A avaliação de microalbuminúria (MA) é frequentemente utilizada em medicina humana para o diagnóstico precoce de doença renal precoce em humanos que pode evoluir concomitantemente durante o curso de várias outras afecções. Quando a doença renal progride para insuficiência renal, a albuminúria pode atingir concentrações elevadas (>30 mg/dL), que recebe, neste momento, a denominação de macroalbuminúria, que, por sua vez, resulta em proteinúria maciça. A coexistência de hipertensão arterial sistêmica pode acelerar a progressão da doença. Em Medicina Veterinária, não há relatos sobre a magnitude desta albuminúria em cães já diagnosticados com insuficiência renal crônica (IRC) como também sobre o grau de coexistência de hipertensão, parâmetros estes que constituíram o escopo do presente estudo. As concentrações urinárias de albumina, detectadas pela técnica ELISA, foram determinadas em 40 cães com IRC e em 40 cães sadios (controles). As pressões sangüíneas sistólicas também foram mensuradas para comparações. A concentração de albumina normalizada (AN), relação albumina:creatinina (RAC) e relação proteína:creatinina (RPC) foram calculadas para todos os cães. Todos os cães controles apresentaram valores abaixo da faixa de microalbuminúria para ambos os índices (AN e RAC).. Nos cães com IRC, 42,5% e 65% apresentaram-se dentro da faixa microalbuminúrica segundo seus valores de AN e RAC, respectivamente. Um aumento gradual nos valores de RPC foi seguido por um aumento igualmente gradual nos valores de RAC. Similarmente, um aumento nos valores de RAC foi acompanhado por um aumento na porcentagem de cães doentes com hipertensão, a qual compreendeu de 87,5 % e 85,7% dos cães macroalbuminúricos, segundo seus valores de AN e RAC, respectivamente. Finalmente, os cães com IRC hipertensos (> 180 mmHg de pressão sistólica) apresentaram valores mais altos de RAC que os cães não hipertensos (P = 0,023). Portanto, como primeiro relato na literatura veterinária, foi demonstrado que a hipertensão pode exercer um efeito adverso sobre o rim de cães com IRC, similarmente ao que é observado na medicina humana. / Detection of microalbuminuria (MA) is commonly recommended by human clinicians to diagnose early renal disease in people presenting different diseases. When kidney disease has progressed to renal failure, albuminuria can reach higher levels (>30 mg/dL), considering that stage as macroalbuminuria, which, in turn, eventually results in overt proteinuria. In veterinary medicine, no data related to what levels of albuminuria can be observed in dogs with chronic renal failure (CRF), as well as the degree of correlation with systemic hypertension, is available, being therefore, the scope of this study. Urinary albumin concentrations, detected by ELISA, were determined in 40 dogs with CRF and 40 healthy dogs (controls). Arterial pressures were registered for comparisons. Normalized albumin concentrations (NAC), urinary albumin to urinary creatinine ratio (UAC) and urinary protein to urinary creatinine ratio (UPC) were calculated for all dogs. All control dogs were below the microalbuminuric range for both parameters. In dogs with CRF, 42,5% and 65% were within the microalbuminuric range based on their AN and UAC values, respectively. A gradual increase in the level of UPC was followed by an also gradual increase in UAC values. Similarly, an increase in the UAC values was accompanied by an increase of the percentage of dogs with hypertension, which affected 87,5 % and 85.7% of the macroalbuminuric CRF dogs, according to their AN and RAC values, respectively. Finally, hypertensive CRF dogs (>180 mmHg mean systolic pressure) had greater UAC values than normotensive CRF dogs (P = 0.023). Thus, for the first time in veterinary literature, it is shown that hypertension seems to exert an adverse effect on renal function of CRF dogs, similarly to what is observed in human medicine.

