Orientador: Roberto Jorge da S. Franco / Coorientador: Luis Cuadrado Martin / Banca: Pasqual Barretti / Banca: Vanessa dos Santos Silva / Banca: Eduardo Barbosa Coelho / Banca: Marcio Dantas / Resumo: A doença renal crônica (DRC) representa um problema de saúde pública global. Os idosos têm diminuição progressiva da função renal e os hipertensos e diabéticos apresentam maior risco de lesão renal. Essas doenças crônicas são comuns aos idosos favorecendo o comprometimento de lesão renal. Com base neste fato, o objetivo do estudo foi identificar o melhor método para avaliar precocemente a filtração glomerular (FG) em indivíduos idosos. Comparando-se as fórmulas baseadas na creatinina sérica, bem como o Clearance de Creatinina de 24h com a fórmula baseada nos níveis séricos de Cistatina C, eleita como padrão ouro. Foi realizado um estudo observacional, analítico, de delineamento transversal sobre a filtração glomerular e o desenvolvimento da doença renal, com base nos resultados obtidos na avaliação clínica e nos exames laboratoriais de bioquímica e urinálise. Participaram do estudo 180 idosos de ambos os sexos, com idade igual ou superior a 60 anos, do Centro de Atenção Integrada da Melhor Idade (CAIMI), da cidade de Manaus-AM. Foram construídos gráficos de dispersão, calculado o coeficiente de correlação, bem como traçados diagramas de Bland Altman e curvas ROC. A média de idade dos 180 idosos foi de 67 anos - 68,8% do sexo feminino, e 31,1% do sexo masculino. Hipertensos representaram 43,5% do total. Renais crônicos representaram 19%. Portadores de diabetes mellitus chegaram a 38,3%. Ao observar a equação de regressão, quando o CKD-epiCys for zero, o Clearance de Creatinina (ClCr) valerá 62,07 ml/min/1,73m2, o que caracteriza uma superestimação do valor real da FG. A média avaliada pelo ClCr e CKD-epiCys foi de 28,8 ml/min/1,73m2. Este valor é bem superior à zero, que seria o ideal. Isto mostra que o ClCr superestima a FG avaliada pelo CKD-epiCys. A curva ROC para o ClCr na discriminação da presença de FG< 60 ml/min avaliada pelo padrão foi de 0,65, com ... / Abstract: Chronic kidney disease (CKD) is a global public health problem. The elderly have progressive decrease of renal function, and those with hypertension and diabetes are at increased risk of kidney damage. These chronic diseases are common to the elderly and promote renal injury. This study aimed to identify the best method to assess early glomerular filtration (GF) in elderly subjects. Formulas based on serum creatinine and creatinine clearance of 24 hours were compared with the formula based on serum cystatin C chosen as gold standard. We conducted an observational, analytical, cross-sectional design of the glomerular filtration rate and the development of kidney disease, through results obtained in clinical evaluation, and biochemistry and urinalysis laboratory tests. Participants were 180 patients of both sexes, aged over 60 years, from the Centro de Atenção Integrada da Melhor Idade [Center for Integrated Management of the Elderly], in the city of Manaus, State of Amazonas, Brazil. Scatter plots were constructed by calculating the correlation coefficient, as well as Bland Altman plotted diagrams and ROC curves. The average age of the elderly participants was 67 years; 68.8% were female and 31.1% male; 43.5% had hypertension; 19%, chronic renal failure; and 38.83%, diabetes mellitus. By observing the regression equation, when the CKD-epiCys was zero, creatinine clearance (CrCl) was 62.07 ml/min/1.73m2, which means overestimation of the real FG rate. The average assessed by CrCl. and CKD-epiCys was 28.8 ml/min/1,73m2, a value above zero, which would be ideal. This shows that CrCl. overestimates FR assessed by CKD-epiCys. The ROC curve for CrCl to discriminate the presence of FG <60 ml / min measured by the standard was 0.65, with 95% confidence interval from 0.56 to 0.76 (p = 0.006). The CrCl had statistically significant predictive power concerning the presence of KD. The regression was assessed by ... / Doutor

