INTRODUÇÃO Pacientes com doença renal crônica sofrem alterações musculoesqueléticas nos estágios iniciais da doença associadas a fatores como alteração de substratos séricos, capacidade funcional, qualidade de vida e parâmetros nutricionais. O objetivo deste estudo foi avaliar o desempenho funcional, qualidade de vida, e parâmetros respiratórios em pacientes com doença renal crônica não dialítica segundo o estágio da doença renal. MÉTODOS Foram selecionados 26 indivíduos acompanhados pelo Serviço de Nefrologia do Instituto Central da Faculdade de Medicina da Universidade de São Paulo, com diagnóstico de doença renal crônica não dialíticos, e taxa de filtração glomerular abaixo de 45 mL/min, foram excluídos pacientes com doenças reumatológicas, respiratórias, neurológicas ou que apresentassem limitações para a execução dos testes funcionais. Foram aplicados os seguintes instrumentos: questionário de Qualidade de Vida (SF-36), o questionário Internacional de Nível de Atividade Física (IPAQ), foi realizado os seguintes testes: teste de Caminhada de Seis Minutos, teste de Sentar e Levantar, e o teste de Preensão Palmar, foram aferidas também as pressões máximas inspiratórias e expiratórias e volumes pulmonares através da manuvacuometria e exames laboratoriais de rotina. RESULTADOS Os dados do grupo geral foram comparados com os encontrados na literatura demonstrando menor capacidade funcional e respiratória do que indivíduos saudáveis de mesmo gênero e faixa etária. Os indivíduos avaliados também foram subdivididos em dois grupos através da estimativa da taxa de filtração glomerular pela formula CKD-EPI, o primeiro grupo com taxa de filtração glomerular menor que 30 mL/min e o segundo grupo com taxa de filtração glomerular maior ou igual a 30 mL/min. Foram encontradas diferenças significantes quanto a: pressão expiratória máxima (P=0.04) onde os pacientes com pior função renal apresentaram maior força muscular expiratória, paratormônio (P= 0.02), fosforo (P= 0.04) e ureia (P= 0.00) . CONCLUSÃO: Concluiu se que indivíduos com doença renal crônica apresentam diferenças em relação aos parâmetros respiratórios, exames séricos diferentes estágios da doença renal crônica antes da terapia renal substitutiva / INTRODUCTION Patients with chronic kidney disease (CKD) suffer musculoskeletal disorders in the early stages of the disease associated with factors such as change in serum substrates, functional capacity, quality of life and nutritional characteristics. The aim of this study was to evaluate the functional performance, quality of life, and respiratory parameters in patients with CKD not requiring dialysis according to the stage of kidney disease. METHODS We selected 26 individuals accompanied by the Nephrology Department of the Central Institute of the Faculty of Medicine, University of São Paulo, diagnosed with chronic kidney disease not on dialysis, and glomerular filtration rate below 45 mL / min, patients were excluded with rheumatic diseases, respiratory, neurological or who present limitations for the execution of functional tests. The following instruments were applied: Quality of Life questionnaire (SF-36), the International Physical Activity Questionnaire (IPAQ), was performed the following tests: the Six Minutes Walk test, Sitting and Rising test, and Hand Grip Strength test were also measured the maximum inspiratory and expiratory pressure and lung volumes through manuvacuometria and routine laboratory tests. RESULTS The results presented by the general group were compared with those found in the literature showing lower