An update on pathology of IgA nephropathy / Atualização em nefropatia da IgA

Abstract IgA Nephropathy (IgAN) is the commonest of the glomerular diseases in the world. Its progression rate of 30-40% of the cases em 20-30 years makes IgAN an important healthcare issue in Nephrology. Diagnosis of IgAN depends on biopsy findings, particularly at immunofluorescence microscopy. The frequence of IgAN diagnosis is variable in different populations and depends on screening and biopsy indication policies. IgAN pathogenesis is considered multifactorial; its primordial defect is the production of galactosis-deficient IgA molecules. This review paper discusses the most uptodate aspects of the pathogenesis, pathological classification and clinical implications of IgAN.

Resumo A Nefropatia da IgA (IgAN) é a mais comum das doenças glomerulares no mundo. Sua taxa de progressão de 30-40% em 20-30 anos torna a IgAN uma importante preocupação em saúde pública na area da Nefrologia. O diagnóstico da IgAN depende dos achados de biópsia, particularmente de microscopia de imunofluorescência. A frequência do diagnóstico é variável em diferentes populações e depende do rastreamento de hematúria e da indicação de biopsia. A IgAN é uma doença multifatorial: o defeito primordial é a produção de moléculas de IgA deficientes em galactose. Esta revisão discute aspectos atualizados da patogênese e classificação patológica da IgAN e suas implicações clínicas.

IgA nephropathy in systemic lupus erythematosus patients: case report and literature review / Nefropatia por IgA em paciente portadora de lúpus eritematoso sistêmico: relato de caso e revisão de literatura

Abstract Systemic erythematosus lupus (SLE) is a multisystemic autoimmune disease which has nephritis as one of the most striking manifestations. Although it can coexist with other autoimmune diseases, and determine the predisposition to various infectious complications, SLE is rarely described in association with non‐lupus nephropathies etiologies. We report the rare association of SLE and primary IgA nephropathy (IgAN), the most frequent primary glomerulopathy in the world population. The patient was diagnosed with SLE due to the occurrence of malar rash, alopecia, pleural effusion, proteinuria, ANA 1: 1,280, nuclear fine speckled pattern, and anticardiolipin IgM and 280 U/mL. Renal biopsy revealed mesangial hypercellularity with isolated IgA deposits, consistent with primary IgAN. It was treated with antimalarial drug, prednisone and inhibitor of angiotensin converting enzyme, showing good progress. Since they are relatively common diseases, the coexistence of SLE and IgAN may in fact be an uncommon finding for unknown reasons or an underdiagnosed condition. This report focus on the importance of the distinction between the activity of renal disease in SLE and non‐SLE nephropathy, especially IgAN, a definition that has important implications on renal prognosis and therapeutic regimens to be adopted in the short and long term.

Resumo O lúpus eritematoso sistêmico (LES) é uma doença autoimune multissistêmica que tem como uma das manifestações mais marcantes a nefrite. Apesar de poder coexistir com outras doenças autoimunes e determinar a predisposição a diversas complicações infecciosas, o LES raramente é descrito em associação a nefropatias de etiologia não lúpica. Relatamos o caso da rara associação entre LES e nefropatia por IgA (NIgA) primária, a glomerulopatia primária mais frequente na população mundial. A paciente foi diagnosticada com LES pela ocorrência de eritema malar, alopecia, derrame pleural, proteinúria, pancitopenia, FAN 1:1.280 padrão nuclear pontilhado fino e anticardiolipina IgM 280 U/mL. A biópsia renal revelou hipercelularidade mesangial com depósitos isolados de IgA, compatível com NIgA primária. Foi tratada com antimalárico, prednisona e inibidor da enzima conversora de angiotensina e apresentou boa evolução. Por consistirem em doenças relativamente frequentes, a coexistência de LES e NIgA pode ser de fato um achado incomum por motivos desconhecidos ou uma condição subdiagnosticada. Este relato atenta para a importância da distinção entre a atividade de doença renal do LES e nefropatias não lúpicas, em especial a NIgA, definição que tem implicações importantes sobre o prognóstico renal e regimes terapêuticos a serem adotados em curto e longo prazo.

