As diretrizes nacionais e internacionais de nefrologia e diabetologia recomendam que, em pacientes com diabete melito (DM), além da aferição anual da excreção urinária de albumina, seja realizada a estimativa da TFG por meio de equações que incluam a creatinina sérica. As equações mais empregadas e analisadas têm sido as dos estudos MDRD (Modification of Diet in Renal Disease) e CKD-EPI (Chronic kidney Disease Epidemiology Collaboration). No entanto, algumas evidências demonstram um pior desempenho dessas equações em indivíduos com DM, com acentuada subestimativa da TFG. Este desempenho limitado parece estar relacionado a peculiaridades do paciente com DM, como a presença de hiperglicemia e hiperfiltração glomerular, mas também a limitações da própria creatinina como marcador pouco sensível e específico da TFG. O uso de novos marcadores endógenos com perfil mais próximo do ideal, como é o caso da cistatina C, tem se mostrado promissor, mas a sua acurácia ainda não foi adequadamente demonstrada no DM. O objetivo desse artigo foi analisar criticamente os métodos disponíveis de medida e de estimativa da TFG em pacientes com DM, enfatizando aspectos peculiares e possíveis interferentes. / The current guidelines of Nephrology and Diabetology recommend that in patients with diabetes mellitus (DM), along with the annual measure of urinary albumin excretion, the glomerular filtration rate (GFR) should be estimated using creatinine-based equations. The most frequently recommended equations were developed by the MDRD (Modification of Diet in Renal Disease) and CKDEPI (Chronic Kidney Disease Epidemiology Collaboration) studies. However, recent evidences show a worse performance of these equations in diabetic patients, with a significant underestimation of GFR. This limited performance seems to be related to the peculiarities of the patient with DM, such as the presence of hyperglycemia and glomerular hyperfiltration, but also due to the limitations in the sensitivity and specificity of serum creatinine as GFR marker. The use of new markers with closer–to-the ideal endogenous profile, like cystatin C, has shown promise, but its accuracy has not been yet adequately demonstrated in DM. The purpose of this article was to critically analyze the current available methods of measurement and estimation of GFR in patients with DM, emphasizing its peculiarities and possible interferences.

INTRODUÇÃO: A cistatina C é uma proteína não glicosilada de baixo peso molecular que é produzida por todas as células nucleadas. A medida da concentração sérica (CS) de cistatina C tem sido aclamada como um marcador de função renal superior à medida da CS de creatinina. No presente estudo, avaliou-se a acurácia diagnóstica da proteína cistatina C em estimar mudanças no Ritmo de Filtração Glomerular (RFG) medido por 51Cr-EDTA, em análise longitudinal prospectiva de pacientes transplantados renais com tempo de transplante recente e tardio. Em uma fase inicial (Fase A), definimos a melhor estratégia metodológica para a realização do RFG por depuração plasmática de 51Cr-EDTA em receptores de enxerto renal utilizando a depuração renal de inulina como método padrão-ouro. MÉTODOS: Medidas simultâneas de depuração renal de inulina e de depuração plasmática de 51Cr-EDTA foram feitas em pacientes transplantados renais. A precisão do método de medida do RFG por 51Cr-EDTA foi avaliada em doadores após um ano de doação de rim. A análise de Bland&Altman foi empregada para avaliar a concordância entre os métodos. Em uma segunda fase, foram realizadas medidas das CS de cistatina C e de creatinina e do RFG por 51Cr-EDTA nos meses 1, 3, 6 e 12 de seguimento clínico do estudo em pacientes transplantados renais. A cistatina C foi dosada em amostras de soro, por técnica de imunonefelometria (N Latex Cystatin C kit - Dade