functional and respiratory capacity than healthy individuals of the same gender and age. The evaluated individuals were also subdivided into two groups by means of the glomerular filtration rate by the formula CKD-EPI, the first group of glomerular filtration rate lower than 30 ml / min and the second group with higher glomerular filtration rate or equal to 30 ml / min. Significant differences were found regarding: maximal expiratory pressure (P 0.04) where patients with poor kidney function had higher expiratory muscle strength, parathyroid hormone (P = 0.02) and phosphorus (P 0.04). CONCLUSION: We conclude that individuals with chronic kidney disease have differences from respiratory parameters, different blood tests stages of chronic kidney disease before renal replacement therapy

Introdução: a doença renal crônica constitui importante problema de saúde pública mundial. Contudo, pouco se sabe sobre suas características em nosso meio. Objetivo: identificar os fatores associados à doença renal crônica em pacientes internados em um hospital universitário. Método: foram selecionados, aleatoriamente, 386 pacientes que constituíram dois grupos: com e sem doença renal crônica. A doença renal crônica foi definida pela presença de diagnóstico médico ou antecedente pessoal. Os dados foram obtidos do prontuário do paciente. Foram comparados os grupos com e sem doença renal crônica e os hipertensos com e sem doença renal crônica, mediante as variáveis de estudo. Estimou-se a taxa de filtração glomerular (eTFG) dos pacientes sem doença renal a partir das equações Modification of Diet in Renal Disease abreviada (MDRD4) e Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Verificou-se a associação da eTFG <90 mL/min/1,73m², pela MDRD4, com dados biossociais e comorbidades. O nível de significância foi de p<0,05. Resultados: a amostra foi 50,5% homens, 64,4% brancos, 50,7% com companheiro e idade de 58,2±18,6 anos. Os pacientes com doença renal crônica se distinguiram daqueles sem a doença (p<0,05) em relação a: viverem com companheiro (59,8% vs 47,3%); idade mais elevada (65,8±15,6 vs 55,3±18,9 anos); menor frequência de fumantes (11,1% vs 29,7%); terem antecedente pessoal de hipertensão arterial (75,2% vs 46,3%), diabetes (49,5% vs 22,4%), dislipidemia (23,8% vs 14,9%), infarto agudo do miocárdio (14,3% vs 6,0%) e insuficiência cardíaca congestiva (18,1% vs 4,3%); evolução a óbito (12,4% vs 1,4%); e maior tempo de internação (11 (818) vs 9 (612) dias); além dos exames laboratoriais, exceto glicemia e perfil lipídico. A análise de regressão logística indicou associação independente da doença renal crônica com as seguintes variáveis (OR, odds ratio; IC, intervalo de confiança de 95%): idade (OR 1,019, IC 1,003-1,036); hipertensão arterial (OR 2,032, IC 1,128-3,660), diabetes (OR 2,097, IC 1,232-3,570) e insuficiência cardíaca congestiva (OR 2,665, IC 1,173-6,056). Os hipertensos com e sem doença renal crônica foram distintos (p<0,05) em relação a: possuíam companheiro (64,3% vs 50,7%); uso de maior número de medicamentos (4,0 (2,05,0) vs 2,0 (0,5 4,0)), não fumantes (9,9% vs 25%); terem antecedentes pessoais para diabetes (53,5% vs 36,4%) e insuficiência cardíaca congestiva (19,8% vs 7,0%); uso de medicamentos anti-hipertensivos (79,1% vs 66,4%,); tratamento com insulina (24,4% vs 7,0%); além dos exames laboratoriais, exceto glicemia, perfil lipídico e ácido úrico. Houve boa concordância da classificação da eTFG de pacientes sem doença renal crônica pelas equações MDRD4 e CKD-EPI (kappa 0,854). De acordo com a equação MDRD4, 54,4% tinham eTFG 90 