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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Avaliação da taxa de filtração glomerular com EDTA-51 Cr em pacientes com anemia falciforme / 51Cr-EDTA measurements of the glomerular filtration rate in patients with sickle cell anemia

Barros, Fabiana Bianchini de 12 August 2018 (has links)
Orientador: Celso Dario Ramos, Carmen Silvia Passos Lima / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-12T10:45:39Z (GMT). No. of bitstreams: 1 Barros_FabianaBianchinide_M.pdf: 2751233 bytes, checksum: 6f21461552f5ea5427e117087a77755a (MD5) Previous issue date: 2007 / Resumo: O c/earance de creatinina tem sido relatado como sendo impreciso para a estimativa da taxa de filtração glomerular (TFG) nos pacientes com anemia falciforme (AF). O c/earance de inulina, método de referência para a medida da TFG, é pouco prático para o uso rotineiro nesses pacientes. As medidas da TFG por depuração plasmática de EDTA51Cr raramente têm sido relatadas em portadores de AF. Visando obter valores da referência para a TFG com EDTA-51Cr nesta doença, foram estudados 70 pacientes, sendo 40 mulheres e 30 homens, com idades de 13 a 59 anos (média: 31,6 anos), portadores de AF na forma homozigótica, com creatinina sérica normal e albuminúria = 200 Jlg/min. Todos os pacientes foram submetidos a injeção única de EDTA-51Cr para análise da TFG, dosagem de albumina urinária e medida do hematócrito. A depuração plasmática do EDTA-51Cr foi calculada em diferentes grupos de idade (< 20, 20-29,30-39,40-49 e > 50 anos). A TFG média (± desvio padrão) obtida para os 70 pacientes foi 111,5 ± 23,1 ml/min/l,73 m2. A análise de variância (ANOVA) para verificar o possível efeito da interação entre a TFG por EDTA-51Cr e o sexo, idade, albumina urinária e hematócrito demonstraram a idade do paciente como sendo o único fator de influência na TFG por EDTA-51Cr (p< 0,001). O coeficiente de correlação de Spearman mostrou uma correlação significativa entre a TFG por EDTA-51Cr e a idade do paciente (r= - 0,44; p= 0,0001), mas não entre as medidas com EDTA-51Cr e a albumina urinaria (r = - 0,17, p= 0,1546) ou o hematócrito (r = 0,079, p= 0,5121). O grupo de pacientes na faixa de 20-29 anos apresentou o mais elevado valor médio de TFG por EDTA-51Cr (126,7 ± 20,4 ml/min/l,73 m2), havendo uma redução progressiva desse valor nos grupos mais velhos. Adultos jovens com AF na forma homozigótica, com creatinina sérica normal apresentam valores supranormais de TFG medida por EDTA-51Cr. Esses valores diminuem rapidamente para níveis semelhantes aos normais em faixas etárias mais elevadas. Não foi evidenciada correlação entre albuminúria e TFG nesses pacientes. / Abstract: Creatinine clearance has been reported to be inaccurate for the glomerular filtration rate (GFR) estimation in patients with sickle celI anemia (SCA). Inulin clearance, the reference method for GFR estimation, is impractical for routine use in these patients. 51Cr EDTA measurements of the GFR have been rarely reported in SCA. In order to obtain reference 51Cr-EDTA values in this disease, we studied 70 patients (40 females, 30 males; 13-59 years old, mean: 31.6 years) with homozygous SCA and normal serum creatinine. AlI patients were submitted to single-injection 51Cr-EDTA to analyze the GFR, urinary albumin and hematocrit measurements. 51Cr-EDTA clearances were calculated in different age groups (<20, 20-29, 30-39,40-49 and >50 years). The mean GFR (± standard deviation) obtained for the 70 patients was 111.5 ± 23.1 ml/min. Analysis ofvariance for evaluation ofthe possible interaction effect between 51CrEDT A clearance and sex, age, urinary albumin and hematocrit demonstrated patient age as the only factor influencing 51Cr-EDTA clearance (p<0.001). The Spearman correlation .coefficient showed a significant relationship between 51Cr-EDT A clearance and patient age (r=-0.44, p=0.0001), but not between 51Cr-EDTA and urinary albumin (r =-0.17, p=0.1546) orhematocrit (r =0.079, p=0.5121). The group aged 20-29 years presented the hi~hest 51CrEDTA clearance mean value (126.7 ± 20.4 ml/min), with a progressive reduction in the older groups. Young adults with homozygous SCA and normal serum creatinine present supranormal 51Cr- EDTA GFR values. These values rapidly decrease to normallevels with aging. We did not find association between albuminuria and GFR in these patients. / Mestrado / Ciencias Basicas / Mestre em Clinica Medica
2

