People of African ancestry (AA) are at greater risk of developing chronic kidney disease than those of non-AA. Much of this risk has been linked to specific genetic haplotypes on chromosome 22, near the genes APOL1, encoding apolipoprotein L1, and MYH9, encoding non-muscle myosin heavy chain IIA (NMHCIIA). The mechanisms by which the disease-associated chromosome 22 haplotypes promote kidney damage are unknown. Apolipoprotein L1 is a circulating protein with no known role in kidney function. However, the kidney disease-associated chromosome 22 haplotypes are protective against trypanosome infection, resulting in positive selective pressure for these haplotypes in western Africa, where trypanosome infection is endemic. In contrast, NMHCIIA may have an important role in glomerular function, and mutations in MYH9 are associated with glomerular disease, yet the disease-associated chromosome 22 haplotypes do not involve coding sequence variations in MYH9. With no clear disease-causing role for genes near the chromosome 22 risk locus, it is plausible that indirect mechanisms of gene regulation may be responsible for the increased disease risk. This study examines several potential pathways for kidney injury, including altered glomerular gene expression in carriers of chromosome 22 risk haplotypes, and the role of altered expression of MYH9 in podocyte cell biology and kidney disease. We found that carriers of chromosome 22 risk variants exhibited differential glomerular gene expression in pathways promoting kidney injury. We also found decreased glomerular NMHCIIA expression in human FSGS kidney biopsies, and altered cell structure and mechanical function when Myh9 is ablated in murine podocytes. Further, Myh9 podocyte deletion predisposed mice to glomerulopathy in response to injury by the DOCA-salt uninephrectomy model of hypertension. Taken together, these findings demonstrate direct and indirect effects of chromosome 22 risk variants on glomerular gene expression which promote kidney injury.

Bakgrund:Njurarnas huvudfunktioner har en vital roll och är en förutsättning till att upprätthålla kroppens balans. Kronisk njursvikt orsakar en kraftig reducering av funktionerna och i värsta fall kan njurarna helt sluta att fungera. Tillståndet leder till döden om inte dialysbehandling eller njurtransplantation genomförs. Under flera decennier har det skett en ökning av patienter som utvecklar kronisk njursvikt och därmed får dialysbehandling. Att leva med kronisk sjukdom orsakar svårigheter och förändringar i livet. Genom en god vård kan sjuksköterskan främja patientens livskvalitet och välbefinnande trots kronisk njursvikt och ett liv med hemodialys.  Syfte: Syftet med litteraturöversikten var att belysa hur patienter med kronisk njursvikt upplever livet med hemodialys.  Metod: Litteraturöversikten baserades på tolv vetenskapliga originalartiklar som analyserats. Metoden innefattade att identifiera likheter och skillnader som sedan bildade nya teman till litteraturöversiktens resultat. Artiklarna inhämtades från databaserna CINAHL Complete och PubMed.  Resultat: Under analysen identifierades femhuvudteman: En förändrande process, Ett liv som begränsar, Hemodialys som en fängslande frihet, En oförutsägbar framtid och Upplevelsen av vårdmiljö & vårdpersonal. En förändrande process kompletterades med två underteman; Emotionell påverkan och Vägen till acceptans. ÄvenHemodialys som en fängslande frihet kompletterades med två underteman; Dialysmaskinen, en vän eller en fiende? och Kroppsliga förändringar.  Diskussion: Resultatdiskussionen tolkar huvudfynden i en större helhet med hjälp av Katie Erikssons vårdvetenskapliga teori, annan forskning samt författarnas egna reflektioner. / Background: The main functions of the kidneys have a vital role and are essential for maintaining the balance of the body. Chronic kidney disease causes a steep reduction in the kidney´s functions, in the worst-case scenario the kidneys may cease to function entirely. The condition leads to death unless treated with hemodialysis or kidney transplantation. For decades, there has been an increase in patients developing chronic kidney disease and thus receive dialysis treatment. Living with chronic disease causes difficulties and changes in life. Through good care, the nurse can promote the patient´s quality of life and well-being despite of chronic kidney disease and a life with hemodialysis. Aim: The aim was to elucidate how patients with chronic kidney disease experience life with hemodialysis. Method: The literature review was based on twelve scientific original articles that were analyzed. The method involved identifying similarities and differences that then formed new themes for the literature review results. The articles were obtained from the databases CINAHL Complete and PubMed. Results: During the analysis five main themes were identified: A changing process, A life that limits, Hemodialysis as a captivating freedom, An unpredictable future, and Experience of care environment & healthcare staff. A changing process was supplemented with two sub-themes; The emotional impact and Path to acceptance.Additionally, Hemodialysis as a captivating freedom was supplemented by two sub-themes; The dialysis machine, a friend or an enemy? and Bodily changes.  Discussion: The results discussion interprets the main findings in a larger whole with the help of Katie Eriksson´s health science theory, other research, and the author´s own reflections.