mL/min/1,73m²; 37,7%, eTFG 60-89 mL/min/1,73m²; e 7,8%, eTFG <60 mL/min/1,73m². Pacientes com eTFG <90 mL/min/1,73m² se destacaram (p<0,05) por apresentar maior frequência de hipertensão arterial (63,3% vs 32,0%), diabetes (29,7% vs 16,3%) e dislipidemia (24,2% vs 7,2%) em relação a pacientes com eTFG 90 mL/min/1,73m². Conclusão: a doença renal crônica esteve associada a fatores de risco cardiovascular, em sua maioria, modificáveis. / Introduction: chronic kidney disease is an important public health problem worldwide. Nevertheless, little is known about its features in our setting. Objective: identify factors associated with chronic kidney disease among hospitalized patients in a university hospital. Method: 386 patients were randomly selected and divided in two groups: with and without chronic kidney disease. Chronic kidney disease was defined by the presence of medical diagnosis or personal history. Data was acquired from medical records. Patients with and without chronic kidney disease, as well as hypertensive patients with and without chronic kidney disease, were compared with regard to the variables under study. Glomerular filtration rate (eGFR) of patients without chronic kidney disease was estimated using abbreviated Modification of Diet in Renal Disease (MDRD4) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. The association between eTFG <90/mL/min/1,73m² and biosocial data and comorbidities was assessed. Significance level was p<0,05. Results: the study sample was 50,5% male, 64,4% white, 50,7% living with partner, and 58,2±18,6 years-old. Patients with chronic kidney disease differed (p<0,05) from patients without, regarding to: living with partner (59,8% vs 47,3%); older age (65,8±15,6 vs 55,3±18,9 years-old); no smokers (11,1% vs 29,7%); personal history of hypertension (75,2% vs 46,3%), diabetes (49,5% vs 22,4%), dyslipidemia (23,8% vs 14,9%), acute myocardial infarction (14,3% vs 6,0%) and congestive heart failure (18,1% vs 4,3%); occurrence of death (12,4% vs 1,4%); and length of hospitalization (11 (818) vs 9 (612) days), as well as laboratory tests, excepted blood glucose level and lipidemic profile. Logistic regression indicated independent association of chronic kidney disease for the following variables (OR, odds ratio; CI, confidence interval at 95%): age (OR 1,019, CI 1,003-1,036); hypertension (OR 2,032, CI 1,128-3,660), diabetes (OR 2,097, CI 1,232-3,570) and congestive heart failure (OR 2,665, CI 1,173-6,056). Hypertensive patients with and without chronic kidney disease were different (p<0,05) regarding to: living with partner (64,3% vs 50,7%); greater number of continuous-use medication (4,0 (2,05,0) vs 2,0 (0,5 4,0)); no smokers (9,9% vs 25%); personal history of diabetes (53,5% vs 36,4%) and congestive heart failure (19,8% vs 7,0%); use of antihypertensive drugs (79,1% vs 66,4%); insulin therapy (24,4% vs 7,0%); as well as laboratory tests, excepted blood glucose level, lipidemic profile and uric acid. Relevant agreement was shown between eGRF classification by MDRD4 and CKD-EPI equations for patients without kidney disease (kappa 0,854). According to MDRD4 equation, 54,4% had eGRF 90 mL/min/1,73m²; 37,7%, eGFR 60-89 mL/min/1,73m²; and 7,8%, eGFR <60 mL/min/1,73m². Patients with eGFR <90 mL/min/1,73m² stood out (p<0,05) from those with eGFR 90 mL/min/1,73m² as presenting higher frequencies of hypertension (63,3% vs 32,0%), diabetes (29,7% vs 16,3%) and dyslipidemia (24,2% vs 7,2%). Conclusion: chronic kidney disease showed association with cardiovascular risk factors, most of which modifiable.

