A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Medicine in Internal Medicine Johannesburg, 2015 / Available literature on primary minimal change nephropathy (MCN) predominantly reflects Western and Asian populations, with little data describing the disease in black patients. We therefore studied the demographic and clinical profile of patients presenting with MCN at the Witwatersrand Academic Complex. The results of 1,618 renal biopsies performed at our centre between 2001 and 2010 were reviewed; 47 patients with MCN were identified (prevalence of 2.9%).The patients were predominantly of black race (83%), the male : female ratio was 1.04:1 and the mean age was 31.8± 12.1 years. The majority of patients (90%) fitted the criteria for the nephrotic syndrome. 18% of patients had elevated serum creatinine levels and 6.4% had associated hypertension. An association was found between gender and age; with a predominance of males amongst younger patients (less than 30 years) compared to a predominance of females amongst the older patients. Records of treatment and outcomes were available for 28 patients, all of whom received initial corticosteroid therapy (average dose of prednisone 0.8mg /kg/day). The average duration of therapy was 29 weeks. 57.1% achieved remission with no further relapse. No clinical or demographic parameters were identified that predicted response to corticosteroid therapy. 39.2% of patients had probable steroid dependance/resistance. Of these patients, 58.3% had a single relapse and 41.7% had double relapses. The mean time to relapse was 27.8±19.4 months with 83% of patients relapsing within 48 months; the mean time to relapse was longer in males (39.3±17.5 months) as compared to females who relapsed in 18±16.9 months, which was significant at the 10% level (P = 0.09). MCN is rare amongst Black Africans but should be considered in the differential diagnosis of nephrotic syndrome. The disorder in these patients may be less responsive to corticosteroids and a longer course of therapy may be required to induce remission. Males may be more likely to remain in remission for a longer time period.

Orientador: Maricilda Palandi de Mello / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-25T05:17:39Z (GMT). No. of bitstreams: 1 Guaragna_MaraSanches_D.pdf: 3317402 bytes, checksum: 18a0edd0d0e225eed7d57b65d9bea76b (MD5) Previous issue date: 2014 / Resumo: A Síndrome Nefrótica (SN) é a principal doença renal na infância, sendo caracterizada por proteinuria, edema, hipoalbuminuria e hiperlipidemia. Usualmente é classificada de acordo com a idade em que se apresenta em Congênita (SNC), quando se manifesta intraútero ou durante os primeiros três meses de vida, Infantil durante o primeiro ano de vida, na Infância, entre o primeiro ano até os 12 anos de idade e Juvenil, entre os 12 e os 18 anos de idade, aproximadamente. De acordo com a resposta ao tratamento com corticoesteróides os pacientes podem ser divididos em córtico-resistentes (CR), córtico-sensíveis (CS) ou córtico-sensíveis com recidiva frequente (CS,RF). Uma disfunção na barreira de filtração glomerular leva às manifestações clínicas decorrentes da síndrome, tais como proteinúria maciça na urina. Mutações em diversos genes vêm sendo correlacionadas com a SN em crianças. No entanto, os genes mais estudados e responsáveis pela maioria dos casos são os genes NPHS1, NPHS2 e WT1. Os objetivos deste trabalho foram identificar e verificar a distribuição de mutações nestes três genes em uma casuística brasileira com SN ou proteinúria isolada e avaliar cada alteração identificada utilizando diversas predições in silico, com o intuito de se esclarecer suas respectivas funções biológicas. Para isto foi realizada a análise molecular de 150 crianças e adolescentes, sendo três não aparentados com SNC e os demais 147 com SN Infantil, SN na infância, SN juvenil e proteinúria isolada, dos quais 134 eram não aparentados. Além destes 150 pacientes, também foram analisados os materiais de biópsias renais fixadas em bloco de parafina de sete pacientes que já foram a óbito com SNC. Para verificar a segregação alélica nas famílias, para os casos nos quais foram identificadas alterações, a análise molecular dos pais foi realizada, quando possível. Um grupo controle de indivíduos saudáveis foi incluído para se avaliar a frequência de alterações não