Benefits of water intake on kidney function in older adults: protocol for a randomized controlled trial / Benefícios da ingestão de água na função renal de idosos: protocolo para um estudo clínico randomizado controlado

Objective: The goal of this study is to evaluate the benefits of an increase in water intake guided by a mathematical formula (per kg of body weight) on kidney function in older adults. Methods: Older adults (≥ 65 years old) cared for at the Internal Medicine Unit of a tertiary hospital will be randomized to receive or not guidance on water intake (30 mL/kg per day) after initial assessment of kidney function. After 14 days, participants will be reevaluated through clinical and laboratory examinations. Patients with uncompensated disease will be excluded. The main outcomes will be glomerular filtration rate and laboratory measures such as serum and urinary osmolality, sodium, urea, 24-h urine volume and serum creatinine, uric acid, and copeptin. The Mini Nutritional Assessment (MNA) questionnaire will be applied to participants at each visit. Categorical variables will be described as numbers of cases (%) and compared using the χ2 test whereas continuous variables will be analyzed with Student's t-test in relation to baseline measures. The Generalized Estimating Equations (GEE) method will be performed to assess differences over time and between groups. This study was approved by the Institution's Research Ethics Committee (grant number 16-0153) and is in accordance with the Declaration of Helsinki. Expected Results:By increasing water intake (ml/Kg) we expect to provide an improvement in kidney function in older population assessed by serum creatinine and cystatin-c applied to eGFR formulas. Relevance:Many conditions, both organic and behavioral, can contribute to chronic dehydration states in older adults. To mention, decreased ability to concentrate urine, reduced kidney mass, blood flow, and glomerular filtration rate (GFR) along with changes in sensitivity to hormones such as renin, vasopressin and natriuretic peptide can generate water imbalance, leading to dehydration. For being simple and inexpensive, this strategy may be broadly used and bring several health benefits to older adults.

Objetivo: O objetivo deste estudo é avaliar os benefícios de um aumento da ingestão de água guiado por uma fórmula matemática (por kg de massa corporal) na função renal de idosos. Metodologia:Idosos (≥ 65 anos) atendidos pelo Serviço de Clínica Médica de um hospital terciário foram randomizados para receber ou não orientação sobre o consumo de água (30 mL/kg por dia) após uma avaliação inicial da função renal. Após 14 dias, os participantes serão reavaliados através de exames clínicos e laboratoriais. Pacientes com doença descompensada serão excluídos. Os desfechos principais são a taxa de filtração glomerular e medidas laboratoriais como osmolaridade, sódio e ureia séricos e urinários, volume de urina de 24 horas e creatinina, ácido úrico e copeptina séricos. A Mini Avaliação Nutricional (MNA) será aplicada aos participantes a cada consulta. Variáveis categóricas serão descritas como números de casos (%) e comparadas usando o teste χ2 , enquanto variáveis contínuas serão analisadas com o teste t de Student em relação às medidas iniciais. O método de Equações de Estimativas Generalizadas (GEE) será usado para avaliar diferenças ao longo do tempo e entre grupos. Este estudo foi aprovado pelo Comitê de Ética em Pesquisa da nossa Instituição (processo número 16-0153) e está de acordo com a Declaração de Helsinki. Resultados esperados:Ao aumentar a ingestão de água (ml/Kg) esperamos proporcionar uma melhora na função renal na população idosa avaliada pela creatinina sérica e cistatina-c aplicada às fórmulas de eGFR. Relevância:Muitas condições, tanto orgânicas quanto comportamentais, podem contribuir para estados de desidratação crônica em idosos. Vale mencionar que a diminuição da capacidade de concentração da urina, redução da massa renal, fluxo sanguíneo e taxa de filtração glomerular (TFG) juntamente com alterações na sensibilidade a hormônios como renina, vasopressina e peptídeo natriurético podem gerar desequilíbrio hídrico, levando à desidratação. Por ser simples e de baixo custo, essa estratégia pode ser amplamente utilizada e trazer diversos benefícios à saúde dos idosos.

Does Cystatin C have a role as metabolic surrogate in peritoneal dialysis beyond its association with residual renal function? / Teria a Cistatina C um papel como substituto metabólico na diálise peritoneal além de sua associação com a função renal residual?

ABSTRACT Introduction: It has been suggested that cystatin C levels are modified by obesity and inflammation. Furthermore, cystatin C has been associated with cardiovascular events and mortality outcomes. Aim: To study the association of cystatin C with the metabolic profile and cardiovascular disease of peritoneal dialysis patients. Methods: Data collected included clinical, laboratorial, and multifrequency bioimpedance assessment of 52 stable peritoneal dialysis patients. Minimal residual renal function was defined as > 2mL/min/1.73m2. Results: Serum cystatin C was not significantly associated with peritoneal or urinary cystatin C excretion. Negative correlation of cystatin C with normalized protein catabolic rate (rho -0.33, p = 0.02) and a trend towards positive correlation with relative body fat (rho 0.27, p = 0.05) were not independent from residual renal function. Cystatin C was not significantly associated with cardiovascular disease (p = 0.28), nor with glycated hemoglobin (p = 0.19) or c-reactive protein (p = 0.56). In the multivariate model, both age and diabetes were the strongest predictors of cardiovascular disease (odds ratio 1.09, p = 0.029 and odds ratio 29.95, p = 0.016, respectively), while relative body fat was negatively associated with cardiovascular disease (p = 0.038); neither cystatin C (p = 0.096) nor minimal residual renal function (p = 0.756) reached a significant association with cardiovascular disease. Conclusions: In this group of peritoneal dialysis patients, cystatin C did not correlate with the metabolic or inflammatory status, nor cardiovascular disease, after adjustment for residual renal function.