A nicotina é o principal componente do tabaco e dos cigarros eletrônicos. A exposição crônica a nicotina, em quantidades semelhantes às atingidas pelo tabagismo humano, é responsável por piora da lesão renal aguda e da doença renal crônica. O gene klotho, predominantemente expresso no rim, foi descoberto após uma mutação insercional, com o surgimento de um fenótipo semelhante ao envelhecimento humano nos camundongos homozigotos para esse transgene. A proteína Klotho transmembrana tem ação de co-receptor do fator de crescimento fibroblástico 23 (FGF-23) e sua forma secretada atua em diversas vias intracelulares e em órgãos a distância. A deficiência de Klotho ocorre no envelhecimento, em situações que levam a lesão renal aguda e na doença renal crônica. A expressão reduzida de Klotho também agrava lesão renal aguda e participa da progressão da doença renal crônica, enquanto o seu aumento, ou a sua reposição, protegem dos processos inflamatórios e do estresse oxidativo. Neste estudo, objetivamos avaliar os efeitos renais, hemodinâmicos e sobre a expressão de Klotho da exposição crônica a nicotina e quais os efeitos dessa exposição nos animais haploinsuficientes para o transgene klotho (Kl+/-). Utilizamos para estas avaliações camundongos Kl+/- e seus controles wild type (Kl+/+), que foram expostos a nicotina (200 mcg/mL) ou veículo (sacarina 2%) diluídos em água por 28 dias. Ao final do estudo foram avaliados diurese, eletrólitos plasmáticos e urinários, ureia, aldosterona, ADH, FGF-23 e PTH intactos plasmáticos, expressão protéica renal de Klotho, alfa7-nAchR, NHE3, ENaC, NKCC2, AQP2, e-NOS, VEGF, MnSOD e renina, expressão genica renal de klotho, interleucinas, TBARS e GSH em tecido renal, taxa de filtração glomerular por FITC-inulina, pressão arterial e frequência cardíaca invasivas, sensibilidade baroreflexa e modulação autonômica cardíaca e periférica por análise espectral. Após a exposição a nicotina, os animais Kl+/+ apresentaram redução da expressão renal da proteína e do RNAm de Klotho e uma tendência a aumento dos níveis plasmáticos de FGF-23, associados a uma queda da diurese e da taxa de filtração glomerular, sem alteração dos níveis de ADH. Esses animais Kl+/+ também apresentaram aumento da sensibilidade barorreflexa em resposta ao nitroprussiato e um predomínio da modulação simpática cardíaca, com redução da expressão renal dos alfa7-nAchR. Os animais Kl+/- tiveram níveis renais ainda menores de Klotho após a exposição a nicotina, com aumento de TBARS, IL-6, uréia e aldosterona em relação aos Kl+/- não expostos. A diurese, a taxa de filtração glomerular e a expressão dos alfa7-nAchR não se reduziram e não houve aumento da sensibilidade barorreflexa após exposição a nicotina, com um predomínio da modulação parassimpática cardíaca, nesses animais Kl+/-. A ingesta hídrica, a pressão arterial e a frequência cardíaca foram semelhantes entre os 4 grupos. A proteinúria foi maior nos animais Kl+/- do que nos animais Kl+/+ após a exposição a nicotina. Podemos concluir que a exposição crônica à nicotina reduz a expressão renal de Klotho, estimula vias de inflamação, fibrose e estresse oxidativo renais e tem efeitos renais e sistêmicos diferentes de acordo com os níveis basais de Klotho / Nicotine is a major compound of tobacco and electronic cigarettes. Chronic exposure to nicotine concentrations that are similar to human smoke worsens acute kidney injury and chronic kidney disease. The klotho (Kl) gene is expressed predominantly by the kidney and was discovered after an unintentional insertional mutation that resulted, in transgenic homozygous mice, in a phenotype similar to human aging. Klotho transmembrane protein acts as a co-receptor to fibroblastic growth factor 23 (FGF-23) and the secreted form interacts in multiple intracellular pathways, with effects in distant organs. Klotho deficiency occurs in aging and in multiple acute kidney injury and chronic kidney disease etiologies, whereas klotho upregulation and replacement protect from inflammation and oxidative stress. Here, we investigated renal and hemodynamic effects of chronic nicotine exposure, its effects over renal expression of Kl, and compared wild type (Kl+/+) and Kl haploinsufficient mice (Kl+/-) in terms of the effects of that exposure. Kl+/- and Kl+/+ mice received nicotine (200 ?g/ml) or vehicle (saccharine 2%) in drinking water for 28 days. We evaluated diuresis, ions in serum and urine, urea, plasma and urinary levels of cotinine, aldosterone, plasma antidiuretic and parathyroid hormone, plasma FGF-23, protein expression of (immunoblotting for) Klotho and ?7 nicotinic acetylcholine receptor, NHE3, NKCC2, ENaC, aquaporin-2, e-NOS, VEGF and renin, klotho mRNA, kidney interleukines, TBARS and GSH, glomerular filtration rate by fluorescein isothiocyanate-inulin clearance, mean arterial pressure, heart rate, baroreflex sensitivity and autonomic cardiac and peripheral modulation by spectral analysis. After nicotine exposure, Kl+/+ mice showed decreased Klotho protein and mRNA and a tendency towards an elevation in plasma FGF-23, which were associated with both diuresis and glomerular filtration rate reductions, without modifications in ADH levels. Besides that, Kl+/+ animals increased baroreflex sensitivity after nitroprusside, a predominant sympathetic cardiac modulation and lower alfa7-nAchR kidney expression. Kl+/- mice reduced even more Klotho renal expression, with higher levels of TBARS, IL-6, urea and aldosterone. Diuresis, glomerular filtration rate, alfa7-nAchR expression and baroreflex sensitivity were the same of their controls. Cardiac parasympathetic modulation predominated in Kl+/- mice. Fluid intake, mean arterial pressure and heart rate were similar across the 4 groups. Renal protein excretion was higher in Kl+/- than in their controls after nicotine exposure. We can conclude that chronic nicotine exposure downregulates Klotho kidney expression induces inflammation and oxidative stress and stimulates fibrosis, with different renal and systemic responses according to basal Klotho levels

A cistatina C sérica tem sido apontada como um marcador de filtração glomerular. Neste trabalho realizamos a validação de um método específico e automatizado, a imunonefelometria, mensurando os níveis séricos de cistatina C através do nefelômetro da empresa Behring (BN II). O ensaio perfaz o intervalo de referência de 0.23-7.25 mg/L, até sete vezes acima dos limites considerados normais. A imprecisão intra e interensaio foram de 8,73% and 5,38% , respectively. A recuperação analítica de cistatina C após adição de controle foi entre 86,7 % e 98% (média 92,3%). A estabilidade da cistatina C a temperatura ambiente, sob refrigeração e sob congelamento foi testada. A perda mais significativa foi encontrada nas amostras armazenadas sob temperatura ambiente, onde foi perdido até 10% da concentração inicial. Nós encontramos CV de 14,79 % para sensibilidade analítica. Durante todo o processo nós comparamos os resultados com o controle de qualidade e obtivemos bons resultados. Depois destes testes, nós comparamos as correlações em 3 grupos de pacientes transplantados renais sob diferentes esquemas de imunossupressão (n=197) [azatioprina (n=36), micofenolato mofetil (n=131) ou sirolimus (n=30)], entre as equações de estimativa de filtração glomerular( Cockroft Gault, Nankivell e MDRD) e cistatina C sérica ou creatinina sérica. Nós concluimos que o ensaio nefelométrico cistatina C pode perfeitamente ser adequado à nossa rotina laboratorial e as correlações entre creatinina sérica e as diferentes equações de estimativa de filtração glomerular são melhores do que quando comparamos as mesmas à cistatina C nos 3 grupos independentemente da terapia imunossupressora utilizada. / Serum cystatin C has been suggested as a marker of glomerular filtration rate (GFR). We describe a validation of an automated and rapid particle-enhanced nephelometric immunoassay (PENIA) for measuring serum cystatin C on the Behring nephelometer (BN II). The assay covers the range 0.23-7.25 mg/L, up to seven times the upper limit of normal. The intra- and interassay imprecision are 8,73% and 5,38% , respectively. The analytical recovery by cystatin C addition between 86,7% and 98% (mean 92,3%). The estability of cistatyn C room temperature, refrigerator temperature and frozen temperature was tested. The higher lost was when we stored sample in a room temperature, when we can lost until 10% of initial concentration. We found CV of 14,79 % for analytical sensibility. During all the process we compare the results with a quality control and we obtained good results. After this validation, we have compared the correlation, in 3 different patients groups after renal transplant (n=197) were using different imunossupressors [azatioprine (n=36), micophenolic acid (n=131) or sirolimus (n=30), between glomerular filtration equations (Cockroft Gault, Nankivell and MDRD) and cystatin C or creatinine serum levels. We concluded cystatin C assay may be perfectly used in our laboratory and the correlation between serum creatinine and glomerular filtration equations are better then cystatin C at the same groups independent of imunosupressor therapy.