Made available in DSpace on 2014-06-11T19:22:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-07-07Bitstream added on 2014-06-13T19:07:26Z : No. of bitstreams: 1 bertotti_mez_me_botfm.pdf: 443897 bytes, checksum: cafb6a105cd129eddcbad5cfad2d81bc (MD5) / Este trabalho analisa alterações odontológicas em pacientes com insuficiência renal crônica, em programa de hemodiálise. As alterações odontológicas estudadas foram índice de dentes cariados, perdidos e obturados (CPOD), presença ou ausência de doença periodontal, número de desdentados totais e parciais. Os pacientes foram submetidos a exame neurológico dos nervos cranianos. Foi determinado o pH da saliva antes e após diálise. Dentre os 44 pacientes estudados, foram encontrados 23 desdentados totais, 7 desdentados parciais e 14 dentados. Vários apresentaram cáries, sem diferenças estatisticamente significativas em relação ao grupo controle; 7 pacientes apresentaram doença periodontal. Alterações de nervos cranianos foram encontradas em 36 pacientes. Os nervos cranianos mais freqüentemente acometidos foram VIII - vestíbulo-coclear, II - óptico e V - trigêmio. Alterações trigeminais foram encontradas em 20 pacientes. É provável que as alterações trigeminais aferentes estejam relacionadas com as perdas dentárias, na insuficiência renal crônica. / This paper analyzes odontological alterations in hemodialysis patients with chronic renal failure. Odontological alterations were: index of decayed, lost, or filled teeth (DLFT); presence or absence of periodontal disease; and totally and partially toothless. Patients were submitted to neurological examination of the cranial nerves. Saliva pH was recorded before and after dialysis. Out of 44 patients, 23 were totally toothless, 7 partially toothless, and 14 dentate. Several had decay, but this was not statistically significant to controls; 7 had periodontal disease. Cranial nerve alterations were found in 36 patients. The most frequently compromised nerves were the VIII - vestibulocochlear, II - optic, and V - trigeminal. Trigeminal alterations were found in 20 patients. Probably afferent trigeminal alterations are related to tooth loss in chronic renal failure.

A insuficiência renal crônica (IRC) é considerada um grande problema de saúde pública, devido às altas taxas de morbidade e mortalidade. Os insuficientes renais crônicos (IRCs) apresentam várias dificuldades em seu cotidiano, como: constantes visitas ao médico, sessões de hemodiálise e restrições alimentares; fatores que desestruturam seu cotidiano e comprometem sua qualidade de vida. Essa pesquisa tem como objetivo avaliar a percepção das pessoas com IRC com relação a atividades cotidianas e ocupacionais, junto a dois serviços públicos de saúde em Ribeirão Preto; assim como avaliar a percepção da qualidade de vida dentro dos seguintes domínios: Físico, Psicológico, Social e Meio Ambiente. A amostragem analisada foi composta por 70 indivíduos adultos que recebiam hemodiálise, de ambos os sexos (35 homens e 35 mulheres), com idades variando entre 17 e 60 anos. Os dados foram coletados através da aplicação de três questionários: o primeiro estruturado para a caracterização de dados sócio-demográficos, o segundo para a auto-avaliação do Funcionamento Ocupacional (SAOF) e o terceiro para a Avaliação de Qualidade de Vida da Organização Mundial da Saúde (WHOQOL-bref). Os instrumentos foram úteis e de importância para avaliar a qualidade de vida e o desempenho ocupacional dessas pessoas: observou-se na aplicação do SAOF que, embora a predominância dos resultados possa ser considerada satisfatória, a área com maior escolha da alternativa “necessidade de melhora” foi a de hábitos e valores (20% e 20,5%, respectivamente). Apesar da porcentagem não ser muito alta, é aqui que as dificuldades com relação à organização do cotidiano são mais evidentes, principalmente frente às mudanças de rotinas e expectativas quanto ao futuro. Na aplicação do WHOQOL-bref, constatou-se que os pacientes que se auto-avaliaram com menor média de qualidade de vida são os que têm cônjuge (54.6%), os que estão há mais de um ano em hemodiálise (52.6%), e os pacientes do sexo masculino (58.6%). A variável “anos de escolaridade” mostrou que as pessoas com menos instrução apresentam