RESUMO Introdução: Tem sido sugerido que os níveis de cistatina C são modificados pela obesidade e inflamação. Além disso, a cistatina C tem sido associada a eventos cardiovasculares e desfechos de mortalidade. Objetivo: Estudar a associação da cistatina C com o perfil metabólico e doença cardiovascular de pacientes em diálise peritoneal. Métodos: Os dados coletados incluíram avaliação clínica, laboratorial e de bioimpedância múltipla de 52 pacientes estáveis em diálise peritoneal. A função renal residual mínima foi definida como > 2mL/min/1,73m2. Resultados: A cistatina C sérica não esteve significativamente associada à excreção peritoneal ou urinária. A correlação negativa da cistatina C com a taxa catabólica protéica normalizada (rho -0,33, p = 0,02) e uma tendência de correlação positiva com a gordura corporal relativa (rho 0,27, p = 0,05) não foram independentes da função renal residual. A cistatina C não se associou significativamente à doença cardiovascular (p = 0,28), nem com hemoglobina glicada (p = 0,19) ou proteína C reativa (p = 0,56). No modelo multivariado, idade e diabetes foram os mais fortes preditores de doença cardiovascular (razões de probabilidade 1,09, p = 0,029 e 29,95, p = 0,016, respectivamente) enquanto a gordura corporal relativa se associou negativamente à doença cardiovascular (p = 0,038). A cistatina C não se associou significativamente com doença cardiovascular (p = 0,096), tampouco a função residual mínima (p = 0,756). Conclusão: Neste grupo de pacientes em diálise peritoneal, a cistatina C não se correlacionou com o estado metabólico ou inflamatório, nem com doença cardiovascular, após ajuste para função renal residual.

Relationship between Serum Cystatin C and Vascular Complications in Type 2 Diabetes Mellitus Patients with Normal Renal Function / 中国医学科学院学报

Objective To investigate the relationship between serum cystatin C(CysC)level and vascular complications in type 2 diabetes mellitus(T2DM)patients with normal renal function. Methods Totally 218 T2DM patients who were treated in the Department of Endocrinology,Affiliated Hospital of Chengde Medical College from January 2017 to May 2018 were enrolled.All subjects were divided into four groups based on the quartiles of serum CysC levels:G1 group:≤ 0.56 mg/L,58 cases;G2 group:0.57-0.73 mg/L,52 cases;G3 group:0.74-1.11 mg/L,56 cases;G4 group:≥ 1.12 mg/L,52 cases.The general data,biochemical indicators,glycated albumin,hemoglobin A

Expressions of plasma cystatin C, D-dimer and hypersensitive C-reactive protein in patients with intracranial progressive hemorrhagic injury after craniocerebral injury, and their clinical significance / Expressões da cistatina C plasmática, dímero D e proteína C reativa hipersensível em pacientes com lesão hemorrágica progressiva intracraniana após trauma crânio-encefálico e seus significados clínicos

ABSTRACT Objective To investigate the expressions of plasma cystatin C (Cys-C), D-dimer (D-D) and hypersensitive C-reactive protein (hs-CRP) in patients with intracranial progressive hemorrhagic injury (IPHI) after craniocerebral injury, and their clinical significance. Methods Forty-two IPHI patients and 20 healthy participants (control) were enrolled. The severity and outcome of IPHI were determined according to the Glasgow Coma Scale and Glasgow Outcome Scale, and the plasma Cys-C, hs-CRP and D-D levels were measured. Results The plasma Cys-C, D-D and hs-CRP levels in the IPHI group were significantly higher than those in the control group (p < 0.01). There were significant differences of plasma Cys-C, D-D and hs-CRP levels among different IPHI patients according to the Glasgow Coma Scale and according to the Glasgow Outcome Scale (all p < 0.05). In the IPHI patients, the plasma Cys-C, D-D and hs-CRP levels were positively correlated with each other (p < 0.001). Conclusion The increase of plasma Cys-C, D-D and hs-CRP levels may be involved in IPHI after craniocerebral injury. The early detection of these indexes may help to understand the severity and outcome of IPHI.

RESUMO Objetivo Investigar as expressões da cistatina C plasmática (Cys-C), dímero-D (D-D) e proteína C-reativa hipersensível (hs-CRP) em pacientes com lesão hemorrágica progressiva intracraniana (IPHI) após lesão craniocerebral e seus significados clínicos. Métodos Quarenta e dois pacientes com IPHI e 20 indivíduos saudáveis (controle) foram incluídos. A gravidade e o resultado do IPHI foram determinados de acordo com a Escala de Coma de Glasgow (GCS) e Escala de Resultados de Glasgow (GOS), e os níveis plasmáticos Cys-C, hs-CRP e D-D foram detectados. Resultados Os níveis plasmáticos de Cys-C, D-D e hs-CRP no grupo IPHI foram significativamente maiores do que no grupo controle (P <0,01). Houve diferença significativa entre os níveis plasmáticos de Cys-C, D-D e hs-CRP entre os diferentes pacientes com IPHI de acordo com a GCS e entre os diferentes pacientes com IPHI de acordo com o GOS, respectivamente (todos P <0,05). Em pacientes com IPHI, os níveis plasmáticos de Cys-C, D-D e hs-CRP foram positivamente correlacionados entre si (P <0,001). Conclusão O aumento dos níveis plasmáticos de Cys-C, D-D e hs-CRP pode estar envolvido no IPHI após trauma crânio-encefálico. A detecção precoce desses índices pode ajudar a entender a gravidade e o resultado do IPHI.