Aspectos laboratoriais do lupus eritematoso sistemico com enfase na excreção urinaria de albumina e alfa-1-microglobulina

Coelho, Maria de Fatima Lino 14 February 2003 (has links)
Orientadores: Celia Regina Garlipp, Paula Virginia Bottini / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-03T15:47:51Z (GMT). No. of bitstreams: 1 Coelho_MariadeFatimaLino_M.pdf: 2815154 bytes, checksum: 44659c328e276bb483558f2694dbe326 (MD5) Previous issue date: 2003 / Resumo: O envolvimento renal é uma causa importante de morbidade e mortalidade no LES. Alterações morfológicas renais são observadas em quase todos os pacientes sendo que 40-75% deles desenvolvem doença renal clínica, indicada por níveis aumentados de creatinina plasmática, proteinúria e/ou hematúria. O presente estudo tem como objetivo avaliar a excreção de proteínas urinárias específicas em pacientes com LES e sua possível correlação com alterações hematológicas, urinárias ou bioquímicas. Foram selecionados 47 pacientes com LES, sem evidência clínica e laboratorial de doença renal e divididos em dois Grupos (Grupo I = 35 pacientes sem história de nefrite e Grupo 2 = 12 pacientes com história de nefrite). Durante o período de um ano e a intervalos regulares de 3 meses, esses pacientes foram avaliados sendo que de cada indivíduo, em cada etapa do estudo, amostras sangüíneas e amostras urinárias isoladas e de 24h, foram coletadas e submetidas às seguintes determinações laboratoriais: hemograma, contagem de plaquetas, velocidade de hemossedimentação, pesquisa de anticorpo anti-DNA nativo, perfil lipídico (colesterol total, HDL-colesterol, triglicerídeos, LDL-colesterol, VLDL-colesterol, lipoproteína (a), apolipoproteína A1 e apolipoproteína B), determinação do clearance de creatinina, dosagens urinárias de proteína total, creatinina (para estabelecer a relação proteína urinária/creatinina), microalbuminúria (indicada pela relação MALB/CREA), alfa1-microglobulina (indicada pela relação A1M/CREA), sedimento urinário e pesquisa de dismorfismo eritrocitário. Excreções alteradas de MALB/CREA (23% no Grupo I e 25% no Grupo II) e de A1M/CREA (17% no Grupo I e 8% no Grupo II) não apresentaram diferenças significativas entre os grupos estudados (p>0,05). O mesmo foi observado em relação aos outros parâmetros avaliados. Pesquisa positiva para anti-DNA nativo e perfis lipídicos alterados não mostraram associação com MALB/CREA (p>0,05). Clearance de creatinina não sofreu alteração ao longo do tempo e não se mostrou dependente da excreção de albumina observando¿se uma fraca correlação estes dois parâmetros (p = 0,0774). Apesar da variabilidade na excreção urinária de albumina ao longo do tempo, não houve associação dessa excreção com alterações lipídicas, lipoproteicas e apolipoproteicas e com ANTI-DNA nativo (p > 0,05). Concluímos que alterações na excreção urinária de albumina e de alfa-1-microglobulina são freqüentes no LES, embora possam ser decorrentes da própria variabilidade biológica da excreção dessas proteínas / Abstract: Renal involvement in systemic lupus erythematosus (SLE) is frequent although the evolution of renal function abnormalities is not completely elucidated. Morphological renal changes are present in virtually all patients, as 40% to 75% develop clinical renal disease. Lupus nephritis is an important cause of mortality and morbidity of the disease. Consequently, the major topic of investigations focus on the diagnosis, treatment and prognosis of this condition.This study was performed to evaluate whether the urinary protein excretion profile in systemic lupus erythematosus (SLE) patients could predict the development of lupus nephritis and their possible relationship with hematological, urinary and biochemical abnormalities. Forty seven patients divided into Group I (GI) with 35 patients without history of lupus nephritis and Group II (GII) with 12 patients with history of nephritis were studied during a year period. Random urine samples, 24-hour urine collection and 12-hour fasting blood samples were collected. Laboratory studies included: hemogram, platelet count, erythrocyte sedimentation rate, anti-dsDNA antibodies, lipid profiles, creatinine clearance, total urine protein, routine urine analysis (including dysmorphic erythrocytes), urinary albumin/creatinine (MALB/CREA) and alpha-1-microglobulin/creatinine (A1M/CREA). Altered excretions of MALB/CREA (23% GI; 25% GII) and A1M/CREA (17% GI; 8% GII) showed no significant differences between the Groups (p>0.05). The same was observed for the other analyzed parameters. Anti-dsDNA and altered lipid profiles were not associated with MALB/CREA (p>0.05). There was a tendency of a correlation between creatinine clearance and MALB/CREA (p=0.0774). Although altered excretions of MALB/CREA and A1M/CREA were frequent in SLE it seems to be due to the daily excretion variability of these proteins / Mestrado / Ciencias Biomedicas / Mestre em Ciências Médicas
3