Submitted by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-09-28T14:52:18Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) dissertação roberto barcellos.pdf: 945783 bytes, checksum: 7e1ee727b4082901916d30284acd2e19 (MD5) / Approved for entry into archive by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-09-28T14:52:43Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) dissertação roberto barcellos.pdf: 945783 bytes, checksum: 7e1ee727b4082901916d30284acd2e19 (MD5) / Made available in DSpace on 2017-09-28T14:52:43Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) dissertação roberto barcellos.pdf: 945783 bytes, checksum: 7e1ee727b4082901916d30284acd2e19 (MD5) Previous issue date: 2014 / Universidade Federal Fluminense / Introdução: Na população norte-americana, os níveis séricos de creatinina em negros são habitualmente maiores do que na população branca, pois estes possuem reconhecidamente maior massa muscular. Esta diferença justificou a partir do ano de 2006, o emprego nos Estados Unidos da América de um ajuste pela raça quando se utiliza as fórmulas para a estimativa das taxas de filtração glomerular (TFG). Questionamos se este ajuste pode ser empregado na população brasileira cuja origem e miscigenação são bastante diferentes da população norte-americana, sem a criação de um viés. Objetivo: O objetivo principal do presente estudo foi de avaliar e comparar os níveis séricos de creatinina em brancos, pardos e negros em uma amostra da população brasileira discutindo a necessidade do uso ajuste pela raça nas fórmulas que empregam a creatinina nesta população. Material e métodos: Os resultados foram extraídos de um estudo de população oriundo do Programa Médico de Família de Niterói (PMF), RJ. A análise da creatinina foi feita pelo método de Jaffé. Compararam-se os níveis séricos de creatinina entre brancos, pardos e negros classificados segundo critérios do IBGE. Posteriormente, foram estimadas as TFGs empregando-se a fórmula Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) com e sem ajuste pela raça. Resultados: Um total de 712 participantes (54,7% do sexo feminino) tiveram seus níveis séricos de creatinina analisados. A média de idade da população foi de 43 ± 12 anos. Trinta por cento eram brancos, 43 % pardos e 27% negros. A média da creatinina nos homens foi maior que a das mulheres (0,99 ± 0,23 mg/dl vs. 0,77 ± 0,17 mg/dl, p<0.001). Entretanto, não foram identificadas diferenças significativas nos níveis séricos de creatinina entre brancos (0,86 ± 22 mg/dl), pardos (0,87 ± 22 mg/dl) e negros (0,88 ± 25 mg/dl). Os níveis séricos de creatinina em mulheres brancas, pardas e negras foram respectivamente 0,76 ± 0,15 mg/dl, 0,77 ± 0,17 mg/dl e 0,79 ± 0,17 mg/dl. Os valores correspondentes para homens foram respectivamente 1,00 ± 0,23 mg/dl, 0,98 ± 0,19 mg/dl e 1,01 ± 0,30 mg/dl. Ao se utilizar a fórmula da CKD-EPI sem ajuste pela raça, não houve diferença significativa entre brancos, pardos e negros. Entretanto, se o ajuste pela raça tivesse sido aplicado, os valores da TFG teriam sido significativamente maiores (p< 0,001) resultando em um erro. Conclusão: Não houve diferença significativa nos níveis de creatinina sérica entre brancos, pardos e negros na população estudada. O emprego do ajuste pelo fator raça na população brasileira poderia trazer um viés no cálculo da TFG, superestimando os valores para pardos e negros / Background: Serum creatinine levels are usually higher among black people in the United States due to increased muscle mass justifying the addition of race adjustment in creatinine-based equations to estimate glomerular filtration rate (GFR). We speculate if this adjustment would create a bias when used in the Brazilian population whose origin and racial admixture is quite different from the American people. Objective: The aim of the present study was to assess if serum creatinine levels are different between white, brown (mixed-race background) and black people in a Brazilian population. Methods: Data were extracted from a community-based health program in Brazil. We compared serum creatinine levels in self-defined white, black and brown adults. Additionally, we also estimated GFR using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, with and without race adjustment. Results: A total of 712 participants (54.7% females, 43 ± 12 years old) were enrolled. Thirty percent of the subjects were white, 43% brown and 27% black. As expected, males had serum creatinine higher than females (0.99 ± 0.23 mg/dl vs. 0.77 ± 0.17 mg/dl, p<0.001). However, no significant differences were found between whites (0,86 ± 22 mg/dl), brown (0,87 ± 22 mg/dl) and blacks (0,88 ± 25 mg/dl). Serum creatinine levels for white, brown and black females were 0.76 ± 0.15 mg/dl, 0.77 ± 0.17 mg/dl and 0.79 ± 0.17 mg/dl, respectively. Correspondent values for males were 1.00 ± 0.23 mg/dl, 0.98 ± 0.19 mg/dl and 1.01 ± 0.30 mg/dl, respectively. When using the CKD-EPI equation without race adjustment, the eGFR was not different between white, brown and black subjects. However, if race-adjustment were adopted, estimated GFR values for Blacks would be significantly higher than for Whites (p<0.001). Conclusion: No significant differences in serum creatinine levels were found between white, brown and black people in this sample of a Brazilian population. It raises the question if the race-adjustment in creatinine-based equations for GFR estimation in our population would be appropriated