Clinical significance of cys-c and hs-crp in coronary heart disease patients undergoing percutaneous coronary intervention

Abstract Objective: To investigate the clinical significance of serum cystatin C (Cys-C) and high-sensitivity C-reactive protein (hs-CRP) in coronary heart disease (CHD) patients undergoing percutaneous coronary intervention (PCI). Methods: One hundred and twenty-eight CHD patients were divided into drug treatment (56 cases) and PCI treatment (72 cases) groups, receiving conventional drug treatment and PCI plus conventional drug treatment, respectively. At admission time and 4 weeks after treatment, the left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter, and left ventricular end systolic diameter were measured. At admission time and 24h, 72h, 1 week, and 4 weeks after treatment, the serum levels of Cys-C and hs-CRP were determined. Results: After 4 weeks of treatment, LVEF in the PCI treatment group was significantly higher than that before treatment (P<0.01) and it was significantly higher than in the drug treatment group at the same time (P<0.01). Cys-C and hs-CRP level in the PCI treatment group were significantly higher than in the drug treatment group 72h and 1 week after treatment (P<0.05 or P<0.01), respectively, but they were significantly lower than in the drug treatment group 4 weeks after treatment (P<0.01). There were obvious interaction effects between grouping factor and time factor in Cys-C (F=3.62, P<0.05) and hs-CRP (F=17.85, P<0.01). Conclusion: Serum levels of Cys-C and hs-CRP are closely related to the heart function in CHD patients undergoing PCI, and they may be used for predicting the outcome of PCI.

Variación biológica de Creatinina, Cistatina C y Tasa de Filtrado Glomerular Estimada a lo largo de 24 horas / Biological Variation of Creatinine, Cystatin C, and Estimated Glomerular Filtration Rate over 24 hours

Antecedentes: La tasa de filtración glomerular estimada (TFGe) es ampliamente utilizada en la práctica clínica. El presente estudio evaluó la variación biológica intraindividual (CVI) de diferentes ecuaciones de TFGe en sujetos con enfermedad renal crónica (ERC) y sin ERC. Los objetivos de este estudio fueron (a) determinar los perfiles de variación biológica durante 24 horas de creatinina, cistatina C y TFGe y (b) determinar si el CVI de la creatinina, la cistatina C y la TFGe cambia el deterioro de la filtración glomerular. Métodos: Se analizaron muestras de sangre cada hora de 37 individuos (17 sin ERC, 20 con ERC) durante 24 h. La creatinina (método enzimático) y la cistatina C se midieron usando un Cobas 8000 (Roche Diagnostics). La TFGe se estimó utilizando la Modificación de la Dieta en la Enfermedad Renal y la Colaboración de Epidemiología de la Enfermedad Renal Crónica basada en creatinina y/o cistatina C. Las muestras de plasma se almacenaron a -80 °C antes del análisis. Se verificaron los análisis de valores atípicos y de homogeneidad antes de realizar un ANOVA anidado para determinar la variación biológica. Resultados: La CVI de creatinina fue más alta en sujetos sin ERC que en aquellos con ERC (6.4% frente a 2.5%) debido principalmente al efecto más marcado del consumo de carne sobre la variabilidad de creatinina en individuos con concentraciones iniciales de creatinina más bajas. A diferencia de la creatinina, las concentraciones de cistatina C no se vieron afectadas por el consumo de carne. La cistatina C mostró alguna variación rítmica diurna y menor en los sujetos con ERC. Los valores de referencia del cambio (VCR) de todas las ecuaciones de TFGe estuvieron dentro del 13% al 20% en ambos grupos de estudio. Conclusiones: A pesar de las diferencias en el CVI de la creatinina, el CVI y el VRC de las ecuaciones de TFGe fueron relativamente similares para los sujetos con o sin ERC.

Background: Estimated glomerular filtration rate (eGFR) is widely used in clinical practice. This study assessed the within-subject biological variation (CVI) of different eGFR equations in people with chronic kidney disease (CKD) and people without CKD. The aims of this study were (a) to determine the 24-h biological variation profiles of creatinine, cystatin C, and eGFR and (b) to determine whether CVI of creatinine, cystatin C, and eGFR changes on deterioration of glomerular filtration. Methods: Hourly blood samples were analyzed from 37 individuals (17 without CKD, 20 with CKD) during 24 h. Creatinine (enzymatic method) and cystatin C were measured using a Cobas 8000 (Roche Diagnostics). eGFR was estimated using the Modification of Diet in Renal Disease and the Chronic Kidney Disease Epidemiology Collaboration based on creatinine and/or cystatin C. Plasma samples were stored at -80 °C before analysis. Outlier and homogeneity analyses were checked before performing a nested ANOVA to determine biological variation. Results: CVI of creatinine was higher in people without CKD than in those with CKD (6.4% vs. 2.5%) owing primarily to the more profound effect of meat consumption on creatinine variability in individuals with lower baseline creatinine concentrations. Unlike creatinine, cystatin C concentrations were unaffected by meat consumption. Cystatin C showed some diurnal rhythmic variation and less in people with CKD. Reference change values (RCVs) of all eGFR equations were within 13% to 20% in both study groups. Conclusions: Despite differences in CVI of creatinine, the CVI and RCV of the eGFR equations were relatively similar for people with or without CKD.