Behring). A tendência da função renal foi obtida por Regressão Linear Simples. RESULTADOS: Na fase A, foram incluídos 44 pacientes transplantados renais e 22 doadores de rim com tempo de doação de 12,4 a 53,5 meses. A depuração de 51Cr-EDTA com amostras de sangue coletadas nos tempos 2, 4, 6 e 8 horas após injeção do radiofármaco apresentou forte correlação e alto grau de concordância com a depuração de inulina; uma estratégia única para todos os níveis de função foi estabelecida com amostras de sangue nos tempos 4 e 6 horas. Em uma segunda fase do estudo, oitenta e dois pacientes foram incluídos, com idade média de 43,4 ± 11,9 anos. A maioria era da raça branca (56%) e do sexo masculino (68%). No mês 1, a média do RFG por 51Cr-EDTA foi de 50,6 ± 17,3 ml/min/1,73m², e foi de 1,62 ± 0,65 mg/L para a CS de cistatina C e de 1,40 ± 0,62 mg/dL para a CS de creatinina. Na análise transversal, foi encontrada uma forte correlação entre o RFG e a medida de CS de cistatina C. Entretanto, na análise longitudinal do seguimento clínico a CS de cistatina C não estimou a tendência de mudança no RFG. CONCLUSÕES: A depuração plasmática de 51Cr-EDTA é uma medida precisa e acurada de RFG que pode ser utilizada em substituição à depuração renal de inulina, em pacientes transplantados renais. Medidas seriadas da CS de cistatina C não foram capazes de detectar mudanças no RFG em pacientes transplantados renais. / INTRODUCTION: Cystatin C is a nonglycosylated protein that is synthesized by all nucleated cells. The present study aimed to analyze the accuracy of serum concentration of cystatin C for detecting longitudinal change in glomerular filtration rate in transplanted recipients, as well to define a better methodological strategy to perform the plasma clearance of 51Cr-EDTA in renal transplant patients using inulin clearance as the gold standard method. METHODS: in the first phase of the study, simultaneous measurements of plasma clearance of 51Cr-EDTA and renal clearance of inulin in stable renal transplanted patients were performed. The within-subject repeatability of the 51Cr-EDTA was evaluated in live kidney donors at least 12 months after donation. Bland&Altman statistical approach was used to quantify the degree of agreement between clearance of inulin and plasma clearance of 51Cr-EDTA. In a second phase, serial measures of plasma clearance of 51Cr-EDTA, serum cystatin C and serum creatinine were examined in folowing at 1, 3, 6 and 12 months in kidney transplanted patients. Serum cystatin C was measured by a nephelometric immunoassay (N latex cystatin C kit - Dade Behring). The trend in renal function over time was obtained by linear regression. RESULTS: In the first phase, 44 transplanted patients and 22 kidney donors at least 12 months after donation (range 12,4 to 53,5 months) were enrolled. Plasma clearance of 51Cr-EDTA with four samples taken at 2, 4, 6 and 8 hours presented a strong association and closely agreement with inulin clearance. An abbreviated strategy was recommended with two blood sampling collected at 4 and 6 hours. In the second phase, 82 kidney transplanted patients were enrolled. Mean age was 43.4 ± 11.9 years. The majority were white (56%) and male (68%). The mean of the plasma clearance of 51Cr-EDTA was 50.6 ± 17.3, and it was 1.62 ± 0.65 mg/L and 1.40 ± 0.62 mg/dL for serum cystatin C and creatinine, respectively, at baseline. In cross-section analysis, serum cystatin C was strongly correlated with plasma clearance of 51Cr-EDTA. However, in longitudinal analysis serum cystatin C was not able for estimate GFR. CONCLUSIONS: Plasma clearance of 51Cr-EDTA is a precise method to measure GFR in renal transplanted recipients. The results showed that serial measurements of serum cystatin C are not able to detect trends in renal function in transplanted patients.