A saliva é um fluído produzido e secretado pelas glândulas salivares. Ela desempenha um importante papel na homeostase dos indivíduos. Diversas doenças afetam a produção ou a composição da saliva secretada, dentre elas a doença renal crônica (DRC). A DRC é definida como um dano renal ou diminuição da função renal por um período igual ou superior a três meses. É classificada em estágios, sendo que em seu grau mais avançado existe a necessidade de terapias de hemodiálise ou transplante renal. Muitos são os estudos que buscaram manifestações orais, alterações de fluxo e composição salivares nestes pacientes, contudo quando buscamos na literatura, não encontramos trabalhos que utilizaram um modelo animal para o estudo de parâmetros de composição salivar na doença renal crônica. O objetivo deste estudo foi analisar alterações em alguns componentes na saliva de ratos estimulada por pilocarpina (1mg/Kg) ou isoproterenol (5mg/Kg), em um modelo de 5/6 de nefrectomia (IRC), comparando com um grupo controle positivo (Sham) e outro controle negativo (C) em dois tempos experimentais de 8 e 12 semanas. A nefropatia crônica foi obtida com 5/6 de nefrectomia pela ligadura de dois ramos da artéria renal esquerda e nefrectomia total direita e os grupos Sham foram submetidos à simulação do procedimento cirúrgico. Ao final dos tempos experimentais, amostras de sangue e saliva foram coletadas de todos os grupos e foram analisados: fluxo salivar, concentração de proteína total, atividades das enzimas amilase e peroxidase, ácido siálico livre e total, bem como as dos íons: cálcio, fósforo, sódio, potássio e concentração de ureia salivar. Foram analisadas também as concentrações séricas de ureia e creatinina. Observamos aumento significativo das concentrações séricas de ureia e creatinina e das concentrações salivares de ureia nos grupos IRC em ambos os tempos experimentais; Com estímulo de pilocarpina, observamos que com 8 semanas ocorreu diminuição significativa da atividade da enzima amilase e com 12 semanas ocorrem aumentos significativos da concentração de proteínas totais e atividade da enzima peroxidase. No estímulo com isoproterenol, observamos que com 8 semanas ocorrem diminuições significativas das atividades das enzimas amilase e peroxidase, com 12 semanas ocorreu diminuição significativa do fluxo salivar do grupo IRC em relação ao grupo Sham, aumento significativo da atividade da enzima amilase e diminuição significativa da atividade da enzima peroxidase no grupo IRC em relação aos grupos controle e sham. Concluímos que o período de 12 semanas pós-cirurgia apresentou maiores alterações da saliva coletada tanto pelo estímulo simpático quanto pelo estímulo parassimpático, devendo este período ser utilizado nas futuras análises em glândulas salivares. / Saliva is a fluid produced and secreted by the salivary glands. It plays an important role in the homeostasis of individuals. Several diseases affect the production or composition of saliva secreted, among them chronic kidney disease (CKD). CKD is defined as a kidney damage or decreased kidney function for a three months exceeding period. It is classified in stages, and in its most advanced level there is a need for hemodialysis therapies or kidney transplantation. Many studies have sought oral manifestations, changes in salivary flow and composition in these patients, however when we look at the literature, we did not found studies that used an animal model for the study of salivary composition in chronic kidney disease. The aim of this study was to analyze changes in some components in the saliva of rats stimulated by pilocarpine (1mg/Kg) or isoproterenol (5mg/kg) in a model of 5/6 nephrectomy (CRF), compared with a positive control group (Sham) and a negative control (C) at two time period of 8 and 12 weeks. The chronic nephropathy was obtained with 5/6 nephrectomy by ligation of two branches of the left renal artery and right radical nephrectomy and Sham groups underwent surgery simulation. At the end of the experimental period, blood and saliva samples were collected from all groups and were analyzed: salivary flow rate, total protein concentration, activities of amylase and peroxidase, free and total sialic acid, as well as the ions calcium, phosphorus, sodium, potassium and urea concentration in saliva. We also evaluate the serum concentrations of urea and creatinine. We observed a significant increase in serum urea and creatinine concentrations and salivary urea in IRC groups in both experimental times; Under pilocarpine stimulation, we found a significant decrease in the activity of the enzyme amylase 8 weeks after the surgery. 12 weeks after the surgery increase in the total protein concentration and peroxidase activity were observed; Under stimulation with isoproterenol, we observed decreases in the activities of amylase and peroxidase after 8 weeks; 12 weeks after the surgery we found decrease in salivary flow compared to the sham group, increase in the activity of the enzyme amylase and decrease of the peroxidase activity in CRF group when compared to control and sham groups. We conclude that the period of 12 weeks after surgery showed greater changes in saliva collected both by sympathetic stimulation and by parasympathetic stimulation, and this period should be used in future analyzes in salivary glands.