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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

<p>Live donor nephrectomy (LDN) is a unique surgical challenge where surgery is performed on healthy individuals. It is of great importance to keep the morbidity of donors as low as possible, as well as harvesting a kidney in optimal condition. Lowering morbidity is the motive for introducing the endoscopic technique in LDN. Oliguria and impaired kidney function can, however, be seen during pneumoperitoneum and endoscopic LDN have been criticized for not yet being proven safe enough.</p><p>The aims of this study were to investigate the changes in renal function during elevated intraabdominal pressure (IAP) in donors and rats and to evaluate donor morbidity and safety of the new endoscopic techniques compared to the open LDN.</p><p>In two studies, a rat model was used. It was found that elevation of IAP diminished glomerular filtration rate (GFR). Cardiac output (CO) and renal blood flow decreased as well. Elevation of IAP activates the renin system and aldosterone was increased. Acute angiotensin II receptor 1 blockade (candesartan) treatment lowered blood pressure significantly and impaired renal function during elevated IAP. Volume expansion prior to, and during, pneumoperitoneum reduces the deleterious effects on renal function.</p><p>Three studies on kidney live donors show that traditional laparoscopic surgery (TLS) takes longer time to perform than open LDN. Hand-assistance facilitates the operation and increases the safety margin as well as shortens the operation by 27% compared to TLS. Evaluation of a hand-assisted retroperitoneoscopy (HARS), performed for the first time ever in Uppsala 2001, show that the operation is short and safe, the donors experience little pain and the renal function is favourable compared to open surgery, TLS and hand-assisted transperitoneal laparoscopic approaches.</p><p>In conclusion, the results indicate that elevated IAP decreases GFR due to decreased CO and activation of the RAAS, which can be avoided with adequate hydration. Endoscopy can be facilitated if hand-assistance is applied and in particular hand-assisted retroperitoneoscopic nephrectomy shows advantages for the donor.</p>

Live donor nephrectomy (LDN) is a unique surgical challenge where surgery is performed on healthy individuals. It is of great importance to keep the morbidity of donors as low as possible, as well as harvesting a kidney in optimal condition. Lowering morbidity is the motive for introducing the endoscopic technique in LDN. Oliguria and impaired kidney function can, however, be seen during pneumoperitoneum and endoscopic LDN have been criticized for not yet being proven safe enough. The aims of this study were to investigate the changes in renal function during elevated intraabdominal pressure (IAP) in donors and rats and to evaluate donor morbidity and safety of the new endoscopic techniques compared to the open LDN. In two studies, a rat model was used. It was found that elevation of IAP diminished glomerular filtration rate (GFR). Cardiac output (CO) and renal blood flow decreased as well. Elevation of IAP activates the renin system and aldosterone was increased. Acute angiotensin II receptor 1 blockade (candesartan) treatment lowered blood pressure significantly and impaired renal function during elevated IAP. Volume expansion prior to, and during, pneumoperitoneum reduces the deleterious effects on renal function. Three studies on kidney live donors show that traditional laparoscopic surgery (TLS) takes longer time to perform than open LDN. Hand-assistance facilitates the operation and increases the safety margin as well as shortens the operation by 27% compared to TLS. Evaluation of a hand-assisted retroperitoneoscopy (HARS), performed for the first time ever in Uppsala 2001, show that the operation is short and safe, the donors experience little pain and the renal function is favourable compared to open surgery, TLS and hand-assisted transperitoneal laparoscopic approaches. In conclusion, the results indicate that elevated IAP decreases GFR due to decreased CO and activation of the RAAS, which can be avoided with adequate hydration. Endoscopy can be facilitated if hand-assistance is applied and in particular hand-assisted retroperitoneoscopic nephrectomy shows advantages for the donor.