depositadas em bancos de dados. No estudo do gene NPHS1 para os casos com SNC identificamos mutações missense, frameshift e em região de splicing nos três pacientes encaminhados no período da tese e em um dos materiais proveniente de biópsia renal. Assim, um total de quatro pacientes com SNC apresentaram mutações que se correlacionam com o grave quadro clínico apresentado. Para os pacientes com SN infantil, SN infância/juvenil e proteinúria isolada, foram triados o gene NPHS2 e os éxons 8-9 do gene WT1. No estudo do gene NPHS2 foram identificadas duas alterações em heterozigose nos padrões de herança autossômica recessiva em 2,7% (4/147), todos CR, enquanto que apenas uma alteração em heterozigose simples foi identificada em 9,5% (14/147) em casos de SN com apresentação menos grave e tardia. Em três dos 14 pacientes com uma alteração no gene NPHS2, alterações no gene NPHS1 foram também identificadas, todas já descritas como polimorfismos frequentes na população em geral. Para o gene WT1, com herança autossômica dominante, foram identificadas mutações em heterozigose simples em 2,04% (3/147). A avaliação da frequência e distribuição de mutações nestes genes em crianças com SN é inédita no Brasil e traz um direcionamento para a análise molecular de grupos específicos das crianças com SN. Além disto, este trabalho contribui para o estabelecimento das bases moleculares da doença na população brasileira, o que tem uma repercussão importante na conduta dos pacientes, uma vez que, nos que apresentam mutações, pode-se considerar o transplante renal a partir de doador vivo, pois para estes considera-se um risco menor de recidiva de glomérulo esclerose focal e segmentar após transplante do que para pacientes sem mutações / Abstract: Nephrotic syndrome (NS) is the main kidney disease in children. It is characterized by proteinuria, edema, hypoalbuminemia and hyperlipidemia. Acccording to the age of the diagnosis, it is usually classified as Congenital (CNS) when it manifests in utero or during the first three months of life, Infantile when the event occurs during the first year of life, in Childhood when symptoms occur between one year and 12 years and Juvenile, with onset between 12 and 18 years old. NS is traditionally separated on the basis of the response to standard steroid treatment as steroid-resistant (SRNS), steroid-sensitive (SSNS) or steroid sensitive with frequent relapses. A dysfunction in the glomerular filtration barrier leads to the characteristic clinical manisfestations of the syndrome such as massive loss of essential proteins in the urine. Mutations in different genes have been associated with NS in children. However, the most studied genes are NPHS1, NPHS2 and WT1, which are responsible for the great majority of the cases. The aims of this study were to identify and verify mutation distributions in those three genes in a Brazilian cohort with NS or isolated proteinuria and to characterize each identified variation by using different in silico prediction programs in order to understand its biological functions. For that, we performed molecular analyses of 150 children and adolescents, being three unrelated children with CNS and the remaining 147 with Infantile, Childhood, Juvenile NS and isolated proteinuria, being 134 unrelated. Besides those 150 patients, paraffin-embebbed renal biopsies of seven patients who had died from CNS have been also analysed. To verify allelic segregation in the family, molecular analyses were also held, whenever possible, for parents of patients in whom mutations were identified. A healthy control group was included in the study to evaluate the frequency of alterations that were absent in the databanks. In the NPHS1 study for CNS cases, we identified missense, frameshift and splicing mutations in the three patients included during the thesis project and in the paraffin-embedded renal biopsy tissue of a patient who had died of CNS. Therefore a total of four CNS cases bore mutations that are associated with the disease. NPHS2 gene and exons 8-9 of WT1 were screened for the 147 patients with infantile NS, childhood/juvenile NS and isolated proteinuria. In the NPHS2 study, two heterozygous alterations compatible to an autossomal recessive inheritance have been identified in 2,7% (4/147), all of the cases were SRNS; whereas, only one heterozygous alteration was identified