Efeito do enalapril na albuminuria de pacientes com doença falciforme

Aoki, Regina Yoko 31 October 1995 (has links)
Orientador: Sara T. O. Saad / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-07-20T18:50:59Z (GMT). No. of bitstreams: 1 Aoki_ReginaYoko_M.pdf: 4498578 bytes, checksum: 863533c47ec61d097c5d554733b9f376 (MD5) Previous issue date: 1995 / Resumo: Os inibidores da enzima conversora da angiotensina 11 (o captopril e o enalapril) têm sido utilizados para reduzir a microalbuminúria, a proteinúria não ne&ótica e a proteinúria ne&ótica nos diabéticos, e nos portadores de estenose renal, arteriolone&oesclerose e insuficiência renal de outras etiologias. Esta redução se deve às alterações nas pressões dos fluxos renais, diminuíndo possívelmente o tono da arteríola eferente glomerular, reduzindo assim a pressão hidrostática intraglomerular. A abertura de novos capilares glomerulares redistribuiriam os fluxos plasmáticos renais, modificando a permeabilidade e seletividade das membranas basais, e o transporte das macromoléculas pelas células mesangiais. Estes fatores diminuiriam a expansão do mesângio e assim reduziriam a proteinúria, com melhora, algumas vezes, do quadro histológico. Este trabalho teve como objetivo avaliar a &equência de microalbuminúria em pacientes com doenças falciformes e o efeito do uso prolongado de inibidores da enzima conversora da angiotensina (ENALAPRIL) na concentração de albumina urinária desses pacientes. Para a pesquisa da &equência da albuminúria nas doenças falciformes, a medida da concentração de albumina urinária foi determinada por radioimunoensaio, em três amostras da primeira Urina do dia, coletadas com intervalo de 15 a 30 dias. Foram estudados 10 controles negróides normais e 56 pacientes portadores de.hemoglobinapatias S ( 42 SS, 10 SC, 4 S~) e desses 22 (19 SS, 2 se e 1 S~) apresentaram concentração de albumina urinária maior do que 30 mgll nas 3 amostras testadas. Para avaliação da resposta ao uso de enalapril, nove pacientes (8 SS, 1 S~) com concentração de albumina urinária anormal, receberam placebo (Complexo B) durante 60 dias e a seguir enalapril (Renitec@) 5mg ao dia por 180 dias ( 6 meses), e foram reavaliados a cada 15 ou 30 dias. Observamos que houve redução significativa da concentração de albumina urinária durante o uso da medicação (Renitec@), com normalização dos valores da albuminúria em 6 pacientes. Num paciente que abandonou o trabalho no terceiro mês de seguimento, observamos uma redução de 70% na albumina urinária em relação aos níveis pré-tratamento. Em 2 pacientes, cujos níveis da albumina urinária excederam o limite de sensibilidade do nosso método, não se observou redução concentração de albumina urinária. Dois anos após a suspensão da droga, a concentração de albumina urinária se manteve nos níveis normais em 2 pacientes; em 2 doentes, voltou aos valores pré-tratamento, e nos demais indivíduos que participaram do estudo, assim como em 2 indivíduos que não utilizaram a droga, houve aumento da concentração de albumina urinária em relação aos níveis iniciais. o clearance de creatinina e lítio, fração de excreção de sódio, potássio e lítio, assim como o sódio e o potássio sérico, não se alteraram durante o uso do enalapril. Entretanto houve redução da pressão arterial média (70,4:t 5,5 mmHg x 61,7:t 3,4 mmHg P = 0,004). Nossos resultados demonstram que o enalapril reduz a concentração de albumina urinária nos pacientes com anemia falciforme. Entretanto, após a suspensão da medicação, a albumina urinária pode aumentar. Estudos