Introdução: A prevalência de doença renal crônica na faixa etária pediátrica ainda é desconhecida. O tratamento de escolha é o transplante renal, independente da idade. Os principais objetivos do tratamento são a manutenção do desenvolvimento físico, neurológico e esquelético, prevenção da doença do metabolismo mineral e ósseo (DMMO), adequada maturação sexual e da função endócrina. O déficit de crescimento está relacionado com a idade de surgimento da insuficiência renal e ocorre devido à má-nutrição energético-calórica, DMMO e uso de corticoide, além dos efeitos deletérios da anemia, uremia e resistência ao hormônio do crescimento. Causas relacionadas ao paciente como retardo de crescimento intra-uterino e malformações congênitas também estão relacionadas. Objetivos: avaliar o desenvolvimento pondero-estatural dos pacientes pediátricos submetidos a transplante renal no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HC FMRP-USP). Casuística: revisão dos prontuários dos pacientes pediátricos submetidos a transplante renal no HC FMRP-USP e análise do desenvolvimento pondero-estatural comparando os score-z altura para idade e índice de massa corporal (IMC) para idade durante o acompanhamento. As variáveis analisadas foram sexo, faixa etária, uso de Basiliximab, realização ou não de diálise, tipo de transplante realizado (doador falecido ou doador vivo relacionado), hipertensão arterial, dose de manutenção de prednisona. Resultados: foi possível avaliar os dados de 31 pacientes, 10 femininos e 21 masculinos. Ao longo do tempo houve ganho significativo em peso (p< 0,0001) e estatura (p< 0,0001) mas nenhuma das variáveis analisadas mostrou diferença estatisticamente significativa. Houve interação significativa do uso de Basiliximab e da faixa etária sobre o IMC e do uso de Basiliximab, faixa etária e dose de prednisona utilizada sobre a evolução da estatura. A estatura manteve abaixo da média padrão durante todo o acompanhamento e nenhum paciente atingiu a altura final esperada. O IMC estava abaixo da média padrão na ocasião do transplante mas a partir do primeiro ano recuperou e manteve estável em torno do percentil 0. Conclusões: a doença renal crônica na infância compromete o desenvolvimento ponderoestatural dos pacientes afetados. / Introduction: The prevalence of chronic kidney disease in the pediatric age range is still unknown. The treatment of choice is a renal transplant, regardless of age. The main objectives of treatment are the maintenance of physical, neurological and skeletal development, the prevention of renal osteodystrophy, and appropriate sexual and endocrine function maturation. The growth deficit is related to the age at onset of renal failure and is due to energy-calorie malnutrition, to renal osteodystrophy and to corticoid use, in addition to the deleterious effects of anemia, uremia and of resistance to growth hormone. Additional patient-related causes are intrauterine growth retardation and congenital malformations. Objectives: to assess the weight-height development of pediatric patients submitted to renal transplantation at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo (HC FMRP-USP). Patients: The medical records of pediatric patients submitted to renal transplantation at HC FMRP-USP were reviewed and weight-height development was analyzed by comparing the zscores for height for age and body mass index (BMI) for age during follow-up. The variables analyzed were: sex, age range, use of Basiliximab, having undergone dialysis or not, type of transplant performed (cadaver donor or related live donor), arterial hypertension, and maintenance dose of prednisone. Results: it was possible to assess the data of 31 patients, 10 girls and 21 boys. A significant weight gain (p<0.0001) and height (p<0.0001) occurred over time but none of the variables analyzed showed a statistically significant difference. There was a significant interaction between age range and BMI, between the use of Basiliximab and age range and between the prednisone dose used and height evolution. Height was below the standard mean value throughout follow-up and no patient reached the expected final height. BMI was below the standard mean value at the time of transplantation, but recovered after the first year and remained stable at a value of about 0. Conclusions: renal failure during childhood compromises the weight-height development of affected patients.