Introdução: A nefropatia crônica do enxerto permanece sendo a principal causa de perda tardia de enxertos renais. No momento, não existe uma estratégia terapêutica definida para minimizar ou reverter a perda da função renal. Diversas tentativas terapêuticas foram empregadas sem resultados definitivos. As estratégias de minimização de inibidores da calcineurina (CNI) com conversão para Micofenolato mofetil (MMF) e conversão para Sirolimo (SRL) são as mais promissoras. Este estudo avaliou a segurança e a eficácia dessas duas estratégias terapêuticas na progressão da nefropatia crônica do enxerto em pacientes transplantados renais. Métodos: Foram selecionados pacientes com filtração glomerular (RFG) medida por depuração de 51Cr-EDTA entre 25 e 60 ml/min/1,73 m2 que apresentaram alterações histológicas compatíveis com nefropatia crônica do enxerto e que não apresentaram proteinúria 24 h superior a 800 mg/24 h. Os pacientes foram randomizados para serem convertidos ao SRL ou manterem-se sob níveis baixos de CNI associados ao MMF e prednisona. O objetivo primário foi avaliar um objetivo composto pelos seguintes eventos: morte, perda do enxerto, rejeição aguda ou perda de RFG inicial superior a 20%. Os pacientes foram acompanhados por 12 meses e a uma análise por intenção de tratar foi realizada ao fim desse período. Resultados: Vinte e nove pacientes foram randomizados para os grupos SRL (n=14) e CNI (n=15). Não houve diferença entre os grupos quanto a os dados demográficos e imunológicos. Os valores de creatinina sérica e a TFG foram semelhantes no momento da randomização. A sobrevida dos pacientes e dos enxertos foi de 100%. Não foram observados episódios de rejeição aguda. Após 12 meses, não houve diferença significativa entre os grupos com relação à TFG. Houve maior número de eventos adversos não-graves no grupo SRL, destacandose, acne, edema, piora de dislipidemia e anemia. Entretanto, o número de eventos adversos graves não foi estatisticamente diferente entre os grupos. SRL foi descontinuado temporariamente em 1 paciente, mas não ocorreu descontinuação definitiva no estudo. Conclusão: Os dois esquemas terapêuticos apresentaram desempenhos rigorosamente semelhantes com relação à evolução da função renal e quanto à evolução histológica, mas houve um número maior de eventos adversos não-graves com o uso de sirolimo / Chronic allograft nephropathy is the main cause of late kidney graft loss. Several treatments have been proposed for this condition without conclusive results. Calcineurin inhibitors minimization and conversion to Sirolimus are the most promising alternatives. This study evaluated the safety and the efficacy of these therapeutic strategies on one-year progression of chronic allograft nephropathy in kidney transplant recipients. Patients with measured glomerular filtration rate (51Cr-EDTA plasmatic clearance) between 25 e 60 ml/min/1,73 m2 and histological findings of CAN, with proteinuria less than 800 mg/24 h were included. They were randomized either to Sirolimus or to low-level of CNI (both groups received MMF and prednisone). The primary end-point was a composite of first occurrence of death, graft loss, acute rejection or a 20% decrease of initial GFR. Patients were followed for 12 months and evaluated as intention-to-treat analysis. Twenty-nine patients were included in this study. Fourteen patients were randomized to SRL group and fifteen to CNI group. At baseline, no differences were detected in any of the demographic and immunologic group characteristics. Also, serum creatinine and GFR were not different at randomization. One year after conversion, patient and graft survival was 100%. At 12 months, there were no differences in GFR between two groups, in SRL group was 41,99 ± 13,48 ml/min/1,73 m2and in CNI group was 41,21 ± 9,10 ml/min/1,73 m2 (p=0,96). Non-serious adverse events, like anemia (p=0,006), acne (p=0,006), edema (p=0,005) and mouth ulcers (p=0,017) were more frequently found in the SRL group. No significant difference in serious adverse events was observed. SRL was temporarily interrupted in one patient. None of the patients dropped-out from the study and none required study drug discontinuation. In conclusion both regimens conferred equal beneficial in GFR preservation in CAN patients. However, SRL was associated with more adverse events