Introduction: Nephrectomy (Nx) for living kidney donation has been supported by studies that report few long-term clinical implications for donors. But the parameters used for donor evaluation are the same as those used for the general population. Hence, it is necessary to review the adequacy of those values and assess obese donors, since the incidence of obesity is increasing worldwide. Objective: To evaluate the impact of the ponderal changes and the values used as references for normal renal function of kidney donors. Methods: The study is a series of cases, with 48 living kidney donors who underwent uninefrectomy, between 1983 and 2006. Anthropometric data, systemic arterial pressure, glomerular filtration rate estimated (eGFR) by creatinine clearance and 24h proteinuria were assessed. Results: 52.08% of the sample showed eGFR between 60 and 89 ml/min and only 4.2% presented eGFR ≥ 120ml/min. It can be inferred that 77.1% were subject to hyperfiltration, if we consider as the normal value for a single kidney 50% of 120 ml/min, used for the population with two kidneys. Proteinuria was observed in 22.9% of the sample and, using the same reasoning as above and taking as reference 75mg/24h, 64.6% showed high levels of proteinuria. At the time of Nx, 10.4% of the sample was obese and has evolved with the increase of the obesity rate to 31.3%. The group also showed an increase in mean BMI. Obese patients had higher values of eGFR and systolic arterial pressure. Individuals with higher levels of proteinuria also showed higher ponderal values. Conclusion: Using the values of eGFR and proteinuria for the single kidney, hyperfiltration and proteinuria were, respectively, 18.3 and 2.8 times higher when compared to rates obtained by using the parameters applied for the general population. After donation, it was found an increase of body mass index (BMI) and obesity in the sample. Therefore, obesity appears to be associated with higher hyperfiltration, systolic arterial hypertension and subsequent proteinuria. Those findings justify a strict ponderal control for that population in order to avoid an overlapping of factors leading to renal injury. / Introdução: A nefrectomia (Nx) para doação renal intervivos é respaldada por trabalhos que relatam poucas alterações clínicas a longo prazo para os doadores. Mas os parâmetros de avaliação são os mesmos empregados para a população geral. Assim, é necessário rever a adequação destes valores e avaliar doadores obesos, visto que a incidência de obesidade está aumentando mundialmente. Objetivo: Avaliar o impacto das variações ponderais e dos valores utilizados como referência para normalidade na função renal de doadores renais. Métodos: O estudo é uma série de casos, com 48 doadores renais, submetidos à uninefrectomia, entre 1983 e 2006. Foram avaliados dados antropométricos, pressão arterial sistêmica, taxa de filtração glomerular estimada (eTFG) pelo clearance de creatinina e proteinúria de 24h. Resultados: A eTFG em 52,08% da amostra apresentava-se entre 60 e 89 ml/min sendo que apenas 4,2% apresentavam eTFG ≥ 120 ml/min. Pode-se inferir que 77,1 % estão submetidos à hiperfiltração, se considerarmos como valor normal para rim único 50% do valor de 120 ml/min utilizado para a população com 2 rins. Em 22,9% observou-se a presença de proteínas na urina, mas se utilizando o mesmo raciocínio anterior e tomando como valor de referência 75mg/24h, 64,6% apresentam valores elevados de proteinúria. A amostra apresentava, na época da Nx, 10,4% de obesos e evoluiu para 31,3%. O grupo estudado também apresentou elevação do IMC médio. Pacientes com obesidade apresentavam maiores valores de eTFG e de pressão arterial sistólica. Os indivíduos com maiores valores de proteinúria apresentavam valores ponderais maiores. Conclusão: Utilizando valores de eTFG e proteinúria para o rim isolado, a hiperfiltração e proteinúria foram respectivamente 18,3 e 2,8 vezes mais elevadas em relação as taxas obtidas quando utilizados os parâmetros empregados para a população geral. Após a doação, houve elevação do IMC e dos obesos na amostra. Assim, obesidade parece estar associada à maior hiperfiltração e à hipertensão arterial sistólica e consequente proteinúria, o que justifica um rigoroso controle ponderal para esta população a fim de evitar uma sobreposição de fatores de injúria renal. / Mestre em Ciências da Saúde

No description available.

