RESUMO
BACKGROUND AND AIM: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulopathy. The Oxford classification was recently updated to include crescents as markers of poor prognosis. The aim of this study was to evaluate the impact of cellular crescents on the prognosis of patients with IgAN in Brazil. METHODS: This was a single-centre retrospective analysis of medical records and renal biopsies in patients with IgAN. The renal biopsy findings were classified according to the revised Oxford classification: mesangial hypercellularity, endocapillary hypercellularity (E), segmental glomerulosclerosis (S), tubular atrophy or interstitial fibrosis (T), and crescent formation (C). We evaluated a composite outcome (progression to end-stage renal disease or creatinine doubling). We performed analyses between the patients with crescents in the renal biopsy specimen (C1/C2 group) and those without such crescents (C0 group). RESULTS: We evaluated 111 patients, of whom 72 (65.0%) were women, 80 (72.0%) self-identified as White, 73 (65.6%) were hypertensive, and 95 (85.6%) had haematuria. The distribution of patients according to cellular crescentic lesions was: C0, 80 (72%); C1, 27 (24.4%); C2, 4 (3.6%). The composite outcome was observed in 33 (29.72%) of the 111 patients. In comparison with the C0 group, the C1/C2 group had higher proportions of patients with hypertension (p = 0.04), haematuria (p = 0.03), worse serum creatinine (p = 0.0007), and worse estimated glomerular filtration rate (p = 0.0007). The C1/C2 group also had higher proportions of patients in whom the biopsy specimen was classified as E1 (p = 0.009), S1 (p = 0.001), or T1/T2 (p = 0.03), In addition, the mean follow-up period was shorter in the C1/C2 group (p < 0.0001). Furthermore, the composite outcome was observed in a greater proportion of patients and in a shorter length of time in the C1/C2 group than in the C0 group (p = 0.002 and p = 0.0014, respectively). In a Cox regression analysis, the independent risk factors for the composite outcome had Oxford classifications of S1, T1/T2, and C1/C2. CONCLUSION: Oxford classification findings of S1, T1/T2, or C1/C2 were independent risk factors for the composite outcome, corroborating previous studies.
Assuntos
Glomerulonefrite por IGA/fisiopatologia , Rim/patologia , Adulto , Brasil , Feminino , Humanos , Masculino , Prognóstico , Estudos RetrospectivosRESUMO
Immunoglobulin A nephropathy (IgAN) was defined as a mesangiopathic disease, since the primary site of deposition of IgA immune material is the mesangium, and proliferation of mesangial cells and matrix excess deposition are the first histopathologic lesions. However, the relentless silent progression of IgAN is mostly due to the development of persistent proteinuria, and recent studies indicate that a major role is played by previous damage of function and anatomy of podocytes. In IgAN, the podocytopathic changes are the consequence of initial alterations in the mesangial area with accumulation of IgA containing immune material. Podocytes are therefore affected by interactions of messages originally driven from the mesangium. After continuous insult, podocytes detach from the glomerular basement membrane. This podocytopathy favours not only the development of glomerular focal and segmental sclerosis, but also the progressive renal function loss. It is still debated whether these lesions can be prevented or cured by corticosteroid/immunosuppressive treatment. We aimed to review recent data on the mechanisms implicated in the podocytopathy present in IgAN, showing new molecular risk factors for progression of this disease. Moreover, these observations may indicate that the target for new drugs is not only focused on decreasing the activity of mesangial cells and inflammatory reactions in IgAN, but also on improving podocyte function and survival.
Assuntos
Mesângio Glomerular/patologia , Glomerulonefrite por IGA/fisiopatologia , Podócitos/patologia , Proteinúria/etiologia , Animais , Progressão da Doença , Glomerulonefrite por IGA/complicações , Humanos , Proteinúria/patologiaRESUMO
La combinación de glomerulopatías es infrecuente en la población pediátrica. Su presencia debe ser sospechada en aquellos pacientes con una enfermedad glomerular de curso clínico atípico. La influencia a largo plazo sobre el deterioro funcional renal permanece incierta. Se presentan dos niños con características histológicas de glomerulopatía combinada.
Combined glomerulopathy is infrequent in pediatric patients. Its presence should be suspected in those patients with glomerulophaties with atypical course. The influence on the long-term renal impairment remains uncertain. Here we report two children with histological findings of combined glomerulopathy.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite Membranosa/psicologia , Glomerulonefrite por IGA/fisiopatologiaRESUMO
Combined glomerulopathy is infrequent in pediatric patients. Its presence should be suspected in those patients with glomerulophaties with atypical course. The influence on the long-term renal impairment remains uncertain. Here we report two children with histological findings of combined glomerulopathy.