Abstract Congenital nephrotic syndrome of the Finnish type (NPHS1, CNF) is an autosomal recessive disease that affects 1:8000 newborns in Finland. NPHS1 is characterised by heavy proteinuria already in utero and typical signs of nephrotic syndrome (NS) are present at or soon after birth. Due to the evident absence of extrarenal symptoms, NPHS1 has been considered a model disease for NS. In this study, the NPHS1 locus on chromosome 19q13.1 was sequenced and analysed with computer programs to identify new genes in the region. Genes were further characterised and sequenced from NPHS1 patient samples, as well as from controls. Analysis of the data resulted in the identification of the affected gene with two mutations that were found to explain 94% of the Finnish NPHS1 cases. The NPHS1 gene was found to encode a novel single-pass transmembrane protein, termed nephrin, which belongs to the immunoglobulin superfamily of cell adhesion molecules. The NPHS1 gene was cloned and recombinant nephrin fragments were produced in prokaryotic and eukaryotic expression systems. These fragments were used to raise antibodies that were utilized to characterise the spatial and temporal expression of nephrin in kidney glomeruli. Nephrin was localised by electron microscopy (EM) in ladder-like structures of the early junctional complexes of developing columnar podocytes at the capillary stage. In mature glomeruli, nephrin was localised to the slit diaphragm (SD) between adjacent glomerular podocyte foot processes. In order to investigate the more general involvement of nephrin in proteinuric disease, its expression was studied in primary acquired NS by immunofluorescence microscopy. The level of nephrin expression was found to be significantly reduced in membranous glomerulonephritis, minimal change disease and in focal segmental glomerulosclerosis. The known effects of nephrin mutations, together with the structure predicted from its sequence and localisation of the protein to the SD, emphasizes its indispensable role in maintaining the integrity of the glomerular filtration barrier. The glomerular basement membrane has long been considered to possess the size-selective filtration property of the filtration barrier. However, the identification of nephrin in the SD, as well as its alterations in proteinuria, has led us to reconsider SD as the final decisive size-selective filter.

Background-Heart failure is common in patients with chronic kidney disease. We studied risk factors for incident heart failure among 3557 participants in the CRIC (Chronic Renal Insufficiency Cohort) Study. Methods and Results-Kidney function was assessed by estimated glomerular filtration rate (eGFR) using serum creatinine, cystatin C, or both, and 24-hour urine albumin excretion. During an average of 6.3 years of follow-up, 452 participants developed incident heart failure. After adjustment for age, sex, race, and clinical site, hazard ratio (95% CI) for heart failure associated with 1 SD lower creatinine-based eGFR was 1.67 (1.49, 1.89), 1 SD lower cystatin C-based-eGFR was 2.43 (2.10, 2.80), and 1 SD higher log-albuminuria was 1.65 (1.53, 1.78), all P< 0.001. When all 3 kidney function measures were simultaneously included in the model, lower cystatin C-based eGFR and higher log-albuminuria remained significantly and directly associated with incidence of heart failure. After adjusting for eGFR, albuminuria, and other traditional cardiovascular risk factors, anemia (1.37, 95% CI 1.09, 1.72, P= 0.006), insulin resistance (1.16, 95% CI 1.04, 1.28, P= 0.006), hemoglobin A1c (1.27, 95% CI 1.14, 1.41, P< 0.001), interleukin-6 (1.15, 95% CI 1.05, 1.25, P= 0.002), and tumor necrosis factor-a (1.10, 95% CI 1.00, 1.21, P= 0.05) were all significantly and directly associated with incidence of heart failure. Conclusions-Our study indicates that cystatin C-based eGFR and albuminuria are better predictors for risk of heart failure compared to creatinine-based eGFR. Furthermore, anemia, insulin resistance, inflammation, and poor glycemic control are independent risk factors for the development of heart failure among patients with chronic kidney disease.