Association Between Increased Levels of Cystatin C and the Development of Cardiovascular Events or Mortality: A Systematic Review and Meta-Analysis / Associação entre Níveis Elevados de Cistatina C e o Desenvolvimento de Eventos Cardiovasculares ou Mortalidade: Uma Revisão Sistemática e Meta-Análise

Abstract Background: Cystatin C seems promising for evaluating the risk of cardiovascular events and mortality. Objective: To evaluate the association between high levels of cystatin C and the development of cardiovascular events or mortality. Methods: The articles were selected in the Medline/PubMed, Web of Science, and Scielo databases. The eligibility criteria were prospective cohort observational trials that assessed the association of high serum levels of cystatin C with the development of cardiovascular events or mortality in individuals with normal renal function. Only studies that evaluated the mortality outcome compared the fourth with the first quartile of cystatin C and performed multivariate Cox's proportional hazard regression analysis were included in the meta-analysis. A p value < 0,05 was considered significant. Results: Among the 647 articles found, 12 were included in the systematic review and two in the meta-analysis. The risk of development of adverse outcomes was assessed by eight studies using the hazard ratio. Among them, six studies found an increased risk of cardiovascular events or mortality. The multivariate regression analysis was performed by six studies, and the risk of developing adverse outcomes remained significant after the analysis in four of these studies. The result of the meta-analysis [HR = 2.28 (1.70-3.05), p < 0.001] indicated that there is a significant association between high levels of cystatin C and the risk of mortality in individuals with normal renal function. Conclusion: There is a significant association between high levels of cystatin C and the development of cardiovascular events or mortality in individuals with normal renal function.

Resumo Fundamento: A cistatina C tem-se mostrado promissora para avaliação do risco de eventos cardiovasculares e mortalidade. Objetivo: Avaliar a associação entre níveis elevados de cistatina C e o desenvolvimento de eventos cardiovasculares ou mortalidade. Métodos: A seleção dos artigos foi realizada por meio das bases de dados Medline/PubMed, Web of Science e Scielo. Os critérios de elegibilidade foram estudos observacionais de coorte prospectivos que avaliaram a associação entre níveis séricos elevados de cistatina C e o desenvolvimento de eventos cardiovasculares ou mortalidade em indivíduos com função renal normal. Apenas os estudos que avaliaram o desfecho mortalidade, que compararam o quarto com o primeiro quartil de cistatina C e que realizaram análise de regressão multivariada de riscos proporcionais de Cox foram incluídos na meta-análise. Foi considerado significativo o valor p < 0,05. Resultados: Dentre os 647 artigos encontrados, 12 foram incluídos na revisão sistemática e dois na meta-análise. O risco de desenvolvimento dos desfechos adversos foi avaliado por oito estudos por meio do cálculo do hazard ratio. Dentre estes, seis estudos encontraram um maior risco de eventos cardiovasculares ou mortalidade. A análise de regressão multivariada foi realizada por seis destes estudos, e o risco de desenvolvimento dos desfechos adversos permaneceu significativo após realização desta análise em quatro destes estudos. O resultado da meta-análise [HR = 2,28 (1,70-3,05), p < 0,001] indicou que há uma associação significativa entre níveis elevados de cistatina C e o risco de mortalidade nos indivíduos com função renal normal. Conclusão: Há uma associação significativa entre níveis elevados de cistatina C e o desenvolvimento de eventos cardiovasculares ou mortalidade em indivíduos com função renal normal.

Cistatina C sérica em cães criticamente enfermos em UTI / Cystatin C in critically ill dogs at UTI

A lesão renal aguda (IRA) é uma síndrome complexa, associada à progressão desfavorável, especialmente em cães na unidade de terapia intensiva (UTI) e apresenta alta morbidade e mortalidade. O diagnóstico de IRA requer combinação de testes laboratoriais, como a creatinina sérica e ureia, considerados pouco sensíveis e específicos para a detecção precoce de graus discretos durante a perda de função renal. O biomarcador cistatina C é considerado superior por apresentar uma melhor correlação com a taxa de filtração glomerular. No entanto, existem poucos estudos que demonstram a utilidade da cistatina C em cães na UTI. O objetivo deste estudo foi comparar a cistatina C com o nível sérico de creatinina para detectar o estágio inicial da IRA em cães em terapia intensiva. As dosagens desses analitos foram realizadas no momento da admissão, 24 e 48 horas após. A cistatina C apresentou concentrações mais elevadas em 78,6%, enquanto a creatinina sérica aumentou apenas em 28,5% dos cães. Os resultados demonstraram que a cistatina C pode ser utilizada para a detecção precoce de lesão renal aguda em cães de UTIs devido à sua maior sensibilidade em relação aos marcadores tradicionais.(AU)