La combinación de glomerulopatías es infrecuente en la población pediátrica. Su presencia debe ser sospechada en aquellos pacientes con una enfermedad glomerular de curso clínico atípico. La influencia a largo plazo sobre el deterioro funcional renal permanece incierta. Se presentan dos niños con características histológicas de glomerulopatía combinada.
Assuntos
Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite Membranosa/diagnóstico , Pré-Escolar , Feminino , Glomerulonefrite por IGA/fisiopatologia , Glomerulonefrite Membranosa/fisiopatologia , Humanos , MasculinoRESUMO
IgA nephropathy (IgAN) is one of the leading causes of glomerulonephritis characterized by the findings of IgA and IgG immune deposits in the mesangium of kidney biopsies from patients with persistent microscopic haematuria. IgAN is frequently detected among adolescents and young adults. IgAN presents a highly variable course that includes a spectrum from a very mild disease to end-stage renal disease (ESRD). There are several clinical and histological factors that strongly determined the final outcome of patients with IgAN. Pathological variables associated with unfavorable outcomes are mesangial hypercellularity, segmental glomerulosclerosis, endocapillary hypercellularity and interstitial fibrosis/tubular atrophy, according to the Oxford classification. Moreover, some studies also suggest a role for complement activation in the pathogenesis of IgAN. In this regard, staining for C4d may be an independent risk factor for the development of ESRD in IgAN. Despite the growing number of studies assessing IgAN risk factors, this kind of investigation in paediatric patients is still very limited. The aim of this article is to revise pathological markers related to deterioration of renal function in paediatric patients with IgAN, particularly those that can independently affect renal survival.
Assuntos
Glomerulonefrite por IGA/patologia , Glomerulosclerose Segmentar e Focal/patologia , Falência Renal Crônica/patologia , Glomérulos Renais/patologia , Adolescente , Fatores Etários , Atrofia , Biomarcadores/análise , Biópsia , Criança , Ativação do Complemento , Complemento C4b/análise , Progressão da Doença , Feminino , Fibrose , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/fisiopatologia , Glomerulosclerose Segmentar e Focal/imunologia , Glomerulosclerose Segmentar e Focal/fisiopatologia , Humanos , Imunoglobulina A/análise , Imunoglobulina G/análise , Falência Renal Crônica/imunologia , Falência Renal Crônica/fisiopatologia , Testes de Função Renal , Glomérulos Renais/imunologia , Glomérulos Renais/fisiopatologia , Masculino , Fragmentos de Peptídeos/análise , Valor Preditivo dos Testes , Prognóstico , Fatores de RiscoRESUMO
This review updates current concepts of the genetic risk factors, etiologic events, nephtitogenic responses and treatment of the major immunologically mediated types of glomerulonephritis (GN). These include post-infectious GN, IgA nephropathy, anti-glomerular basement membrane (GBM) antibody disease, ANCA-associated vasculitis (AAV) and lupus nephritis. Although the etiology(s) of most GNs remain undefined, many are now believed to be initiated by environmental insults, particularly infectious processes, that trigger host responses in genetically susceptible individuals which lead to GN. Mechanistic concepts of these diseases have evolved from earlier views that most were consequent to glomerular trapping of preformed immune complexes to the current view that most of these diseases are auto-immune in nature mediated by both antibodies and T cells reactive with self-antigens. Therapy of GN has lagged behind advances in understanding pathogenesis. Newly appreciated roles for older mediators like complement and complement regulatory proteins offer new therapeutic targets.
Assuntos
Glomerulonefrite/fisiopatologia , Glomerulonefrite/terapia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/fisiopatologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Glomerulonefrite por IGA/fisiopatologia , Glomerulonefrite por IGA/terapia , Humanos , Glomérulos Renais/fisiopatologia , Nefrite Lúpica/fisiopatologia , Nefrite Lúpica/terapiaRESUMO
Resumo A presente revisão traz os conceitos mais atuais acerca dos fatores de risco genéticos, eventos etiológicos, respostas nefritogênicas e tratamento dos principais tipos de glomerulonefrite (GN) imunomediada. Tais patologias incluem GN pós-infecciosa, nefropatia por IgA, doença por anticorpo antimembrana basal glomerular (anti-MBG), vasculite associada a ANCA (VAA) e nefrite lúpica. Apesar da(s) etiologia(s) da maioria dos casos de GN permanecer indefinida, acredita-se que seu início se deva, em grande parte, a insultos ambientais, particularmente na forma de processos infecciosos que deflagram respostas de hospedeiro em indivíduos geneticamente suscetíveis, levando assim a quadros de GN. A concepção mecanicista em torno dessas patologias evoluiu a partir da visão mais antiga de que a maioria seria consequência do aprisionamento glomerular de complexos imunes pré-formados para a percepção atual de que as mesmas, em sua maioria, são doenças autoimunes por natureza mediadas por anticorpos e linfócitos T reativos a auto-antígenos. O tratamento da GN não tem acompanhado os progressos na compreensão de sua patogênese. Os papéis recentemente atribuídos a mediadores mais antigos como complemento e proteínas reguladoras do complemento lançam luz sobre novos alvos terapêuticos.
