Orientadora: Marileda Bonafim Carvalho / Banca: Flávio Ruas de Moraes / Banca: Sandra Regina Ribeiro da Silva / Resumo: Os rins desempenham papel fundamental no balanço de água e eletrólitos. Na doença renal crônica (DRC) a manutenção da homeostase de água e sódio é o primeiro problema a ser contornado pelo organismo e com o agravamento das lesões renais surgem outros problemas graves relacionados à homeostase de cálcio e fósforo. O presente estudo tem por escopo avaliar a excreção renal de cálcio, fósforo, sódio e potássio, e o perfil sérico destes eletrólitos em cães normais e em cães com DRC naturalmente adquirida. Foram avaliados três grupos de cães adultos, machos ou fêmeas, de raças variadas. Animais normais compuseram o grupo controle (G1) e os cães com DRC foram distribuídos em dois grupos de acordo com os estágios de comprometimento da função renal (G2 e G3, respectivamente, estágios 1-2 e estágios 3-4, descritos pela IRIS 2006 staging CKD). Os cães do G3 apresentaram aumento das concentrações séricas de cálcio ionizado e fósforo, além de diminuição da concentração sérica de sódio. Quanto à excreção renal dos eletrólitos analisados, os animais dos grupos G1 e G2 apresentaram diminuição de carga filtrada e aumento de excreção fracionada, mas as excreções urinárias não variaram significativamente. Os resultados são indicativos de que os rins de cães com DRC podem manter a excreção urinária dos eletrólitos em valores semelhantes aos dos normais. O mecanismo envolve aumento da excreção fracionada à medida em que haja diminuição da filtração glomerular. Esse processo de compensação, entretanto, pode perder a eficiência nos estágios mais avançados da enfermidade no que se refere à manutenção das concentrações séricas de fósforo e sódio. / Abstract: The kidneys play a fundamental role in the balance of water and electrolytes. In chronic kidney disease (CKD), the first problem to be solved by the organism is to maintain water and sodium homeostasis and, with the worsening of the renal injuries, other severe problems related to the calcium and phosphorus homeostasis emerge. The present study has as a purpose to evaluate the renal excretion and serum profile of calcium, phosphorus, sodium and potassium in healthy dogs and in dogs with naturally acquired CKD. Three groups of adult male and female dogs of varied breeds were evaluated. Normal animals were in the control group (G1) and the CKD dogs were distributed in two groups in accordance with the stage of renal function impairment (G2 e G3, respectively, stages 1-2 and stages 3-4, proposed by IRIS 2006 staging CKD). The G3 dogs showed increased serum levels of ionized calcium and phosphorus, in addition to the reduction of sodium level. Regarding the renal excretion of the analyzed electrolytes, G1 and G2 groups of animals showed a decrease of filtered load and increase of fractional excretion, yet there were no significant variations on the urinary excretions. The results suggest that the kidneys of the CKD dogs can maintain similar values of electrolytes urinary excretion as the normal dogs do. The mechanism involves an increase of fractional excretion while glomerular filtration decreases. This compensation process, however, can lose its efficiency in the later stages of the disease, in relation to the maintenance of phosphorus and sodium serum levels. / Mestre

Introdução: Nefrectomia radical tem sido o tratamento mais utilizado para o carcinoma de células renais. Atualmente, a preservação da função renal do paciente após a cirurgia tem sido um fator de preocupação, já que a sobrevida desses pacientes vem aumentando, assim como a detecção de lesões pequenas, incidentais e assintomáticas. Vários estudos tentam identificar fatores preditores da função renal pós-operatória, no entanto poucos avaliam os achados não-neoplásicos do parênquima renal. Objetivos: O estudo tem como objetivos: 1) descrever as alterações nãoneoplásicas do parênquima renal encontradas nos espécimes de nefrectomia; 2) correlacionar os achados com a função renal pós-operatória dos pacientes e 3) correlacionar essas alterações com o laudo anatomopatológico original. Materiais e métodos: Foram revisados 262 exames anatomopatológicos de espécimes de nefrectomias realizadas em pacientes adultos por neoplasias primárias renais no Hospital de Clínicas de Porto Alegre durante o período de 2005 a 2009. O laudo anatomopatológico e o prontuário eletrônico desses pacientes foram revisados de forma cegada. Um patologista renal realizou a revisão de todas lâminas histopatológicas do estudo. Posteriormente, nos pacientes com dados clínicos e laboratoriais disponíveis, foram correlacionadas as alterações