menor avaliação de sua qualidade de vida nos domínios Físicos (51.1%), Social (61.0%) e Meio Ambiente (61.1%). Entende-se, portanto, que a Terapia Ocupacional apresenta recursos instrumentais para a reestruturação do cotidiano desses pacientes, podendo constituir-se em valiosa contribuição para a assistência. / The chronic renal failure (CRF) is considered a great problem of public health due to the high rates of morbidity and mortality. Persons with chronic renal insufficients (CRIs) present various difficulties in their daily life such as constant visits to the doctor, hemodialysis sessions and food restrictions disorganizing therefore their daily life and quality of life. This research has the aim to evaluate the perception of persons with CRF about the daily life in relation to their occupational functioning in two public health services in Ribeirão Preto and evaluate the perception of quality of life within the following domains: Physical, Psychological, Social and Environmental. The sample studied was composed of 70 adult individuals undergoing hemodialysis, of both genders (35 men and 35 women) in ages varying between 17 and 60. The data was gathered through the application of three questionnaires: one was structured for the characterization of social-demographic data, the second for Self Assessment of Occupational Functioning (SAOF) and the third for evaluation of the Quality of Life according to the World Health Organization’s Quality of Life Evaluation Instrument (WHOQOL-bref). The instruments were useful and of importance to evaluate the quality of life and the occupational performance of those persons. It was noticed from the SAOF that although the most of the results might be considered satisfactory, the area with the greatest choice of the alternative “necessity of improvement” was the one of habits and values (20% and 20.5% respectively). Despite the percentage not being high, there were the difficulties regarding the daily life mainly in face of changes in routine as well as expectations regarding the future. From the application of the WHOQOL-bref, it could be noticed that the patients who self-evaluated themselves with the lowest average of quality of life are the ones who have spouses (54.6%), the ones who have been undergoing hemodialysis for over a year (52.6%) and the male patients (58.6%). The variable years of schooling demonstrated that the persons with less education present lower evaluation of their quality of life in following domains: Physical (51,1%), Social (61,0%) and Environment (61.1%). It is understood, therefore, that the Occupational Therapy presents instrumental resources for the reorganization of those patients’ daily life, constituting a valuable contribution for assistance.

A doença renal crônica (DRC) atinge cada vez mais uma parcela significativa da população, e entre os pacientes adultos as doenças metabólicas são as principais causas, respondendo por aproximadamente 70% dos pacientes em tratamento dialítico. Porém, há poucas publicações sobre levantamento epidemiológico de DRC em crianças disponíveis na literatura. O objetivo deste trabalho foi descrever o perfil clínico-epidemiológico das crianças e adolescentes com DRC atendidos pelo Serviço de Nefrologia Pediátrica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), contemplando 22 anos de experiência. Para tanto, foram revisados 121 prontuários e coletadas 21 variáveis de cada um deles. Do total, 58,7% eram do sexo masculino, e 41,3% do sexo feminino. A média de idade de entrada foi 59,1 meses. Os pacientes menores que 5 anos somaram 62,5% do total. Os pacientes procedentes de Ribeirão Preto ou de cidades com até 300km de distância somaram 63% dos casos. As causas básicas de DRC foram: uropatias (48,8%), glomerulopatias (20,7%), displasias renais congênitas ou policísticas (7,4%), vasculopatias (6,6%), tubulopatias (2,5%), outras causas (7,4%) e causa indeterminada (6,6%). Das glomerulopatias, os tipos histológicos encontrados foram a glomeruloesclerose segmentar e focal (GESF) (25,0%), a proliferação mesangial difusa (PMD) (20,8%), a glomerulonefrite (GN) avançada (12,5%), a glomerulonefrite crescêntica (GNC) (8,3%) e a Síndrome de Alport (8,3%), sendo que 4,2% dos casos foram considerados