Unexpectedly High Prevalence of Low Alpha-Galactosidase A Enzyme Activity in Patients with Focal Segmental Glomerulosclerosis

OBJECTIVES: Fabry disease (FD) is a rare disease associated with sphingolipid accumulation. Sphingolipids are components of plasma membranes that are important in podocyte function and accumulate in various glomerular diseases such as focal segmental glomerulosclerosis (FSGS). Both FD and FSGS can cause podocyte damage and are classified as podocytopathies. In this respect, FD and FSGS share the same pathophysiologic pathways. Previous screening studies have shown that a significant proportion of end-stage renal disease (ESRD) patients receiving hemodialysis (HD) have unsuspected FD, and the prevalence of low alpha-galactosidase A (αGLA) enzyme activity in these patients is higher than that in the normal population. We aimed to compare αGLA enzyme activity in patients with biopsy-proven FSGS and ESRD receiving HD. METHODS: The records of 232 patients [62 FSGS (F/M: 33/29); 170 HD (M/F: 93/79)] were evaluated retrospectively. The screening was performed based on the αGLA enzyme activity on a dried blood spot, with the confirmation of plasma LysoGb3 levels, and the known GLA mutations were tested in patients with low enzyme activities. The two groups were compared using these parameters. RESULTS: The mean level of αGLA enzyme activity was found to be lower in FSGS patients than in the HD group (2.88±1.2 μmol/L/h versus 3.79±1.9 μmol/L/h, p<0.001). There was no significant relationship between the two groups with regard to the plasma LysoGb3 levels (2.2±1.22 ng/ml versus 1.7±0.66 ng/ml, p: 0.4). In the analysis of GLA mutations, a D313Y mutation [C(937G>T) in exon p] was found in one patient from the FSGS group. CONCLUSIONS: We found that αGAL activity in patients with FSGS is lower than that in patients undergoing HD. The low enzyme activity in patients with FSGS may be explained by considering the similar pathogenesis of FSGS and FD, which may also lead to sphingolipid deposition and podocyte injury.

Pattern, clinical features and response to corticoids of glomerular diseases in a Brazilian population. An analytical cross-sectional study / Perfil, características clínicas e resposta a corticoides das doenças glomerulares em uma população brasileira. Um estudo transversal analítico

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 ...

Profile of glomerular diseases in a public hospital of Federal District, Brazil / Perfil das doenças glomerulares em um hospital público do Distrito Federal

INTRODUÇÃO: As doenças glomerulares são uma causa frequente de doença renal crônica, sobretudo nos países em desenvolvimento. OBJETIVO: O objetivo deste estudo foi determinar o perfil destas glomerulopatias em um hospital público da cidade de Brasília, Distrito Federal. MÉTODOS: Foram realizadas 121 biopsias renais pela equipe de nefrologia do Hospital Regional da Asa Norte (HRAN) entre agosto de 2005 e maio de 2009. Foram excluídas oito biopsias realizadas em pacientes transplantados renais e analisados os prontuários dos 113 pacientes restantes. Dados analisados: sexo, idade, exames laboratoriais, síndrome glomerular, diagnóstico clínico, grau de fibrose intersticial, uso de imunossupressores, necessidade de diálise e desfecho clínico. RESULTADOS: A média de idade foi 34,9 ± 16,2 anos, com predomínio masculino (51,3 por cento). As principais síndromes glomerulares foram: síndrome nefrótica (41,6 por cento) e glomerulonefrite rapidamente progressiva (35,4 por cento). Entre as glomerulopatias primárias, houve predomínio da glomeruloesclerose segmentar e focal (26,9 por cento) e da nefropatia por IgA (25 por cento) e entre as secundárias a nefrite lúpica (50 por cento) e a glomerulonefrite proliferativa exsudativa difusa (34,2 por cento). A maioria dos pacientes fez uso de imunossupressores (68,1 por cento) e quase um terço deles (29,2 por cento) necessitou de diálise durante a internação. Evoluíram para terapia dialítica crônica 13,3 por cento dos pacientes e 10,6 por cento evoluíram a óbito. CONCLUSÃO: Este estudo poderá contribuir para melhor entendimento epidemiológico das doenças glomerulares no Distrito Federal, orientando na adoção de políticas públicas visando permitir rápido diagnóstico e manejo clínico das mesmas.