encontradas com a variação da função renal dos mesmos (creatinina sérica e o cálculo da fórmula de Cockroft-Gault, antes e cerca de seis meses após a cirurgia). Resultados: Na amostra inicial, houve uma predominância de pacientes masculinos (57,6%), de raça branca (88%), com uma idade média de 60 anos. Cerca de 76% foram submetidos a nefrectomias radicais e 70% dos pacientes apresentavam estágio tumoral T1 e T2, sendo o tamanho tumoral médio de 6,0 cm e o tipo histológico mais frequente o de células claras (67%). Hipertensão, tabagismo, diabetes melitus e obesidade foram encontrados em, respectivamente, 53%, 32%, 19% e 9% dos pacientes. Apenas 10% dos casos cujas lâminas foram revisadas não apresentavam alterações parenquimatosas. As alterações vasculares foram as mais frequentes, e destas a aterosclerose a mais comum. Esclerose diabética estava presente em quatro pacientes. As variações das estimativas da função renal entre o período pré e pós-operatório não apresentaram diferença significativa entre os grupos de pacientes com e sem alterações parenquimatosas. Foi encontrada diferença significativa entre os valores da creatinina pré e pós-operatória em ambos os grupos e dos valores da fórmula de Cockroft-Gault no grupo com alterações (p<0,001). Em apenas 50 laudos anatomopatológicos originais, haviam sido descritas alterações parenquimatosas. Conclusões: O estudo mostrou que os patologistas gerais se mostram despreparados ou não conscientes acerca da recente inclusão da descrição dos achados não-neoplásicos nos checklists dos laudos anatomopatológicos de neoplasia renais primárias, portanto acreditamos que a mesma deva ser encorajada. Além disso, investigações futuras prospectivas que acompanhem os pacientes por um longo período e utilizem formas mais acuradas de estimativa da função renal devem ser conduzidas para que o real impacto desses achados na função renal dos pacientes após a cirurgia seja bem estudada. / Background: Radical nephrectomy has been the most common treatment for renal cell carcinoma. Besides, the preservation of the renal function after surgery has been a worrisome factor. Patient’s survival rates are increasing, along with the detection of small, incidental and asymptomatic lesions. Several studies have attempted to identify predictors of postoperative renal function, yet few assessed the findings of non-neoplastic renal parenchyma. Objectives: The study aims at: 1) describing the findings in non-neoplastic renal parenchyma found in nephrectomy specimens, 2) correlating these findings with postoperative renal function and 3) correlating these changes with the original pathology report. Materials and Methods: The specimens of two-hundred and sixty-two nephrectomies performed in adult patients for primary renal neoplasms at Hospital de Clinicas de Porto Alegre during the period of 2005 to 2009 were reviewed. The pathology report and electronic medical records of these patients were reviewed in a blinded fashion. A renal pathologist performed the histopathological review of the renal parenchyma slides. After that, in patients with clinical and laboratory data available, the alterations found were correlated with the renal function. Results: There was a predominance of male patients (57.6%) and caucasians (88%), with a mean age of 60 years. About 76% underwent radical nephrectomy and 70% of patients had tumor stage T1 or T2. The average tumor size was 6.0 cm and the most common histological type was clear renal cell carcinoma (67%). Hypertension, smoking, diabetes mellitus and obesity were found in respectively 53%, 32%, 19% and 9% of the patients. Only 10% of the cases whose slides were reviewed had no abnormalities. The vascular changes were the most frequent, and of these the most common was atherosclerosis. Diabetic sclerosis was present in four patients. Renal function variations between the pre and postoperative estimates showed no significant difference between the groups of patients with and without parenchymal abnormalities. Significant difference was found between the pre and postoperative creatinine in both groups and the Cockroft-Gault formula in the group with changes (p<0.001). Only 50 original pathology reports described non-neoplastic abnormalities. Conclusions: The study showed that general pathologists are unaware of the recent inclusion of the non-neoplastic findings in the primary renal neoplasm’s protocols. Therefore, we believe that the evaluation of these findings should be encouraged. In addition, future prospective investigations monitoring patients over a long period of time and using more accurate ways of estimating renal function on postoperative period should be performed.