in 9,5% (14/147), such cases had a less severe and late onset form of NS. Three out of those 14 patients presented sequence variations also in NPHS1 gene, but they have been described as neutral polymorphisms. For the WT1 gene whose mutations present a dominant pattern of inheritance, heterozygous alterations have been identified in 2,04% (3/147). This is the first study focusing frequency evaluation and mutation distribution in Brazilian children with NS and provides a guidance to the molecular analysis of specific case groups of SN. Moreover, this work contributes to the establishment of the molecular bases of this disease in the Brazilian population, what reflects mainly in the conduction of patients, since those bearing mutations can be considered for receiving a kidney from a living donor, because for them it is considered a lower risk of recurrent focal segmental glomerulosclerosis after kidney transplant than for patients without mutations / Doutorado / Genetica Animal e Evolução / Doutora em Genética e Biologia Molecular

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

Nephrotic syndrome (NS) is the second leading cause of pediatric chronic kidney disease. Pathogenic de novo C-terminal truncating variants in the gene TRIM8 (tripartite motif containing 8) causes a syndrome of NS and epilepsy. In contrast, N-terminal truncating variants are observed in gnomAD control subjects, indicating haploinsufficiency does not cause disease. Based on previously reported TRIM8-TRIM8 interactions, we hypothesized that NS-associated TRIM8 variants may impact wildtype TRIM8 through dominant-negative effects. Alternatively, these variants may have gain-of-function mechanisms in the development of NS. MG132, a 26S proteasome inhibitor, was used to modulate wildtype (WT) and patient variant containing (PV) TRIM8 protein levels. Protein-protein interactions were determined using co-immunoprecipitation of WT- and PV-TRIM8 protein upon transfection of immortalized podocytes with tagged cDNA constructs. Ubiquitination of WT and PV TRIM8 protein was measured by immunoprecipitation and western blotting upon overexpression of tagged Ubiquitin and TRIM8 cDNA constructs in immortalized podocytes. MYC-tagged WT and PV TRIM8 half-lives were determined through cycloheximide (CHX) treatment over a five-hour timed trial. CHX, used to inhibit the elongation step in eukaryotic protein translation, was administered to prevent protein synthesis. CHX-chase assay was performed to determine steady state protein stability of PV-TRIM8 relative to WT. Tagged TRIM8 WT protein levels increased upon treatment with MG132 whereas protein levels of tagged TRIM8 PV proteins were not. Flag-tagged TRIM8 PV proteins, but not flag-tagged WT protein, co-immunoprecipitated with MYC-tagged TRIM8 WT protein. MG132 rescued co-immunoprecipitation of FLAG- and MYC-tagged WT TRIM8 proteins. Tagged TRIM8 WT protein undergoes polyubiquitination, which is impaired by TRIM8 patient variants. PV-TRIM8 had a significantly longer half-life when compared to the WT. TRIM8 PV cause reduced TRIM8 polyubiquitination, impaired 26S proteasomal degradation, and increased TRIM8-TRIM8 interactions, conferring a gain-of-function mechanism of disease. / 2026-03-07T00:00:00Z

A dissertation presented in fulfillment of part of the requirements for the degree of Master of Medicine (Pathology) in the Faculty of Medicine, University of the Witwatersrand, Johannesburg, November, 1966. / WHSLYP2017

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Thesis (DMed)--Stellenbosch University, 2011. / ENGLISH ABSTRACT: Background and Objective: The most common cause of severe proteinuria/nephrotic syndrome (NS) in children worldwide is minimal change disease (MCD). This is also the pattern observed in white and Indian children in South Africa (SA). By contrast, black and mixed race/coloured children of Southern Africa in the 1960s to 1990s were shown to have a different pattern of NS. One of the main differences was the frequency of hepatitis B virus (HBV) associated glomerulonephritis, usually membranous glomerulonephritis (MGN). The objective of this project was a clinicopathological study of this subgroup of nephrotic children to document the disease further and in particular to seek correlations between pathological and clinical features including prognosis. A central