Introdução: O conhecimento da função renal é fundamental para o seguimento dos receptores de transplante renal pediátrico. A habilidade do enxerto em adaptar-se a uma demanda aumentada durante o crescimento parece um fator importante para a função do aloenxerto no longo prazo. O estudo tem por objetivo comparar a função do enxerto renal em receptores pediátricos de acordo com o tipo de doador: adulto ou pediátrico e vivo ou falecido. Metodologia: Examinamos a taxa de filtração glomerular, através da depuração de inulina, em uma coorte pediátrica submetida a transplante renal no período de 2000 a 2010 e a sua associação com as idades do receptor e do doador. Um modelo de classe latente foi utilizado para identificar trajetórias de evolução da função renal pós-transplante. O seguindo passo da análise foi quantificar os efeitos dos fatores de risco na probabilidade de pertencer ao grupo de trajetória de pior evolução. Resultados: Este modelo identificou três trajetórias de função do enxerto renal após o transplante: “baixa e decrescente”, “moderada e estável” e “alta e decrescente”. A probabilidade de pertencer à trajetória de pior resultado (baixa e decrescente) aumentou com o doador falecido comparativamente ao vivo (odds ratio ajustado: 50), com a idade do receptor (odds ratio ajustado: 1,2 por ano de vida do receptor) e com a diferença de idade receptor-doador (odds ratio ajustado: 1,13 por ano adicional). Conclusão: O presente estudo identifica três trajetórias de função do enxerto renal após o transplante renal pediátrico. Os achados sugerem que o doador vivo e o recurso de doadores mais jovens são fatores importantes para a função do enxerto no longo prazo. / Introduction: The knowledge of renal function is crucial for the management of pediatric kidney transplant recipients. The graft ability to adapt to an increasing demand during growth is important factor for long-term allograft function. We aimed to evaluate the long-term progress of glomerular filtration rate in pediatric recipients and the importance of the recipient and donor ages in predicting the risk of poor transplant outcome Methods: We examined the glomerular filtration rate using inulin clearance in a pediatric cohort who underwent kidney transplantation between 2000 and 2010. A longitudinal latent class modeling technique was used to identify renal function trajectories after transplant. The second step of the analysis was the quantification of the effects of the risk factors on the probability of belonging to the poor outcome trajectory group. Results: The study identified three trajectories of renal allograft function after pediatric kidney transplantation: “low and decreasing”, “moderate and stable”, and “high and sharply decreasing” trajectories. The observed probability to belong to the poor outcome group (low and decreasing) increased with deceased versus living donor (adjusted odds ratio: 50), with age recipient (adjusted odds ratio: 1,2 per year of recipient ageing), and with the donor-recipient age difference (adjusted odds ratio: 1,13 per additional year). Conclusion: The present evaluation identified three trajectories of renal allograft function after pediatric kidney transplantation. This results suggests that donor source (living or deceased), age recipient, and age difference between the donor and the recipient are important factors for long-term allograft function.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-06-14T13:17:26Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese Doutorado Milton Cezar.pdf: 1351763 bytes, checksum: 943b1f06e1c61f7137dcc7b3c7413adf (MD5) / Made available in DSpace on 2016-06-14T13:17:26Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese Doutorado Milton Cezar.pdf: 1351763 bytes, checksum: 943b1f06e1c61f7137dcc7b3c7413adf (MD5) Previous issue date: 2013-02-27 / A esquistossomose é uma doença crônica e debilitante que afeta cerca de 240 milhões de pessoas em todo o mundo e outras 700 milhões vivem em áreas endêmicas de países em desenvolvimento, o que tem sido um problema de saúde pública. Em 2009, havia 6.780.683 casos confirmados da doença no Brasil. A esquistossomose crônica pode levar a processos inflamatórios hepáticos graves, desencadear distúrbios renais e danos celulares que incluem o aumento do estresse oxidativo e a disfunção endotelial. Isto contribui para o surgimento da microalbuminúria, uma perda de proteínas que pode ser um preditor precoce de doenças cardiovasculares e renais. Neste estudo, foi investigado