prospectivos de longa duração são necessários para avaliar se o uso dos inibidores da enzima conversora da angiotensina pode retardar o desenvolvimento da insuficiência renal crônica em pacientes com doenças faIciformes / Abstract: The angiotensin - converting enzyme inhibitor (captopril and enalapril) are able to reduce albuminuria and proteinuria in patients with diabetic nephropathy as well as proteinuria in patients with renal disease of various origins. The reduction. of proteinuria is most likely related to decreased renal vascular resistance, particularly in postglomerular arterioles, which results in a fali in intraglomerular capillary pressure. The purpose of this study was to determine the prevalence of microalbuminuria and to evaluate the effects of enalapril, an angiotensin - converting enzyme inhibitor, on albuminuria associated with sickle cell anemia. The microalbuminuria was measured by radioimmunoassay. The urine samples were collected on three separate occasions at intervals of 15 to 30. days. The study included 42 patients with sickle cell anemia (SS), 10. patients with hemoglobin SC disease (SC), 4 patients with S~ thalassenrnia (S~) and 10. normal controls. Nineteen SS patients (45%) and 2 SC (20.%) and 1 S~ (25%) patients presented mean urinary albumin excretion above normal values (30. mg/l). Nine patients with sickle cell anemia and albuminuria received B complex for 60. days and after tha~, they took oral enalapril (Renitec@) 5 mg daily for 180. days. Ali measurements were repeated every 15 to 30. days. Enalapril reduced in 6 patients, the pretreatment hyperalbuminuria to normal values and one patient had a 70. % reduction. In two patients it was not possible to demonstrate a variation in the albuminuria because the values were above the limit of detection by our method. Two years after enalapril was discontinued, we repeated ali measurements in 6 patients who had received the drug and in 2 sickle cell anemia patients who presented hyperalbuminuria, but did not participate in the study. Urinary albumin concentration increased in all individuais, except for 4 patients who had received enalapril. The urinary albumin concentration retumed to pretreatment levels in 2. The other 2 still had values below 30. mg/l. There were no change in sodium, potassium or creatinine levels and fractional excretion of sodium, potassium, and lithium during the treatment. Mean arterial pressure decreased by 8,6 :f: 0.,42 mm Hg. Qur results demonstrate that enalapril reduced albuminuria in patients with sickle cell anemia. After discontinuation ofthe drug, howéver, the albuminuria may increase to pretreatment levels or higher. Whether the reduction in urinary albumin concentration by angiotensin converting enzyne inhibitors can delay the developrnent of progressive renal failure in sickle cell anemia patients rernains to be established. / Mestrado / Medicina Interna / Mestre em Ciências Médicas
4

NLR and microalbuminuria: Are these markers significantly associated?

Umeres-Francia, Gianfranco E., Rojas-Fernández, María V., Benítes-Zapata, Vicente A. 27 November 2017 (has links)
Carta al Editor / Revisión por pares
5

The association of dietary factors with abnormal albuminuria in subjects with type 2 diabetes mellitus in Semarang Indonesia /

Puruhita, Niken. January 2004 (has links) (PDF)
Thesis (M.Med.Sc.) - University of Queensland, 2002. / Includes bibliography.
6

Podocyte-specific Overexpression of Human Angiotensin-converting Enzyme 2 Attenuates Diabetic Nephropathy in Mice