focus was to document the detailed ultrastructural examination of the renal biopsies of these children and to correlate the spectrum of pathological features with demographic, clinical, laboratory and prognostic features. The hypothesis was that the clinicopathological features of HBV MGN in children differed substantially from idiopathic MGN in general (children and adults) and also from HBV MGN in adults and that HBV MGN in children should be viewed as a distinct disease. Patients and methods: The childhood (12 years and younger) patient cohort was 309 children with severe proteinuria/nephrotic syndrome who presented at Tygerberg Hospital (TBH) over a 21 year period from 1974-1995, including 67 children from Namibia. The study group was 71 children with HBV MGN who were followed up to 2005. The comparative adult group was 45 adults with MGN of whom 12 had HBV MGN and 33 idiopathic MGN. (A comparison could not be made with idiopathic MGN in childhood as this centre only had 2 such patients during the study period.) Demographic, clinical, laboratory and renal pathology data were collected, compared and correlated. Results: HBV associated MGN was the most frequent cause of NS in the Namibian subgroup, 25/67 (37%) and the third most frequent, 71/309 (23%) in the childhood cohort as a whole. The MGN group was 86% (71/83) of the total HBV childhood nephrotic cohort, by far the dominant subgroup. The average age of the 71 children with HBV MGN was 6.0 years (range 2-12 years) at presentation and boys comprised 80% of the group. Hepatitis B envelope antigen (HBeAg) was identified in the serum of 87% of children tested. Laboratory features different from idiopathic MGN included more prominent haematuria, mildly raised serum transaminases and more frequently lowered serum C3 and C4 levels. Light microscopic examination of renal biopsies showed mesangial proliferation in all patients but with minimal glomerular sclerosis and interstitial disease. On ultrastructural examination mesangial and subendothelial deposits were common and prominent as was mesangial interposition. The MGN of HBV in children therefore frequently showed mesangiocapillary glomerulonephritis (MCGN) features in addition to the subepithelial deposits of MGN. The subgroup of 23 whose renal biopsies displayed severe mesangial interposition in addition to the subepithelial deposits of MGN were termed the mixed HBV MGN-mesangiocapillary GN group. Virus like bodies and tubuloreticular inclusion bodies were both found in more than 80% of biopsies of childhood HBV MGN. HBeAg was identified in the subepithelial deposits in the glomeruli. This was the first time this feature was demonstrated in Africa. The 46 South African children with HBV MGN showed a cumulative remission rate of 25% at 2 years and 52% at 4 years. Seven of the children (10%) of the total cohort developed chronic renal failure (CRF). Age of 6 years and above at presentation and severe mesangial deposits on biopsy correlated with fewer remissions and poorer outcome. In 3 patients the interval between the diagnosis of HBV MGN and the onset of CRF was more than 19 years with the longest being 23 years. The 358 cases of childhood HBV MGN from Southern Africa constitute 37% of the reported childhood patients. Comparative data A comparison was made between the 71 children with HBV MGN, 12 adults with HBV MGN and 33 adults with idiopathic MGN. The main differences were that both HBV MGN groups included only coloured and black patients and were more predominantly male while the idiopathic MGN group included all races. In the HBV patients, haematuria was more frequent and severe, liver enzymes were frequently raised and C3 more frequently reduced than in the idiopathic cohort. Both groups of adult MGN patients had normal C4 levels while the childhood HBV MGN group had reduced C4 levels. The immune complex pattern in both of the HBV MGN adult and childhood groups on biopsy was similar with more mesangial and subendothelial deposits as well as mesangial interposition than the idiopathic group. Despite this similarity between the two HBV groups, both adult groups showed more glomerular sclerosis and interstitial disease than the childhood group. The clinical outcome of the children’s cohort was better than the other 2 groups with remission (52%) more frequent at 4 years (p<0.01) and better