticosteroide, prevalência de remissão total, progressão para doença renal crônica estágio 5 (DRC5) e necessidade de terapia de substituição renal por DRC5. Resultados: Níveis iniciais de creatinina sérica foram 24% mais elevados entre pacientes com GESF (p = 0,02) e os de proteinúria foram 36% mais altos em LM (p < 0,001). Pacientes com LM foram córtico-sensíveis em 80% dos casos, com remissão total em 74%, e os pacientes com GESF em 58% (p = 0,01), com remissão total em 30% (p = 0,002). A prevalência de insuficiência renal aguda em pacientes com GESF foi de 39% (vs. 12%, p = 0,013) e DRC5 de 10% (vs. 0%, p < 0,001). Remissão completa ou parcial com o uso de corticosteroide reduziu em 83% o risco de DRC5 (p < 0,001) e remissão total associou-se a redução no risco de DRC5 de 89% (p < 0,001). Conclusão: A resposta positiva à corticoterapia foi o fator mais importante relacionado à preservação da função renal ao longo de mais de uma década de seguimento, e GESF relacionou-se a menor índice de resposta a corticosteroide.
Abstract Introduction: There is scarce data on the clinical profile of adult Brazilian patients with nephrotic syndrome caused by minimal change disease (MCD) and focal segmental glomerulosclerosis. Objective: We evaluated the clinical characteristics and response to treatment in adult patients with nephrotic syndrome having a histological diagnosis of MCD or FSGS. Methods: This is a retrospective analysis of 50 patients with MCD and 120 with FSGS. All patients were initially treated with steroids. The study outcomes were: steroid responsiveness, prevalence of total remission, progression to chronic renal failure and need of renal replacement therapy due to end-stage renal disease (ESRD). Results: Initial serum creatinine level was 24% higher among patients with FSGS (p = 0.02), and proteinuria levels were 36% higher in MCD (p < 0.001). Patients with MCD were sensitive to steroid therapy in 80% of the cases, with total remission in 74%, while patients with FSGS were sensitive in 58% (p = 0.01), with total remission in 30% (p = 0.002). Patients with FSGS had an acute renal failure prevalence of 39% (vs. 12%, p = 0.013) and ESRD of 10% (vs. 0%, p < 0.001). Steroid responsiveness reduced in 83% the risk of ESRD (p < 0.001), while total remission was associated to a reduction in risk of 89% (p < 0.001). Conclusion: A positive response to steroid therapy was the most important factor related with preservation of renal function and FSGS was related with less steroid responsiveness.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Adulto Joven , Esteroides/uso terapéutico , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Nefrosis Lipoidea/tratamiento farmacológico , Síndrome Nefrótico/etiología , Proteinuria/diagnóstico , Brasil , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Estudios Retrospectivos , Estudios Longitudinales , Creatinina/sangre , Nefrosis Lipoidea/complicaciones , Síndrome Nefrótico/tratamiento farmacológicoRESUMEN
Idiopathic nephrotic syndrome is the most common glomerular disease in childhood, affecting 1 to 3 per 100,000 children under the age of 16. It most commonly occurs in ages between 2 and 10. Its cause is unknown and its histology corresponds to minimal change disease in 90% of cases, or focal segmental glomerulosclerosis. 80 to 90% of cases respond to steroids (steroid-sensitive nephrotic syndrome) with good prognosis and long-term preservation of renal function over time. 70% of patients with SSNS have one or more relapses in their evolution, and of these, 50% behave as frequent relapsing or steroid-dependent, a group that concentrate the risk of steroid toxicity. Patients with steroid-resistant nephrotic syndrome have a poor prognosis and 50% of them evolve to end-stage renal disease. The goal of therapy is to induce and maintain remission of the disease, reducing the risk secondary to proteinuria while minimizing the adverse effects of treatments, especially with prolonged use of corticosteroids. This paper is the result of the collaborative effort of the Nephrology Branch of the Chilean Society of Pediatrics with aims at helping pediatricians and pediatric nephrologists to treat pediatric SNI. In this first part, recommendations of steroid-sensitive nephrotic syndrome are discussed.