Introdução: Nefrectomia radical tem sido o tratamento mais utilizado para o carcinoma de células renais. Atualmente, a preservação da função renal do paciente após a cirurgia tem sido um fator de preocupação, já que a sobrevida desses pacientes vem aumentando, assim como a detecção de lesões pequenas, incidentais e assintomáticas. Vários estudos tentam identificar fatores preditores da função renal pós-operatória, no entanto poucos avaliam os achados não-neoplásicos do parênquima renal. Objetivos: O estudo tem como objetivos: 1) descrever as alterações nãoneoplásicas do parênquima renal encontradas nos espécimes de nefrectomia; 2) correlacionar os achados com a função renal pós-operatória dos pacientes e 3) correlacionar essas alterações com o laudo anatomopatológico original. Materiais e métodos: Foram revisados 262 exames anatomopatológicos de espécimes de nefrectomias realizadas em pacientes adultos por neoplasias primárias renais no Hospital de Clínicas de Porto Alegre durante o período de 2005 a 2009. O laudo anatomopatológico e o prontuário eletrônico desses pacientes foram revisados de forma cegada. Um patologista renal realizou a revisão de todas lâminas histopatológicas do estudo. Posteriormente, nos pacientes com dados clínicos e laboratoriais disponíveis, foram correlacionadas as alterações encontradas com a variação da função renal dos mesmos (creatinina sérica e o cálculo da fórmula de Cockroft-Gault, antes e cerca de seis meses após a cirurgia). Resultados: Na amostra inicial, houve uma predominância de pacientes masculinos (57,6%), de raça branca (88%), com uma idade média de 60 anos. Cerca de 76% foram submetidos a nefrectomias radicais e 70% dos pacientes apresentavam estágio tumoral T1 e T2, sendo o tamanho tumoral médio de 6,0 cm e o tipo histológico mais frequente o de células claras (67%). Hipertensão, tabagismo, diabetes melitus e obesidade foram encontrados em, respectivamente, 53%, 32%, 19% e 9% dos pacientes. Apenas 10% dos casos cujas lâminas foram revisadas não apresentavam alterações parenquimatosas. As alterações vasculares foram as mais frequentes, e destas a aterosclerose a mais comum. Esclerose diabética estava presente em quatro pacientes. As variações das estimativas da função renal entre o período pré e pós-operatório não apresentaram diferença significativa entre os grupos de pacientes com e sem alterações parenquimatosas. Foi encontrada diferença significativa entre os valores da creatinina pré e pós-operatória em ambos os grupos e dos valores da fórmula de Cockroft-Gault no grupo com alterações (p<0,001). Em apenas 50 laudos anatomopatológicos originais, haviam sido descritas alterações parenquimatosas. Conclusões: O estudo mostrou que os patologistas gerais se mostram despreparados ou não conscientes acerca da recente inclusão da descrição dos achados não-neoplásicos nos checklists dos laudos anatomopatológicos de neoplasia renais primárias, portanto acreditamos que a mesma deva ser encorajada. Além disso, investigações futuras prospectivas que acompanhem os pacientes por um longo período e utilizem formas mais acuradas de estimativa da função renal devem ser conduzidas para que o real impacto desses achados na função renal dos pacientes após a cirurgia seja bem estudada. / Background: Radical nephrectomy has been the most common treatment for renal cell carcinoma. Besides, the preservation of the renal function after surgery has been a worrisome factor. Patient’s survival rates are increasing, along with the detection of small, incidental and asymptomatic lesions. Several studies have attempted to identify predictors of postoperative renal function, yet few assessed the findings of non-neoplastic renal parenchyma. Objectives: The study aims at: 1) describing the findings in non-neoplastic renal parenchyma found in nephrectomy specimens, 2) correlating these findings with postoperative renal function and 3) correlating these changes with the original pathology report. Materials and Methods: The specimens of two-hundred and sixty-two nephrectomies performed in adult patients for primary renal neoplasms at Hospital de Clinicas de Porto Alegre during the period of 2005 to 2009 were reviewed. The pathology report and electronic medical records of these patients were reviewed in a blinded fashion. A renal pathologist performed the histopathological review of the renal parenchyma slides. After that, in patients with clinical and laboratory data available, the alterations found were correlated with the renal function. Results: There was a predominance of male patients (57.6%) and caucasians (88%), with a mean age of 60 years. About 76% underwent radical nephrectomy and 70% of patients had tumor stage T1 or T2. The average tumor size was 6.0 cm and the most common histological type was clear renal cell carcinoma (67%). Hypertension, smoking, diabetes mellitus and obesity were found in respectively 53%, 32%, 19% and 9% of the patients. Only 10% of the cases whose slides were reviewed had no abnormalities. The vascular changes were the most frequent, and of these the most common was atherosclerosis. Diabetic sclerosis was present in four patients. Renal function variations between the pre and postoperative estimates showed no significant difference between the groups of patients with and without parenchymal abnormalities. Significant difference was found between the pre and postoperative creatinine in both groups and the Cockroft-Gault formula in the group with changes (p<0.001). Only 50 original pathology reports described non-neoplastic abnormalities. Conclusions: The study showed that general pathologists are unaware of the recent inclusion of the non-neoplastic findings in the primary renal neoplasm’s protocols. Therefore, we believe that the evaluation of these findings should be encouraged. In addition, future prospective investigations monitoring patients over a long period of time and using more accurate ways of estimating renal function on postoperative period should be performed.