Immunoglobulin a nephropathy and malaria falciparum infection; a rare association

Glomerular involvement occurs as a rare form of renal manifestation in Plasmodium falciparum malaria. Here, we report a rare case of falciparum malaria-associated IgA nephropathy. A 28-year-old man was admitted because of fever and abdominal pain. Ultrasound and computed tomography [CT] showed right kidney pyonenphrosis. Despite placing a nephrostomy tube, fever continued. Repeated CT was in favor of focal pyelonephritis. In addition, peripheral blood smear suggested malaria. Anti-malarial drugs were initiated and right nephrectomy was performed. One year after recovery from malaria, a persistent rise in serum creatinine was detected. A left kidney biopsy showed mesangial proliferation and dominant IgA deposits in immunofluorescence study while C[1q] was not deposited. The impression was IgA nephropathy with M[1]E[0]S[0]T[0] of Oxford classification. The patient was prescribed a combination of low dose prednisolone and angiotensin converting enzyme inhibitor. Six months after treatment serum creatinine decreased from 1.6 mg/dL to 1.3mg/dL and urine abnormalities were disappeared. Our findings suggest that malaria infection might be associated with IgA nephropathy

Nefropatia por IgA nas espondiloartrites / IgA nephropathy in spondyloarthritis

Pacientes com espondiloartrites poderiam ser mais acometidos pela nefropatia por IgA do que a população geral, havendo, possivelmente, um mecanismo etiopatogênico comum. O seguinte artigo relaciona quatro casos que exemplificam essa possível associação.

Spondyloarthritis patients can be more frequently affected by IgA nephropathy than the general population, and a common etiopathogenic mechanism can be involved. We report four cases that may exemplify that association.

IgA nephropathy: an update on pathogenesis and classification

IgA nephropathy is a primary glomerulopathy characterized by deposition of IgA containing immune deposits in the kidney. Its diagnosis is based on histopathologic and immunoflourescence studies on renal biopsy. The disorder is poorly understood. This review is focused on updates regarding its pathogenesis and discussion on a new proposed histopathological classification of IgA nephropathy

Diffuse Glomerular Basement Membrane Lamellation in Post-Transplant IgA Nephropathy

Diffuse glomerular basement membrane (GBM) lamellation, reminiscent of Alport's syndrome, has rarely, and exclusively, been reported in renal allografts from pediatric donors to adult recipients. We report on a similar lesion, identified in a 42-year-old male, who received a kidney from an unrelated 21-year-old living male donor. The disease of the recipient was unknown. Renal allograft biopsies were performed 3.5 and 4.8 years after the renal transplantation, due to massive proteinuria and serum creatinine elevation. The histological features of both biopsies were similar, but more advanced in the second biopsy. Glomerular mesangium was widened and had an IgA deposit in the first biopsy. In addition to the presence of mesangial electron dense deposits, the GBM showed diffuse lamellation and splintering on the subepithelial side, but no definite deposits. In the second biopsy, IgA deposits were extended to the peripheral capillary walls, but electron microscopic examination was not available. Two months after the second biopsy, the patient returned for hemodialysis.

Diffuse Glomerular Basement Membrane Lamellation in Post-Transplant IgA Nephropathy

Diffuse glomerular basement membrane (GBM) lamellation, reminiscent of Alport's syndrome, has rarely, and exclusively, been reported in renal allografts from pediatric donors to adult recipients. We report on a similar lesion, identified in a 42-year-old male, who received a kidney from an unrelated 21-year-old living male donor. The disease of the recipient was unknown. Renal allograft biopsies were performed 3.5 and 4.8 years after the renal transplantation, due to massive proteinuria and serum creatinine elevation. The histological features of both biopsies were similar, but more advanced in the second biopsy. Glomerular mesangium was widened and had an IgA deposit in the first biopsy. In addition to the presence of mesangial electron dense deposits, the GBM showed diffuse lamellation and splintering on the subepithelial side, but no definite deposits. In the second biopsy, IgA deposits were extended to the peripheral capillary walls, but electron microscopic examination was not available. Two months after the second biopsy, the patient returned for hemodialysis.