I Objetivos.- Determinar el valor diagnostico del estudio de Radiorrenograma con Dtpa – Tc99m para estimar la tasa de filtración glomerular en pacientes con enfermedad renal crónica en el Hospital Central de la Policía Nacional del Perú “Luis N. Sáenz. Diseño: Estudio observacional, descriptivo, prospectivo y de corte transversal. Institución:”; Lima, Perú. Materiales: Historias Clínicas. II Intervenciones.- estudio de historias clínicas de pacientes con una muestra poblacional, no probabilístico. De los cuales por no cumplir con los criterios de inclusión quedaron un total de 34 historias clínicas, siendo estos 20 de sexo masculino y 14 de sexo femenino los cuales se encuentran dentro de un rango de edad, de 25 años a más. La muestra se obtuvo revisando cada historia clínica, estos presentaban un informe de laboratorio con la filtración glomerular y la orden de estudio de Radiorrenograma con DTPA-Tc99m entre el periodo marzo-mayo del 2015. III Principales medidas de resultados.- Sensibilidad, especificidad, valor predictivo positivo y negativo del Radiorrenograma con DTPA-Tc99m para la estimación de filtración glomerular. Resultados: con los datos recabados, se calculó el valor diagnostico del Radiorrenograma con DTPA-Tc99m para la estimación de filtración glomerular. La sensibilidad del Radiorrenograma con DTPA-Tc99m es de 69.23% (IC 95%,40.30% al 98.17%); una especificidad de 90.48% (IC 95%, 75.54% al 100%); un valor predictivo positivo de 81.82%( IC 95%,54.48% al 100%) y un valor predictivo negativo de 82.61% (IC 95%,64.94% al100%) para la estimación de filtrado glomerular. IV Conclusiones.- El Radiorrenograma con DTPA-Tc99m es el estudio isotópico adecuado para la estimación de filtración glomerular en la enfermedad renal crónica. / I. Purpose -. To determine the diagnostic value of Radiorrenograma with DTPA-Tc99m studying, to estimate glomerular filtration rate in patients with chronic kidney disease at Central Hospital of the National Police of Peru " Luis N. Sáenz. Design: Observational, descritptive, porspective and cross-sectioanl study. Institution: Central Hospital of the National Police of Peru "Luis N. Sáenz, Lima, Peru. Materials: Medical Records II. interventions.- study of medical records of patients with a sample population, which no probabilistic. Of which not meet the inclusion criteria were a total of 34 medical records, and these 20 males and 14 females who are within an age range of 25 years more The sample was obtained bye reviewing medical recods each, they presented a report of the laboratory test with glomerular flitration and the order of study of Radiorrenograma with DTPA-Tc99m between the period March – may 2015 III. Main outcome measures-. Sentitivity, specificity, positive an negative predictive value of Radiorrenograma with DTPA-Tc99m for estimating glomerular filtration. Results: With the data collected; the diagnostic value of Radiorrenograma with DTPA-Tc99m for estimating glomerular filtration was calculated.Radiorrenograma with DTPA-Tc99m sensitivy is 69.23 % (95% CI, 40.30% to 98.17%); a specificity of 90.48 % (95% CI, 75.54% to 100%); a positive predictive value of 81.82 % (95% CI, 54.48% to 100%) and negative predictive value of 82.61 % (95% CI, 64.94 % al 100%) for estimating glomerular filtration. IV. Conclusions -. The Radiorrenograma with DTPA - Tc99m is right isotopic study for estimating GFR in chronic renal disease. Keywords: Radiorrenograma; DTPA – Tc99m; glomerular filtration; Chronic kidney diseas

The domestic dog, Canis lupus familiaris, plays many roles in the lives of humans. Additionally, the dog is recognized for its potential as a model for many human hereditary diseases. Thus, the genetics and genomics of the dog are being studied extensively in order to facilitate its use as a model, as well as to help the dog for its own sake. As part of this research effort, our laboratory has added type I markers (i.e., the acidic and basic keratins, c-kit, type I and IV collagens, and the gene encoding uromodulin) to the emerging map of the canine genome. The mapping of genes, particularly those in large gene families such as the