INTRODUCTION: Glomerular diseases are a frequent etiology of chronic kidney disease, especially in the developing countries. OBJECTIVE: To determine the profile of such glomerulopathies in a public hospital located in the city of Brasilia, Federal District. METHODS: 121 renal biopsies in different patients were performed by the Renal Division of Hospital Regional da Asa Norte (HRAN) between August 2005 and May 2009. Eight renal biopsies in renal-transplant patients were excluded and the medical records of 113 remaining patients were analyzed. Analyzed data: sex, age, laboratory exams, glomerular syndrome, clinical diagnosis, degree of interstitial fibrosis, immunosuppressants use, need for dialysis and clinical outcome. RESULTS: The age average was 34.9 ± 16.2 years-old, a predominance of male patients (51.3 percent). Major glomerular syndromes were: nephrotic syndrome (41.6 percent) and the rapidly- progressive glomerulonephritis (35.4 percent). Among primary glomerulopathies focal glomerulosclerosis (26.8 percent) followed by IgA nephropathy (25 percent) were predominant; and among the most prevalent secondary glomerulopathies we had lupus nephritis (50 percent) and diffuse exudative proliferative glomerulonephritis (34.2 percent).The majority of the patients used immunosuppressants (68.1 percent) and almost one third of them (29.2 percent) needed dialysis during their hospitalization. Progressed to chronic dialysis therapy 13.3 percent of the patients and 10.6 percent died. CONCLUSION: This study may contribute to better epidemiological understanding of glomerular diseases in the Federal District, guiding the adoption of public policies aiming the quick clinical treatment of such diseases.

Histopathological pattern in childhood glomerulonephritis

To determine the histopathological pattern in childhood glomerulonephritis [CGN]. This retrospective analysis of renal biopsies of 118 children with various clinical syndromes of CGN was carried out at the National Institute of Child Health [NICH] and The Kidney Center [TKC], Karachi, from July 2005 to December 2009. The age ranged from 6 months to 16 years. All biopsies were studied under light microscopy [LM] and immunoflourescence [IMF] Histopathological lesions [HPL] were classified as primary and secondary glomerular diseases. Demographic data, indications and HPL were retrieved and analyzed using descriptive statistics. Out of 118 patients, 62 [52.54%] were males and 56[47.45%] females. Mean age was 8.2 +/- 3.9 years. Major indications for biopsy were primary nephrotic syndrome [PNS 86, 72.88%]. secondary GN [SGN, 17, 14.4%] and nephritic-nephrotic syndrome [NNS 13, 11%]. Overall, primary glomerular diseases [PGD] accounted for 84.74% of all biopsies. Minimal change disease [MCD 38, 32.2%] and focal segmental glomerulosclerosis [FSGS 35, 29.66%] were the two most common lesions and accounted for 43% and 33.72% respectively in PNS. Other important lesions were membranous GN [MGN 10, 8.47%], membranoproliferative [MPGN 9, 7.16%], post-infective [PIGN 4, 3.38%] and IgM nephropathy [IgMN 3, 2.54%]. Among secondary glomerular diseases [SGD], lupus nephritis [LN 11, 9.32%] was the most common lesion followed by Henoch-Schonlein nephritis [HSN] and haemolytic uraemic syndrome [HUS] each in 3 [2.52%]. Overall, MCD and FSGS were the two most common HPL in PGD and both dominated in PNS. Lupus nephritis was the leading lesion in SGD. These histopathological pattern of CGN in our study is in conformity with the existing literature from Pakistan

Renal histological findings in adults in Jamaica / Hallazgos histológicos renales en adultos en Jamaica