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Nefrosis Lipoidea/tratamiento farmacológico , Síndrome Nefrótico/tratamiento farmacológico , Adolescente , Niño , Preescolar , Chile , Progresión de la Enfermedad , Glomeruloesclerosis Focal y Segmentaria/epidemiología , Glomeruloesclerosis Focal y Segmentaria/fisiopatología , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéutico , Humanos , Fallo Renal Crónico/etiología , Fallo Renal Crónico/prevención & control , Nefrosis Lipoidea/epidemiología , Nefrosis Lipoidea/fisiopatología , Síndrome Nefrótico/epidemiología , Síndrome Nefrótico/fisiopatología , Pronóstico , Proteinuria/etiologíaRESUMEN
CONTEXT AND OBJECTIVE: Glomerular disease registries are increasing all around the world. The aim of this study was to evaluate the clinical characteristics and treatment response among patients with glomerular diseases followed up in a tertiary hospital in Brazil. DESIGN AND SETTING: Analytical cross-sectional study; tertiary-level public hospital. METHODS: This study included patients with glomerular diseases followed up at a tertiary hospital in Fortaleza, northeastern Brazil. Clinical and laboratory data on each patient were registered. The response to specific treatment was evaluated after 3, 6 and 12 months. RESULTS: The study included 168 patients of mean age 37 ± 14 years. The most prevalent glomerular diseases were focal segmental glomerulosclerosis FSGS] (19.6%), minimal change disease MCD] (17.9%), membranous nephropathy MN] (16.7%) and lupus nephritis LN] (11.9%). The main clinical presentations were nephrotic proteinuria (67.3%) and renal insufficiency (17.9%). The mean proteinuria value decreased after the treatment began. Regarding 24-hour proteinuria on admission, there was no significant difference between patients with a good response and those with no response (7,448 ± 5,056 versus 6,448 ± 4,251 mg/24 h, P = 0.29). The glomerular disease with the highest remission rate was MCD (92%). Absence ...
CONTEXTO E OBJETIVO: Registros de glomerulopatias estão aumentando em todo o mundo. O objetivo deste estudo é avaliar as características clínicas e a resposta do tratamento de pacientes com glomerulopatias acompanhados em um hospital terciário no Brasil. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico. Hospital público terciário. MÉTODOS: O estudo incluiu pacientes com glomerulopatias acompanhados em um hospital terciário de Fortaleza, Ceará, Brasil. Foi realizado registro dos dados clínicos e laboratoriais para cada paciente. A resposta ao tratamento específico foi avaliada após 3, 6 e 12 meses. RESULTADOS: Foram incluídos 168 pacientes, com média de idade de 37 ± 14 anos. A glomerulopatia mais prevalente foi a glomerulosclerose segmentar e focal GESF] (19,6%), seguida pela doença de lesão mínima DLM] (17,9%), nefropatia membranosa NM] (16,7%) e nefrite lúpica NL] (11,9%). As principais manifestações clínicas foram proteinúria nefrótica (67,3%) e insuficiência renal (17,9%). A média dos valores de proteinúria diminuiu após o início do tratamento. Com relação à proteinúria de 24 horas na admissão, não houve diferença significativa entre os pacientes com boa resposta ao tratamento ...