em 130 pacientes com esquistossomose hepatoesplênica ou hepatointestinal a ocorrência de microalbuminúria, e sua correlação com o aumento dos níveis pressóricos. A função renal também foi avaliada utilizando biomarcadores (Cistatina C / Creatinina) e estimada através da medida da taxa de filtração glomerular. Os valores obtidos foram comparados com 40 pessoas (Grupo Controle) saudáveis, advindos das mesmas classes sociais. Por fim, foi investigado em ratos infectados pelo parasita Schistosoma mansoni, a elevação da pressão arterial, a ocorrência de proteinúria, o estresse oxidativo renal e o estresse oxidativo hepático. Dos 130 pacientes (grupo Schistosoma mansoni) avaliados, 14,6% (11 homens e 8 mulheres) apresentaram microalbuminúria (valores entre 30 e 300 mg / g de creatinina) em comparação ao grupo controle, que mostrou apenas 5 % (um homem e uma mulher) com microalbuminúria. Dos 19 pacientes que apresentaram microalbuminúria, 15 tinham esquistossomose hepatoesplênica, e 4 tinham esquistossomose hepatointestinal. A taxa de filtração glomerular renal e a pressão arterial aumentaram no grupo Schistossoma mansoni em relação ao Grupo Controle. O resultado obtido na avaliação da taxa de filtração glomerular com a Cistatina C sérica foi superior ao resultado obtido com a Creatinina sérica. No estudo realizado com animais, os ratos infectados pelo parasita Schistossoma mansoni tiveram aumento da pressão arterial e perda de proteína na urina em comparação ao grupo controle. Este processo foi mais intenso em animais infectados e tratados com sobrecarga de sódio. Os animais não infectados pelo parasita Schistossoma mansoni e que não foram tratados com a sobrecarga de sódio, não tiveram proteinúria, nem aumento dos níveis pressóricos. Todos os resultados obtidos permitem sugerir que a microalbuminúria pode ser utilizada como um novo marcador não invasivo para o diagnóstico precoce de hipertensão arterial e de glomerulopatia esquistossomótica. / Schistosomiasis is a debilitating chronic disease that affects nearly 240 million people around the world and another 700 million live in endemic areas in developing countries, representing a serious public health issue. In 2009, there were 6,780,683 confirmed cases of the disease in Brazil. Chronic schistosomiasis can lead to severe hepatic inflammatory processes, and trigger kidney dysfunction and cellular damage, including an increase of oxidative stress and endothelial dysfunction. This contributes to the appearance of microalbuminuria, a loss of proteins that may serve as an early predictor of cardiovascular and kidney diseases. This study investigated the occurrence of microalbuminuria in 130 patients with hepatosplenic or hepatointestinal schistosomiasis, and its correction with the increase of pressure levels. Kidney function was also evaluated using biomarkers (Cystatin C / Creatinine) and estimated through the measurement of the glomerular filtration rate. The values obtained were compared with 40 healthy persons (Control Group) from the same social classes. Finally, the study investigated – in rats infected by the Schistosoma mansoni parasite – the elevation of arterial pressure, the occurrence of proteinuria, kidney oxidative stress and hepatic oxidative stress. From the 130 patients (Schistosoma mansoni group) evaluated, 14.6% (11 men and 8 women) presented microalbuminuria (values between 30 and 300 mg / g of creatinine) in comparison to the Control Group, which showed only 5% (one man and one woman) as having microalbuminuria. From the 19 patients who presented microalbuminuria, 15 had hepatosplenic schistosomiasis, and 4 had hepatointestinal schistosomiasis. The kidney glomerular filtration rate and the arterial pressure increased in the Schistossoma mansoni group in relation to the Control Group. The result obtained from the evaluation of the glomerular filtration rate with serum Cystatin C, was higher than that obtained with serum Creatinine. In the study carried out with animals, the rats infected by the Schistossoma mansoni parasite had an increase in arterial pressure and loss of protein in the urine, compared with the Control Group. The animals that were not infected with the Schistossoma mansoni parasite and that were not treated with a sodium overload, did not have proteinuria or an increase in the pressure levels. All the results obtained suggest that microalbuminuria may be used as a new non-invasive marker for early diagnosis of arterial hypertension and schistosomal glomerulopathy.

Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2017-03-24T16:31:04Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Andrea Camello Esteves Perrelli Valenca.pdf: 1213084 bytes, checksum: 49afd36a6ed947bb9618ba6b504c0d22 (MD5) / Made available in DSpace on 2017-03-24T16:31:04Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Andrea Camello Esteves Perrelli Valenca.pdf: 1213084 bytes, checksum: 49afd36a6ed947bb9618ba6b504c0d22 (MD5) Previous issue date: 2016-08-31 / A doença renal crônica (DRC) caracteriza-se por perda irreversível e progressiva da função renal, definida por redução da taxa de filtração glomerular (TFG) ou alteração renal estrutural. É bastante prevalente no Brasil e no mundo e está associada a alta morbimortalidade por doença cardiovascular (DCV). Apesar de ser a principal causa de mortalidade, a DCV nestes pacientes com frequência é subdiagnosticada e subtratada. Estudos mostram que a prevalência de alterações cardíacas aumenta a medida que ocorre declínio da função renal. A forma mais frequentemente utilizada para estimar a TFG é através da dosagem sérica da creatinina. No entanto, a cistatina C tem se sobressaído como marcador mais fidedigno por apresentar vantagens em relação à creatinina, como por exemplo, não sofrer influência de massa muscular, sexo ou idade. Entretanto, estudos sugerem que a TFG calculada pela combinação das medidas da creatinina e da cistatina C é mais precisa do que as medidas isoladas. O uso combinado destes marcadores pode ser útil para distinguir melhor os estágios de disfunção renal e, desta maneira, identificar mais precocemente a necessidade de estudo ecodopplercardiográfico para detecção de alterações cardíacas subclínicas estruturais e funcionais. Objetivou-se realizar um estudo de corte transversal em pacientes com DRC em tratamento conservador avaliando a TFG estimada pela creatinina, cistatina C e combinação de ambas e suas associações com alterações cardíacas. Os pacientes foram classificados em estágios da DRC, de acordo com as diretrizes do Kidney Disease Impoving Global Outcomes e com a TFG estimada, utilizando a equação Chronic Kidney Disease Epidemiology Collaboration, através das medidas séricas da creatinina e da cistatina C. Para critério de comparação os pacientes classificados em estágios 3a, 3b e 4 foram considerados grupo 1 e os pacientes do estágio 5, grupo 2. As alterações ecodopplercardiográficas avaliadas incluíram: disfunção diastólica, disfunção sistólica, alterações de geometria do ventrículo esquerdo (VE) e disfunção valvar. Foram avaliados 140 pacientes, em um único centro de referência em nefrologia, por um período de 6 meses. Quando a TFG foi estimada pela cistatina C, observou-se associação inversa entre o grau de disfunção renal e a presença de alteração de geometria do VE (45,4% no grupo 1 e 87,5% no grupo 2, p = 0,028) e disfunção valvar (8,3% no grupo 1 e 50 % no grupo 2, p = 0,005). Essa associação não foi observada quando a TFG foi estimada pela creatinina ou pela combinação de creatinina e cistatina C. Não houve associação entre o grau de disfunção renal e a presença de disfunção diastólica e disfunção sistólica. Concluiu-se que a TFG estimada pela combinação de creatinina e cistatina C não foi 9 superior ao uso isolado dos marcadores em predizer alterações ecodopplercardiográficas em pacientes portadores de DRC em tratamento conservador. / Chronic kidney disease (CKD) is characterized by irreversible and progressive loss of renal function with decreased glomerular filtration rate (GFR) or renal structural damage. CKD is a common disease in Brazil and worldwide and it is associated with high morbidity and mortality rates, mainly due to cardiovascular disease (CVD). Despite being the main cause of mortality among CKD patients, CVD is often underdiagnosed and undertreated. Several studies have shown that the prevalence of cardiac abnormalities increases as the renal function declines. GFR has been most frequently calculated with the dosage of serum creatinine. However, cystatin C has been considered as the most reliable GFR marker as it presents advantages over creatinine, since it is not influenced by muscle mass, sex, or age. Recent studies have shown that estimated GFR, calculated with a combination of creatinine and cystatin C, more accurately reflects measured GFR than either marker alone. This finding suggests that the combined use of these two markers may be useful to distinguish kidney dysfunction stages better than either marker alone, and subsequently, allowing the earlier identification for the need of a Doppler echocardiography performance test in order to detect subclinical cardiac structural and functional changes. Thus, a cross-sectional study was conducted in patients with CKD undergoing conservative treatment evaluating estimated GFR by the creatinine, cystatin C, and combination of both markers, and their association with cardiac changes. Patients were classified in the CKD stages, according to KDIGO guidelines (Kidney Disease impoving Global Outcomes) and the GFR was estimated using the CKD-EPI equation (Chronic Kidney Disease - Epidemiology Collaboration) through serum measurements of creatinine and cystatin C. For comparison criteria patients classified in stages 3a, 3b and 4 were considered as group 1 and patients in stage 5 as group 2. The Doppler echocardiographic changes evaluated included: diastolic dysfunction, systolic dysfunction, left ventricular geometry abnormalities and valvular dysfunction. We evaluated 140 patients in a single center of reference in nephrology, for a 6 months period. When GFR was estimated by cystatin C, we observed an inverse association between the degree of renal dysfunction and the presence of left ventricular geometry change (45.4% in group 1 and 87.5% in group 2, p = 0.028) and valvular dysfunction (8.3% in group 1 and 50% in group 2, p = 0.005). This association was not observed when GFR was estimated by creatinine or the combination of creatinine and cystatin C. There was no association between the degree of renal dysfunction and diastolic dysfunction or systolic dysfunction. It was concluded that the GFR estimated by combining creatinine and cystatin C was not greater than the isolated use 11 of markers to predict cardiac changes in patients with CKD undergoing conservative treatment.