Introdução: Dentre as anomalias congênitas obstrutivas do trato urinário a Válvula de Uretra Posterior (VUP) apresenta elevado risco para a sobrevida do recém-nascido e é a causa mais comum de doença renal crônica terminal na infância. Seu tratamento envolve múltiplas especialidades e necessita seguimento no longo prazo. Com esses aspectos torna-se imperativo a permanente reavaliação de condutas. Objetivo: Descrever os aspectos clínicos e evolutivos dos pacientes portadores de Válvula de Uretra Posterior buscando avaliar a necessidade de adequações ao protocolo de atendimento. Casuística e Métodos: Constituída por 68 pacientes portadores de VUP atendidos no HCFMRP-USP no período entre 1990 e 2015. Foram revistos os dados relativos ao nascimento, encaminhamento, exames complementares, cirurgias realizadas e evolução clínica. Resultados: houve predomínio da raça branca (76,5%) e procedentes da DRS XIII (82,4%). A maioria das crianças vieram encaminhadas de outros hospitais (80,9%), alguns já submetidos à derivação urinária. Quanto à idade ao encaminhamento, 52,7% chegaram após o primeiro ano de vida embora o diagnóstico tenha sido feito em 76,5% antes do primeiro ano. Avaliação ultrassonográfica pré-natal foi realizada em 40 gestantes (48,8%) e oligoâmnio observado em16/40 (40,0%). Dentre os exames complementares para diagnóstico e seguimento ambulatorial ressaltamos a urografia excretora (16,2%), cintilografia renal (70,6%) e renograma (29,4%). Uretrocistografia foi realizada em todos os pacientes. Quanto aos principais procedimentos, derivação vesico-amniótica intrauterina foi realizada em 3 pacientes, cateterismo vesical de demora em 20, derivação alta em 4 pacientes, vesicostomia em 33, ressecção parcial do colo vesical em 9 e cauterização da VUP em 67. Dez pacientes foram transplantados. Discussão e Conclusões: os resultados apresentados são comparáveis àqueles divulgados na literatura pelas melhores instituições quanto ao diagnóstico, procedimentos cirúrgicos e evolução. O que fica evidente são as condições sócioeconômicas e culturais do nosso País onde a obtenção de melhores resultados terapêuticos tropeça em questões sociais e educacionais, necessitando de ações conjuntas visando educação continuada e organização social. Exame pré-natal adequado, diagnóstico precoce e rápido encaminhamento a centros que possam absorver estes pacientes são cruciais para a melhor evolução clínica. O protocolo mínimo de assistência deve ser objeto de difusão aos profissionais de saúde de diferentes especialidades visando o reconhecimento do quadro clínico. É desejável a inclusão, no protocolo de atendimento, de exames laboratoriais com capacidade prognóstica relacionada à evolução para doença renal crônica. / Introduction: Among congenital anomalies of the urinary tract, the posterior urethral valve (PUV) has a high risk for newborn´s mortality and is the most frequent cause of terminal chronic kidney disease in children. Its treatment involves multidisciplinary approach and long-term follow-up is necessary. Therefore, it is mandatory to permanently re-evaluate conducts. Objective: To describe the clinical and evolutive aspects of patients with PUV, aiming to evaluate the need for care protocol adjustments. Patients and Methods: The records of 68 boys with PUV who were treated at HCFMRP-USP between 1990 and 2015 have been reviewed. The data analyzed consisted of information regarding birth, age at referral, complementary exams, surgeries and clinical evolution. Results: There was a predominance of Caucasian (76.4%) and patients have been referred from region DRS XIII (82.4%). Most of the children have already been referred from other hospitals (80.8%), and some of them were already submitted to urinary diversion. Regarding the age of referral, 52.7% arrived after the first year of life, although the children were diagnosed before the first year of