renal and patient survival. Including the 83 cases from this series, at least 1243 renal biopsy proven cases of HBV MGN have been reported in the English literature; children (80%) and adults (20%). The male gender predominance in both age groups for HBV MGN is similar (children 79%; adults 84%) and significantly greater than for idiopathic MGN. Conclusions: The findings confirm that HBV MGN in children is a distinct form of GN which broadens the classical morphologic description of MGN by often including a number of mesangiocapillary GN features. The subgroup of renal biopsies with the most severe mesangiocapillary GN features was classified as the mixed HBV MGNmesangiocapillary GN group. The MGN spectrum as a whole comprised 86% of the HBV positive childhood group. HBV MGN was the most frequent association with NS/severe proteinuria in the Namibian subgroup (37%) and the third largest group (19%) in the SA children. It showed a relatively high spontaneous remission rate but at least 10% of the children developed renal failure. Age of 6 years and above at presentation and severe mesangial deposits on biopsy correlated with fewer remissions and poorer outcome. Extended follow up (more than 15 years) was required to demonstrate renal failure in some patients in the poor outcome group. Urbanisation, associated with lower HBV carrier rates, and HBV vaccination (initiated routinely in 1995 in SA), have already lead to a sharply decreasing incidence of this disease in SA. HBV MGN has been a valuable and possibly unique model of human GN and MGN in particular in that the HBeAg has been identified in both the serum and glomeruli enabling confirmation of the aetiological role of HBeAg. het ’n kumulatiewe remissie koers van 25% teen 2 jaar en van 52% teen 4 jaar getoon. Sewe van die kinders (10%) van die hele kohort het kroniese nierversaking (KNV) ontwikkel. Ouderdom van 6 jaar en meer by presentasie en erge mesangiale neerslae in ‘n biopsie het met minder remissies en ’n swakker uitkoms gekorreleer. Drie pasiënte het meer as 19 jaar na aanvanklike voordoening ooglopende KNV ontwikkel, waarvan 23 jaar die langste interval was. Die 358 gevalle van kinderjare HBV MGN van Suidelike-Afrika maak 37% uit van die gerapporteerde kinder pasiënte. Vergelykende data ’n Vergelyking is getref tussen die 71 kinders met HBV MGN, 12 volwassenes met HBV MGN en 33 volwassenes met idiopatiese MGN. Die hoof verskille was dat beide HBV groepe net kleurling en swart pasiënte ingesluit het en meer oorwegend manlik was, terwyl die idiopatiese groep alle rasse ingesluit het. In die HBV pasiënte was hematurie meer algemeen en erg, lewer ensieme meer dikwels verhoog en C3 meer dikwels verlaag as in die idiopatiese kohort. Beide groepe van volwasse MGN pasiënte het normale C4 vlakke getoon terwyl die kindergroep met HBV MGN verlaagde C4 vlakke bewys het. Die immuunkompleks patroon in biopsies van die HBV MGN volwasse en kindergroepe was soortgelyk met meer mesangiale en subendoteliële neerslae asook meer mesangiale interposisie as in die idiopatiese groep. Ten spyte van hierdie ooreenkoms tussen die twee HBV groepe, het die twee volwasse groepe meer glomerulêre sklerose en interstisiële siekte as die kindergroep vertoon. Die kliniese uitkoms van die kinderkohort was beter as die ander twee groepe met remissie (52%) wat meer algemeen was teen 4 jaar (p< 0.01) en met beter nier- en pasïent oorlewing. Ingeslote die 83 gevalle van hierdie reeks, is ten minste 1243 nierbiopsie bewysde gevalle van HBV MGN in kinders (80%) en volwassenes (20%) in die Engelse literatuur gerapporteer. Die manlike oorheersing in beide ouderdomsgroepe van HBV MGN is soortgelyk (kinders 79%; volwassenes 84%) en betekenisvol meer as vir idiopatiese MGN. Gevolgtrekkings: Die bevindinge bevestig dat HBV MGN in kinders ’n afsonderlike vorm van GN is wat die klassieke beskrywing van MGN verbreed deur die algemene insluiting van ’n aantal mesangiokapillêre GN kenmerke. Die ondergroep van nier biopsies met erge mesangiokapillêre GN kenmerke is as die gemengde HBV MGNmesangiokapillêre GN groep geklassifiseer. Die MGN spektrum in geheel het 86% van die HBV positiewe kindergroep behels. HBV MGN was die mees algemene assosiasie met NS/erge proteïenurie in die Namibiese subgroep (37%) en die derde grootse groep (19%) onder die SA kinders. Die siekte het ’n relatiewe hoë spontane