Made available in DSpace on 2016-08-17T17:39:02Z (GMT). No. of bitstreams: 1 Dissertacao-DyegoJoseAraujoBrito.pdf: 1513824 bytes, checksum: b707b62757a7a930f3393f77c7984e48 (MD5) Previous issue date: 2016-03-21 / BACKGROUND: Atherosclerotic lesions are highly prevalent among afrodescendants leading to increased morbidity and mortality from cardiovascular events. Thus, the aim of this study was to investigate the association between atherosclerosis and kidney injury markers in hypertensive afrodescendants from quilombo remnants communities in northern of Maranhão. METHODS: Cross-sectional study that assessed hypertensive afrodescendants from PREVRENAL cohort underwent two different imaging methods for diagnosis of atherosclerosis disease: 1- Carotid doppler ultrasonography (doppler US) to assess the intima-media thickness (cIMT) and/or 2- Coronary computed tomography for determination calcium score (CCS). The kidney damage markers evaluated were 1- estimated glomerular filtration rate (eGFR) and; 2- albuminuria. Information about clinical, laboratory and imaging data were collected in PREVRENAL study database. To evaluate factors associated with the occurrence of coronary and carotid atherosclerosis was adjusted Poisson model with robust variance. The significance level was 5%. Statistical analysis was performed using Stata 12.0 software. RESULTS: Two hundred-six patients (mean age 61.32±12.44 years and 61.65% women) underwent carotid doppler US and 155 patients (mean age 61.42±12.42 years and 62.58% women) underwent coronary CT were included in the study. cIMT presented high in 59.22% individuals evaluated and 41.94% of patients had CCS> 0. In the multivariate regression model, age ≥60 years (PR 1.23, p-value = 0.001), ACR> 30mg/g (PR 1.18, p-value = 0.040) and eGFR/CKD-EPI <60mL/min using cystatin C (PR 1.25, p-value = 0.045) were independently associated with carotid atherosclerosis. The model for coronary calcification were associated with CCS: male gender (PR 1.53, p-value = 0.010), age ≥ 60 years (PR 1.78, p-value = 0.001), use of ASA (PR 1.67, p-value = 0.018) and smoking (PR 1.51, p-value = 0.011). CONCLUSION: The occurrence of atherosclerotic lesions was high in this group. Kidney injury markers were associated only with carotid lesions, whereas traditional factors for atherosclerotic disease were associated with coronary lesions. Thus, afrodescendants with similar clinical and epidemiological characteristics should be strictly monitored and treated to reduce the risk of cardiovascular events. / INTRODUÇÃO: As lesões ateroscleróticas são altamente prevalentes entre afrodescendentes, determinado o aumento da morbi-mortalidade por eventos cardiovasculares. Desta forma, o objetivo principal deste estudo foi investigar a associação entre doença aterosclerótica e marcadores de lesão renal em afrodescendentes hipertensos residentes em comunidades remanescentes de quilombo no Norte do Maranhão. MÉTODOS: Estudo transversal que avaliou afrodescendentes hipertensos da coorte PREVRENAL, submetidos a dois diferentes métodos de imagem para diagnóstico de doença aterosclerótica: 1- US Doppler de carótidas para avaliação da espessura médio-intimal (EMIC) e 2- Tomografia computadorizada coronariana para determinação do escore de cálcio (ECC). Os marcadores de lesão renal avaliados foram: 1- Taxa de filtração glomerular estimada (TFGe) e 2- Albuminúria. Os dados clínicos, laboratoriais e de imagem foram coletadas no banco de dados do PREVRENAL. Para avaliar os fatores associados à ocorrência de aterosclerose coronariana e carotídea foi ajustado o modelo de Poisson com variância robusta. O nível de