collagens, is valuable because it rapidly increases the density of gene loci on the map and provides insight regarding conservation of synteny between the dog and other mammals. The major focus of work reported here is the genetics of X-linked Alport syndrome (XLAS), a terminal renal disease that affects the human and the dog. The disease results from mutations in COL4A5, a type IV collagen gene. Reported here are the 1) sequencing and mapping of the canine cDNA encoding uromodulin, 2) mapping of the type I and type IV collagen genes, 3) sequencing of the full-length cDNA of canine COL4A5, 4) identification of a 10 bp deletion in COL4A5, causative for XLAS in our colony of mixed breed dogs, 5) development of a genetic test for identification of affected and carrier dogs in the colony and 6) assessment of gene expression in the kidneys of normal and XLAS-dogs. This assessment was performed using a canine-specific oligonucleotide microarray. XLAS dogs demonstrated up-regulation of many genes involved in extracellular matrix reorganization, cell structure, and immune response, as expected in a glomerulopathy with tubulointerstitial nephritis. Trends were verified by quantitative RT-PCR. A review of the current status of canine genetics research, and current understanding of hereditary diseases in the dog, concludes this dissertation.

No description available.

La Enfermedad Renal Crónica (ERC) representa actualmente un importante problema de salud de ámbito mundial. Los datos del Registro de Enfermos Renales de la Sociedad Española de Nefrología (SEN) coinciden en señalar que España se encuentra entre los países europeos con una mayor prevalencia de ERC terminal, factor estrechamente relacionado con la mayor longevidad de la población actual y la mayor prevalencia de diabetes mellitus e hipertensión arterial. En base a las importantes limitaciones para la estimación del Filtrado Glomerular (FG) mediante la aplicación de las técnicas isotópicas e imprecisiones asociadas a la utilización de la creatinina plasmática, se han desarrollado a partir de grandes estudios epidemiológicos diferentes fórmulas predictivas que intentan relacionar matemáticamente diferentes variables sociodemográficas, analíticas y nutricionales para el cálculo de la función renal. Entre más de 40 ecuaciones de estimación calculadas hasta la fecha, las más conocidas y validadas en distintos grupos poblacionales son la fórmula de Cockcroft-Gault (CG) y la ecuación del estudio MDRD "Modification of Diet in Renal Disease". Sin embargo, cuando se utilizan estas ecuaciones en pacientes con ERC, debe tenerse en cuenta el hecho de que las poblaciones incluidas en los estudios epidemiológicos originales estaban muy seleccionadas. Por lo tanto, a pesar de las recomendaciones actuales de las guías clínicas, debemos enumerar y matizar cuáles son las principales limitaciones derivadas de la utilización de estas fórmulas en los grupos poblacionales no incluidos en los estudios originales. El objetivo del primer artículo fue evaluar la exactitud de diferentes ecuaciones predictivas durante la monitorización ambulatoria de una cohorte de pacientes diabéticos tipo 2. Durante el periodo de seguimiento se realizaron un total de 525 determinaciones con 125I-iotalamato en 87 pacientes diabéticos seguidos una media de 10 años (rango:7-15). En conclusión, la aplicación de las ecuaciones predictivas no resulta útil durante la monitorización ambulatoria de los pacientes diabéticos tipo 2 con normofunción renal e hiperfiltración. Es a partir de los estadios 2-3 de ERC (FG: 89-30 ml/min/1,73m²) y con una creatinina plasmática &#8805; 133 µmol/l (1,5 mg/dl), cuando la ecuación MDRD puede comenzarse a utilizar en este subgrupo de pacientes.El objetivo del segundo articulo fue evaluar la aplicación de las ecuaciones predictivas según el estado nutricional (CP: tasa de producción de creatinina) y la edad, en un grupo de 87 pacientes adultos Caucasianos mediterráneos con ERC estadios 4-5 (rango FG: 8-30 ml/min/1,73m²). En base a los resultados obtenidos en pacientes con buen estado nutricional (CP>0,90) y edad &#8804; 64 años, no se evidenció que