BACKGROUND: In 2006, it was reported that Focal and Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD) and Membranous Glomerulonephritis (MGN) were the commonest primary glomerular diseases identified from percutaneous kidney biopsies done in Jamaica for that year (n = 76). The sample size was thought to be small and might have affected the reported findings. So a threeyear review of percutaneous kidney biopsies in Jamaica was carried out. METHODS: Histology reports and clinical data were reviewed for percutaneous kidney biopsies performed from January 2005 to December 2007. Demographic data (age, gender), laboratory investigations such as serum urea, serum creatinine, proteinuria, haematuria, 24-hour urinary protein, and creatinine clearance, and clinical diagnosis were collected from the histology requisition form. RESULTS: There was a total of 224 native kidney biopsies performed. There were 91 males (40.6%) and 133 females (59.4%). Age distribution showed a total number of 25 paediatric cases (11.2%) and 199 adult cases (88.8%). Proteinuria was present in 171 cases (76.3%) and haematuria in 86 cases (38.4%). Of the total biopsies done, 78 cases (39.2%) had primary glomerular diseases, 110 cases (55.3%) had secondary glomerular diseases and 11 (5.5%) biopsies were reported as either normal or inadequate for histological diagnosis. The most common reasons indicated for percutaneous kidney biopsy were proteinuria, haematuria and staging of lupus nephritis. Most common histological findings for primary glomerular disease after percutaneous kidney biopsy were FSGS (n = 34), MGN (n = 15) and MCD (n = 12). In secondary glomerular diseases (n = 110), there were more females (70.8%) than males. Systemic lupus erythematosus was present in 63.3%. Histology of lupus nephritis according to the International Society of Nephrologists classification shows Membranous Lupus Nephritis [MLN] (40.2%), Diffuse Lupus Nephritis [DLN] (19.5%) and Minimal Mesangial Lupus Nephritis [MMLN] (14.3%) as the common histological types. CONCLUSIONS: The most common histological finding for primary glomerular disease following percutaneous kidney biopsy was FSGS, MCD and MGN. Membranous Lupus Nephritis was the commonest histological type for lupus nephritis in this series.

ANTECEDENTES: En 2006, se reportó que la Glomeruloesclerosis Segmentaria y Focal (GESF), la Enfermedad de Cambios Mínimos (ECM) y la Glomerulonefritis Membranosa (GNM) fueron las enfermedades glomerulares primarias más comunes identificadas a partir de las biopsias renales percutáneas realizadas en Jamaica ese año (n = 76). El tamaño de la muestra se consideró pequeño y pudo haber afectado los hallazgos reportados. De manera que se realizó un examen de tres años, de las biopsias renales percutáneas en Jamaica. MÉTODOS: Se revisaron los reportes de histología y los datos clínicos correspondientes a las biopsias renales percutáneas realizadas desde enero de 2005 a diciembre de 2007. RESULTADOS: Hubo un total de 224 biopsias de riñón nativo. Se realizaron 74, 78 y 72 biopsias renales en 2005, 2006 y 2007 respectivamente. Hubo 91 varones (40.6%) y 133 hembras (59.4%). La distribución por edades mostró un total de 25 casos pediátricos (11.2%) y 119 casos de adultos (88.8%). La proteinuria estuvo presente en 171 casos (76.3%) y la hematuria en 86 casos (38.4%). Del total de biopsias realizadas, 78 casos (39.2%) tenían enfermedades glomerulares primarias, 110 casos (55.3%) tenían enfermedades glomerulares secundarias y 11 (5.5%) biopsias fueron reportadas como normales, o como inadecuadas para el diagnóstico histológico. Las razones más comunes señaladas para la biopsia renal percutánea fueron la proteinuria, la hematuria y la estadificación de la nefritis por lupuso nefritis lúpica. Los hallazgos histológicos más comunes para la enfermedad glomerular primaria tras la biopsia renal percutánea fueron GESF (n = 34), GNM (n = 15) y ECM (n = 12). En relación con las enfermedades glomerulares secundarias (n = 110), hubo más hembras (70.8%) que varones. El lupus eritematoso sistémico estuvo presente en 63.3%. De acuerdo con la clasificación de la Sociedad Internacional de Nefrología, la histología de la nefritis por lupus muestra la nefritis lúpica membranosa (NLM) [40.2%], la nefritis lúpica difusa (NLD) [19.5%], y la nefritis lúpica mesangial mínima (NLMM) [14.3%], como los tipos histológicos más comunes. CONCLUSIÓN: Los hallazgos histológicos más comunes para la enfermedad glomerular primaria tras la biopsia renal percutánea, fueron GESF, ECM y GNM. La nefritis lúpica membranosa fue el tipo de histología más común para la nefritis por lupus en esta serie.