Abstract This review updates current concepts of the genetic risk factors, etiologic events, nephtitogenic responses and treatment of the major immunologically mediated types of glomerulonephritis (GN). These include post-infectious GN, IgA nephropathy, anti-glomerular basement membrane (GBM) antibody disease, ANCA-associated vasculitis (AAV) and lupus nephritis. Although the etiology(s) of most GNs remain undefined, many are now believed to be initiated by environmental insults, particularly infectious processes, that trigger host responses in genetically susceptible individuals which lead to GN. Mechanistic concepts of these diseases have evolved from earlier views that most were consequent to glomerular trapping of preformed immune complexes to the current view that most of these diseases are auto-immune in nature mediated by both antibodies and T cells reactive with self-antigens. Therapy of GN has lagged behind advances in understanding pathogenesis. Newly appreciated roles for older mediators like complement and complement regulatory proteins offer new therapeutic targets.
Assuntos
Humanos , Glomerulonefrite/fisiopatologia , Glomerulonefrite/terapia , Nefrite Lúpica/fisiopatologia , Nefrite Lúpica/terapia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/fisiopatologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Glomerulonefrite por IGA/fisiopatologia , Glomerulonefrite por IGA/terapia , Glomérulos Renais/fisiopatologiaRESUMO
IgA nephropathy (IgAN) is the most prevalent form of chronic glomerulonephritis in the world. The underlying pathogenesis of this autoimmune disease comprises the formation of immune complexes, including glycan-specific IgA1 or IgG antibodies and an aberrant glycosylation of IgA1. Until now, anatomopathological analysis of renal biopsies is essential for the diagnosis of IgAN and different histological classification systems have been proposed, e.g. the Oxford classification. However, a percutaneous renal biopsy is frequently not performed for several reasons and the Oxford classification system has some limitations. Since the poor prognosis of IgAN patients is partly the result of a delayed diagnosis, there is an urgent need for reliable noninvasive biomarkers that might be applicable in routine clinical practice. This article reviews the advances on the understanding of the underlying pathophysiological mechanisms of IgAN and discusses in depth the recent development of new biomarkers, including the use of proteomics and microRNAs.
Assuntos
Glomerulonefrite por IGA/imunologia , Imunoglobulina A/imunologia , Biomarcadores/análise , Biópsia , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/fisiopatologia , Glicosilação , Humanos , MicroRNAs/genética , ProteômicaRESUMO
BACKGROUND: IgA nephropathy (IgAN) is the third most frequent cause of renal graft loss among patients with primary glomerulonephritis. OBJECTIVES: To assess clinical and laboratorial profile of patients with pre and/or post transplant IgAN, in addition to patient and graft survival in both groups. DESIGN: Data from 146 patients who had received a renal transplant were retrospectively collected and were divided in two groups: group 1-patients with biopsy-documented IgAN as the underlying native kidney disease (n = 128); group 2-patients who developed post-transplant IgAN independent of the underlying disease (n = 18). PARTICIPANTS: Patients submitted to renal transplantation (1998-2010) with pre and/or post transplant IgAN. MEASUREMENTS: Clinical and laboratorial evaluation of renal function of 146 post transplant IgAN patients. RESULTS: Recipients and deceased donors exhibited a higher degree of HLA compatibility (1.0 vs. 2.5 mismatches for groups 1 and 2, respectively). The main post-transplant IgAN presentation was haematuria associated with non-nephrotic proteinuria (44.4%). A histological pattern of focal segmental glomerulosclerosis was observed in 59.2% of biopsy samples. The 10-year patient survival was 93.5% in group 1 and 100% in group 2, and the graft survival rates were 58.5 and 87.2%, respectively. CONCLUSION: The rate of post-transplant IgA diagnosis in our case series was 11%, and IgAN was diagnosed late in the course of transplantation. In most cases, IgAN manifested as haematuria and non-nephrotic proteinuria, without renal graft dysfunction, and this picture might explain late indication of graft biopsies. The 10-year patient survival rates were excellent.