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Os efeitos da suplementação de creatina sobre a função renal são debatidos intensamente na literatura científica. Os poucos trabalhos sobre o tema envolvendo humanos têm sido severamente criticados por apresentarem ausência de randomização, dosagens não uniformes de creatina, baixo poder estatístico e, sobretudo, ausência de marcadores padrão-ouro de função renal. Além disso, embora tenhamos mostrado recentemente que a suplementação de creatina não prejudica a função renal em sujeitos submetidos a treinamento aeróbio, a natureza desse tipo de atividade, bem como o habitual consumo de proteína dessa amostra, não permite que generalizemos nossos achados à população que mais utiliza creatina: praticantes de treinamento de força sob dietas ricas em proteína. Desta forma, foi conduzido um ensaio randomizado, duplo-cego, controlado por placebo, com o objetivo de investigar os efeitos da suplementação de creatina e sua possível interação com o alto consumo de proteínas sobre a função renal, em praticantes de treinamento de força. Os sujeitos foram divididos aleatoriamente em 2 grupos: a) suplementação de creatina (20g/dia durante cinco dias e 5g/dia até o término do estudo) e b) placebo (dextrose). No período basal e após 12 e 24 semanas, os sujeitos tiveram acompanhamento do consumo alimentar, e foram analisados o clearance de 51Cr-EDTA, creatinina sérica, sódio e potássio séricos e urinários e microalbuminúria. Não foram encontradas diferenças significativas nas variáveis analisadas após 12 e 24 semanas. Demonstrando assim, a ausência de alteração da função renal decorrente da suplementação de creatina, em praticantes de treinamento de força recreacionais com consumo proteico >=1,2g/kg peso/dia / The effects of creatine supplementation on renal function are discussed extensively in the literature. Few studies on the topic involving humans have been severely criticized because of the absence of randomization, non-uniform doses of creatine, low statistical power and, above all, the absence of a gold standard markers of renal function. Furthermore, although we have recently shown that creatine supplementation does not impair renal function in subjects undergoing aerobic training, the nature of this type of activity, as well as the usual protein intake in this sample does not allow generalization of our findings to the population who consume creatine: practitioners of strength training with a high protein intake. Thus, we conducted a randomized, double-blind, placebo-controlled study, in order to investigate the effects of creatine supplementation and its possible interaction with high protein intake on renal function in practicioners of strength training. The subjects were randomly assigned to 2 groups: a) creatine supplementation (20g/day during five days and 5g/day until the end of the study) and b) placebo (dextrose). At baseline and after 12 and 24 weeks, food intake, 51Cr-EDTA clearance, serum creatinine, sodium and potassium serum and urinary microalbuminuria was assessed. No significant differences were observed throughout the trial. Demonstrating that creatine supplementation on practitioners of strength training with high protein intake does not harm renal function

Orientador: Roberto Jorge da S. Franco / Coorientador: Luis Cuadrado Martin / Banca: Pasqual Barretti / Banca: Vanessa dos Santos Silva / Banca: Eduardo Barbosa Coelho / Banca: Marcio Dantas / Resumo: A doença renal crônica (DRC) representa um problema de saúde pública global. Os idosos têm diminuição progressiva da função renal e os hipertensos e diabéticos apresentam maior risco de lesão renal. Essas doenças crônicas são comuns aos idosos favorecendo o comprometimento de lesão renal. Com base neste fato, o objetivo do estudo foi identificar o melhor método para avaliar precocemente a filtração glomerular (FG) em indivíduos idosos. Comparando-se as fórmulas baseadas na creatinina sérica, bem como o Clearance de Creatinina de 24h com a fórmula baseada nos níveis séricos de Cistatina C, eleita como padrão ouro. Foi realizado um estudo observacional, analítico, de delineamento transversal sobre a filtração glomerular e o desenvolvimento da doença renal, com base nos resultados obtidos na avaliação clínica e nos exames laboratoriais de bioquímica e urinálise. Participaram do estudo 180 idosos de ambos os sexos, com idade igual ou superior a 60 anos, do Centro de Atenção Integrada da Melhor Idade (CAIMI), da cidade de Manaus-AM. Foram construídos gráficos de dispersão, calculado o coeficiente de correlação, bem como traçados diagramas de Bland Altman e curvas ROC. A média de idade dos 180 idosos foi de 67 anos - 68,8% do sexo feminino, e 31,1% do sexo masculino. Hipertensos