Diabetic nephropathy is the main cause for initiation of renal replacement therapy and early symptoms in patients include increased glomerular filtration rate (GFR), decreased oxygen tension and albuminuria, followed by a progressive decline in GFR and loss of kidney function. Experimental models of diabetes display increased GFR, decreased tissue oxygenation and nitric oxide bioavailability. These findings are likely to be intertwined in a mechanistic pathway to kidney damage and this thesis investigated their roles in the development of diabetic nephropathy. In vivo, diabetes-induced oxidative stress stimulates renal tubular Na+ transport and in vitro, proximal tubular cells from diabetic rats display increased transport-dependent oxygen consumption, demonstrating mechanisms contributing to decreased kidney oxygenation. In control animals, endogenous adenosine reduces vascular resistance of the efferent arteriole via adenosine A2-receptors resulting in reduced filtration fraction. However, in diabetes, adenosine A2-signalling is dysfunctional resulting in increased GFR via increased filtration fraction. This is caused by reduced adenosine A2a receptor-mediated vasodilation of efferent arterioles. The lack of adenosine-signaling in diabetes is likely due to reduced local adenosine concentration since adenosine A2a receptor activation reduced GFR only in diabetic animals by efferent arteriolar vasodilation. Furthermore, sub-optimal insulin treatment also alleviates increased filtration pressure in diabetes. However, this does not affect GFR due to a simultaneously induction of renal-blood flow dependent regulation of GFR by increasing the filtration coefficient. In diabetes, there is decreased bioavailability of nitric oxide, resulting in alterations that may contribute to diabetes-induced hyperfiltration and decreased oxygenation. Interestingly, increased plasma concentration of l-arginine, the substrate for nitric oxide production, prevents the development of increased GFR and proteinuria, but not increased oxygen consumption leading to sustained intra-renal hypoxia in diabetes. This thesis concludes that antioxidant treatment directed towards the NADPH oxidase as well maneuvers to promote nitric oxide production is beneficial in diabetic kidneys but is targeting different pathways i.e. transport-dependent oxygen consumption in the proximal tubule by NADPH oxidase inhibition and intra-renal hemodynamics after increased plasma l-arginine. Also, the involvement and importance of efferent arteriolar resistance in the development of diabetes-induced hyperfiltration via reduced adenosine A2a signaling is highlighted.

Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. The complex, interaction between the kidney and the cardiovascular system is incompletely understood, particularly at the early stages of the cardiovascular continuum. The overall aim of this thesis was to clarify novel aspects of the interplay between the kidney and the cardiovascular system at different stages of the cardiovascular continuum; from risk factors such as insulin resistance, inflammation and oxidative stress, via sub-clinical cardiovascular damage such as endothelial dysfunction and left ventricular dysfunction, to overt cardiovascular death. This thesis is based on two community-based cohorts of elderly, Uppsala Longitudinal Study of Adult Men (ULSAM) and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The first study, show that higher insulin sensitivity, measured with euglycemic-hyperinsulinemic clamp technique was associated to improve estimated glomerular filtration rate (eGFR) in participants with normal fasting plasma glucose, normal glucose tolerance and normal eGFR. In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function during follow-up. In the second study, eGFR was inversely associated with different inflammatory markers (C-reactive protein, interleukin-6, serum amyloid A) and positively associated with a marker of oxidative stress (urinary F2-isoprostanes). In line with this, the urinary albumin/creatinine ratio was positively associated with these inflammatory markers, and negatively associated with oxidative stress. In study three, higher eGFR was associated with better endothelial function as assessed by the invasive forearm model. Further, in study four, higher eGFR was significantly associated with higher left ventricular systolic function (ejection fraction). The 5th study of the thesis shows that higher urinary albumin excretion rate (UAER) and lower eGFR was independently associated with an increased risk for cardiovascular mortality. Analyses of global model fit, discrimination, calibration, and reclassification suggest that UAER and eGFR add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent cardiovascular disease. Conclusion: this thesis show that the interaction between the kidney and the cardiovascular system plays an important role in the development of cardiovascular disease and that this interplay begins at an early asymptomatic stage of the disease process.

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