significância adotado foi de 5%. A análise estatística foi realizada através do software Stata 12.0. RESULTADOS: Duzentos e seis pacientes (média de idade de 61,32±12,44 anos e 61,65% de mulheres) que realizaram US Doppler de carótidas e 155 pacientes (média de idade de 61,42±12,42anos e 62,58% de mulheres) submetidos à tomografia coronariana foram incluídos no estudo. Apresentaram EMIC elevada 59,22% dos indivíduos avaliados e 41,94% tinham ECC>0. No modelo de regressão ajustada, idade >60 anos (RP 1,23, p-valor=0,001), RAC >30mg/g (RP 1,18, pvalor= 0,040) e TFGe/CKD-EPI <60mL/min utilizando a cistatina C (RP 1,25, pvalor= 0,045) estiveram independentemente associados com aterosclerose carotídea. No modelo para calcificação coronariana, apresentaram associação com ECC: sexo masculino (RP 1,53, p-valor=0,010), idade >60 anos (RP 1,78, p-valor=0,001), uso de AAS (RP 1,67, p-valor=0,018) e tabagismo (RP 1,51, p-valor=0,011). CONCLUSÃO: A ocorrência de lesões ateroscleróticas foi expressiva no grupo estudado. Marcadores de lesão renal foram associados apenas com lesões carotídeas, enquanto que fatores tradicionais para doença aterosclerótica foram associados com as lesões coronarianas. Desta forma, indivíduos afrodescendentes com características clínico-epidemiológicas semelhantes devem ser estritamente monitorizados e tratados para reduzir o risco de ocorrência de eventos cardiovasculares.

Introdução: Rosiglitazone (RGL) é um ligante dos receptores PPAR e vem sendo usada no tratamento do Diabetes Mellitus tipo 2 e nas doenças inflamatórias. Mas, RGL pode reduzir a filtração glomerular (FG), a carga excretada de sódio na urina (UVNa) e aumentar a expressão da Na+,K+- ATPase na medula renal. Então, RGL pode causar edema e insuficiência cardíaca congestiva. Entretanto, não tem sido reportado se RGL pode induzir insuficiência renal aguda (IRA). Objetivo: Verificar se a redução da FG causada pelo tratamento com RGL predispõe à IRA em ratos. Avaliar em condições basais e de vasoconstrição renal e se há diferenças entre ratos normocolesterolêmicos (NC) e hipercolesterolêmicos (HC). Métodos: A FG foi medida pelo clearance de inulina no 8º dia em ratos (~200g) NC e HC tratados ou não com RGL (48 mg/kg/dieta) na situação basal e durante a infusão endovenosa de Ang II (40 ng/kg/min). Além disso, a atividade da Na+,K+-ATPase foi avaliada em homogenato renal em outra série de animais. Resultados: Na situação basal, NC e HC apresentaram FG semelhante e o tratamento com RGL reduziu a FG apenas em NC de 0,78±0,03 para 0,50±0,05* ml/min/100g, *p<0,001. Apesar da redução da FG, a UVNa em NC+RGL não se modificou. Durante a infusão de Ang II, a FG de NC, HC e HC+RGL reduziu-se para o mesmo patamar de NC+RGL e um significante aumento da UVNa foi observada apenas em NC+RGL (NC= 3,32±0,88; NC+RGL=5,86±1,04*; HC= 2,63±0,43 e HC+RGL= 2,23±0,39 uEq/min, *p<0,01). Além disso, RGL induziu aumento na atividade da Na+,K+-ATPase em HC+RGL e não modificou em NC+RGL. Os valores expressos em M Pi/mg proteína.h-1 foram de 45±7 em NC, 43±5 em NC+RGL, 48±7 em HC e 64±4* em HC+RGL, *p<0,05. Analisando todos os resultados em conjunto, a redução da FG associada com a alta natriurese e ausência da modulação da atividade da Na+,K+-ATPase em NC+RGL sugerem lesão renal neste grupo. Conclusão: Os mecanismos de ação da RGL diferem de acordo com a condição metabólica. Então, RGL deve ser prescrita com cautela na ausência de hipercolesterolemia e requer a monitoração da função renal principalmente nas situações de vasoconstrição / Introduction: Rosiglitazone (RGL) is a ligand for PPAR used to treat type 2 Diabetes Mellitus and inflammatory