representaram 43,5% do total. Renais crônicos representaram 19%. Portadores de diabetes mellitus chegaram a 38,3%. Ao observar a equação de regressão, quando o CKD-epiCys for zero, o Clearance de Creatinina (ClCr) valerá 62,07 ml/min/1,73m2, o que caracteriza uma superestimação do valor real da FG. A média avaliada pelo ClCr e CKD-epiCys foi de 28,8 ml/min/1,73m2. Este valor é bem superior à zero, que seria o ideal. Isto mostra que o ClCr superestima a FG avaliada pelo CKD-epiCys. A curva ROC para o ClCr na discriminação da presença de FG< 60 ml/min avaliada pelo padrão foi de 0,65, com ... / Abstract: Chronic kidney disease (CKD) is a global public health problem. The elderly have progressive decrease of renal function, and those with hypertension and diabetes are at increased risk of kidney damage. These chronic diseases are common to the elderly and promote renal injury. This study aimed to identify the best method to assess early glomerular filtration (GF) in elderly subjects. Formulas based on serum creatinine and creatinine clearance of 24 hours were compared with the formula based on serum cystatin C chosen as gold standard. We conducted an observational, analytical, cross-sectional design of the glomerular filtration rate and the development of kidney disease, through results obtained in clinical evaluation, and biochemistry and urinalysis laboratory tests. Participants were 180 patients of both sexes, aged over 60 years, from the Centro de Atenção Integrada da Melhor Idade [Center for Integrated Management of the Elderly], in the city of Manaus, State of Amazonas, Brazil. Scatter plots were constructed by calculating the correlation coefficient, as well as Bland Altman plotted diagrams and ROC curves. The average age of the elderly participants was 67 years; 68.8% were female and 31.1% male; 43.5% had hypertension; 19%, chronic renal failure; and 38.83%, diabetes mellitus. By observing the regression equation, when the CKD-epiCys was zero, creatinine clearance (CrCl) was 62.07 ml/min/1.73m2, which means overestimation of the real FG rate. The average assessed by CrCl. and CKD-epiCys was 28.8 ml/min/1,73m2, a value above zero, which would be ideal. This shows that CrCl. overestimates FR assessed by CKD-epiCys. The ROC curve for CrCl to discriminate the presence of FG <60 ml / min measured by the standard was 0.65, with 95% confidence interval from 0.56 to 0.76 (p = 0.006). The CrCl had statistically significant predictive power concerning the presence of KD. The regression was assessed by ... / Doutor

National Kidney Disease Education Program has initiated a serum creatinine standardization program. Glomerular filtration rate (GFR) can be re-estimated from standardized serum creatinine measurements. How the standardized estimated GFR (eGFR) influences hypertension prevalence has not been evaluated. In this study, cross-sectional data from 21 205 participants aged 18 years in the National Health and Nutrition Examination Survey 1999-2006 were analyzed. The differences between standardized and non-standardized eGFRs in the prevalence of hypertension and low eGFR were evaluated. Multiple logistic regression models were conducted to determine the association of standardized eGFR with hypertension prevalence. The prevalence of low eGFR estimated from standardized eGFR was higher than that from non-standardized eGFR (all P0.01), except for the 2005-2006 survey. The prevalence of hypertension under standardized eGFR was not significantly different from that under non-standardized eGFR in both groups of participants with eGFR60 and eGFR60 ml min 1 per 1.73 m 2. Adjusted for age, education, gender, race/ethnicity, smoking, serum cholesterol and diabetes mellitus, the participants with standardized eGFR60 ml min 1 per 1.73 m 2 had 56.1% more chance to be hypertensive patients than those with normal eGFR (P0.0001). The difference in the relationship to hypertension prevalence between standardized and non-standardized eGFR was not found significant.

Dialysis patients are often denied hospice benefits unless they forego dialysis treatments. However, many of those patients might benefit from as-needed dialysis treatments to palliate symptoms of uremia, fluid overload, etc. The current Medicare payment system precludes this "palliative dialysis" except in those few cases where the terminal diagnosis is unrelated to renal failure. As approximately three quarters of all US patients on dialysis have Medicare as their primary insurance, a of review of Medicare policy is suggested, with a goal of creating a new "palliative dialysis" category that would allow patients to receive treatments on a less regular schedule without affecting the quality statistics of the dialysis center.