Durante a evolução da doença renal crônica (DRC) em cães, um dos mecanismos importantes envolvidos na autoperpetuação e progressão da lesão renal envolvem, teoricamente, o comprometimento inicial do glomérulo pelo mecanismo de hiperfiltração glomerular, e este processo pode acarretar no desenvolvimento de microalbuminúria ou de proteinúria pela presença de proteínas de alto peso molecular (albumina). Com o progredir da doença, as altas concentrações de proteína no filtrado glomerular pode também desencadear lesões tubulares e intersticiais, ocasionando a perda urinária também de proteínas de baixo peso molecular (PM) pelo comprometimento da reabsorção dessas proteínas pelos túbulos renais. Outras teorias de progressão da lesão renal também são suscitadas tais como o comprometimento inicial da porção túbulo-intersticial. Assim, espera- -se que durante a evolução da DRC, a avaliação das proteínas urinárias quanto à qualidade (determinação de albumina e os pesos moleculares) e a quantidade possam trazer informações relevantes sobre a velocidade de progressão e o local da lesão renal. O objetivo deste estudo foi de avaliar, sequencialmente, a albuminúria e a proteinúria (pelos métodos quantitativos e qualitativos - eletroforese de proteínas) dos cães com DRC nos estágios 1, 2 ou 3 ao longo do período de pelo menos 5 meses, e verificar a existência de alterações na intensidade ou no aparecimento de proteinúria e/ou albuminuria. Dezesseis cães (Grupo 1= 5 cães do estágio 1; Grupo 2= 5 cães do estágio 2 e Grupo 3= 6 cães do estágio 3), 9 fêmeas e 7 machos de raças variadas e idades entre 24 a 168 meses, foram acompanhados por 5 a 18 meses e os exames clínico e laboratorial realizados a cada 30 dias. Os cães dos Grupos 1 e 2 apresentaram bom controle clínico, entretanto o Grupo 3 apresentou evolução mais rápida da doença (3 cães vieram a óbito). No Grupo 1, o aumento da razão proteína:creatinina urinária (RPC; variação de 0,154 a 1,14) foi observada somente em um dos cães (no 1) e esta não era decorrente de albuminúria, mas sim da presença de proteínas de baixo peso molecular (lesão tubular) e também foi constatada diminuição progressiva da taxa de filtração glomerular pelo o aumento das concentrações de cistatina C sérica; os demais cães deste grupo apresentaram RPC e razão albumina:creatinina urinária (RAC) normais, entretanto com predomínio de proteínas de baixo peso molecular em 2 cães. No Grupo 2 fato semelhante também foi constatado, nos cães no 6 (inicialmente hipertenso) e 8 em que a RPC variou de 4,89 a 12,77 e 0,5 a 1,0, respectivamente; no cão no6 foi não foi detectada macroalbuminuria, mas somente microalbuminúria e com o predomínio de proteínas de baixo PM (lesão tubular), como também no cão no 8 (ausência de micro ou macroalbuminuria) em que houve o predomínio de 78 a 100% de proteínas de baixo PM e com 3 a 6 bandas. No Grupo 3, proteinúria foi constatada nos cães de no 11, 13 e 15 e a microalbuminúria somente no cão no11; o predomínio de proteínas de baixo PM foi observada nos cães no 11 e 13 e proteinúria mista no cão no 15. Assim, a avaliação sequencial ou seriada da proteinúria, pelo conjunto de informações obtido pela RPC, RAC e eletroforese de proteínas urinárias nos com cães com doença renal crônica, ao longo de um período, trouxe informações mais precisas acerca da qualidade das proteínas, identificando os segmentos do néfron que provavelmente foram comprometidos ao longo da evolução da doença. / During the course of chronic kidney disease (CKD) in dogs, one of the mechanisms involved in the autoperpetuation and progression of renal disease, in theory, is glomerular hyperfiltration, and this process may result in the development of microalbuminuria or proteinuria due to the presence of high molecular weight proteins (albumin). As the disease progresses, the presence of high concentrations of proteins in the glomerular filtrate may also cause the development of interstitial and tubular injuries, and in consequence the presence of low molecular weight proteins in urine as the impairment of tubular reabsorption mechanism of proteins is affected. Other theories of progression of renal injury are also raised such as the initial involvement of the tubulointerstitial segment. Thus, it is expected that during the course of CKD, the evaluation of the quality (determination of albumin and molecular weights) and quantity of urinary proteins may indicate relevant information about the location and rate of progression of renal injury. The objective of this study was to evaluate, longitudinally, albuminuria and proteinuria (by quantitative and qualitative methods - protein electrophoresis) of dogs with CKD in stages 1, 2 and 3 over the period of at least 5 months, and observe the changes in intensity or the appearance of proteinuria and / or albuminuria. Sixteen dogs (Group 1 = 5 dogs in stage 1, Group 2 = 5 dogs in stage 2 and Group 3 = 6 dogs in stage 3), 9 females and 7 males of various breeds and ages ranging from 24 to 168 months, were followed-up for 5-18 months and medical and laboratory monitoring data were recorded every 30 days. Dogs of Groups 1 and 2 showed good clinical control, however the Group 3 had a progressive deterioration of the disease (3 dogs died). In Group 1, the increase in urinary protein-to-creatinine ratio (UPC; ranging from 0.154 to 1.14) was observed in only one dog (no. 1) and albuminuria was not involved, however low molecular weights proteins (LMWP) were detected (tubular injury) and also the progressive decrease in glomerular filtration rate was noticed by the increase of serum concentrations of cystatin C; the remaining dogs in this group demonstrated normal UPC and UAC (urinary albumin-to-creatinine ratio), however the predominance of LMWP in 2 dogs was observed. In Group 2, similar findings were also noticed in CKD dogs no. 6 (initially hypertensive) and 8 , UPC ranged from 4.89 to 12.77 and 0.5 to 1.0, respectively; dog no. 6 demonstrated no macroalbuminuria but only microalbuminuria, and the predominance of LMWP (tubular injury) was observed as well as the dog no. 8 that had 78 to 100% of LMWP with 3 to 6 bands and no micro or macroalbuminuria was detected. Group 3 presented proteinuria in dogs no. 11, 13 and 15 and microalbuminuria was only observed in dog no. 11; the predominance of LMWP was noticed in dogs no.11 and 13, and mixed proteinuria in dog no. 15. Thus, the sequential or longitudinal study of proteinuria by means of several information obtained of UPC, UAC and urine protein electrophoresis in dogs with chronic kidney disease, followed-up over a period, could give more accurate information about the quality of proteins, allowing the possible identification of the segments of the nephron involved that could probably be affected throughout the course of the disease.

A doença renal crônica (DRC) tem sido considerada um problema de saúde pública mundial. Estima-se que cerca de 17% da população adulta dos EUA apresente algum grau de comprometimento da função renal. No Brasil, um estudo realizado na cidade de Bambuí - Minas Gerais detectou-se alteração da função renal variando de 0,48% a 8,19%, sendo mais frequente nos pacientes idosos. Os pacientes que evoluem para DRC terminal necessitam de algum tipo de terapia renal substitutiva (TRS), sendo as opções disponíveis: a hemodiálise (HD), a diálise peritoneal (DP) e o transplante renal (TX renal). No caso da DP, a membrana peritoneal realiza a função de filtrar o sangue do paciente, e esta é utilizada através da implantação de um cateter na cavidade abdominal. No Brasil, segundo dados do Censo Brasileiro de Diálise (2016) existem aproximadamente 122.825 pacientes em diálise, sendo 8,6% em DP. O objetivo do estudo foi analisar a evolução dos pacientes que foram admitidos na Unidade de Diálise do HCFMRP para submeterem-se à DP nos últimos 22 anos. Os dados foram coletados dos prontuários dos pacientes atendidos no período de 1993 a 2015, de onde foram extraídas variáveis demográficas, clínicas e laboratoriais. É um estudo de coorte retrospectiva de 199 prontuários de pacientes atendidos na Unidade de Diálise do HCFMRP-USP. Os resultados demonstram que a população do estudo é em sua maioria do sexo feminino, com média de idade 57 anos. Foi encontrada a mudança de TRS para a hemodiálise como desfecho clínico mais frequente, seguida por óbito. A etiologia da DRC mais frequente foi a hipertensão arterial sistêmica (HAS), seguida por Diabetes mellitus (DM) tipo 2. Houve associação com menor média de idade de entrada em programa (48 anos), desfecho clínico óbito e maior tempo de seguimento (10 anos) com o grupo de pacientes que entraram em programa de diálise em 1993 (p<0,05). Encontramos associação do uso de medicamentos (Cloridrato de Sevelamer e Análogos da vitamina D3 com níveis categorizados de paratormônio, cálcio total e fósforo (p<0,05). CONCLUSÃO: Os pacientes que entraram em programa no período de 1993-2000 apresentaram menor média de idade e maior tempo de acompanhamento quando comparados aos demais grupos. O desfecho clínico mais frequente foi a transferência para HD, tendo como causa principal a ocorrência de peritonites. / INTRODUCTION: Chronic kidney disease (CKD) has been considered a worldwide public health problem, as well as the progressive increase of the population in renal replacement therapy (TRS). With the technological advances accumulated, the survival of patients on dialysis has increased greatly. Peritoneal dialysis (PD) is considered a safe and effective method of SRT, a challenge for the binomial patienthealth team. OBJECTIVES: To analyze the main characteristics and outcomes of patients in a PD program. METHODS: This was a retrospective cohort study of 199 patients submitted to PD in the Dialysis Unit of the HCFMRP-USP from 1993 to 2015. The primary source of data was the individual medical records. The variables were classified as: demographic, clinical and laboratorial. Statistical analyzes were performed using the Chi-square test, ANOVA and Kruskal Wallis. RESULTS: The mean age of the patients was 57 years, with a predominance of females (51.5%); the most frequent clinical outcome was the change in HRT for hemodialysis (37.2%). Type 2 diabetes mellitus (DM) was the most common cause of CKD (31,7). There was an association between lower mean age of program entry, clinical outcome and longer follow-up (10 years) in the group of patients who entered the dialysis program in the period from 1993 to 2000 (p <0.05). There was an association between the use of medications (Sevelamer\'s Hydrochloride and vitamin D3 analogues) with categorized values of parathormone, total calcium and phosphorus (p <0.05). CONCLUSION: Patients who entered the program in 1993-2000 had a lower mean age and longer follow - up when compared to the other groups. The most frequent clinical outcome was the transfer to HD, the main cause being the occurrence of peritonitis.