Asunto(s)
Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Corticoesteroides/uso terapéutico , Glomerulonefritis/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Brasil/epidemiología , Estudios Transversales , Ciclosporina/uso terapéutico , Estudios de Seguimiento , Glomerulonefritis/epidemiología , Glomerulonefritis/patología , Glomeruloesclerosis Focal y Segmentaria/epidemiología , Glomeruloesclerosis Focal y Segmentaria/patología , Prevalencia , Pronóstico , Proteinuria/sangre , Remisión Espontánea , Insuficiencia Renal/complicaciones , Centros de Atención Terciaria/estadística & datos numéricos , Factores de Tiempo , Resultado del TratamientoRESUMEN
CONTEXT AND OBJECTIVE: Glomerular disease registries are increasing all around the world. The aim of this study was to evaluate the clinical characteristics and treatment response among patients with glomerular diseases followed up in a tertiary hospital in Brazil. DESIGN AND SETTING: Analytical cross-sectional study; tertiary-level public hospital. METHODS: This study included patients with glomerular diseases followed up at a tertiary hospital in Fortaleza, northeastern Brazil. Clinical and laboratory data on each patient were registered. The response to specific treatment was evaluated after 3, 6 and 12 months. RESULTS: The study included 168 patients of mean age 37 ± 14 years. The most prevalent glomerular diseases were focal segmental glomerulosclerosis FSGS] (19.6%), minimal change disease MCD] (17.9%), membranous nephropathy MN] (16.7%) and lupus nephritis LN] (11.9%). The main clinical presentations were nephrotic proteinuria (67.3%) and renal insufficiency (17.9%). The mean proteinuria value decreased after the treatment began. Regarding 24-hour proteinuria on admission, there was no significant difference between patients with a good response and those with no response (7,448 ± 5,056 versus 6,448 ± 4,251 mg/24 h, P = 0.29). The glomerular disease with the highest remission rate was MCD (92%). Absence of interstitial fibrosis presented a strong correlation with remission (remission in patients without fibrosis = 83.4% versus 16.3% in those with fibrosis, P = 0.001). CONCLUSIONS: The present study found that the most frequent glomerular disease was FSGS, followed by MCD, MN and LN. The presence of interstitial fibrosis was a predictor of poor therapeutic response.
Asunto(s)
Corticoesteroides/uso terapéutico , Glomerulonefritis/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Adolescente , Adulto , Anciano , Brasil/epidemiología , Estudios Transversales , Ciclosporina/uso terapéutico , Femenino , Estudios de Seguimiento , Glomerulonefritis/epidemiología , Glomerulonefritis/patología , Glomeruloesclerosis Focal y Segmentaria/epidemiología , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Proteinuria/sangre , Remisión Espontánea , Insuficiencia Renal/complicaciones , Centros de Atención Terciaria/estadística & datos numéricos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
The pathogenesis of focal segmental glomerulosclerosis (FSGS) appears to be associated with type-2 cytokines and podocyte dysfunction. In this study, we tested the hypothesis that immunization with the polysaccharide fraction of Propionibacterium acnes (PS), a pro-Th1 agonist, may subvert the type-2 profile and protect podocytes from adriamycin-induced glomerulosclerosis. Adriamycin injection resulted in albuminuria and increased serum creatinine in association with loss of glomerular podocin and podoplanin expression, which is consistent with podocyte dysfunction. Renal tissue analysis revealed the expression of transcripts for GATA3 and fibrogenic-related proteins, such as TGF-ß, tissue inhibitor of metalloproteinase-1 (TIMP-1) and metalloproteinase 9 (MMP9). In association with the expression of fibrogenic transcripts, we observed peri-glomerular expression of α-smooth muscle actin (α-SMA), indicating epithelial-to-mesenchymal transition, and increased expression of proliferating cell nuclear antigen (PCNA) in tubular cells, suggesting intense proliferative activity. Previous immunization with PS inhibited albuminuria and serum creatinine in association with the preservation of podocyte proteins and inhibition of fibrogenic transcripts and the expression of α-SMA and PCNA proteins. Tissue analysis also revealed that PS treatment induced expression of mRNA for GD3 synthase, which is a glycosiltransferase related to the synthesis of GD3, a ganglioside associated with podocyte physiology. In addition, PS treatment inhibited the influx of inflammatory CD8(pos) and CD11b(pos) cells to kidney tissue. Finally, PS treatment on day 4 post-ADM, a period when proteinuria was already established, was able to improve renal function. Thus, we demonstrate that the PS fraction of P. acnes can inhibit FSGS pathogenesis, suggesting that immunomodulation can represent an alternative approach for disease management.