la ecuación del estudio MDRD fuera superior al CG fórmula en la estimación del filtrado glomerular calculado mediante el método isotópico. Desaconsejamos la utilización de las fórmulas derivadas del aclaramiento en orina de 24 horas, por representar los métodos con mayor variabilidad e imprecisión en la estimación de la función renal. La aplicación de todas las ecuaciones predictivas, resulta inexacta e imprecisa en pacientes con ERC estadios 4 y 5 y mal estado nutricional (CP &#8804; 0,90) con o sin edad avanzada (> 64 años). Su aplicación en estas circunstancias clínicas implica importantes errores de programación e inicio prematuro del tratamiento renal sustitutivo.La aplicación de las ecuaciones predictivas resulta útil para el diagnóstico precoz, la clasificación y el control ambulatorio de pacientes con ERC. Sin embargo, la utilización de dichas fórmulas, resulta imprecisa al introducir importantes sesgos en situaciones de normofunción renal e hiperfiltración, situaciones de estado nutricional deficiente y edad avanzada. En estas circunstancias clínicas que limitan su utilización, deberá estimarse el filtrado glomerular mediante la utilización de técnicas isotópicas. / The Chronic Kidney Disease (CKD) represents one of the pathologies with greater incidence and prevalence in the present sanitary systems. The ambulatory application of different methods that allow a suitable detection, monitoring and stratification of the renal functionalism is of vital importance in the habitual practice. On the basis of the vagueness obtained by means of the application of the serum creatinine, they have been developed to everything a set of predictive equations for the estimation of the glomerular filtration rate (GFR). The current guidelines of the "European Renal Association" (ERA-EDTA) and the "Kidney Disease Outcomes Quality Initiative" (K/DOQI) recommend the Cockcroft-Gault (CG) formula and the MDRD (Modification of Diet in Renal Disease) equation in adult patients with CKD stage 4 (GFR: 29-15 ml/min/1,73m²). Nevertheless, it is essential the knowledge of the limitations in clinical practice. The main aim of first article was to evaluate the accuracy of different prediction equations for the ambulatory follow-up of a cohort of patients with type 2 diabetes mellitus (a total of 525 isotopic determination with 125I-iothalamate clearance in 87 patients). The control mean using the isotopic technique was 10 years (range: 7-15). In conclusion, based on our results, the use of the prediction equations during the follow-up period of type 2 diabetic patients proved inaccurate in cases of hyperfiltration and normal renal function. It is in situations of CKD stages 2-3 (GFR: 89-30 ml/min/1,73m²), with mean creatinine levels &#8805; 133 µmol/l (1,5 mg/dl), that the MDRD equation can be started to be used for GFR estimation during the monitoring and follow-up of patients with type 2 diabetes receiving insulin and/or oral antidiabetic drugs. The main aim of second article was to ascertain the usefulness of prediction equations with respect to nutritional status and age in a group of 87 Caucasian adult patients with CKD stages 4-5 (GFR range: 8-30 ml/min/1,73m²). According to our results in the group of patients with higher creatinine production (CP) and age &#8804; 64, results of the present data offered no evidence for superiority of the MDRD equation over the CG formula in patients with advanced renal failure. Thus, we do not recommend the use of the mean creatinine and urea clearance adjusted to 1,73 m² of BSA which was the most imprecise equation. The application of all the equations is inaccurate in patients with lower CP with or without advanced age, implying the premature start of renal substitution treatment.In conclusion, it is essential for clinical the knowledge of limitations in the application of prediction equations, specially in situations of normal renal function and hyperfiltration, certain associate pathologies and extreme situations of nutritional status and age. In these cases, is more recommendable the application of isotopic techniques for the calculation of renal function.