Bose, Renisha Padmini 04 February 2013 (has links)
Angiotensin-converting enzyme 2 (ACE2) is an important component of the renin-angiotensin system (RAS). ACE2 is thought to have a renoprotective effect in diabetic nephropathy because it is capable of degrading profibrotic angiotensin II to potentially protective angiotensin-(1-7). Podocyte death and detachment is a key component of diabetic nephropathy. ACE2 is localized in the podocyte and during a diabetic state, podocyte ACE2 expression is reduced. The purpose of this study was to determine the effects of podocyte-specific ACE2 overexpression on the course of diabetic nephropathy. Diabetes was induced using streptozotocin in transgenic mice with podocyte-specific overexpression of human ACE2. The following parameters were assessed: systolic blood pressure, glomerular filtration rate, urinary albumin excretion, mesangial and glomerular area, and podocyte number. Transgenic diabetic mice showed a significant transient attenuated increase in albuminuria, an attenuated increase in mesangial area, decreased glomerular area, and preserved podocyte number, compared to wildtype diabetic mice. This was independent of a change in blood pressure. This study showed that the podocyte-specific overexpression of human ACE2 attenuates the development of diabetic nephropathy.
7

Development of new methods for drugs analysis, disease diagnosis, and protein analysis by using modern mass spectrometry

Cho, Yi-tzu 25 July 2011 (has links)
New methods for drugs analysis, disease diagnosis, and protein analysis by using modern mass spectrometry are developed in this thesis. In drugs analysis, we develop a rapid assessment of molecular similarity between an extremely complex innovator product and a candidate biosimilar by mass spectrometry. Protease digestion combined with Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry were successfully used to peptides mapping and de novo peptides sequencing. Overall ion signals obtained by MALDI-TOF/MS were processed by two multivariate statistics including principle component analysis (PCA) and hierarchical clustering analysis. Based on the variances of the peptide profile, innovator product and normally synthesized biosimilar were grouped on the PCA score plot, while impure biosimilar or abnormally synthesized biosimilar were distinctly separated. The results of hierarchical cluster analysis also revealed high conformity between innovator product and normally synthesized biosimilar. Abnormally synthesized products, as a set of quality controller, could be discriminated from innovator product favorably. Another quality control strategy developed in this study is building classification model, batches of product is successfully evaluated. Furthermore, the similarity of molecular weight distribution between these complex drugs is determined. Another target of drug analysis is to develop a vital analytical method to directly detect the peptides synthesized on the resin. Except an organic solvent is transformed to disperse the resin-peptides samples, no other sample pretreatments are required before the MS detection. When using conventional destructive analytical methods to characterize masses of compounds on the solid supports, acid hydrolysis or acid cleavage of the peptide molecules depart from insoluble resin is required. In consequence, side-reactions such as de-blocked or de-protected cause additional fragments in the system, and determination of the intermediates or products are confusing and difficult. Unlike these acid release methods, the molecular weight information of the intact peptide molecules can be obtained in our direct analyses system, and sample consumption is also great reduced. Moreover, our strategy performed the analysis in the ambient environment is more straightforward for real-time monitor reaction and quality control than those techniques in high vacuum system. This direct non-destructive on-line monitoring method would allow following step by step peptide solid-phase synthesis be well quality controlled. In the disease diagnose part, MALDI-TOF mass spectrometry combined with statistics were used to perform semi-quantitative albuminuria diagnoses. Based on the fact that the contributions of singly, doubly, triply, and quadruply charged albumin ions from the samples were inflected according to the concentration change. The severity of albuminuria of patients can be estimated by 2D peaks distribution (peaks ranking by p-value) or supervised principal component analysis (PCA). In protein analysis study, we use liquid electrospray laser desorption ionization mass spectrometry (liquid-ELDI/MS) to directly characterized the proteins stored in different solutions containing acids, bases, buffers, organic solvents, or detergents without extra sample pretreatment. A drop of the sample solution was applied on a stainless steel plate., and then the surface of the sample drop was irradiated with a pulsed laser. The laser energy absorbed by the metal plate and surrounding solvent led to the desorption of protein molecules or the formation of fine droplets containing protein molecules. The desorbed protein species were then post-ionized within an electrospray plume to generate the ESI-like protein ions. Since no pH or composition adjustment of the sample solution is needed, this technique is useful for rapid and high throughput screening of the proteins in a solution to check their integrality after storage or prior to further biochemical treatment. In addition,, native and denatured conformation of the proteins can be distinctly examined by using acid-free and organic solvent-reduced ESI solutions in liquid-ELDI.
8