life in 70,6% of the cases. Prenatal ultrasound evaluation has been performed in 40 pregnant women (48.8%) and oligohydramnios was found in 16/40 (40,0%). Concerning the complementary exams for diagnosis and outpatient follow-up we highlighted excretory urography (16.2%), renal scintigraphy (70,6%) and renogram (29,4%). Voiding cistourethrography was performed in all patients. Regarding the main procedures, intrauterine vesico-amniotic shunt was performed in 3 patients, temporary drainage of urinary tract with vesical catheterization in 20, higher diversion in 4 patients, vesicostomy in 33, partial resection of the bladder neck in 9 and ablation during cystoscopy of the VUP in 67 patients. Ten patients were submitted to transplantation. Discussion and Conclusions: the results presented are comparable to those published in the literature by the best institutions regarding diagnosis, surgical procedures and patient evolution. What has become evident are the socioeconomic and cultural conditions of our country, where obtaining better therapeutic results stumbles on social and educational issues, requiring joint actions aimed continuing education and social organization. Proper prenatal examination, early diagnosis and early referral to institutions that can absorb these patients are crucial for the best clinical outcome. The minimum protocol of assistance should be disseminated to health professionals of different specialties in order to recognize the clinical picture. It is desirable to include, in the attendance protocol, laboratory tests with prognostic capabilities regarding evolution to chronic kidney disease.

Vitamin D deficiency in patients with chronic kidney disease, measured by reduced serum concentrations of 25 hydroxy vitamin D, is highly prevalent and associated with both endothelial dysfunction and an increased risk of cardiovascular disease. Observational studies in chronic kidney disease have demonstrated that vitamin D therapy reduces the risk of cardiovascular disease. In patients with chronic kidney disease and concomitant vitamin D deficiency, the effect of vitamin D therapy on endothelial function, which is associated with cardiovascular disease, is poorly understood. The mechanism by which vitamin D affects endothelial function is unclear. Methods Presented in this thesis, two studies have addressed these issues: 1. A double blind, randomized controlled trial evaluating the effect of ergocalciferol compared to placebo on microcirculatory endothelial function in patients with non-dialysis chronic kidney disease and concomitant vitamin D deficiency 2. In vitro and in vivo experiments to determine the mechanistic effect of ergocalciferol on endothelial function in an experimental model of uraemia. Results In the clinical study, ergocalciferol increased vitamin D serum concentrations and improved microcirculatory endothelial function measured by laser Doppler flowmetry after iontophoresis of acetylcholine. Oxidative stress measured by skin autofluorescence for advanced glycation end products did not change in the ergocalciferol group but increased significantly in the placebo group. Ergocalciferol increased endothelial nitric oxide synthase expression and activity in cultured human endothelial cells and improved endothelial function in an in vivo model of mild uraemia. The findings from the in vivo and clinical studies occurred independently of changes in blood pressure, conduit artery function, serum calcium, phosphate and parathyroid hormone supporting in vitro findings that ergocalciferol acts directly on the endothelium. Conclusion Ergocalciferol improved endothelial function in both rodent and human subjects with chronic kidney disease. Experimental evidence suggests this effect occurs through an endothelium dependent mechanism involving changes in the upregulation and function of endothelial nitric oxide synthase.

