Immunoexpression of gelatinase and apolipoprotein E in induced glomerulosclerosis in adult male albino rat

Introduction: The abnormal expressions of gelatinase are implicated in the pathogenesis of extracellular matrix accumulation in glomerulosclerosis [GS]. Apolipoprotein E [apoE] is an important plasma protein in cholesterol that plays a key role in the progression of GS

Aim: The aim of this work was to study the immunoexpression of gelatinases and apoE in experimentally induced GS

Materials and methods: Twenty male rats were divided into two equal groups: a control group and a GS model group [each n=10]. The GS was induced by an injection of adriamycin [5 mg/kg]. At the end of 4 weeks, the 10 rats in each group were killed and kidney specimens were processed for [histological and immunohistochemical study] biochemical studies

Results: Serum total protein and serum albumin in the GS group were reduced compared with those of the control group [P<0.01]. Compared with the control group, the values of 24-h urine total protein, 24-h urine excretion for albumin, blood urea nitrogen, serum creatinine, and GS index in the GS group were significantly increased [P<0.01]. In the GS group, there was glomerular hypercellularity and hypertrophy with focal obliteration of some capillaries. Interstitial fibrosis and inflammation were detected. The immunostaining for gelatinase was decreased, whereas apoE, transforming growth factor-beta1, and alpha-smooth muscle actin were increased

Conclusion: In induced GS, an increased expression of apoE was associated with decreased expression of gelatinase and this led to accumulation of extracellular material in glomeruli

Study of the morphologic variants of focal segmental glomerulosclerosis: a Brazilian report / Estudo brasileiro das variantes morfológicas da glomerulosclerose segmentar e focal

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is the most frequent primary glomerulopathy in Brazil and its incidence is increasing worldwide. Pathogenesis is related to podocyte injury, which may be due to several factors including viruses, drugs, genetics and immunological factors. In 2004, the Columbia classification of FSGS identified five histological variants of the disease: collapsing (COL), usual (NOS), tip lesion (TIP), perihilar (PHI) and cellular variant (CEL). The objective of this study was to classify the FSGS biopsies in these morphological variants. METHODS: One hundred thirty-one cases of renal biopsies with primary FSGS diagnosis, which had been performed at a Brazilian reference center from 1996 to 2006, were classified according to the Columbia criteria. RESULTS: FSGS cases were distributed as follows: 38.2% NOS variant, 36.6% COL, 14.5% TIP, 6.9% PHI and 3.8% CEL. CONCLUSION: COL variant of FSGS seems to be more prevalent in Brazil in comparison with other centers worldwide, which may be related to environmental and socioeconomic factors.

INTRODUÇÃO: A glomerulosclerose segmentar e focal (GESF) é a glomerulopatia primária mais frequente no Brasil e sua incidência está aumentando em todo o mundo. Sua patogênese está relacionada com a lesão de podócitos, que pode ser devida a vários fatores, incluindo vírus, drogas, fatores genéticos e imunológicos. Em 2004, a classificação de Columbia GESF definiu cinco variantes histológicas da doença: colapsante (COL), usual (NOS), lesão apical (TIP), Peri-hilar (PHI) e variante celular (CEL). O objetivo deste estudo foi classificar as biópsias com diagnóstico de GESF nessas variantes morfológicas. MÉTODOS: Cento e trinta e um casos de biópsias renais com diagnóstico de GESF primária em um centro brasileiro de referência em nefrologia, no período de 1996 a 2006, foram classificados de acordo com os critérios de Columbia. RESULTADOS: Os casos se distribuíram da seguinte forma: 38,2% da variante de NOS; 36,6% de COL; 14,5% de TIP; 6,9% de PHI; 3,8% de CEL. CONCLUSÃO: A variante COL de GESF parece ser mais prevalente no Brasil do que em outros centros internacionais e isso pode ser reflexo de fatores socioeconômicos e ambientais.

Síndrome nefrótico cortico-resistente secundario a mutación genética, a propósito de 2 casos clínicos / Corticoresistant nephrotic syndrome secondary to genetic mutation, 2 Case-report

Background: Around 10-30 percent patients with Corticoresistant Nephrotic Syndrome (CRNS) have hereditary glomerulopathy. Objective: Describe 2 children with CRNS on chronic peritoneal dyalisis (CPD), with positive Podocin mutation genetic study. Case-report 1: A 4 years-old male with CRNS and diagnosis of focal segmental glomerulosclerosis (FSGS) at renal biopsy, with positive R 229Q and A 284V Podocin mutation genetic study. The treatment included Enalapril, steroids and Cyclophosphamide without remission, requiring CPD at 12 years-old. Case-report 2: A 6 years-old female with CRNS and diagnosis of focal segmental glomerulosclerosis (FSGS) at renal biopsy, with positive R 229Q and A 284V Podocin mutation genetic study. The treatment included Enalapril, steroids and Cyclophosphamide without remission, requiring CPD at 7 years-old. Conclusion: The genetic mutation study should be included in all CRNS cases, in order to guide the therapy and prognosis of the disease.