Acute kidney injury (AKI) is a complex syndrome, associated with unfavorable progression, especially in dogs in the intensive care unit (ICU), and presents high morbidity and mortality. The diagnosis of AKI requires a combination of laboratory tests, such as serum creatinine and urea, considered to be poorly sensitive and specific for the early detection of discrete degrees during loss of renal function. The biomarker cystatin C is considered superior because it has a better correlation with the glomerular filtration rate. However, there are few studies that demonstrate the utility of cystatin C in dogs in ICU. The objective of this study was to compare cystatin C to creatinine serum level to detect early stage of AKI in dogs in an intensive care. Measurements of these analytes were performed at the time of admission, 24 and 48 hours after. Serum cystatin C presented higher concentrations in 78.6% while serum creatinina elevated in only 28.5% of the dogs. The results demonstrated that cystatin C can be used for the early detection of acute kidney injury in dogs in ICUs because of its greater sensitivity compared to traditional markers.(AU)

Abdominal obesity and reduction of glomerular filtration

SUMMARY The objective was to evaluate the association between nutritional status and the glomerular filtration rate (GFR) in remaining quilombolas. Cross-sectional study carried out on 32 remaining quilombola communities in the municipality of Alcântara-MA. The nutritional indicators (IN) used were: body mass index (BMI); Waist circumference (WC); Waist-to-hip ratio (WHR); Waist-to-height ratio (WHtR); conicity index (CI) and estimated visceral adipose tissue (VAT). GFR was estimated from the CKD-EPI creatinine-cystatin C formula. The Shapiro Wilk test was used to evaluate the normality of the quantitative variables. In order to compare the second IN sex, the chi-square test was applied. The Anova or Kruskal-Wallis tests were used to verify the association between IN and GFR. Of the 1,526 remaining quilombolas studied, 89.5% were black or brown, 51.2% were women, 88.6% belonged to economic classes D and E and 61.2% were farmers or fishermen. Clinical investigation revealed 29.2% of hypertensive patients, 8.5% of diabetics and 3.1% with reduced GFR. The BMI revealed 45.6% of the remaining quilombolas with excess weight. When compared to men, women presented a higher prevalence of overweight by BMI (56.6% vs 33.8%, p <0.001) and abdominal obesity CC (52.3% vs 4.3%), WHR (76,5% vs 5.8%), WHtR (82.3% vs 48.9%) and VAT (27.1% vs 14.5%) (p <0.001). Comparing the means of IN according to the GFR, it was observed that the higher the mean value of the IN lower the GFR (p <0.05). The GFR reduced with increasing mean values of nutritional indicators of abdominal obesity, regardless of sex.

RESUMO O objetivo foi avaliar a associação entre o estado nutricional e a taxa de filtração glomerular (TFG) em remanescentes quilombolas. Estudo transversal, realizado em 32 comunidades remanescentes de quilombolas, no município de Alcântara - MA. Os indicadores nutricionais (IN) utilizados foram: índice de massa corporal (IMC); circunferência da cintura (CC); relação cintura-quadril (RCQ); relação cintura-estatura (RCEst); índice de conicidade (Índice C) e tecido adiposo visceral estimado (TAVe). A TFG foi estimada a partir da fórmula do CKD-EPI creatinina-cistatina C. O teste Shapiro Wilk foi utilizado para avaliar a normalidade das variáveis quantitativas. Para comparar os IN segundo sexo foi aplicado o teste qui-quadrado. Os testes Anova ou Kruskal-Wallis foram usados para verificar a associação entre os IN e a TFG. Dos 1.526 remanescentes quilombolas estudados, 89,5% eram da cor preta ou parda, 51,2% eram mulheres, 88,6% pertenciam às classes econômicas D e E e 61,2% eram lavradores ou pescadores. A investigação clínica revelou 29,2% de hipertensos, 8,5% de diabéticos e 3,1% com TFG reduzida. O IMC revelou 45,6% dos remanescentes quilombolas com excesso de peso. Quando comparadas aos homens, as mulheres apresentaram maior prevalência de excesso de peso pelo IMC (56,6% vs. 33,8%; p <0,001) e obesidade abdominal CC (52,3% vs. 4,3%), RCQ (76,5% vs. 5,8%), RCEst (82,3% vs. 48,9%) e TAVe (27,1% vs. 14,5%) (p<0,001). Comparando as médias dos IN segundo a TFG observou-se que, quanto maior o valor médio dos IN, menor a TFG (p<0,05). A TFG foi reduzida com o aumento dos valores médios dos indicadores nutricionais de obesidade abdominal, independentemente do sexo.