indeterminados e 20,8% dos pacientes não foram submetidos a biópsia. A grande maioria dos pacientes (59,8%) tinha estatura abaixo do 5º percentil para idade e sexo no momento do diagnóstico. O tempo de seguimento clínico variou de 2 a 263 meses, com média de 67,5 meses. A creatinina sérica no momento do diagnóstico variou de 0,5 a 12,1 mg/dL, com média igual a 3,0 mg/dL. A média de RFG calculado pela Fórmula de Schwartz no momento do diagnóstico foi 27,4 mL/min/1,73m2. A maioria dos casos (62,3%) chegou ao serviço em DRC estágios 4, 5 ou em diálise. Hipertensão arterial (HA) foi detectada em 56,2% dos pacientes em algum momento do curso clínico. Acidose metabólica foi detectada em 53,7% dos pacientes no momento do diagnóstico. Do total de pacientes, 38,0% foram submetidos a tratamento dialítico, sendo as modalidades peritoneais preferidas em 80,4% dos casos. Transplante renal foi realizado em 24,8% dos pacientes, sendo as proporções de doador vivo relacionado (DVR) e doador cadáver (DC) semelhantes. A proporção de óbitos no período do estudo foi 22,3%. Dos demais pacientes, 17,4% foram transferidos para seguimento pela Clínica Médica do HCFMRP-USP, e 38,8% dos casos ainda estavam em seguimento pela Nefrologia Pediátrica em dezembro de 2005. Concluímos que a população estudada mostrou características clínico-epidemiológicas semelhantes às publicações nacionais e internacionais consultadas. / The prevalence of chronic renal failure (CRF) increases every day, and among adult patients, the principal causes are metabolic diseases, responsible to almost 70% of patients who are under dialysis. However, there are few studies regarding epidemiologic data of CRF in children. The objective of this study was to describe clinical and epidemiological profiles of children and adolescents with CRF who have been followed up by the Pediatric Nephrology Team of the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), along 22 years of experience. Data of 121 medical records have been reviewed, and 21 variables have been collected from each of them. From the total of the patients, 58.7% were male and 41.3% were female. The average of age of registration was 59.1 months. Patients who were younger than 5 years summed 62.5% of all. From the total of patients, 63% lived in Ribeirão Preto or in cities until 300km far. The primary renal diseases described were: uropathies (48.8%), glomerulopathies (20.7%), congenital or polycystic renal dysplasia (7.4%), vasculopathies (6.6%), tubular diseases (2.5%), miscellaneous (7.4%) and unknown causes (6.6%). Among the glomerulopathies group, the histological patterns described were: Focal Segmental Glomerulosclerosis (25.0%), Diffuse Mesangial Proliferation (20.8%), Advanced Glomerulonephritis (12.5%), Crescentic Glomerulonephritis (8.3%) and the Alport Syndrome (8.3%). From total of biopsies, 4.2% were not able to define a diagnosis, and 20.8% of the glomerulopathies\' patients were not undergone renal biopsy. From the total, 59.8% of the patients were under the 5o percentile of the NCHS curve in their registration, related to their height. The follow up showed a variation of 2 to 263 months, which average was 67.5 months. The blood creatinine level showed a variation of 0.5 to 12.1 mg/dL, which average was 3.0 mg/dL. The average Glomerular Filtration Rate, estimated by the Schwartz\'s formula, was 27.4 mL/min/1,73m2. At the onset, 62.3% of the patients were classified at the stages 4, 5 or under dialysis. Hypertension was described in 56.2% of the patients at any time of the follow up. Metabolic acidosis was described in 53.7% of the patients at the onset. Patients who underwent dialysis summed 38.0%, and the peritoneal modalities performed 80.4% of all cases. Renal transplantation was performed in 24.8% of the patients, with similar proportions of live-related and cadaveric donors. The proportion of deaths during the 22 years of study was 22.3% of all. The rest of them were delivered to the Clinical Team of the HCFMRP-USP (17.4%) or still had been followed up by the Pediatric Nephrology Team by December 2005 (38.8%). We concluded that the population described had similar clinical and epidemiological characteristics to the other Brazilian and international data available.