Orientador: Bárbara Perez Vogt / Resumo: INTRODUÇÃO: Atualmente, várias sociedades internacionais reconhecem a presença da sarcopenia nas doenças catabólicas, como a doença renal crônica. Sarcopenia afeta qualidade de vida e atividades diárias dos indivíduos. O objetivo deste trabalho foi avaliar o diagnóstico, prevalência e associação de parâmetros clínicos e nutricionais com a sarcopenia em pacientes em diálise peritoneal (DP). MÉTODOS: Realizado busca ativa da sarcopenia em pacientes prevalentes em DP maiores de 18 anos. Avaliação da massa muscular pelo índice de massa apendicular (IMMA) e da função muscular pela força de preensão manual (FPM) foram realizadas. Diagnóstico de sarcopenia foi realizado de acordo com o European Working Group on Sarcopenia in Older People (EWGSOP) e sua gravidade foi avaliada por teste de velocidade de marcha (VM). Para análise estatística, foi utilizado teste Kolmogorov-Smirnov, seguido de qui quadrado ou exato de Fisher, Mann-Whitney ou Teste t de Student, de acordo com a distribuição dos dados. Posteriormente, foi realizada regressão logística multivariada. As variáveis com significância <0,1 na análise univariada foram incluídas no modelo de regressão. RESULTADOS: Foram incluídos cinquenta indivíduos em DP, média de idade de 55,74±16,22 anos, 52% eram mulheres. A prevalência de sarcopenia em DP foi de 10% (n=5), sendo 8% (n=4) considerados com sarcopenia severa. Comparando os grupos de pacientes de acordo com a presença de sarcopenia, foram encontradas diferenças significativas c... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: INTRODUCTION: Currently, several international societies recognize the presence of sarcopenia in catabolic diseases, such as chronic kidney disease. Sarcopenia affects quality of life and daily activities of individuals. The aim of this study was to evaluate the diagnosis, prevalence and association of clinical and nutritional parameters with sarcopenia in patients on peritoneal dialysis (PD). METHODS: Screening for sarcopenia was performed in prevalent patients in PD older than 18 years. Muscle mass by appendicular skeletal muscle mass index (ASMMI) and muscle function by handgrip strength (HGS) were evaluated. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People (EWGSOP) and its severity was assessed by gait speed (GS). For statistical analysis, Kolmogorov-Smirnov test was used, followed by Chi-square or Fisher's exact test, Mann-Whitney or Student´s t Test, according to data distribution. Later, binary logistic regression was performed. Variables with significance <0.1 in the univariate analysis were included in the binary logistic regression model. RESULTS: Fifty subjects on PD were included, mean age 55.74±16.22 years, 52% female. Sarcopenia prevalence was 10% (n=5), and 8% (n=4) were classified as severe sarcopenia. Comparing the groups of patients according to the presence of sarcopenia, significant differences were found regarding body weight (55.34±7.01kg vs 70.78±15.60kg, p=0.003), body mass index (BMI) (22.75±1.45kg/m² vs 2... (Complete abstract click electronic access below) / Mestre

Acute kidney injury (AKI) is a major risk factor for chronic kidney disease (CKD). For patients who recover from AKI, there is a 25% increase in the risk of CKD, and a mortality rate of up to 50% after 10 years. Nuclear factor kappa-B (NF-κB) is a family of transcription factors that regulates the transcription of many proteins that play a key role in inflammation. Inhibitor of IκB kinase (IKK) is directly upstream of NF-κB. My aim was to investigate a) the role of IKK in the progression of AKI to CKD, and b) whether its inhibition attenuates renal fibrosis. In this thesis I used a model of unilateral renal ischaemia-reperfusion injury with contralateral nephrectomy, to firstly map the acute time course of AKI. From the data generated from the time course, I decided to treat the animals at 24 h post reperfusion with the IKK inhibitor, IKK16, as i) this was at the peak of renal dysfunction (24 h post reperfusion), and ii) prior to the activation of NF-κB (48 h post reperfusion). The inhibition of IKK at 24 hours post reperfusion, as a delayed treatment, successfully attenuated renal dysfunction, NF-κB activation and renal structural damage. I subsequently increased the recovery time after ischaemia-reperfusion in my rat model to 28 days to study the development of fibrosis post AKI. The inhibition of IKK at 24 hours post reperfusion successfully attenuated the development of fibrosis, formation of myofibroblasts, macrophage infiltration, the expression of pro-fibrotic markers and the deposition of extracellular matrix components at 28 days post reperfusion. In addition, the delayed inhibition of IKK at days 7-13 post unilateral ureteral obstruction in a rat model, successfully attenuated the development of fibrosis, formation of myofibroblasts, macrophage infiltration, the expression of pro-fibrotic markers and the deposition of extracellular matrix components. These data indicate that the activation of the IKK complex drives tubulointerstitial fibrosis, and suggests that the inhibition of IKK could be a useful pharmacological tool for the creation of therapies to combat AKI and the subsequent development of fibrosis, via the reduction of both inflammation and the prevention of the expression of pro-fibrotic markers.