Association of different biomarkers of renal function with D-dimer levels in patients with type 1 diabetes mellitus (renal biomarkers and D-dimer in diabetes)

ABSTRACT Objective This study aimed to evaluate the association between different renal biomarkers with D-Dimer levels in diabetes mellitus (DM1) patients group classified as: low D-Dimer levels (< 318 ng/mL), which included first and second D-Dimer tertiles, and high D-Dimer levels (≥ 318 ng/mL), which included third D-Dimer tertile. Materials and methods D-Dimer and cystatin C were measured by ELISA. Creatinine and urea were determined by enzymatic method. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI equation. Albuminuria was assessed by immunoturbidimetry. Presence of renal disease was evaluated using each renal biomarker: creatinine, urea, cystatin C, eGFR and albuminuria. Bivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels and odds ratio was calculated. After, multivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels (after adjusting for sex and age) and odds ratio was calculated. Results Cystatin C presented a better association [OR of 9.8 (3.8-25.5)] with high D-Dimer levels than albuminuria, creatinine, eGFR and urea [OR of 5.3 (2.2-12.9), 8.4 (2.5-25.4), 9.1 (2.6-31.4) and 3.5 (1.4-8.4), respectively] after adjusting for sex and age. All biomarkers showed a good association with D-Dimer levels, and consequently, with hypercoagulability status, and cystatin C showed the best association among them. Conclusion Therefore, cystatin C might be useful to detect patients with incipient diabetic kidney disease that present an increased risk of cardiovascular disease, contributing to an early adoption of reno and cardioprotective therapies.

The effect of tadalafil therapy on kidney damage caused by sepsis in a polymicrobial septic model induced in rats: a biochemical and histopathological study

ABSTRACT Introduction Sepsis is an inflammatory reaction to bacteria involving the whole body and is a significant cause of mortality and economic costs. The purpose of this research was to determine whether tadalafil exhibits a preventive effect on sepsis in a septic model induced in rats with cecal ligation and puncture (CLP). Materials and Methods Rats were randomly separated into groups, 10 rats in each: (i) a sham (control) group, (ii) an untreated sepsis group, (iii) a sepsis group treated with 5mg/kg tadalafil and (iv) a sepsis group treated with 10mg/kg tadalafil. A polymicrobial sepsis model was induced in rats using CLP. Rats were sacrificed after 16h, and blood and kidney tissues were collected for biochemical and histopathological study. Results Levels of the inflammatory parameter IL-6 decreased significantly in the sepsis groups receiving tadalafil in comparison with the untreated sepsis group (p<0.05). In terms of histopathology, inflammation scores investigated in kidney tissues decreased significantly in the sepsis groups receiving tadalafil compared to the untreated sepsis group (p<0.05). In addition, levels of creatinine and cystatin C measured in septic rats receiving tadalafil were lower by a clear degree than in septic rats (p<0.05). Conclusion In this study, tadalafil exhibited a preventive effect for sepsis-related damage by suppressing inflammation in serum and kidney tissue of septic rats in a polymicrobial sepsis model induced with CLP.

Prognostic value of cystatin C in patients with nasopharyngeal carcinoma: a retrospective study of 1063 patients

OBJECTIVE: Patients with nasopharyngeal carcinoma experience highly variable outcomes despite receiving similar therapeutic regimens. Identifying biomarkers that predict survival and guide individualized therapy is urgently needed. Cystatin C has been explored as a valuable prognostic marker in several malignancies. We retrospectively assessed the relationship between serum cystatin C levels and nasopharyngeal carcinoma prognosis in a large cohort of nasopharyngeal carcinoma patients receiving long-term follow-up. METHODS: A total of 1063 consecutive patients diagnosed with nasopharyngeal carcinoma from June 2006 to December 2010 were retrospectively analyzed. The serum levels of cystatin C at the time of diagnosis were collected. Receiver operating characteristic curve analysis, the Kaplan-Meier method and multivariate analyses using a Cox regression model were performed to assess the correlation of cystatin C levels with overall survival, progression-free survival, distant metastasis-free survival and loco-regional recurrence-free survival. RESULTS: The median follow-up duration was 68.3 months. The optimal cut-off value of cystatin C levels for predicting death was 0.945 mg/L. Compared with the low cystatin C group, the high cystatin C group experienced significantly shorter overall survival (hazard ratio=1.47, p=0.050), progression-free survival (hazard ratio=1.65, p=0.004), distant metastasis-free survival (hazard ratio=2.37, p<0.001) and loco-regional recurrence-free survival (hazard ratio=2.40, p=0.002). Based on multivariate analysis, a high cystatin C level was identified as a significant and independent negative predictor of overall survival (hazard ratio=1.47, p=0.050), progression-free survival (hazard ratio=1.65, p=0.004), distant metastasis-free survival (hazard ratio=2.37, p<0.001), and loco-regional recurrence-free survival (hazard ratio=2.40, p=0.002). CONCLUSION: Cystatin C levels are associated with the prognosis of nasopharyngeal carcinoma patients. A high cystatin C level is an independent indicator of poor prognosis for nasopharyngeal carcinoma patients.