Polimorfismo do gene da enzima de conversäo da angiotensina em pacientes com nefropatia crônica / Angiotensin converting enzyme polymorphism in patients with chronic nephropathy

O polimorfismo (I/D) inserçäo/deleçäo do gene da enzima de conversäo da angiotensina (ECA) se correlaciona com a concentraçäo celular e circulante da ECA. Indivíduos com genótipo D/D têm concentraçäo circulante de ECA mais elevada de que aqueles com genótipo I/I. O genótipo I/D tem concentraçäo intermediária. O genótipo D/D tem sido associado com o desenvolvimento e/ou progressäo da doença renal e como fator de risco para doença cardiovascular, podendo ser um marcador de hipertrofia ventricular esquerda (HVE). Este trabalho avalia o polimorfismo do gene da ECA por técnica de PCR em 23 pacientes hemodialisados com IRC terminal de diversas etiologias e também sua associaçäo com HVE. Foram estudados 12 pacientes do sexo masculino e 11 do sexo feminino, com idade de 33,9 ñ 16,0 anos. A distribuiçäo dos genótipos da ECA foi comparada com 20 indivíduos saudáveis, sendo 11 do sexo masculino e 9 do sexo feminino, com idade de 31,4 ñ 8,0 anos. A distribuiçäo do genótipo da ECA nos pacientes renais crônicos foi de 60,9 por cento I/D, 34,8 por cento D/D e 4,3 por cento I/I. No grupo-controle foi de 6,0 por cento I/D, 25,0 por cento D/D e 15,0 por cento I/I. Näo houve diferença estatisticamente significante na distribuiçäo do genótipo entre os grupos (P>0,05). Todos os pacientes apresentavam HVE e näo houve diferença estatística significante no índice de massa do ventrículo esquerdo entre os pacientes com genótipo I/D ou D/D. Concluímos que na populaçäo estudada de pacientes com IRC terminal näo houve associaçäo entre o genótipo D/D da ECA e a presença de nefropatia crônica ou hipertrofia ventricular esquerda.

Immunoglobulin A nephropathy in patients with non-insulin dependent diabetes mellitus

The occurrence of immunoglobulin A nephropathy (IgAN) in patients with noninsulin dependent diabetes mellitus (NIDDM) is a rare event and of pathogenetic interest. It is not clear whether this is merely coincidence. We report here five patients with IgAN in NIDDM associated with or without diabetic glomerulosclerosis. All of the patients were Korean males. In three patients, diabetes mellitus was diagnosed at the same time with diagnosis of IgAN, and the known duration of the diabetes in the other two patients were three and seven years, respectively. There was no evidence of diabetic retinopathy in four patients, but it was found in one patient. In all cases, the diagnosis of IgAN was made by immunohistology.

Acute appendicitis: as a predisposing factor for acute glomerulonephritis--report of two cases

This is a review of two children who developed acute glomerulonephritis (AGN) following acute gangrenous appendicitis (AGA) with periappendicular collections. The first patient presented with AGN during the course of appendicitis. The second patient developed AGN after appendectomy. Both patients did not have any other predisposing factors. AGN resolved in both patients after massive intravenous antibiotics. This is the first report of acute appendicitis as a predisposing factor for AGN

Role of mononuclear cells of IgA nephropathy on ICAM-1 expression in mesangial cells

OBJECTIVES: To investigate the possible role of mononuclear cells and their products in the pathogenesis of IgA nephropathy, in vitro expression of ICAM-1 on cultured mouse mesangial cell (MC) was examined after stimulation with mononuclear cell culture supernatant from patients with IgA nephropathy. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated and cultured from 18 patients with primary IgA nephropathy, 8 normal controls and 5 patients with non-IgA nephropathy (FSGS 1, MGN 3, MPGN 1). ICAM-1 expression on cultured mouse MC by TNF-alpha, IL-1 beta and culture supernants of PBMC were analyzed using a cell ELISA method. The concentration of IL-1 beta and TNF-alpha in culture supernatants was measured by using a commercially available radioimmunoassay kit. RESULTS: Addition of human recombinant TNF-alpha induced an increased ICAM-1 expression in a dose-dependent manner. The expression of ICAM-1 was further increased after co-stimulation with TNF-alpha and IL-1 beta. Addition of PBMC culture supernatants into mouse MC induced significantly higher expression of ICAM-1 by supernatants from the patients with IgA nephropathy compared with that from normal controls. The concentration of TNF-alpha and IL-1 beta in supernatants from the patients with IgA nephropathy was significantly higher than that from those with non-IgA nephropathy. CONCLUSION: TNF-alpha and IL-1 released from mononuclear cells induced the up-regulation of ICAM-1 expression and this may be related to the immune pathogenesis of IgA nephropathy.