Submitted by Rosina Valeria Lanzellotti Mattiussi Teixeira (rosina.teixeira@unisantos.br) on 2016-08-11T18:51:28Z No. of bitstreams: 1 Polianne Brito.pdf: 1107426 bytes, checksum: 5c3c4fadb4db605f31557ca7bf8c3609 (MD5) / Made available in DSpace on 2016-08-11T18:51:29Z (GMT). No. of bitstreams: 1 Polianne Brito.pdf: 1107426 bytes, checksum: 5c3c4fadb4db605f31557ca7bf8c3609 (MD5) Previous issue date: 2016-04-14 / Introduction: Chronic renal disease is considered nowadays, as one of the main public health problems in the world, being an important cause of morbidity and mortality. The diagnosis leads to the need for continuous treatment, submitting the patient to a constant coming and going to the hospital, and this impacting and wearing routine, many times moves the individual partially or totally away from work activities, bringing consequences with the family income, limiting their lives in many aspects, submitting the individual to the dependence of the family or health service. Objective: To analyze from the perspective of the patient with chronic renal disease, the repercussions of the disease and strategies to confront the treatment in a hemodialysis unit in the municipality of Patos-PB. Methodology: This was a qualitative study with chronic renal patients who were in hemodialysis treatment in a private clinic in the municipality of Patos-PB, where SUS (which is a Unified Health System) is the financial transfer so that the carriers are not charged for the treatment. The data was collected by means of a semi-structured interview, in the pre-dialysis period. Preliminary information regarding the study was provided, the signature of the informed consent form was requested and then the interview was recorded with the consent of the participants and fictitious names were used. After the collection, the interviews were transcribed and categories and sub-categories were established for Bardin¿s qualitative content analysis. Results: 06 chronic renal disease patients were interviewed; where, 03 were men and 03 were women in hemodialysis treatment, ageing between 20 to 55 years. The majority of the participants were single and catholic, with educational levels varying from illiterate to complete secondary level, none of them were working at the time of the interviews and 05 of them received a health care benefit of a minimum salary. All the interviewed were referred from a public hospital service, with immediate access to the hemodialysis treatment. Changes occurred in the social and daily life, work, feeding and leisure of all the participants. Alterations in general health due to the treatment were also reported by the majority of the clients. The main confrontation strategies found to deal with the disease and the treatment were the support of the family, partners, and religion. The main difficulties to start and maintain the hemodialysis treatment were the lack of knowledge about the disease and the treatment and the lack of transportation, in order to dislocate the patients to the hemodialysis service .The friendly reception of the multi-professional team, faith and the support of the family and other clinically well patients, were pointed out as being facilitator factors to start and maintain the treatment. Conclusion: the study revealed that the chronic renal disease causes great repercussions in the life of the hemodialysis patients, altering their lifestyle and daily routine; the support of the family, religion and the multi-professional team represented the main confronting strategies for the adhesion to and maintenance of the treatment of the interviewed patients. / Introdução: A doença renal crônica é considerada hoje, um dos principais problemas de saúde pública no mundo, sendo importante causa de morbidade e mortalidade. O diagnóstico conduz à necessidade de um tratamento continuado, submetendo o paciente a idas e vindas ao hospital e essa rotina impactante e desgastante muitas vezes afasta o indivíduo parcial ou totalmente das atividades laborais, com consequências na renda familiar, limitando sua vida em vários aspectos, submetendo-o à dependência da família e de um serviço de saúde. Objetivo: Analisar a partir da perspectiva do portador de doença renal crônica as repercussões da doença e estratégias de enfrentamento para seu tratamento em uma unidade de hemodiálise no município de Patos-PB. Metodologia: tratou-se de um estudo qualitativo com doentes renais crônicos e em tratamento de hemodiálise em uma clínica privada do município de Patos-PB, onde o SUS faz o repasse financeiro para que os portadores realizem sem custo próprio. Os dados foram coletados por meio de entrevista semiestruturada, no período pré-dialítico, foram fornecidas informações prévias sobre o estudo e solicitada a assinatura do termo de consentimento livre e esclarecido e a entrevista foi gravada com consentimento dos participantes e uso de nomes fictícios. Após a coleta, as entrevistas foram transcritas e estabelecidas categorias e subcategorias para análise qualitativa de conteúdo de Bardin. Resultados: foram entrevistados 06 portadores de doença renal crônica, sendo 03 homens e 03 mulheres em tratamento de hemodiálise, com idade entre 20 e 55 anos. A maioria dos participantes era solteira e católica, com escolaridade variando de não alfabetizado a ensino médio completo, nenhum