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/etiología , Polisacáridos Bacterianos/farmacología , Propionibacterium acnes/química , Sustancias Protectoras/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Doxorrubicina/efectos adversos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fibrosis/genética , Regulación de la Expresión Génica/efectos de los fármacos , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glomérulos Renales/efectos de los fármacos , Glomérulos Renales/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Polisacáridos Bacterianos/administración & dosificación , Polisacáridos Bacterianos/aislamiento & purificación , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/aislamiento & purificación , Proteinuria/tratamiento farmacológico , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal/tratamiento farmacológico , Linfocitos T/inmunología , Linfocitos T/metabolismo , Células Th2/inmunología , Células Th2/metabolismo , Transcripción GenéticaRESUMEN
BACKGROUND: Recent evidence suggests that treatment of type 2 diabetes with thiazolidinediones [peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists], ameliorates glomerulosclerosis and tubulointerstitial fibrosis in the rat kidney. In the current work, we have investigated whether these drugs, and specifically pioglitazone (PGT), act by preventing fibrosis and kidney dysfunction mainly through antioxidant and anti-inflammatory effects, independently of glycaemic control. METHODS: Male 2- to 3-month-old obese Zucker fa/fa (OZR) and ZDF fa/fa rats (ZDFR), and their control the lean Zucker rat (LZR), were used. Diabetic rats were given either a low dose (0.6 mg/kg/day) or a high dose (12 mg/ kg/day) of PGT in the chow for 2 or 4-5 months. Glycaemia, blood pressure, creatinine clearance and proteinuria were determined, and the underlying histopathology was defined with markers of fibrosis, glomerular damage, oxidative stress and inflammation by immunohistochemistry/ quantitative image analysis in tissue sections, and western blots and ad hoc assays in fresh tissue. RESULTS: PGT at low doses given for 4-5 months considerably reduced blood pressure, proteinuria and creatinine clearance. This was associated with amelioration of renal tissue damage and fibrosis, evidenced by the glomerulosclerosis, tubulointerstitial fibrosis, tubular atrophy and podocyte injury indexes, and of oxidative stress and inflammation, as shown by the decrease in the respective markers, although glycaemia remained high and obesity was not affected. CONCLUSIONS: These results indicate that low doses of PGT ameliorate renal fibrosis and preserve renal function in this animal model of metabolic syndrome, independently of glycaemic control or effects on body weight.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Túbulos Renales/patología , Obesidad/tratamiento farmacológico , Tiazolidinedionas/uso terapéutico , Animales , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/patología , Fibrosis/prevención & control , Inflamación/prevención & control , Riñón/metabolismo , Riñón/patología , Pruebas de Función Renal , Masculino , Obesidad/patología , Estrés Oxidativo/efectos de los fármacos , Pioglitazona , Ratas , Ratas ZuckerRESUMEN
BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is characterized by abnormalities in cerebral white matter and neurologic symptoms. It can be caused by immunosuppressive drugs or autoimmune diseases. We describe a case of PRES in a patient with collapsing focal glomeruloesclerosis (collapsing FGS) with complete recovery after withdrawal of cyclosporine (CSA). CASE REPORT: A 27-year-old male presented a corticosteroid-resistant nephrotic syndrome secondary to collapsing FGS corticosteroid. Treatment with CSA was started after a nonresponding course of prednisone. Three weeks later, he developed an abrupt elevation of blood pressure (210/120 mmHg), with headaches, mental confusion, and generalized seizures. Magnetic resonance imaging (MRI) showed lesions suggestive of PRES. CSA was withdrawn, and a new MRI was normal after 2 months. CONCLUSIONS: PRES is a rare syndrome that must be suspected in every patient presenting neurologic symptoms in the course of immunosuppression. It can be induced by CSA and is totally reversible when the drug is rapidly withdrawn.