Background: Diabetes mellitus is a chronic disease that manifests as an increased level of glucose in the blood. According to the World Health Organization (WHO), 347 million people have diabetes worldwide. In year 2004, 3.4 million people died from the consequences of high blood glucose. In the Swedish population the prevalence of diabetes is estimated to 3-4 %, out of which 85-90% are Type 2. Among senior citizens a prevalence of diabetes is seen in Sweden up to 14 - 15%. Diabetes is increasing globally, particularly in developing countries, which is probably a consequence of the increased prevalence of overweight and obesity combined with low physical activity. Angiotensin converting enzyme (ACE) inhibitors are the first-line therapy in the treatment of high blood pressure among diabetics and patients suffering from congestive heart failure. The action of these inhibitors results in a decreased formation of angiotensin 2, an endogenous hormone peptide that raises the blood pressure by contracting the blood vessels. ACE inhibitors are also beneficial in the treatment of patients with renal insufficiency.Objective: The aim of this project was, with the help of published clinical trials and meta-analysis, to examine the effect of ACE inhibitors on cardiovascular diseases and mortality in type 2 diabetic and diabetic in hypertensive patients.Results: Appraisals of clinical trials within the frame of this project revealed thatACE inhibitor in patients with diabetes reduces:- Myocardial infarction (NNT = 37 during 4.5 years),- Development of stroke (NNT = 32 during 2.8 years),- Cardiovascular events (NNT = 29 during 4.5 years),- Total mortality (NNT = 20 during 2.8 years).- Left ventricular dysfunction (NNT = 6 during 3.4 years)- Complications that usually occur in association with diabetes such as nephropathy (NNT = 83 during 5 years).Conclusion: ACE inhibitors are considered well-established and safe drugs. Despite that, only 38% of the patients with diabetic in Sweden are prescribed ACE inhibitors or angiotensin II antagonists. Due to the high efficacy of ACE-inhibitors among patients with diabetes (i.e. treating 15 high-risk diabetic patients with ACE-inhibitors for a median of 4.5 years prevents one incidence of myocardial infarction, stroke, or cardiovascular mortality) measures ought to be taken in favour of a more widespread use of ACE-inhibitors among patients with diabetes. This will result not only in medical benefits, but also in reducing cost of caring for the elderly diabetics in the community. For most diabetic patients it is very cost effective to prescribe an ACE-inhibitor therapy.

Relative changes are detectable in the blood of end-stage renal disease (ESRD) patients during hemodialysis (HD) treatment using optical spectroscopy. However, the potential impacts of several confounding factors that could affect the detection of these changes have not been evaluated. The objectives of this thesis were to: 1) investigate how the variations and/or changes in acid-base and oxygen parameters during HD treatment can affect the optical signature of whole blood of ESRD patients, 2) to investigate the effect of heparin on the optical properties of whole blood and its impact on our method. Blood samples were drawn from 23 ESRD patients at 5 time points during a 4 hour HD treatment and sent for blood gas and blood spectroscopy analyses. No significant correlations were found between the changes in the blood transmittance spectra and acid-base and oxygen parameters. This indicates that the perturbations in these parameters due to HD procedures do not confound the detection of changes in the blood transmittance spectra of ESRD patients during HD treatment. Additionally, the effect of heparin in modifying the optical properties of whole blood does not confound the detection of changes in the blood of ESRD patients due to HD treatment using whole blood-based optical spectroscopy. ANOVA revealed significant (P<0.05) measurable changes in the blood transmittance spectra of ESRD patients during HD treatment. Significant spectral differences (P<0.05) were found between ESRD patients. The lack of uniform spectral characteristics across patients is

A doença renal crônica (DRC) tem sido considerada um problema de saúde pública mundial. Estima-se que cerca de 17% da população adulta dos EUA apresente algum grau de comprometimento da função renal. No Brasil, um estudo realizado na cidade de Bambuí - Minas Gerais detectou-se alteração da função renal variando de 0,48% a 8,19%, sendo mais frequente nos pacientes idosos. Os pacientes que evoluem para DRC terminal necessitam de algum tipo de terapia renal substitutiva (TRS), sendo as opções disponíveis: a hemodiálise (HD), a diálise peritoneal (DP) e o transplante renal (TX renal). No caso da DP, a membrana peritoneal realiza a função de filtrar o sangue do paciente, e esta é utilizada através da implantação de um cateter na cavidade abdominal. No Brasil, segundo dados do Censo Brasileiro de Diálise (2016) existem aproximadamente 122.825 pacientes em diálise, sendo 8,6% em DP. O objetivo do estudo foi analisar a evolução dos pacientes