Glomerular diseases in a Hispanic population: review of a regional renal biopsy database / Enfermedades glomerulares en una población hispánica: resultados de un registro regional de biopsias renales

CONTEXT AND OBJECTIVE: Epidemiological data provide useful information for clinical practice and investigations. This study aimed to determine glomerular disease frequencies in a region of Colombia and it represents the basis for future studies. DESIGN AND SETTING: Single-center retrospective analysis at the University of Antioquia, Colombia. METHODS: All native renal biopsies (July 1998 to December 2007) were reviewed, but only glomerular diseases were analyzed. The diagnosis of each case was based on histological, immunopathological and clinical features. RESULTS: A total of 1,040 biopsies were included. In 302 cases (29.0 percent), the patient's age was < 15 years. Primary glomerular diseases were diagnosed in 828 biopsies (79.6 percent) and secondary in 212 (20.4 percent). The most common primary diseases were focal and segmental glomerulosclerosis (FSGS) (34.8 percent), immunoglobulin A (IgA) nephropathy (IgAN) (11.8 percent), membranous glomerulonephritis (MGN) (10.6 percent), minimal change disease (MCD) (10.6 percent), crescentic glomerulonephritis (GN) (5.6 percent), and non-IgA mesangial proliferative GN (5.6 percent). Postinfectious GN represented 10.7 percent of the diagnoses if included as primary GN. Lupus nephritis corresponded to 17.8 percent of the entire series. In adults, the order of the most frequent primary diseases was: FSGS, IgAN, MGN, crescentic GN and MCD. In children (< 15 years), the most frequent were: FSGS, postinfectious GN, MCD, non-IgA mesangial proliferative GN, endocapillary diffuse GN and IgAN. CONCLUSIONS: As among Afro-Americans, FSGS is the most frequent type of glomerulopathy in our population, but in our group, there are more cases of IgAN. The reasons for these findings are unclear. This information is an important contribution towards understanding the prevalence of renal diseases in Latin America.

CONTEXTO Y OBJETIVO: Los datos epidemiológicos dan información útil en clínica e investigación. Nuestro objetivo fue determinar frecuencias de enfermedad glomerular en una región de Colombia y representa la base para trabajos futuros. DISEÑO Y UBICACIÓN: Análisis retrospectivo en un único centro: Universidad de Antioquia, Colombia. MÉTODOS: Todas las biopsias de riñón nativo fueron revisadas (1998 - 2007), pero solo analizamos enfermedades glomerulares. El diagnóstico en cada caso estuvo basado en histología, inmunopatología y características clínicas. RESULTS: 1.040 biopsias fueron incluidas. En 302 casos (29,0 por ciento) la edad del paciente fue < 15 años. El diagnóstico fue enfermedad primaria en 828 biopsias (79,6 por ciento) y secundaria en 212 (20,4 por ciento). Las enfermedades primarias más frecuentes fueron glomeruloesclerosis focal y segmentaria (GEFyS) (34,8 por ciento), nefropatía IgA (NIgA) (11,8 por ciento), glomerulonefritis membranosa (GNM) (10,6 por ciento), enfermedad de cambios mínimos (ECM) (10,6 por ciento), glomerulonefritis (GN) extracapilar (5,6 por ciento) y GN proliferativa mesangial no-IgA (5,6 por ciento). La GN postinfecciosa representa el 10,7 por ciento de glomerulopatías primarias. La nefritis lúpica corresponde al 17,8 por ciento de todos los casos. En adultos el orden de frecuencia de enfermedades primarias es: GEFyS, NIgA, GNM, GN extracapilar y ECM. En niños (< 15 años) las más frecuentes fueron: GEFyS, GN postinfecciosa, ECM, GN mesangial no-IgA, GN endocapilar difusa y NIgA. CONCLUSIONES: Al igual que en afro-americanos, en nuestra población la GEFyS es la glomerulopatía más frecuente, pero en nuestro grupo hay más NIgA. Las razones para estos hallazgos no se conocen. La información presentada aquí es una contribución importante para el entendimiento de la prevalencia de enfermedades renales en Latinoamérica.

Non-neoplastic renal diseases in Kerala, India--analysis of 1592 cases, a two year retrospective study.

A retrospective analysis of 1592 renal biopsies received from various hospitals all over Kerala over a period of two years was done. Of the 1544 native kidney biopsies majority of cases (300; 18.84%) were focal segmental glomerulosclerosis. Next infrequency was IgA nephropathy (227; 14.26%). The other diagnoses included post infectious glomerulonephritis (GN) (150; 9.42%), lupus nephritis (131; 8.23%), membranous glomerulonephritis (118; 7.41%), minimal change disease (94; 5.94%), interstitial nephritis 87(5.46%), membranoproliferative glomerulonephritis (MPGN) and severe glomerulosclerosis (74; 4.64% each), IgM nephropathy (72; 4.52%), acute tubular necrosis and diabetic glomerulopathy (24; 1.5% each), ANCA-related GN (21;1.32%), amyloidosis (13; 0.82%), Henoch Schonlien purpura (12; 0.75%) atd thrombotic microangiopathy (10; 0.63%). Afew others like myeloma cast nephropathy, cholesterol embolism, Clq nephropathy, oxalosis, mixed connective tissue disorder (MCTD, Wegner's granulomatosis etc. also were seen occasionally. 48 cases were allograft biopsies (3.02%).