Asunto(s)
Ciclosporina/efectos adversos , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Inmunosupresores/efectos adversos , Síndrome de Leucoencefalopatía Posterior/inducido químicamente , Adulto , Humanos , Imagen por Resonancia Magnética , Masculino , Síndrome de Leucoencefalopatía Posterior/diagnósticoRESUMEN
The possible long-term renoprotective effects of treatment with thiazides, either as monotherapy or associated with renin-angiotensin suppressors, have not been assessed. We investigated the effect of hydrochlorothiazide (H), alone or combined with losartan (L), in the 5/6 renal ablation model (Nx). Adult male Munich-Wistar rats underwent Nx, remaining untreated for 1 mo. At this time, functional and morphological studies were performed in 21 rats (group Nx(pre)). The remaining rats were distributed among groups: Nx, no treatment; Nx+L, receiving L, 50 mg kg(-1) day(-1) in the drinking water; Nx+H, receiving H, 6 mg kg(-1) day(-1) in drinking water; and Nx+L+H, receiving both L and H as described. At 30 days of treatment, systemic and glomerular pressures were markedly elevated in group Nx. Both H and L attenuated hypertension, whereas combined L+H treatment completely normalized both pressures. Eight months after Nx, mortality approached 70% in untreated rats, whereas severe albuminuria, hypertension, glomerulosclerosis, and interstitial expansion were observed. H and L attenuated, but did not prevent, mortality, hypertension, and renal injury. Combined L+H treatment completely prevented mortality, normalized albuminuria and blood pressure, and arrested renal injury at levels found 1 mo after ablation, despite the unusually long period of observation. Combined L+H treatment may represent an effective therapeutic alternative to prevent progression of chronic nephropathies.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Diuréticos/uso terapéutico , Hidroclorotiazida/uso terapéutico , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/fisiopatología , Losartán/uso terapéutico , Nefrectomía , Animales , Sinergismo Farmacológico , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/patología , Inmunohistoquímica , Enfermedades Renales/patología , Pruebas de Función Renal , Masculino , Ratas , Ratas Wistar , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , Circulación Renal/efectos de los fármacos , Circulación Renal/fisiología , Cola (estructura animal)/irrigación sanguíneaRESUMEN
BACKGROUND: Mutations in the NPHS2 gene encoding the protein podocin have recently been found in a recessive form of steroid-resistant nephrotic syndrome. Focal segmental glomerulosclerosis (FSGS) was the histologic diagnosis in many of the patients harboring these mutations. FSGS is a heterogeneous glomerular lesion with diverse origins and outcomes. Although mutational analysis in children permits the identification of an unresponsive group before initiating treatment, there is not much information on adult-onset patients with FSGS. METHODS: We performed NPHS2 gene mutational analysis in 39 adult Brazilian patients with primary FSGS, and evaluated the clinical course of the disease and response to treatment; in addition, we performed urinary screening in 44 relatives of these patients. RESULTS: In this group, only 1 patient (with familial FSGS) had a mutation in the NPHS2 gene with double heterozygosity. The absence of mutations in all other patients evaluated suggests its rarity in sporadic cases of adult-onset (steroid sensitive or resistant) FSGS in our population. CONCLUSIONS: Our results suggest that the analysis of the NPHS2 gene mutation is not indicated as a routine diagnostic procedure in our population for adult-onset patients with FSGS.