que foram admitidos na Unidade de Diálise do HCFMRP para submeterem-se à DP nos últimos 22 anos. Os dados foram coletados dos prontuários dos pacientes atendidos no período de 1993 a 2015, de onde foram extraídas variáveis demográficas, clínicas e laboratoriais. É um estudo de coorte retrospectiva de 199 prontuários de pacientes atendidos na Unidade de Diálise do HCFMRP-USP. Os resultados demonstram que a população do estudo é em sua maioria do sexo feminino, com média de idade 57 anos. Foi encontrada a mudança de TRS para a hemodiálise como desfecho clínico mais frequente, seguida por óbito. A etiologia da DRC mais frequente foi a hipertensão arterial sistêmica (HAS), seguida por Diabetes mellitus (DM) tipo 2. Houve associação com menor média de idade de entrada em programa (48 anos), desfecho clínico óbito e maior tempo de seguimento (10 anos) com o grupo de pacientes que entraram em programa de diálise em 1993 (p<0,05). Encontramos associação do uso de medicamentos (Cloridrato de Sevelamer e Análogos da vitamina D3 com níveis categorizados de paratormônio, cálcio total e fósforo (p<0,05). CONCLUSÃO: Os pacientes que entraram em programa no período de 1993-2000 apresentaram menor média de idade e maior tempo de acompanhamento quando comparados aos demais grupos. O desfecho clínico mais frequente foi a transferência para HD, tendo como causa principal a ocorrência de peritonites. / INTRODUCTION: Chronic kidney disease (CKD) has been considered a worldwide public health problem, as well as the progressive increase of the population in renal replacement therapy (TRS). With the technological advances accumulated, the survival of patients on dialysis has increased greatly. Peritoneal dialysis (PD) is considered a safe and effective method of SRT, a challenge for the binomial patienthealth team. OBJECTIVES: To analyze the main characteristics and outcomes of patients in a PD program. METHODS: This was a retrospective cohort study of 199 patients submitted to PD in the Dialysis Unit of the HCFMRP-USP from 1993 to 2015. The primary source of data was the individual medical records. The variables were classified as: demographic, clinical and laboratorial. Statistical analyzes were performed using the Chi-square test, ANOVA and Kruskal Wallis. RESULTS: The mean age of the patients was 57 years, with a predominance of females (51.5%); the most frequent clinical outcome was the change in HRT for hemodialysis (37.2%). Type 2 diabetes mellitus (DM) was the most common cause of CKD (31,7). There was an association between lower mean age of program entry, clinical outcome and longer follow-up (10 years) in the group of patients who entered the dialysis program in the period from 1993 to 2000 (p <0.05). There was an association between the use of medications (Sevelamer\'s Hydrochloride and vitamin D3 analogues) with categorized values of parathormone, total calcium and phosphorus (p <0.05). CONCLUSION: Patients who entered the program in 1993-2000 had a lower mean age and longer follow - up when compared to the other groups. The most frequent clinical outcome was the transfer to HD, the main cause being the occurrence of peritonitis.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13328号 / 論医博第2196号 / 新制||医||1044(附属図書館) / (主査)教授 柳田 素子, 教授 佐藤 俊哉, 教授 長船 健二 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

La transplantation rénale est reconnue comme le traitement de choix de l’insuffisance rénale terminale chez l’enfant et l’adulte jeune et est associée à une augmentation de la survie et une amélioration de la qualité de vie des patients tout en étant le traitement le plus coût efficace à long terme. Néanmoins, il persiste de nombreuses questions sur la prise en charge des patients avant, pendant et après la transplantation. Le but de cette étude est d’analyser le parcours de soin des enfants présentant une maladie rénale chronique afin de mettre en évidence d’éventuelles disparités dans la prise en charge des patients et de fournir des outils d’aide à la décision afin d’améliorer la prise en charge et le traitement de ces patients.Nous avons utilisé différentes sources de données : le registre français des patients avec traitement de suppléance rénale (registre REIN), le registre européen de traitement de suppléance rénale (ESPN/ERA-EDTA registry) et la base de données médico-administrative des hospitalisations (PMSI).Tout d’abord, nous avons étudié les facteurs médicaux et non-médicaux pouvant induire des inégalités et avons mis en évidence que le sexe féminin est associé à un accès retardé à la transplantation rénale et particulièrement à la transplantation rénale préemptive. Ce désavantage pourrait être en parti expliqué par une progression plus rapide vers l’insuffisance rénale terminale même chez des patients présentant la même maladie. Nous avons également montré que les pratiques des centres de traitements impactaient de façon importante la trajectoire des patients. C’est un déterminant majeur du choix de la modalité de suppléance rénale initiale (hémodialyse ou dialyse péritonéale) et de l’accès à la transplantation rénale essentiellement par le biais de la