An analysis of 4,514 cases of renal biopsy in Korea

To evaluate the distribution and changing patterns of renal diseases in Korea, a total of 4,514 cases of renal biopsy collected over a 23-year period between 1973 and 1995 were reviewed. Of 4,200 cases excluding 314 unsatisfactory biopsies, adult cases comprised 59.5% and pediatric cases, 40.5%. The male to female ratio was 1.5:1 in adults and 2.2:1 in children. Glomerulonephritis (GN) comprised 80.0% of the total. The most common primary GN in adults was minimal change disease (MCD) (26.6%), followed by IgA nephropathy (IgAN) (22.1%), membranous GN (MGN) (11.8%), and membranoproliferative GN (MPGN) (5.9%). In children, the primary GN incidence rates were MCD (24.8%), IgAN (10.3%), poststreptococcal (including postinfectious) GN (PSGN) (8.6%), and focal segmental glomerulosclerosis (FSGS) (4.0%). The most common secondary GN in adults was lupus nephritis and in children Henoch-Schonlein purpura nephritis. The most common cause of nephrotic syndrome was MCD in both adults and children, followed by MGN and FSGS. The elderly, aged sixty years and older, comprised 2.7% of cases and recorded equal numbers of MCD and MGN. The proportion of the biopsies found to be seropositive for HBs antigen was 27.9%, and these showed either MGN or MPGN pattern. Repeat biopsy was performed in 168 patients, due to previous biopsy failure in 15.5%. When the primary GN cases were analyzed at 5-year intervals, the prevalence of PSGN, which was greater than 25% during the 1973-1982 period, decreased abruptly in children thereafter, whereas the prevalence of FSGS increased slowly since the 1988-1992 period in both adults and children. The decrease of PSGN and the increase of FSGS suggest a role for socioeconomic and environmental factors in Korea.

Idiopathic foca and segmental glomerulosclerosis in Jamaica: a 10 year review

Idiopathic focal and segmental glomerulosclerosis (IFSGS) in a predominantly black population does not appear to behave any differently than in Caucasian patients. Response to steroid therapy and cyclophosphamide had favourable prognostic significance. There may be a subgroup of IFSGS which responds more slowly to steroids. The duration of steroid therapy should extend beyond four months

Prevalência de glomerulopatias pós-transplante renal: classificaçäo morfológica / Prevalence of post-transplantation glomerulopathies: morphological classification

Foi realizado estudo retrospectivo (1980 a 1989) e prospectivo (1990 a 1992) de 625 biópsias de rins transplantados, no Departamento de Anatomia Patológica e Medicina Legal (APM) da Faculdade de Medicina (FM) da UFMG. Apenas 343 permitiram análise e as conclusöes foram calcadas nestas. As biópsias foram provenientes de diferentes hospitais de Belo Horizonte e de outras cidades do interior de Minas Gerais, determinando-se: a) a incidência de biópsias de transplante renal (Tx) dentro da casuística global de patologia renal do serviço; b) prevalência de glomerulopatias pós-transplante; e c) os padröes morfológicos de glomerulopatias observados. No presente estudo foi utilizada microscopia óptica convencional. O número total de biópsias analisadas no serviço foi de 69.455; delas, 3.871 eram biópsias renais. Foi observado que as biópsias de Tx (625) constituem percentual significativo (16,14 por cento) dentro da patologia renal e com aumento expressivo nos três últimos anos. Observamos que 61,8 por cento dos casos estudados (343) mostravam alteraçöes glomerulares: esclerosantes (28 por cento), proliferativas (24 por cento), mistas (34 por cento) e outras lesöes (14 por cento). Essas alteraçöes eram mais frequentes nos casos com mais de um ano de sobrevida do transplante (35,9 por cento) e associadas a quadros de rejeiçäo crônica. Concluimos que o estudo sistematizado das biópsias de Tx permite avaliar e identificar padröes morfológicos, suas modificaçöes e seu potencial perfil evolutivo. A análise da nossa casuística mostrou que o número de biópsias de Tx aumentou em forma significativa no decorrer do período estudado, sendo também mais frequentes nos casos de glomerulopatias pós-transplante.