diseases. However, RGL can reduce the glomerular filtration rate (GFR), urinary sodium excretion (UVNa) and increase the expression of Na+, K+-ATPase in renal medulla. Thus, RGL may induce edema and congestive heart failure. However, acute renal failure (ARF) provoked by RGL treatment has not been reported. Aim: To test whether reduced GFR by RGL may predispose to ARF at baseline and during a renal vasoconstriction state, and if the findings differ between normocholesterolemic (NC) and hypercholesterolemic (HC) rats. Methods: GFR was measured by inulin clearance on the 8th day in NC and HC rats (~200g) treated or not with RGL (48 mg/kg diet) at baseline and during intravenous infusion of Ang II (40 ng/kg/min). Furthermore, the Na+,K+- ATPase activity was determined in renal homogenates in other series of animals. Results: At baseline, NC and HC had similar GFR and the treatment with RGL reduced GFR only in NC from 0.78±0.03 to 0.50±0.05* ml/min/100g, *p<0.001. Although GFR was reduced, UVNa was unchanged in NC+RGL. During Ang II infusion, GFR was significantly reduced in NC, HC and HC+RGL and it remained at the same reduced level in NC+RGL. At this time, when GFR was reduced the same range in all groups, a significant increment in UVNa was only observed in NC+RGL (NC = 3.32±0.88; NC+RGL = 5.86±1.04*; HC = 2.63±0.43 and HC+RGL = 2.23±0.39 Eq/min, *p<0.01). Moreover, RGL induced an increase in the activity of Na+, K+-ATPase in HC+RGL, but it did not modify the activity of this enzyme in NC+RGL. The values expressed in M Pi/mg.protein.h-1 were 45±7 in NC, 43±5 in NC+RGL, 48±7 in HC and 64±4* in HC+RGL, *p<0.05. Taken together, reduction in GFR associated with high natriuresis and without changes in the Na+, K+-ATPase activity in renal medulla of NC+RGL may suggest renal injury in this group. Conclusion: RGL may act distinctly in normocholesterolemia and in hypercholesterolemia. Thus, RGL may be prescribed with caution in absence of hypercholesterolemia and requires monitoring of renal function specially if a renal vasoconstriction state is associated.

Background: Glomerular filtration rate (GFR) is a clinically important measurement of kidney function and estimating the GFR is of great importance in healthcare. Methods available today either lack in precision or are overly time consuming. Proenkephalin (PENK) has been shown to correlate well with the GFR and has therefore been proposed as a novel biomarker for kidney function. Aim: To evaluate a new point-of-care test for measuring PENK in blood and to assess its correlation to GFR measured by iohexol plasma clearance (mGFRiohexol). Materials and methods: Blood was collected from 21 patients with varying indications for the iohexol plasma clearance test. PENK was measured with IB10 Sphingotest penKid in whole blood, plasma and serum respectively. The concentration was correlated to the mGFRiohexol and results were compared to those from measurement of the routine markers for kidney function, i.e. creatinine and cystatin C. Results: Fourteen men and seven women were included. The median age was 57 years. PENK in plasma correlated weakly with mGFRiohexol (R2=0.22, p=0.042). No significant correlation was shown for PENK in whole blood or serum. Creatinine also showed a weak correlation with mGFRiohexol (R2=0.35, p=0.0046). In contrast, cystatin C was strongly correlated with mGFRiohexol (R2= 0.87, p&lt;0.0001). Conclusion: Our results indicate that PENK is a biomarker of low clinical value for estimating the GFR. However, further studies are needed before this can be assured. Cystatin C, on the contrary, seems to be an accurate biomarker for estimating the GFR.