Purpose: To evaluate the diagnostic performance of Coronary Computed Tomography Angiography (CCTA) in predicting Myocardial Perfusion Scintigraphy (MPS) perfusion defects in low likelihood patients with End Stage Renal Disease (ESRD) awaiting transplant. Materials and Methods: In total, 131 consecutive patients with ESRD awaiting transplant were prospectively enrolled in this study (86 men; 54±9years). All patients underwent MPS as per standard of care and in addition non-enhanced CT for calcium scoring (CAC score) and Coronary Computed Tomography Angiography (CCTA). Results: The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CAC score in predicting MPS perfusion defects were 88%, 35%, 28% and 92%, respectively. The sensitivity, specificity, PPV and NPV of CCTA in predicting MPS perfusion defects at the patient level were 55%, 87%, 57% and 87%, respectively, and 48%, 92%, 41% and 94% at the vessel level. The diagnostic performance of CCTA in predicting MPS perfusion defects improved when patients with CAC score higher than 1000 (15/70, 21%) were excluded from the analysis. In patients with positive CAC score up to 1000 sensitivity, specificity, PPV and NPV at the patient level were 60%, 93%, 75% and 86% respectively. These were 53%, 91%, 36% and 95%, respectively, at the vessel level. Conclusion: Non-enhanced CT for CAC score and CCTA can be considered useful diagnostic tools in the ESRD population, particularly in identifying patients without coronary artery disease. This approach however had limitations in the presence of high CAC score.

O diabetes mellitus (DM) é uma doença crônica com alto índice de morbidade e mortalidade, sendo considerado um dos maiores problemas de saúde pública do século 21, afetando aproximadamente 415 milhões de pessoas. As complicações em longo prazo do DM incluem a doença renal, a qual pode levar à falência renal, a retinopatia com perda potencial da visão e neuropatia, bem como o risco de amputações. A hemoglobina glicada (A1c) é considerada o parâmetro de referência na avaliação do controle glicêmico de pacientes com DM. No entanto, a mensuração da A1c pode não ser adequada para avaliar as variações em curto prazo do controle glicêmico, devido ao longo tempo de vida dos eritrócitos (120 dias). Existem ainda algumas limitações do uso deste teste, como em pacientes com hemoglobinas variantes, persistência hereditária à hemoglobina fetal, anemia hemolítica, anemia renal, entre outros. A avaliação da glicação da albumina é considerada, por alguns autores, como um melhor marcador para o controle glicêmico do que a A1c, em situações onde a A1c é de difícil interpretação devido à presença de interferentes, uma vez que a glicação da albumina não é afetada pela alteração no tempo de sobrevida das hemácias, como ocorre com a A1c. Atualmente, não há nenhum teste de albumina glicada (AG) disponível na rotina prática no Brasil, sendo um método limitado à pesquisa. No entanto, vários estudos mostram dados promissores em relação à AG e o controle do DM em situações específicas. Assim, a AG tem sido considerada um marcador alternativo no controle glicêmico e há necessidade de maior investigação sobre a utilização deste teste na prática clínica. / Diabetes mellitus (DM) is a chronic disease with high morbidity and mortality, being considered one of the biggest public health problems of the 21st century, affecting approximately 415 million people. Long-term complications of DM include renal disease, which can lead to kidney failure, retinopathy with potential loss of vision and neuropathy, as well as the risk of amputations. Glycated hemoglobin (A1c) is considered the reference in the assessment of glycemic control in patients with diabetes mellitus (DM). However, A1c measurement may not be adequate to evaluate the short-term variations of glycemic control due to the long lifespan of erythrocytes (120 days). There are also some limitations of using this test, such as in patients with variant hemoglobins, hereditary persistence to fetal hemoglobin, hemolytic anemia, renal anemia, among others. The evaluation of albumin glycation is considered by some authors to be a better marker for glycemic control than A1c in situations where A1c is difficult to interpret due to the presence of interferents, since albumin glycation is not affected by alteration in the survival time of red blood cells, as occurs with A1c. Currently, there is no glycated albumin (GA) test available in routine practice in Brazil, being a method limited to the research. However, several studies show promising data about GA in DM control in specific situations. Therefore, GA has been considered an alternative marker in glycemic control and there is a need of further investigation into the use of this test in clinical practice.