Objetivos: El objeto de estudio es la membrana basal glomerular (M.B.G.) y la distribución de dos de las moléculas estructurales de las matrices extracelulares del corpúsculo renal, la fibronectina y la laminina. el estudio se ha realizado con cuatro especies aparentemente próximas de un mismo grupo zoológico (Rodentia) dado que experimentalmente, se incorporan nuevas especies como animales de laboratorio, comparando un animal estándar de laboratorio, con especies silvestres, con distintas estrategias tróficas.Material y métodos: Se han utilizado individuos adultos de Mus musculus (cepa isogénica BALB/c), y Mus spretus, Apodemus sylvaticus y Clethrionomys glareolus precedentes de capturas "in vivo" realizadas en el medio natural. El material histológico ha sido procesado mediante M.O. (tinción del PAS-Azul de Alcián/He. y dos técnicas de localización inmunohistoquímica, inmunoperoxidasa e inmunofluorescencia para anticuerpos anti-fibronectina y anti-laminina) y mediante M.E.T. (estándar y de inmunolocalización de anticuerpos anti-fibronectina y anti-laminina mediante oro coloidal).Resultados: La M.E.T. no muestra diferencias morfológicas entre los glomérulos de las diferentes especies utilizadas, excepto para la M.B.G. ya que en todas las especies silvestres utilizadas, el material que conforma toda la M.B.G. aparece con densidad uniforme. Con la inmunolocalización mediante oro coloidal los resultados para la distribución de fibronectina en M. musculus muestran marcaje positivo en la matriz mesangial, y negativo en la M.B.G. y en la membrana basal peritubular. Los resultados para M. spretus y C. glareolus son semejantes a los obtenidos para M. musculus; si bien con un valor de reacción menor al observado para M. musculus.Con la inmunolocalización mediante oro coloidal los resultados para la distribución de laminina, en M. musculus muestran marcaje positivo en la matriz mesangial, en la membrana basal tubular y en la M.B.G., en ésta última con tendencia a localizarse en las dos láminas raras. Los resultados para M. spretus y C. glareolus son semejantes a los obtenidos para M. musculus aunque con un valor de reacción menor al observado para el ratón de laboratorio.Las muestras procedentes de A. sylvaticus, no mostraron reactividad positiva frente a ninguno de los dos anticuerpos, anti-fibronectina y anti-laminina, utilizados.Conclusiones: La ultraestructura trilaminar de la M.B.G. presente en M. musculus no se observa en las otras especies utilizadas; en éstas existe densidad prácticamente uniforme en todo su espesor: Tampoco existe diferencia en el límite entre la M.B.G. pericapilar, la M.B.G. perimesangial y la matriz mesangial.En las especies M. musculus, M. spretus y C. glareolus la fibronectina se localiza única y exclusivamente en la matriz mesangial y en ningún caso en las M.B.G. mientras que la laminina se localiza tanto en las M.B.G. como en la cápsula de Bowman, la membrana basal tubular y la matriz mesangial. Mostrando en la M.B.G. pericapilar una ligera tendencia a localizarse en las láminas raras externa e interna.El marcaje menos intenso en M. spretus y C. glareolus y su ausencia en A. sylvaticus para la fibronectina y la laminina en la M.B.G. y la matriz mesangial puede indicar un carácter de divergencia filogenética.ENGLISH / DISTRIBUTION OF FIBRONECTIN AND LAMININ IN RENAL CORPUSCLE OF DIVERSE SPECIES OF RODENTSPropose: The aim of this study is the glomerular basement membrane (GBM) and the distribution of two of structural molecules of the extracellular matrices of the renal corpuscle: fibronectin and laminin. The study has been performed with four apparently closed species of a same zoological group (Rodentia) since experimentally, new species like laboratory animals are starting being breeded, comparing a standard laboratory animal with wild species with different trophic strategies.Material and methods: Adults exemplars of Mus musculus (isogenic strain BALB/c), Mus spretus, Apodemus sylvaticus and Clethrionomys glareolus proceeding of captures "in vivo" made in natural fields have been used. The histological material has been processed by means of OM (stain PAS-Alcian Blue/H) and two