Hipotiroidismo autoinmune asociado a nefropatía por IgA

La nefropatía por IgA, cuya incidencia en la población pediátrica oscila entre 1.5 y 56.21 según reportes publicados en el sur de Europa, Australia y Japón, se reporta como primera causa de glomerulonefritis primaria en niños. La nefropatía por IgA puede ser primaria o secundaria, se diagnostica por demostración de IgA predominantemente mesangial o IgA codominante en el glomérulo sin evidencia de lupus eritematoso. La mayoría de los pacientes presenta hematuria macroscópica y el pronóstico depende de los marcadores genéticos y la severidad de la lesión histológica renal. A continuación presentamos el reporte de un caso de una paciente con evidencia de hipotiroidismo primario autoinmune y nefropatía por IgA.

Consumo de alcohol y glomerulonefritis por depósito mesangial de IgA: enfermedad de Berger / Alcohol comsumption and glomerulonephritis by mesangial IgA store: Berger's disease

Alcohol ingestion is considered as a possible pathogenic agent for Berger's disease, since IgA mesangial deposits have been described in liver cirrhosis. Aiming to assess this issue, 28 patients with Berger's disease (BD) and 40 patients with other glomerulopathies (NBD) were subjected to an enquiry about alcohol ingestion. Data was corroborated with 21 closed relatives of BD patients and 34 relatives of NBD patients. No differences were observed in report alcohol intake between BD patients and their relatives, however relatives of NBD patients understimated their alcohol intake. No differences in alcohol intake, either self reported or reported by relatives, were observed between BD and NBD patients. It is concluded that no differences in alcohol intake were observed between patients with Berger's disease and subjects with other glomerulopathies

Glomerulonefrítis Mesangial por depósitos de IgA (Enfermedad de Berger)

La nefropatía mesangial IgA o nefropatia IgA, fue descrita primero por Berger en 1968 y puede ser identificada por la localización mesangial glomerular del IgA, con una localización meangial menos intensa de IgG o IgM, o ambos y C3. La etiologia y la patogénesis de la nefropatía IgA son desconocidas. Su frecuente asociación con las infecciones no estreptocócicas del tracto respiratorio superior sugieren que una nefropatía IgA puede representar una nefritis por complejo inmune en la cual, la infección de la mucosa provee un antígeno exógeno, posiblemente viral, que se combina con IgA para producir un complejo que se localiza en el mesangio. Existe muy poca información para evaluar la utilidad de la terapia en la nefropatía IgA.

IGA nephropathy in schistosoma mansoni infected patients

Of the 43 studied patients with schistosomal nephropathy, 31 were males [72.1%] and 12 were females [27.9%]. Proteinuria was encountered in all patients, hematuria was found in 62.8% and hypertension was detected in 20.9% of patients. Isolated proteinuria without hematuria or hypertension was present in 16.3% of patients. Non of the measured serologic markers was significantly distributed among the three groups of patients apart from significant lowering of the serum C[3] concentration in the group of patients with hepatosplenic schistosomiasis [Group III]. The main renal pathologic lesions were FSGS [39.53%] and MPGN [30.23%], while amyloid kidney was observed in only one case [2.33%]. Renal deposits of schistosomal antigens [CCA and CAA] were found in 15 patients [34.88%]. These patients showed predominant deposits of lgG [46.66%], IgM [73.33%], C[3] [80%] and C[4] [40%] which were significantly higher than that in patients without schistosomal antigens deposits. IgA glomerular deposits were found in 7 [16.3%] patients. All were normotensive males. They had no distinctive clinical, laboratory or pathological features that distinguish them from schistosomal nephropathy patients without IgA deposits