Podocyte-specific Overexpression of Human Angiotensin-converting Enzyme 2 Attenuates Diabetic Nephropathy in Mice

Bose, Renisha Padmini 04 February 2013 (has links)
Angiotensin-converting enzyme 2 (ACE2) is an important component of the renin-angiotensin system (RAS). ACE2 is thought to have a renoprotective effect in diabetic nephropathy because it is capable of degrading profibrotic angiotensin II to potentially protective angiotensin-(1-7). Podocyte death and detachment is a key component of diabetic nephropathy. ACE2 is localized in the podocyte and during a diabetic state, podocyte ACE2 expression is reduced. The purpose of this study was to determine the effects of podocyte-specific ACE2 overexpression on the course of diabetic nephropathy. Diabetes was induced using streptozotocin in transgenic mice with podocyte-specific overexpression of human ACE2. The following parameters were assessed: systolic blood pressure, glomerular filtration rate, urinary albumin excretion, mesangial and glomerular area, and podocyte number. Transgenic diabetic mice showed a significant transient attenuated increase in albuminuria, an attenuated increase in mesangial area, decreased glomerular area, and preserved podocyte number, compared to wildtype diabetic mice. This was independent of a change in blood pressure. This study showed that the podocyte-specific overexpression of human ACE2 attenuates the development of diabetic nephropathy.
9