Unilateral ischemia-reperfusion (UIR) injury leads to progressive renal atrophy and tubulointerstitial fibrosis (TIF) and is commonly used to investigate the pathogenesis of the acute kidney injury-chronic kidney disease transition. Although it is well known that contralateral nephrectomy (CNX), even 2 wk post-UIR injury, can improve recovery, the physiological mechanisms and tubular signaling pathways mediating such improved recovery remain poorly defined. Here, we examined the renal hemodynamic and tubular signaling pathways associated with UIR injury and its reversal by CNX. Male Sprague-Dawley rats underwent left UIR or sham UIR and 2 wk later CNX or sham CNX. Blood pressure, left renal blood flow (RBF), and total glomerular filtration rate were assessed in conscious rats for 3 days before and over 2 wk after CNX or sham CNX. In the presence of a contralateral uninjured kidney, left RBF was lower (P < 0.05) from 2 to 4 wk following UIR (3.6 + 0.3 mL/min) versus sham UIR (9.6 + 0.3 mL/min). Without CNX, extensive renal atrophy, TIF, and tubule dedifferentiation, but minimal pimonidazole and hypoxia-inducible factor-1α positivity in tubules, were present at 4 wk post-UIR injury. Conversely, CNX led (P < 0.05) to sustained increases in left RBF (6.2 ∓ 0.6 mL/min) that preceded the increases in glomerular filtration rate. The CNX-induced improvement in renal function was associated with renal hypertrophy, more redifferentiated tubules, less TIF, and robust pimonidazole and hypoxia-inducible factor-1α staining in UIR injured kidneys. Thus, contrary to expectations, indexes of hypoxia are not observed with the extensive TIF at 4 wk post-UIR injury in the absence of CNX but are rather associated with the improved recovery of renal function and structure following CNX.

Yes / Acute kidney injury (AKI) can occur rarely in patients exposed to iodinated contrast and result in contrast-induced AKI (CI-AKI). A key risk factor is the presence of pre-existing chronic kidney disease (CKD), therefore it is important to assess patient risk and obtain kidney function measurement prior to administration. Point of care (PoC) testing provides an alternative strategy but there remains uncertainty, with respect to diagnostic accuracy and clinical utility. A device study compared three PoC analysers (Nova StatSensor, Abbott i-STAT, Radiometer ABL800 FLEX) with a reference laboratory standard (Roche Cobas 8000 series, enzymatic creatinine). Three hundred adult patients attending a UK hospital phlebotomy department were recruited to have additional blood samples for analysis on the PoC devices. The ABL800 FLEX had the strongest concordance with laboratory measured serum creatinine (mean bias=-0.86, 95% limits of agreement = -9.6 to 7.9) followed by the i-STAT (average bias=3.88, 95% limits of agreement = -8.8 to 16.6) and StatSensor (average bias=3.56, 95% limits of agreement = -27.7 to 34.8). In risk classification, the ABL800 FLEX and i-STAT identified all patients with an eGFR≤30, whereas the StatSensor resulted in a small number of missed high-risk cases (n=4/13) and also operated outside of the established performance goals. The screening of patients at risk of CI-AKI may be feasible with PoC technology. However in this study it was identified that the analyser concordance with the laboratory reference varies. It is proposed that further research exploring PoC implementation in imaging department pathways is needed. / Yorkshire and Humber Academic Health Science Network (Grant Number: YHP0318)

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

<p>Endotelin-1 je najpotentniji vazokontstriktorni peptid koji značajno doprinosi funkcionalnim i strukturnim bubrežnim promenama i poslednjih godina se izdvojio kao značajan faktor u razvoju i progresiji dijabetesne nefropatije. Cilj ovog istraživanja bio je odrediti nivo plazmatskog endotelina-1 kod bolesnika sa tipom 2 &scaron;ećerne bolesti u odnosu na zdravu populaciju kao i ispitati odnos plazmatskog endotelina-1 i funkcionog statusa bubrega kod bolesnika sa &scaron;ećernom bolesti tip 2 i dijabetesnom nefropatijom. U istraživanje je uključeno sto dvadeset ispitanika sa tipom 2 dijabetesa i sekundarno inzulin zavisni, koji&nbsp; su podeljeni u dve grupe u odnosu na izmerenu jačinu glomerulske filtracije: Grupa I (n=60) ispitanici sa jačinom glomerulske filtracije većom od 60 ml/min/1.73m2 i grupa II (n=60) ispitanici sa jačinom glomerulske filtracije manjom od 60 ml/min/1.73m2. Kod svih ispitanika izmerena je plazmatska