trabalhava na ocasião das entrevistas e 05 recebiam auxílio-doença de um salário mínimo. Todos os entrevistados foram encaminhados de serviço público hospitalar, com acesso imediato ao tratamento de hemodiálise. Ocorreram mudanças na vida social, no cotidiano, trabalho, alimentação e lazer de todos os participantes. Alterações na saúde geral em virtude do tratamento também foi relatada pela maioria dos clientes. As principais estratégias de enfrentamento encontradas para lidar com a doença e tratamento foram apoio familiar, do companheiro e religioso. As principais dificuldades para iniciar e manter o tratamento de hemodiálise foram a falta de conhecimento sobre a patologia e o tratamento e a falta de transporte para se deslocarem até o serviço de hemodiálise. O acolhimento da equipe multiprofissional, a fé, o apoio familiar e a convivência com outros pacientes clinicamente bem, foram apontados como facilitadores para iniciar e manter o tratamento. Conclusão: o estudo revelou que a doença renal crônica causa grandes repercussões na vida dos doentes em hemodiálise, alterando seu estilo de vida e rotina diária. O apoio familiar, a religião e a equipe multiprofissional representaram as principais estratégias de enfrentamento para a adesão e manutenção do tratamento dos entrevistados

<p>Cardiovascular disease (CVD) is the major cause of death in patients with chronic renal failure (CRF). Endothelial function and oxidative stress (OS) have previously been shown to be important in the pathogenesis of CVD. In this thesis, the endothelium-dependent vasodilatation (EDV) and OS were investigated in the patients with CRF. Also the influence of L-arginine, erythropoietin and diclofenac on EDV were evaluated in patients with CRF. </p><p>Patients with CRF were found to be characterized by a defect EDV even after correction for traditional cardiovascular risk factors. This impairment was related to the degree of renal failure. </p><p>Measurement of OS markers in CRF patients demonstrated that these patients were in a state of OS compared to healthy controls. The most informative indices to evaluate the degree of OS in CRF were: oxidized glutathione (GSSG) level, ratio between oxidized and reduced glutathione (GSSG/GSH ratio), lag phase of lipoprotein fraction (LPF) and baseline diene conjugation level of LPF. </p><p>Simultaneously investigated OS markers and EDV demonstrated a relationship between OS and EDV in patients with CRF. EDV was positively correlated with total antioxidative activity, reduced glutathione (GSH) and lag phase of LDL. </p><p>Local infusion of L-arginine as a substrate for nitric oxide synthesis and diclofenac as an inhibitor of cyclooxygenase-derived vasoconstrictive agents augmented EDV in patients CRF. In contrast, the erythopoietin treatment (both acute and long-term) impaired EDV in CRF patients. </p><p>In conclusion, patients with CRF have increased levels of OS markers and impaired endothelial vasodilatory function. These factors may be important with respect to the high morbidity and mortality of CVD found in patients with CRF. One possible mechanism to reduce CVD in patients with CRF is to improve endothelial function and eliminate OS. Locally administrated L-arginine and diclofenae improved EDV but erythropoietin administration impaired EDV in patients with CRF. </p>

Cardiovascular disease (CVD) is the major cause of death in patients with chronic renal failure (CRF). Endothelial function and oxidative stress (OS) have previously been shown to be important in the pathogenesis of CVD. In this thesis, the endothelium-dependent vasodilatation (EDV) and OS were investigated in the patients with CRF. Also the influence of L-arginine, erythropoietin and diclofenac on EDV were evaluated in patients with CRF. Patients with CRF were found to be characterized by a defect EDV even after correction for traditional cardiovascular risk factors. This impairment was related to the degree of renal failure. Measurement of OS markers in CRF patients demonstrated that these patients were in a state of OS compared to healthy controls. The most informative indices to evaluate the degree of OS in CRF were: oxidized glutathione (GSSG) level, ratio between oxidized and reduced glutathione (GSSG/GSH ratio), lag phase of lipoprotein fraction (LPF) and baseline diene conjugation level of LPF. Simultaneously investigated OS markers and EDV demonstrated a relationship between OS and EDV in patients with CRF. EDV was positively correlated with total antioxidative activity, reduced glutathione (GSH) and lag phase of LDL. Local infusion of L-arginine as a substrate for nitric oxide synthesis and diclofenac as an inhibitor of cyclooxygenase-derived vasoconstrictive agents augmented EDV in patients CRF. In contrast, the erythopoietin treatment (both acute and long-term) impaired EDV in CRF patients. In conclusion, patients with CRF have increased levels of OS markers and impaired endothelial vasodilatory function. These factors may be important with respect to the high morbidity and mortality of CVD found in patients with CRF. One possible mechanism to reduce CVD in patients with CRF is to improve endothelial function and eliminate OS. Locally administrated L-arginine and diclofenae improved EDV but erythropoietin administration impaired EDV in patients with CRF.