immunohistochemical techniques, immunoperoxidase and immunofluorescence for antibodies anti-fibronectin and anti-laminin and by TEM (standard and immunolocalization of antibodies anti-fibronectin and anti-laminin by colloidal gold).Results: TEM does not show morphological differences between the glomeruli of the different species used, except for the GBM , showing the material that conforms all the GBM a uniform density in all the wild species. With the immunolocalization by colloidal gold, the results for the distribution of fibronectin in M. musculus is positive in the mesangial matrix, and negative in the GBM and the peritubular basement membrane. The results for M. spretus and C. Glareolus are similar to obtained for M. musculus; although with a smaller reaction to that observed for M. musculus. With the immunolocalization by colloidal gold the results for the distribution of laminin, in M. musculus is positive in the mesangial matrix, the tubular basement membrane and the GBM; the latter with tendency to be located in two laminae rara. The results for M. spretus and C. glareolus are similar to obtained for M. musculus although with a smaller reaction to the observed for the laboratory mouse.The samples from A. sylvaticus, did not show positive reactivity again the anti-fibronectin and anti-laminin antibodies used.Conclusions: The trilaminar ultrastructure of the GBM presents in M. musculus is not observed in the other species used; in those a uniform density in all its thickness exists. Differences in the limit among the pericapillary GBM, the perimesangial GBM and the mesangial matrix does not exist either. In M. musculus, M. spretus and C. glareolus species fibronectin are exclusively located in the mesangial matrix and never in the GBM, whereas laminin is located mainly in the GBM and also in the Bowman's capsule, the tubular basement membrane and the mesangial matrix; showing in the pericapillary GBM a slight tendency to be located in external and internal laminae rara. The less intense labelling in M. spretus and C. glareolus and its absence in A. sylvaticus for fibronectin and laminin in the GBM and the mesangial matrix may suggest a philogenetic divergence.

The domestic dog, Canis lupus familiaris, plays many roles in the lives of humans. Additionally, the dog is recognized for its potential as a model for many human hereditary diseases. Thus, the genetics and genomics of the dog are being studied extensively in order to facilitate its use as a model, as well as to help the dog for its own sake. As part of this research effort, our laboratory has added type I markers (i.e., the acidic and basic keratins, c-kit, type I and IV collagens, and the gene encoding uromodulin) to the emerging map of the canine genome. The mapping of genes, particularly those in large gene families such as the collagens, is valuable because it rapidly increases the density of gene loci on the map and provides insight regarding conservation of synteny between the dog and other mammals. The major focus of work reported here is the genetics of X-linked Alport syndrome (XLAS), a terminal renal disease that affects the human and the dog. The disease results from mutations in COL4A5, a type IV collagen gene. Reported here are the 1) sequencing and mapping of the canine cDNA encoding uromodulin, 2) mapping of the type I and type IV collagen genes, 3) sequencing of the full-length cDNA of canine COL4A5, 4) identification of a 10 bp deletion in COL4A5, causative for XLAS in our colony of mixed breed dogs, 5) development of a genetic test for identification of affected and carrier dogs in the colony and 6) assessment of gene expression in the kidneys of normal and XLAS-dogs. This assessment was performed using a canine-specific oligonucleotide microarray. XLAS dogs demonstrated up-regulation of many genes involved in extracellular matrix reorganization, cell structure, and immune response, as expected in a glomerulopathy with tubulointerstitial nephritis. Trends were verified by quantitative RT-PCR. A review of the current status of canine genetics research, and current understanding of hereditary diseases in the dog, concludes this dissertation.