Evaluation of creatinine-based and cystatin C-based equations for estimation of glomerular filtration rate in type 1 diabetic patients

ABSTRACT Objective Several formulas based in different biomarkers may be used to estimate glomerular filtration rate (GRF). However, all of them have some limitations, and it is very important to evaluate their performances in different groups of patients. Therefore, we compared GFR, as estimated by creatinine-based and cystatin C-based equations, according to albuminuria, in type 1 diabetes (T1DM), in an observational case-control study. Subjects and methods T1DM patients were classified according to albuminuria: normoalbuminuric (n = 63), microalbuminuric (n = 30), macroalbuminuric (n = 32). GFR was calculated using creatinine-based and cystatin C-based (aMDRD, CKD-EPIcr, CKD-EPIcys, MacIsaac, Tan and CKD-EPIcrcys) equations. Spearman Correlation was used to evaluate the correlation of GFR estimated by the formulas with albuminuria. ROC curves were constructed to compare AUCs of GFR estimated by equations, in reference to macroalbuminuria. Sensibility, specificity and accuracy were calculated for a cut-off < 60 mL/min/1.73 m2. Results GFR estimated by creatinine-based and cystatin C-based equations significantly differed among normoalbuminuric, microalbuminuric and macroalbuminuric patients. Spearman correlation and AUCs of GFR estimated by creatinine-based and cystatin C-based formulas were very similar to each other, though cystatin C-based equations presented better correlation with albuminuria and higher AUCs than the creatinine-based ones, and the best accuracy to detect macroalbuminuric patients. Conclusion Although GFR estimated by all creatinine-based and cystatin C-based equations permitted the differentiation between T1DM patients, according to albuminuria, cystatin C-based equations presented best accuracy to detect macroalbuminuria in T1DM patients and should be considered in the clinical routine in order to increase the possibility of early diagnostic of chronic renal disease.

Comparing Results of Five Glomerular Filtration Rate-Estimating Equations in the Korean General Population: MDRD Study, Revised Lund-Malmö, and Three CKD-EPI Equations

BACKGROUND: Estimated glomerular filtration rate (eGFR) is a widely used index of kidney function. Recently, new formulas such as the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations or the Lund-Malmö equation were introduced for assessing eGFR. We compared them with the Modification of Diet in Renal Disease (MDRD) Study equation in the Korean adult population. METHODS: The study population comprised 1,482 individuals (median age 51 [42-59] yr, 48.9% males) who received annual physical check-ups during the year 2014. Serum creatinine (Cr) and cystatin C (CysC) were measured. We conducted a retrospective analysis using five GFR estimating equations (MDRD Study, revised Lund-Malmö, and Cr and/or CysC-based CKD-EPI equations). Reduced GFR was defined as eGFR <60 mL/min/1.73 m2. RESULTS: For the GFR category distribution, large discrepancies were observed depending on the equation used; category G1 (≥90 mL/min/1.73 m2) ranged from 7.4-81.8%. Compared with the MDRD Study equation, the other four equations overestimated GFR, and CysC-based equations showed a greater difference (-31.3 for CKD-EPI(CysC) and -20.5 for CKD-EPI(Cr-CysC)). CysC-based equations decreased the prevalence of reduced GFR by one third (9.4% in the MDRD Study and 2.4% in CKD-EPI(CysC)). CONCLUSIONS: Our data shows that there are remarkable differences in eGFR assessment in the Korean population depending on the equation used, especially in normal or mildly decreased categories. Further prospective studies are necessary in various clinical settings.

Cystatin C: An Early Marker of Cardiac Complications in Diabetics.

Introduction: Cardiovascular disease is one of the common complications of Diabetes mellitus. Serum Cystatin C level has been suggested as a marker for cardiac complications in diabetes. Material and Methods: We studied serum Cystatin C level in Diabetics to fi nd if correlation exists between cardiac complications and elevated Cystatin C levels. Results: A total of 50 diabetics were studied out of whom 25 had cardiac complications and the rest did not have cardiac complications. No signifi cant diff erence was observed between Serum Cystatin C levels of diabetics with cardiac complications (mean 1∙5±0∙45) and diabetics without cardiac complications (1∙4±0∙46) although Cystatin C levels were found to be elevated in diabetic cases. Conclusion: Keeping in view the signifi cant diff erence (p=0∙000) in Cystatin C levels of healthy and diabetic patients, it is reasonable to accept the importance of Cystatin C as an indicator of diabetes and its associated complications.

Garlic supplemented diet attenuates gentamicin nephrotoxicity ın rats

Purpose To demonstrate the effect of a 4% pulverized garlic supplemented diet on the nephrotoxicity induced by gentamicin in rats. Materials and Methods Twenty four healthy male Wistar rats, weighing between 220 - 260grams, were divided into three groups. The rats were randomly assigned to either the gentamicin injection without garlic supplementation group (Group I, n = 8), gentamicin injection with garlic supplementation group (Group II, n = 8), and control group (Group III, n = 8). Urine from the rats was collected and the volume (mL), microalbumin (mg/L), creatinine (mg/dL), Na (mmol/L), K (mmol/L), Cl (mmol/L), P (mg/dL), N-acetyl glucosamine (NAG) (U/L) and pH values were measured. Then urea (mg/dL), creatinine (mg/dL), total protein (g/dL) and cystatin (mg/L) values were measured for the blood samples obtained from tail veins. Results The median NAG value for the control group (52.050 U/L) was similar to value for Group II (56.400 U/L), which received gentamicin and the garlic diet. However, the median NAG value for Group I (77.030 U/L), which received gentamicin without garlic supplementation, was determined to be statistically significantly higher (p = 0.010) than the value for the control group. In addition, the mean cystatin value for Group II (1.360 U/L) was found to be statistically significantly lower than the value for the Group I (2.240 U/L) (p = 0.015). Conclusions In this study we showed the effect of 4% pulverized garlic supplemented diet for preventing nephrotoxicity induced by gentamicin in rats by using as parameters NAG in urine samples and cystatin C in serum samples. .