remissiekoers getoon, maar ten minste 10% van die kinders het nierversaking ontwikkel. Ouderdom van 6 jaar en meer by presentasie en erge mesangiale neerslae in ‘n nierbiopsie het met minder remissies en ’n slegter uitkoms gekorreleer. Uitgebreide opvolg (meer as 15 jaar) was nodig om nierversaking in sommige van die swak uitkomsgroep aan te toon. Verstedeliking is geassosieerd met laer HBV draersyfers en hierdie faktor saam met algemene HBV inenting in die kinderjare (wat in 1995 in SA begin was), het ’n skerp daling in die voorkoms van hierdie siekte in SA teweeg gebring. HBV MGN is ’n waardevolle en moontlik unieke model van menslike GN en MGN, veral omdat die HBeAg in beide die serum en glomeruli identifiseer kon word om die etiologiese rol van HBeAg te bevestig. / AFRIKAANSE OPSOMMING: Agtergrond en Doelwit: Die algemeenste oorsaak van erge proteïenurie/nefrotiese sindroom (NS) in kinders wêreldwyd is minimale veranderingsiekte. Hierdie patroon kom ook voor in blanke- en Indiër kinders in Suid-Afrika. In teenstelling hiermee is aangetoon dat swart en kleurling/gemengde ras kinders in Suider Afrika tussen die jare 1960s tot 1990s ’n ander patroon van nefrotiese sindroom gehad het. Een van die hoof verskille was die algemene voorkoms van hepatitis B virus (HBV) geassosieerde glomerulonefritis, gewoonlik membraneuse glomerulonefritis (MGN). Die doelwit van hierdie projek was ’n klinies-patologiese studie van hierdie subgroep van nefrotiese kinders ten einde die siekte verder te beskryf en veral om korrelasies te tref tussen patologiese en kliniese kenmerke insluitende prognose. Die gedetaileerde ultrastrukturele ondersoek van die kinders se nierbiopsies en die korrelasie van die spektrum patologiese kenmerke met demografiese, kliniese, laboratorium en prognostiese kenmerke was ‘n sentrale fokusarea. Die hipotese was dat die klinies-patologiese kenmerke van HBV MGN in kinders wesenlik van idiopatiese MGN in die algemeen verskil (in kinders en volwassenes) en ook van HBV MGN in volwassenes, en dat die beeld in kinders as ’n afsonderlike siekte beskou behoort te word. Pasiënte en metodes: Die kinder kohort (12 jaar en jonger) was 309 kinders met erge proteïenurie/nefrotiese sindroom wie in Tygerberg Hospitaal (TBH) behandel was oor ‘n 21 jarige periode vanaf 1974 tot 1995, insluitende 67 kinders van Namibië. Die studiegroep was 71 kinders met HBV MGN wie waar moontlik tot 2005 opgevolg was. Die vergelykende volwasse groep was 45 volwassenes met MGN van wie 12 HBV MGN gehad het en 33 idiopatiese MGN. (’n Vergelyking met idiopatiese MGN in kinders kon nie gedoen word nie omdat hierdie sentrum net twee sulke pasiënte tydens die studietyd behandel het.) Demografiese, kliniese, laboratorium en nierpatologie inligting is versamel, vergelyk en gekorreleer. Resultate: HBV geassosieerde MGN was die algemeenste oorsaak van NS in die Namibiese subgroep, 25/67 (37%) en die derde mees algemeen, 71/309 (23%) in die kinder kohort as geheel. Die MGN groep was 86% (71/83) van die totale HBV kinder nefrotiese kohort en verreweg die oorheersende subgroep. Die gemiddelde ouderdom van die 71 kinders met HBV MGN by presentering was 6.0 jaar (reikwydte 2-12 jaar) en seuns het 80% van die groep behels. Hepatitis B omhullingsantigeen (envelope antigen- HBeAg) is aangetoon in die serum van 87% van die kinders wie daarvoor getoets is. Laboratoriumkenmerke wat van idiopatiese MGN verskil het, het ingesluit meer prominente hematurie, gering verhoogde serum transaminases en meer dikwels verlaagde serum C3 en C4 vlakke. Ligmikroskopiese ondersoek van die nierbiopsies het mesangiale proliferasie in elke pasiënt getoon, maar met minimale glomerulêre sklerose en interstisiële siekte. Met ultrastrukturele ondersoek was mesangiale en subendoteliële neerslae asook mesangiale interposisie algemeen. Die MGN van HBV in kinders het dus dikwels kenmerke van mesangiokapillêre glomerulonefritis getoon bo en behalwe die subepiteliële neerslae van MGN. Die ondergroep van 23 van wie die nierbiopsies erge mesangiale interposisie aangetoon het asook die subepiteliale neerslae van MGN is die gemengde HBV MGN-mesangiokapillêre GN groep genoem. Virustipe liggaampies en tubuloretikulêre insluitingsliggaampies is in meer as 80% van die biopsies bevestig. HBeAg was in die subepiteliële neerslae identifiseer. Dit was die eerste keer dat hierdie kenmerk in Afrika identifiseer is. Die 46 Suid-Afrikaanse kinders