vrednost endotelina-1 i izvr&scaron;ena procena funkcionog statusa bubrega merenjem jačine glomerulske filtracije, efektivnog bubrežnog protoka plazme i ostalih parametara bubrežne funkcije: serumske koncentracije cistatina C, uree, kreatinina, mokraćne kiseline kao i određivanje 24h albuminurije i proteinurije. Dobijeni rezultati upoređivani su sa rezultatima kontrolne grupe ispitanika (n= 30). Postoji statistički značajna razlika u medijanama vrednosti endotelina-1 između ispitivanih grupa (p&lt;0.001). Značajno niže vrednosti plazmatske koncentracije endotelina-1 su imali ispitanici kontrolne grupe (0.80 &plusmn;0.3) u odnosu na ispitanike sa &scaron;ećernom bolesti i JGF&gt;60 ml/min (1.4&plusmn;0.4) kao i u odnosu na dijabetesne bolesnike sa JGF&lt;60ml/min (2.5 &plusmn;0.8). Značajno vi&scaron;e vrednosti endotelina-1 su&nbsp; imali bolesnici sa &scaron;ećernom bolesti i većim stepenom redukcije jačine glomerulske filtracije u odnosu na bolesnike sa manjim stepenom redukcije jačine glomerulske filtracije (p&lt;0.001). U grupi bolesnika sa tipom 2 &scaron;ećerne bolesti postoji statistički značajna inverzna korelacija između plazmatskog nivoa endotelina-1 i izmerene vrednosti jačine glomerulske filtracije i efektivnog bubrežnog protoka plazme (r= -0,75; p=0,000; r= -0,74; p=0,000) odnosno bolesnici sa &scaron;ećernom bolesti kod kojih postoje povi&scaron;ene vrednosti plazmatskog endotelina-1 imaju veći stepen redukcije jačine glomerulske filtracije i efektivnog bubrežnog protoka plazme. Kod bolesnika sa tipom 2 dijabetes melitusa i različitim stepenom bubrežne hipofunkcije endotelin-1 u značajnoj meri utiče na vrednosti jačine glomerulske filtracije i efektivnog bubrežnog protoka plazme ali i druge funkcijske parametre bubrega i samim tim može imati važnu ulogu u nastanku i razvoju dijabetesne nefropatije.</p> / <p>Endothelin-1, potent vasoconstrictor peptide may contribute to the functional and structural renal changes and in recent years emerged as a significant factor in the development&nbsp; and progression of diabetic nephropathy. The aim of&nbsp; this study was to determine the level of plasma endothelin-1 levels in patients with type 2 diabetes and compared to healthy&nbsp; population as well as to examine the relationship of plasma endothelin-1 and the functional status of the kidneys in patients with type 2 diabetes. The study included one hundred&nbsp; and&nbsp; twenty patients&nbsp; with type 2 diabetes and insulin-dependent secondary, which are divided into two groups with respect to the measured GFR: Group I (n = 60) subjects with by glomerular filtration rate greater than 60 ml /min/1.73m2 and group II (n&nbsp; =&nbsp; 60) subjects with by glomerular filtration rate of less than 60ml/min/1.73m2 . Plasma levels of endothelin-1, glomerular filtration rate and effective renal plasma flow were determined using appropriate methods in all subjects. Other renal function parameters such as serum&nbsp; concentrations of cystatin C, urea, creatinine, uric acid, 24h albuminuria and proteinuria were measured additionaly. The results were compared with control groups of subjects (n= 30). There was a statistically significant difference in median values of endothelin-1 between the groups (p&lt;0.001). Significantly lower plasma concentrations of endothelin-1 had control subjects (0.80&nbsp; &plusmn;&nbsp; 0.3) compared to subjects with diabetes and GFR&gt;60 ml/min (1.4 &plusmn; 0.4) and in relation to diabetic patients with GFR &lt;60 ml/min (2.5 &plusmn; 0.8). Significantly higher values of endothelin-1 had patients with diabetes and a higher degree of reduction of glomerular filtration rate compared with patients with a lower degree of&nbsp; reduction of glomerular filtration rate (p &lt;0.001). In the group of patients with type 2 diabetes, there was a statistically significant inverse correlation between plasma levels endothelin-1 and the measured values of glomerular filtration rate and effective renal plasma flow (r= -0.75; p=0.000; r= -0.74; p=0.000) and patients with diabetes who have the higher values of&nbsp; plasma endothelin-1 have a higher degree of reduction of glomerular filtration rate and effective renal plasma flow. In patients with type 2 diabetes mellitus and various degrees of renal hypofunction endothelin-1 significantly affects the value of the glomerular filtration rate and effective renal plasma flow or other parameters of renal function and thus can play an important role in thedevelopment of diabetic nephropathy.</p>