Estudo da albuminuria em pacientes com diagnostico de mieloma multiplo

Garcia, Sonia San Martin 06 July 2002 (has links)
Orientador : Maria Almerinda Vieira Fernandes Ribeiro Alves / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-02T08:21:50Z (GMT). No. of bitstreams: 1 Garcia_SoniaSanMartin_M.pdf: 38429536 bytes, checksum: fba6453b150c2d20b85ef1f80f1537f2 (MD5) Previous issue date: 2002 / Resumo:o comprometimento renal em pacientes com mieloma múltiplo (MM) é, na maioria dos casos, devido às alterações túbulo-intersticiais causadas pela presença excessiva de cadeias leves no filtrado glomerular. Tal comprometimento tem como manifestação freqüente o aumento da excreção urinária de proteínas tubulares, como a alfa 1 microglobulina. A presença de albuminúria em pequenas quantidades também tem sido observada e, da mesma forma,atribuída à competição pelos locais de absorção nos túbulos proximais. A doença glomerular, menos freqüente nesses pacientes e geralmente causada por amiloidose ou doença de cadeia leve, é lembrada somente em situações de albuminúria importante e, por isso, o encaminhamento ao nefrologista costuma acontecer tardiamente, em situações de síndrome nefrótica ou de insuficiência renal avançada. Estudamos retrospectivamente 68 pacientes com MM, acompanhados em nosso Ambulatório, com a finalidade de comparar o seu comportamento clínico-Iaboratorial com as resultados da literatura e observamos, num estudo prospectivo, o comportamento da cadeias leves, alfa1 microglobulina e albumina de 17pacientes, durante o seu tratamento.O estudo foi dividido em duas partes: Estudo retrospectivo - Observamos dois grupos de pacientes: grupo I (n=41) com creatinina sérica menor ou igual A 1,2 mg/dL e grupo n (n=27) com creatinina sérica > 1,2 mgldL. No grupo de pacientes com MM que se apresentou, ao diagnóstico, com perda de função renal, observou-se proteinúria mais freqüentemente e a calcemia foi mais elevada, ambas associadas à perda de função renal. Os pacientes mais jovens apresentaram maior tendência à recuperação da função renal A albuminúria esteve presente na maioria dos pacientes, independente da creatinina sérica inicial.Estudo prospectivo - Analisaram-se, durante 18meses, albumina, alfa1 microglobulina e cadeias leves em amostras seriadas de urina de 17 pacientes com diagnóstico de MM e com creatinina sérica < 1,2 mgldL. Observamos correlação positiva entre as quantidades eliminadas na urina durante o acompanhamento: cadeias leves - albumina (p= 0.006), cadeias leves - alfa 1 microglobulina (p=0.003) e albumina - alfa1 microglobulina (p=0.0002). Concluímos que a albuminúria, nos pacientes em que foi estudada, é um achado freqüente, independente do grau de comprometimento da função renal. Em pacientes com creatinina : menor ou igual a 1,2 mg/dL a diminuição da quantidade de cadeias leves na urina é acompanhada por diminuição de albumina e de alfa 1 microglobulina.Este resultado sugere a presença de glomerulopatia e /ou tubulopatia incipiente nos casos de MMe m que a diminuição de cadeias leves na urina não seja acompanhada por diminuição paralela da albuminúria e/ou da alfa1 microglobulinúria, respectivamente / Abstract: Renal dysfunction in patients with multiple myeloma (MM) is, in most cases, a consequence of tubulointerstitial alterations caused by the excessive presence of light chains in the glomerular filtrate, that ftequently results in increased urinary excretion of tubularproteins, such as alpha 1microglobulin. The presence small amounts ofalbuminuria has also been observed in this patients and is attributed to the competition for absorptive sites in the proximal tubules. The less frequent glomerular disease in these patients is usually caused by amiloidosis or light chain disease and, despite of the presence o macroalbuminuria, frequently the patient is referred to the nephrologist in presence of advanced renal damage with nephritic syndrome or renal failure. This study was divided in two parts: the retrospective study included 68 patients with MM, followed at our outclinics, in order to compare the clinical and laboratory data with previous reports. We also analysed the urinary excretion of alpha 1 microglobulin, albumin and light chains during the MM treatment, in a prospective group of 17 patients. Results: Retrospective study - Included 2 groups of patients, Group I (n=41) with serum creatinine - 1,2 mgldL and Group II (n=27) with serum creatinine > 1,2 mgldL. We observed, in the group of patients that presented reduction of renal function at diagnosis, a more frequent proteinuria and higher calcemia, both associated with loss of renas function. The younger patients presented a higher tendency to recovery of renal function. Albuminuria was found in the majorityof patients, independently ofthe initial serum creatinine levels. Prospective study - During a period of 18months, excretion of albumin, alpha 1microglobulin and light chains in serial urine samples ftom 17 patients with MM diagnosis and serum creatinine < 1,2 mgldL were analysed. A positive correlation between the urinary excretion oflight chains & albumin (p= 0.006), light chains & alpha 1 microglobulin (p=O.003) and albumin & alpha 1 microglobulin (p=0.0002)was observed in this group. In conclusion,in the present study albuminuria was a frequent finding, independently of the creatinine levels. In patients with creatinine lower than 1,2 mgldL, decrease in urinary light chains excretion was followed by a decrease in urinary albumin and alpha 1 microglobulin. This outcome suggests that in presence of subtle glomerulopathy and/or tubulopathy in MM,the decrease in light chain excretion do not present a parallel decrease of urinary albumin and/or of alpha 1 microglobulin / Mestrado / Clinica Medica / Mestre em Clinica Medica
10

Podocyte-specific Overexpression of Human Angiotensin-converting Enzyme 2 Attenuates Diabetic Nephropathy in Mice

Bose, Renisha Padmini January 2013 (has links)
Angiotensin-converting enzyme 2 (ACE2) is an important component of the renin-angiotensin system (RAS). ACE2 is thought to have a renoprotective effect in diabetic nephropathy because it is capable of degrading profibrotic angiotensin II to potentially protective angiotensin-(1-7). Podocyte death and detachment is a key component of diabetic nephropathy. ACE2 is localized in the podocyte and during a diabetic state, podocyte ACE2 expression is reduced. The purpose of this study was to determine the effects of podocyte-specific ACE2 overexpression on the course of diabetic nephropathy. Diabetes was induced using streptozotocin in transgenic mice with podocyte-specific overexpression of human ACE2. The following parameters were assessed: systolic blood pressure, glomerular filtration rate, urinary albumin excretion, mesangial and glomerular area, and podocyte number. Transgenic diabetic mice showed a significant transient attenuated increase in albuminuria, an attenuated increase in mesangial area, decreased glomerular area, and preserved podocyte number, compared to wildtype diabetic mice. This was independent of a change in blood pressure. This study showed that the podocyte-specific overexpression of human ACE2 attenuates the development of diabetic nephropathy.

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