nÃo hà / INTRODUÃÃO: as glomerulopatias ainda sÃo uma das principais causas de insuficiÃncia renal crÃnica no mundo. à crescente o surgimento de registros de glomerulopatias em diversos paÃses, inclusive no Brasil. Os dados sobre incidÃncia e prevalÃncia das glomerulopatias no Brasil sÃo escassos. As conseqÃÃncias da lesÃo glomerular sÃo basicamente: proteinÃria, hematÃria, queda de filtraÃÃo glomerular, podendo evoluir para oligo-anÃria e hipertensÃo arterial decorrente da retenÃÃo de sÃdio. OBJETIVOS: determinar o perfil clÃnico, patolÃgico e epidemiolÃgico dos pacientes em acompanhamento no ambulatÃrio de glomerulopatias do ServiÃo de Nefrologia do Hospital Geral de Fortaleza. MÃTODOS: a populaÃÃo do estudo consistiu de pacientes portadores de doenÃa glomerular, submetidos à biÃpsia renal que foram atendidos no ambulatÃrio do serviÃo de Nefrologia do Hospital Geral de Fortaleza, CearÃ, durante o perÃodo de fevereiro de 2010 e setembro de 2011. RESULTADOS: foram incluÃdos no estudo um total de 168 pacientes. A idade mÃdia foi de 37  14 anos, variando de 14-77 anos. Desse total 84 pacientes (50%) eram do sexo feminino. Na avaliaÃÃo dos resultados das amostras biopsiadas obteve-se uma mÃdia de 20  12 glomÃrulos por amostra. Um total de 154 biÃpsias (92,2%) apresentaram um nÃmero maior ou igual a 8 glomÃrulos por amostra. SÃndrome nefrÃtica, foi a principal apresentaÃÃo clÃnica, correspondendo a um total de 113 pacientes (67,3%). As glomerulopatias mais prevalentes foram a GESF (19,6%), a LesÃo MÃnima (17,9%), a Glomerulopatia Membranosa (16,7%) e a Glomerulonefrite LÃpica (11,9%). As glomerulopatias primÃrias foram mais prevalentes, total de 124 casos (74,7%). Em relaÃÃo a resposta ao tratamento medicamentoso instituÃdo, 81 pacientes (68,6%) responderam ao tratamento.CONCLUSÃO: a GESF foi a glomerulopatia primÃria mais freqÃente e sÃndrome nefrÃtica a forma clÃnica de apresentaÃÃo mais comum na admissÃo. As amostras das biÃpsias renais colhidas foram satisfatÃrias em 92,2% dos casos. / INTRODUCTION: glomerulonephritis still are one of the main causes of Chronic Renal Failure (CRF). The number of cases is increasing, especially in Brazil. There are few data regarding the incidence and prevalence of glomerulonephritis in our country. Glomerular damage results in proteinuria, hematuria, decrease in glomerular filtration rate (GFR), oliguria, anuria and hypertension due to sodium overload. OBJECTIVES: the aim of this study is to determine the clinical, pathological and epidemiological features of the patients with glomerular diseases followed at the General Hospital of Fortaleza. METHODS: the study population consisted of patients with biopsy proven glomerular disease followed at the Nephrology Department of the General Hospital of Fortaleza, CearÃ, in the period between February 2010 and July 2011. RESULTS: a total of 168 patients were included. The mean age was 37  14 years. The mean number of glomeruli in each renal biopsy was 20  12. A total of 154 biopsies (92,2%) had at least 8 glomeruli per sample. Half of them were women, 84 patients (50%). The most common clinical presentation at admission was nephrotic syndrome, observed in 113 patients (67,3%). The most prevalent glomerulonephritis were Focal Segmental Glomerulosclerosis (FSGS) (19,6%), Minimal Change Disease (17,9%), Membranous Nephropathy (16,7%), and Lupus Nephritis (11,9%). Primary glomerulopathies were more common, 124 cases (74,7%). A total of 81 patients (68.6%) presented a good response to therapy, and 37 patients (31,4%) did not respond well to treatment. CONCLUSION: FSGS was the most frequent glomerulonephritis in the present study, and nephrotic syndrome was the most common clinical presentation at admission. Renal biopsies had an adequate sample size in 92,2%.

Thesis (MD.) - University of Glasgow, 2007. / MD thesis submitted to the Faculty of Medicine, Division of Cardiovascular and Medical Sciences, University of Glasgow, July 2007. Includes bibliographical references. Print version also available.

Thesis (Ph. D.)--University of Sydney, 2008. / Title from title screen (viewed Jan. 28, 2009) Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Public Health, Faculty of Medicine. Includes bibliographical references and list of publications. Also available in print form.