Serum cystatin C is a sensitive early marker for changes in the glomerular filtration rate in patients undergoing laparoscopic surgery

OBJECTIVE: Pneumoperitoneum during laparoscopy results in transient oliguria and decreased glomerular filtration and renal blood flow. The presence of oliguria and elevated serum creatinine is suggestive of acute renal injury. Serum cystatin C has been described as a new marker for the detection of this type of injury. In this study, our aim was to compare the glomerular filtration rate estimated using cystatin C levels with the rate estimated using serum creatinine in patients with normal renal function who were undergoing laparoscopic surgery. METHODS: In total, 41 patients undergoing laparoscopic cholecystectomy or hiatoplasty were recruited for the study. Blood samples were collected at three time intervals: first, before intubation (T1); second, 30 minutes after the establishment of pneumoperitoneum (T2); and third, 30 minutes after deflation of the pneumoperitoneum (T3). These blood samples were then analyzed for serum cystatin C, creatinine, and vasopressin. The Larsson formula was used to calculate the glomerular filtration rate based on the serum cystatin C levels, and the Cockcroft-Gault formula was used to calculate the glomerular filtration rate according to the serum creatinine levels. RESULTS: Serum cystatin C levels increased during the study (T1 = T2<T3; p<0.05), whereas serum creatinine levels decreased (T1 = T2>T3; p<0.05). The calculated eGlomerular filtration rate-Larsson decreased, whereas the eGlomerular filtration rate-Cockcroft-Gault increased. There was no correlation between cystatin C and serum creatinine. Additionally, Pearson's analysis showed a better correlation between serum cystatin C and the eGlomerular filtration rate than between serum creatinine and the eGlomerular filtration rate. CONCLUSION: This study demonstrates that serum cystatin C is a more sensitive indicator of changes in the glomerular filtration rate than serum creatinine is in patients with normal ...

Cistatina C, PCR, Log TG/HDLc e Sindrome Metabolica estao Relacionados a Microalbuminuria na Hipertensao / Cystatin C, CRP, log TG/HDLc and metabolic syndrome are associated with microalbuminuria in hypertension

Fundamento: Em pacientes com hipertensão arterial sistêmica, a microalbuminúria é um marcador de lesão endotelial e está associada a um risco aumentado de doença cardiovascular. Objetivo: O objetivo do presente estudo foi determinar os fatores que influenciam a ocorrência de microalbumiúria em pacientes hipertensos com creatinina sérica menor que 1,5 mg/dL. Métodos: Foram incluídos no estudo 133 pacientes brasileiros atendidos em um ambulatório multidisciplinar para hipertensos. Pacientes com creatinina sérica maior do que 1,5 mg/dL e aqueles com diabete mellitus foram excluídos do estudo. A pressão arterial sistólica e diastólica foi aferida. O índice de massa corporal (IMC) e a taxa de filtração glomerular estimada pela fórmula CKD-EPI foram calculados. Em um estudo transversal, creatinina, cistatina C, colesterol total, HDL colesterol, LDL colesterol, triglicerídeos, proteína C-reativa (PCR) e glicose foram mensurados em amostra de sangue. A microalbuminúria foi determinada na urina colhida em 24 horas. Os hipertensos foram classificados pela presença de um ou mais critérios para síndrome metabólica. Resultados: Em análise de regressão múltipla, os níveis séricos de cistatina C, PCR, o índice aterogênico log TG/HDLc e a presença de três ou mais critérios para síndrome metabólica foram positivamente correlacionados com a microalbuminuria (r2: 0,277; p < 0,05). Conclusão: Cistatina C, PCR, log TG/HDLc e presença de três ou mais critérios para síndrome metabólica, independentemente da creatinina sérica, foram associados com a microalbuminúria, um marcador precoce de lesão renal e de risco cardiovascular em pacientes com hipertensão arterial essencial. .

Background: In patients with systemic hypertension, microalbuminuria is a marker of endothelial damage and is associated with an increased risk for cardiovascular disease. Objective: To determine the factors that may lead to the occurrence of microalbuminuria in hypertensive patients with serum creatinine lower than 1.5 mg/dL. Methods: This cross-sectional study included 133 Brazilians with essential hypertension followed up at a hypertension outpatient clinic. Those with serum creatinine higher than 1.5 mg/dL, as well as those with diabetes mellitus, were excluded. Systolic and diastolic blood pressures were measured, and body mass index (BMI) and GFR estimated by using the CKD-EPI formula were calculated. The serum levels of the following were assessed: CysC, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, C-reactive protein (CRP) and fasting glucose. Microalbuminuria was determined in 24-hour urine. Hypertensive patients were classified according to the presence of one or more criteria for metabolic syndrome. Results: In a multiple regression analysis, the serum levels of CysC and CRP, the atherogenic index log TG/HDLc and the presence of three or more criteria for metabolic syndrome were positively correlated with microalbuminuria (r2: 0.277, p < 0.05). Conclusion: CysC, CRP, log TG/HDLc, and the presence of three or more criteria for metabolic syndrome, regardless of serum creatinine, were associated with microalbuminuria, an early marker of kidney damage and cardiovascular risk in patients with essential hypertension. .