Activated coagulation Factor XII (FXIIa) elevates blood pressure (BP) acutely by stimulating adrenomedullary catecholamine (CA) release in Brown Norway (BN) bioassay rats. These effects are absent in kininogen-deficient BN Katholiek (BNK) bioassay rats, indicating that these FXIIa-induced responses require an intact kallikrein-kinin system (KKS). In three hypertensive anephric pediatric patients, ΔFXIIa concentrations tracked peri-dialytic ΔBP. We hypothesized that FXIIa exerts a vasoconstrictor pro-hypertensive action, via the KKS, particularly evident in chronic renal failure (CRF). In CRF patients (n=11) receiving conventional hemodialysis, mean plasma FXIIa concentrations were 3-fold (p<0.05) greater than in healthy controls. Although conversion from conventional to nocturnal hemodialysis did not change mean FXIIa concentrations there was intra-session variation within individuals, such that ΔFXIIa concentrations correlated with changes in mean arterial pressure (MAP, r=0.66, p=0.026) and total peripheral resistance (TPR, r=0.75, p=0.007). In normotensive BN rats, FXIIa infusion (85 ng/min/kg for 60 mins) increased MAP (10±1 mmHg), TPR (0.5±0.1 Units), and CA, whilst left-ventricular end-diastolic volume (LVEDV) and heart rate decreased (all p<0.05). After adrenalectomy, FXIIa infusion decreased MAP (5±1 mmHg), did not raise CA or induce sustained vasoconstriction, and caused a greater fall in LVEDV (all p<0.05). In the 5/6 nephrectomized (NX) rodent CRF model, MAP and TPR were significantly greater in BN NX (n=16) than in BNK NX (n=15) (147±4 vs. 133±2 mmHg, 2.8±0.2 vs. 2.3±0.2 Units; all p<0.05). Plasma FXIIa measured using our semi-quantitive ELISA was 3-fold higher in both BN NX and BNK NX than in controls (p<0.01), but only correlated with MAP (r=0.48, p=0.01) in the BN NX. Plasma CA were elevated in the BN NX (p<0.05) but not in BNK NX. Infusion of a specific FXIIa inhibitor into BN NX decreased MAP (-12 mmHg) and TPR (-0.5 Units) proportionally to baseline FXIIa (ΔMAP: r=-0.72, p=0.002; ΔTPR: r=-0.57, p=0.021), and plasma CA fell by 40-67% (all p<0.05). No such changes occurred in the BNK NX. In summary, a significant component of the hypertension of CRF can be attributed to FXIIa-induced vasoconstriction mediated via the KKS and stimulated CA release. In normal rats, FXIIa appears also to directly or indirectly decrease preload and heart rate.