En pacientes portadores de Síndrome Nefrótico Córtico Resistente (SNCR) se ha demostrado que entre el 10 y 30 por ciento presentan glomerulopatías hereditarias. Objetivo: Describir dos niños portadores de SNCR en diálisis peritoneal crónica (DPC), cuyo estudio genético para mutación de podocina fue positivo. Caso 1: Paciente de sexo masculino, debuta a los 4 años con un SNCR, biopsia renal informa una Glomerulo Esclerosis Focal Segmentaria (GEFS), se maneja con enalapril, esteroides y ciclofosfamida, sin lograr remisión. A los 12 años ingresa a DPC, estudio genético resulta positivo para mutación del gen de la podocina en los alelos R 229Q y A 284V. Caso 2: Paciente de sexo femenino, a los 6 años de edad debuta con un SNCR, biopsia renal informa GEFS, recibe tratamiento clásico sin respuesta, a los 7 años inicia DPC. Su estudio reporta mutación de podocina alelos R229Q y A284V. Conclusión: El estudio genético debería ser incorporado en el estudio etiopatogénico de todo SNCR para orientar el tratamiento y pronóstico de la enfermedad.

Interleukin-10 Promoter Polymorphism is Associated with the Predisposition to the Development of IgA Nephropathy and Focal Segmental Glomerulosclerosis in Korea

The roles of interleukin-10 (IL-10) have been emphasized in several models of glomerulonephritis (GN). Three biallelic polymorphisms within the IL-10 promoter region, at positions -1,082, -819, and -592 from the transcription initiation site, were shown to affect the level of IL-10 production. To investigate the effect of IL-10 promoter polymorphisms on the predisposition to development of GN in Korea, IL-10 promoter polymorphisms were assayed by polymerase chain reaction followed by restriction fragment length polymorphism in 108 patients with IgA nephropathy (IgAN), 49 focal segmental glomerulosclerosis (FSGS), and 100 healthy controls. In comparison with the control, the frequency of -1,082*G alleles were lower in IgAN and the frequencies of -592*C and -819*C were lower in FSGS, respectively. As for the haplotype, GCC haplotype was less frequent among IgAN than the control and ATA haplotype was more frequent among FSGS than the control (p<0.05). The frequency of intermediate producer genotypes (GCC/ACC and GCC/ATA) were lower among IgAN or FSGS than the control. Our findings suggested that IL-10 promoter polymorphism predisposed to the development of IgAN and FSGS in Korean patients.

The role of ACE gene polymorphism in rapidity of progression of focal segmental glomerulosclerosis.

BACKGROUND: The insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene has been associated with progression of renal diseases. AIMS: We investigated its role in the rate of progression of focal segmental glomerulosclerosis (FSGS). METHODS: Forty-seven patients with end-stage renal disease (ESRD) due to FSGS were evaluated. RESULTS: The distribution of ACE genotype was II-25.5%, ID-55.5%, and DD-19%, as compared to 40 controls with genotype of 7.5%, 60%, and 32.5%, respectively (p= NS). In African Americans (AA) the gene frequencies among patients and controls were I-43%, D-57% vs I-36%, D-64%, respectively. This was different than the gene frequencies in White/Hispanic (W/H) patients I-61.5%, D-38.5% vs I-38.6%, D-61.4%, in controls (P < 0.05). In 22 patients with rapid progression (RP) of FSGS to ESRD the genotype distribution was II-18%, ID -64%, and DD-18%. In 25 patients with FSGS who progressed slowly (SP) the genotype was similar (II-32%, ID-48% and DD-20%, P >0.05). With respect to rate of progression, D allele frequency was similar in AA patients (RP 64% vs SP 50%) and W/H patients (RP 36% vs SP 40%). CONCLUSION: Our study reveals no association between the I/D polymorphism of the ACE gene and the presence of and rapidity progression of FSGS.

Idiopathic focal segmental glomerulosclerosis and HLA antigens

The objective of the present study was to investigate a possible association between HLA class II antigens and idiopathic focal segmental glomerulosclerosis (FSGS), HLA-A, -B, -DR and -DQ antigens were determined in 19 Brazilian patients (16 white subjects and three subjects of Japanese origin) with biopsy-proven FSGS. Comparison of the HLA antigen frequencies between white patients and white local controls showed a significant increase in HLA-DR4 frequency among FSGS patients (37.7 vs 17.2 percent, P<0.05). In addition, the three patients of Japanase extraction, not included in the statistical analysis, also presented HLA-DR4. In conclusion, our data confirm the association of FSGS with HLA-DR4 previously reported by others, thus providing further evidence for a role of genes of the HLA complex in the susceptibility to this disease.