rapidité d’inscription sur la liste d’attente.Nous nous sommes focalisé sur le sous-groupe des patients les plus jeunes, débutant le traitement de suppléance avant l’âge de 2 ans, dont la prise en charge reste un challenge. Nous avons confirmé d’important progrès dans la prise en charge de ces patients en montrant que seul la présence de comorbidités extra-rénales restait associée à une survie inférieure à celle des autres patients en insuffisance rénale terminale. Concernant la durée de vie des greffons, nous avons montré l’importance du matching de taille entre le donneur et le receveur avec un ratio de taille donneur/receveur optimal entre 1.4 et 1.8. De même, nous retrouvons l’importance du matching HLA classe 2 sur la survie du greffon. Nous allons combiner ces facteurs de risques dans un outils de prédiction pour aider les cliniciens dans le choix des greffons et allons réaliser une validation externe de cet outil sur une autre cohorte.A partir des données d’hospitalisation, nous avons montré que les infections sont la première cause d’hospitalisation post-transplantation devant les rejets et les cancers.Enfin, Du fait de la durée de vie limitée des greffons rénaux et de l’amélioration importante de l’espérance de vie, ces jeunes patients ont la particularité de nécessité fréquemment des transplantations répétées plus ou moins précédées de périodes de dialyse. De ce fait, il convient de considérer la trajectoire globale de ces patients afin de maximiser le temps passé avec un greffon fonctionnel et de minimiser le temps passé en dialyse. Nous avons développé un outil de simulation permettant de tester des modifications de stratégies de prise en charges (ex : augmentation du don vivant ou de la transplantation préemptive, modification des exigences de matching HLA) et leurs effets sur la trajectoire des patients. Cet outil sera développé afin de répondre à des questions plus complexes sur des sous-groupes de patients. / Renal transplantation is nowadays recognized as the treatment of choice for end-stage renal disease in children and young adults. It is associated with improved survival, better quality of life and better long-term cost-effectiveness. However, many questions remain considering the optimal management of the patients before transplantation, during the transplantation process and after transplantation. We aim to analyze the care and treatment received by children with chronic kidney diseases, to detect potential disparities in patients’ management and to provide useful tools to help decision-making and treatment planning.We used several data sources including the French renal replacement therapy (RRT) registry (REIN), the European RRT registry (ESPN/ERA-EDTA) and the French National medico-administrative Hospital Discharge database (PMSI).First, we focused on medical and non-medical factors that may induce disparity and found that besides medical factors, female gender was associated with a delayed access to renal transplantation and especially to preemptive transplantation. This might be partially explained by a faster decline of renal function in girls that remains to be explored. Aside for patients’ characteristics, we found that centers’ practices strongly impact patients’ trajectories. It is a main factor both in the choice of the first modality of RRT (hemodialysis or peritoneal dialysis) and in the access to renal transplantation especially through a faster access to the renal transplant waiting list.Then, we focused on the subgroup of the younger patients starting RRT before 2 years old, whose management is particularly challenging. We confirmed the great improvement in the care of those patients with only extrarenal comorbidities being still associated with a poorer survival. Considering renal transplant survival, we assess the importance of a matching in height between the donor and the recipient with an optimal donor/recipient height ratio between 1.4 and 1.8 and the importance of HLA matching especially in class 2. We aim to combine those risk factors in a prediction tool to help clinicians in their choices and will perform an external validation of this tool on another cohort.Based on the hospital discharge data, we studied post-transplant complications requiring a hospitalization and found that infections are the main cause of hospitalization post-transplant, far more frequent than graft rejection or cancer.Finally, given the longevity of children undergoing kidney transplantation, most pediatric recipients will inevitably develop graft failure, requiring a return to dialysis or a second transplant so that one should consider the complete trajectory of the patients and try to maximize the time spent with a functioning transplant and minimize the time spent on dialysis. We developed a simulation tool allowing us to test modifications of treatment strategies (e.i: increase in transplantation from living-donor kidney or in preemptive transplantation, better HLA-matching at first transplantation) and their effect on patients’ trajectories. This tool will be further implemented to answer more complex questions on specific subgroups of patients.