Activated coagulation Factor XII (FXIIa) elevates blood pressure (BP) acutely by stimulating adrenomedullary catecholamine (CA) release in Brown Norway (BN) bioassay rats. These effects are absent in kininogen-deficient BN Katholiek (BNK) bioassay rats, indicating that these FXIIa-induced responses require an intact kallikrein-kinin system (KKS). In three hypertensive anephric pediatric patients, ΔFXIIa concentrations tracked peri-dialytic ΔBP. We hypothesized that FXIIa exerts a vasoconstrictor pro-hypertensive action, via the KKS, particularly evident in chronic renal failure (CRF). In CRF patients (n=11) receiving conventional hemodialysis, mean plasma FXIIa concentrations were 3-fold (p<0.05) greater than in healthy controls. Although conversion from conventional to nocturnal hemodialysis did not change mean FXIIa concentrations there was intra-session variation within individuals, such that ΔFXIIa concentrations correlated with changes in mean arterial pressure (MAP, r=0.66, p=0.026) and total peripheral resistance (TPR, r=0.75, p=0.007). In normotensive BN rats, FXIIa infusion (85 ng/min/kg for 60 mins) increased MAP (10±1 mmHg), TPR (0.5±0.1 Units), and CA, whilst left-ventricular end-diastolic volume (LVEDV) and heart rate decreased (all p<0.05). After adrenalectomy, FXIIa infusion decreased MAP (5±1 mmHg), did not raise CA or induce sustained vasoconstriction, and caused a greater fall in LVEDV (all p<0.05). In the 5/6 nephrectomized (NX) rodent CRF model, MAP and TPR were significantly greater in BN NX (n=16) than in BNK NX (n=15) (147±4 vs. 133±2 mmHg, 2.8±0.2 vs. 2.3±0.2 Units; all p<0.05). Plasma FXIIa measured using our semi-quantitive ELISA was 3-fold higher in both BN NX and BNK NX than in controls (p<0.01), but only correlated with MAP (r=0.48, p=0.01) in the BN NX. Plasma CA were elevated in the BN NX (p<0.05) but not in BNK NX. Infusion of a specific FXIIa inhibitor into BN NX decreased MAP (-12 mmHg) and TPR (-0.5 Units) proportionally to baseline FXIIa (ΔMAP: r=-0.72, p=0.002; ΔTPR: r=-0.57, p=0.021), and plasma CA fell by 40-67% (all p<0.05). No such changes occurred in the BNK NX. In summary, a significant component of the hypertension of CRF can be attributed to FXIIa-induced vasoconstriction mediated via the KKS and stimulated CA release. In normal rats, FXIIa appears also to directly or indirectly decrease preload and heart rate.

The Severity of Renal Disease Scale (SORDS) was developed to provide a single score reflecting disease severity of renal patients independent of confounding psychosocial influences. This study examined SORDS' reliability and validity and its relevance as a research tool assessing the psychological effect of illness severity. Data was collected from 127 renal patients (predialysis, HD, CAPD). SORDS was compared with the Endstage Renal Disease Severity Index (ESRD-SI), the SF-36, the Beck Depression Inventory - 2nd Edition and a subset of BDI-II items reflecting cognitive features only at differing stages of renal disease and time on dialysis. SORDS and ESRD-SI data from twenty-two CAPD patients was included in reliability analyses. SORDS reliability estimates were low suggesting that the use of SORDS with medical chart data at this time is problematic. SORDS should be used only by medical practitioners who are aware of patients' standing on SORDS variables. There was however strong support for SORDS' validity. Validity was demonstrated by correlations between SORDS and the ESRD-SI. Compared to the ESRD-SI, SORDS was better able to discriminate between dialysis and pre-dialysis patients. SORDS and ESRD-SI scores were related to self-perceptions of decreased health status on the SF-36 independent of dialysis duration and age. SORDS utility in psychosocial research with renal patients was demonstrated by a finding that disease severity differentially impacts levels of depression for HD versus CAPD patients independent of age or dialysis duration. At the lowest level of illness severity as assessed by SORDS, CAPD patients scored in the moderate range of depression and were significantly more depressed than HD patients. Using the same analyses but with the ESRD-SI, no differences in level of depression were detected. These results imply a relationship between adjustment to treatment and illness severity. It is concluded that SORDS is a valid index of renal disease severity and that illness severity as assessed by SORDS may have an important role as a moderator variable in psychosocial research with renal patients. These results may have important implications for treatment assignment and psychosocial assessment and intervention of renal patients and their families.