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/genética , Proteínas de la Membrana/genética , Mutación/genética , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Brasil , Resistencia a Medicamentos/genética , Femenino , Frecuencia de los Genes , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Humanos , Péptidos y Proteínas de Señalización Intracelular , Masculino , Persona de Mediana EdadRESUMEN
Renal histological features of focal segmental glomerulosclerosis (FSGS) are found in 75% of pediatric patients with steroid-resistant nephrotic syndrome. In order to evaluate the predictive factors of chronic kidney disease (CKD), we retrospectively reviewed the records of 110 children with biopsy-proven FSGS admitted between 1972 and 2004. Renal survival was analyzed by the Kaplan-Meier method and Cox's regression model. Two multivariate models were developed: (1) from the onset of symptoms to the occurrence of CKD and (2) from the time of renal biopsy to CKD. Mean follow-up time was 10 years [standard deviation ((SD) 5.5], and 24 patients (21.8%) progressed to CKD. At baseline, after adjustment three variables remained as independent predictors of CKD: age >6.5 years (RR=3.3, 95% CI=1.3-7.8), creatinine >1 mg/dl (RR=2.5, 95% CI=0.97-6.5), and non-response to steroids (RR=7.3, 95% CI=2.7-19.7). In a model with continuous variables only age and non-response to steroids were associated with CKD. At the time of renal biopsy, after adjustment two variables remained as independent predictors of CKD: hematuria (RR=3.0, 95% CI=1.2-7.3) and creatinine >0.8 mg/dl (RR=4.3, 95% CI=1.7-10.6). In a model with continuous variables four factors predicted CKD: age, creatinine, hematuria, and percentage of global sclerosis.
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/complicaciones , Fallo Renal Crónico/etiología , Adolescente , Biopsia , Niño , Preescolar , Creatinina/sangre , Femenino , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/fisiopatología , Glucocorticoides/uso terapéutico , Humanos , Incidencia , Lactante , Fallo Renal Crónico/tratamiento farmacológico , Fallo Renal Crónico/fisiopatología , Masculino , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The purpose of this retrospective cohort study was to report the clinical course of children and adolescents with primary focal segmental glomerulosclerosis (FSGS). The records of 110 patients with biopsy-proven FSGS admitted between 1972 and 2004 were retrospectively reviewed. Demographic, clinical and laboratory data were recorded and histopathological data were reanalyzed by one pathologist who had no information about the outcome of the patients. Renal survival analysis was performed using the Kaplan-Meier method. Differences between subgroups (response to corticosteroids) were assessed by the two-sided log rank test. The median age at admission was 5 years (range: 1-15 years). Forty-two patients (38.2%) presented with hematuria at admission, and 55 (50%) presented blood pressure levels above the 95th percentile. Mean follow-up time was 10 years (SD 5.5). Twenty-four patients (21.8%) presented chronic kidney disease (CKD). It was estimated that the probability of CKD was 8% at 5 years, 17% at 10 years, and 32% at 15 years after diagnosis of nephrotic syndrome. In conclusion, on the basis of the clinical and histological characteristics observed, apparently our cohort of idiopathic FSGS is comparable with other published series. However, the long-term overall renal survival seems to be better in our cohort.
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/mortalidad , Humanos , Lactante , Masculino , Estudios Retrospectivos , Factores de TiempoRESUMEN
Heparin may have a beneficial effect in proteinuric renal diseases, where negative charges of the glomerular capillary membrane are compromised. We evaluated the role of low molecular weight heparin (LMWH - 3000 Da) in puromycin aminonucleoside (PAN)-induced focal and segmental glomerulosclerosis in male Wistar rats: Controls (C) n=7, LMWH-treated group, n=9, subcutaneously (SC), 6 mg/kg every day. The PAN group (n=7) received 7 doses on weeks 0, 1, 2, 4, 6, 8, 10 (SC - 2mg/100g), and a group PAN+LMWH (n=6). After 12 weeks, cholesterol and triglycerides were higher in nephrotic groups, as well as proteinuria and urinary IgG. Kidney weight, glomerular volume, and glomerular sclerosis index were higher in the PAN-treated groups. Glomerular capillary length density (L(Vcap)) and glomerular capillary surface density (S(Vcap)) were lower in the PAN group, and mesangial fractional volume was higher. Fibronectin immunostaining was more intense in the PAN group, and collagens I and III were absent in the studied glomeruli. Thus, LMWH prevented mesangial expansion and capillaries changes, showing antiproliferative properties, despite worsening glomerular permeability changes in the PAN model. In conclusion, LMWH interferes in the complications of PAN model, but not through inhibition of the proteinuria.