Is screening for chronic kidney disease in patients with diabetes mellitus being properly conducted in primary care? / O rastreio da doença renal crônica nos pacientes com diabetes mellitus está sendo realizado adequadamente na atenção primária?

Abstract Introduction: Screening patients with diabetes mellitus (DM) for chronic kidney disease (CKD) enables early diagnosis and helps to establish adequate treatment and avoid possible damages to health associated with disease progression. This study aimed to verify whether screening for CKD has been properly conducted in populations with diabetes mellitus seen at primary care clinics. Methods: This descriptive study included 265 individuals with DM seen at Basic Healthcare Clinics in Divinópolis, MG, Brazil. Clinical and laboratory data were collected from the Integrated Health System. Frequency of testing and kidney function evaluations performed within the last 12 months were calculated along with the proportion of patients with increased urinary albumin excretion (UAE) and decreased glomerular filtration rate (GFR) to determine the proportion of patient with kidney involvement. Results: We found that 41.2% of the patients had kidney involvement and that 61.2% of the individuals with kidney involvement were on nephroprotective medication. Of the 21.9% tested for isolated albuminuria, 46.5% had increased UAE. The albumin-to-creatinine ratio (ACR) was measured in 12.1% of the patients, with 43.8% having an increased ACR. We found that 89.0% of the patients had their serum creatinine levels measured, and that 33.1% had a decreased GFR. Conclusion: CKD screening was more frequently performed via the GFR than UAE, a parameter analyzed only in a small proportion of patients. Therefore, CKD screening for patients with diabetes is not being performed properly in primary care.

Resumo Introdução: O rastreio da doença renal crônica (DRC) em pacientes com diabetes (DM) possibilita o diagnóstico precoce e ajuda a estabelecer um tratamento adequado, evitando possíveis danos à saúde pela progressão da doença. O objetivo deste trabalho foi verificar se o rastreio da DRC está sendo feito de maneira adequada entre diabéticos acompanhados na atenção primária à saúde. Métodos: Estudo descritivo com 265 pacientes com DM atendidos nas Unidades Básicas de Saúde de Divinópolis, MG. A coleta de dados clínicos e laboratoriais foi realizada por meio de consulta ao Sistema Integrado de Saúde. Foram calculadas a frequência de realização dos exames de avaliação da função renal nos últimos 12 meses e a frequência de pacientes com excreção urinária de albumina (EUA) aumentada e a taxa de filtração glomerular (TFG) reduzida, e assim determinada a frequência de pacientes com comprometimento renal. Resultados: Foi observado que 41,2% dos pacientes têm comprometimento renal; dentre esses, 61,2% utilizam algum medicamento nefroprotetor. Apenas 21,9% realizaram o exame de albuminúria isolada, dos quais 46,5% apresentaram albuminúria aumentada. O exame de relação albumina/creatinina (RAC) foi realizado por 12,1% dos pacientes, dos quais 43,8% apresentaram RAC aumentada. Foi observado que 89,0% dos pacientes realizaram o exame de creatinina sérica, dos quais 33,1% apresentaram TFG reduzida. Conclusão: Foi observado maior índice de rastreio da DRC por meio da TFG em relação ao rastreio por meio da EUA, o qual foi realizado por pequeno número de pacientes. Portanto, o rastreio da DRC não está sendo realizado adequadamente na atenção básica ao diabético.

Interferência de medicamentos na avaliação do perfil lipídico: uma revisão de literatura / Interference of medications in the evaluation of the lipid profile: a review of the literature

A estrita relação entre doenças cardiovasculares e dislipidemias exige o monitoramento periódico do perfil lipídico através de dosagens séricas de colesterol total, triglicérides, colesterol da lipoproteína de baixa densidade (c-LDL) e colesterol da lipoproteína de alta densidade (c-HDL). Contudo, esses testes laboratoriais estão sujeitos à interferência medicamentosa in vivo e in vitro. O objetivo desta revisão da literatura foi disponibilizar os principais medicamentos que podem interferir nos exames de avaliação do perfil lipídico, com seus respectivos mecanismos de interferência in vivo ou in vitro. Alguns fármacos podem causar como reação adversa o aumento dos níveis de c-LDL e triglicérides, ou a redução dos níveis de c-HDL, o que está associado a um maior risco de eventos cardiovasculares. Por outro lado, outros fármacos podem reduzir os níveis de c-LDL e triglicérides, ou aumentar os níveis de c-HDL. Alguns medicamentos ainda podem interferir in vitro na dosagem dos biomarcadores de avaliação do perfil lipídico. O monitoramento e diagnóstico das dislipidemias devem levar em consideração estas interferências medicamentosas, já que a interpretação equivocada dos exames laboratoriais pode resultar em tratamento desnecessário ou falta de tratamento farmacológico, gastos desnecessários e prejuízo na qualidade de vida do paciente.

The strict relationship between cardiovascular disease and dyslipidemia requires periodic monitoring of the lipid profile through serum measurements of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c). However, these laboratory tests are subject to drug interference in vivo and in vitro. The purpose of this literature review was to make available the main drugs that can interfere with lipid profile assessment tests, with their respective in vivo or in vitro interference mechanisms. Some drugs can cause as adverse reaction the increase of LDL-c and triglycerides levels, or the reduction of HDL-c levels, which is associated with a greater risk of cardiovascular events. On the other hand, other drugs can reduce LDL-c and triglycerides levels, or increase HDL-c levels. Some medications can still interfere in vitro in the dosage of biomarkers to assess the lipid profile. The monitoring and diagnosis of dyslipidemia should take into account these drug interferences, since the misinterpretation of laboratory tests may result in unnecessary treatment or lack of pharmacological treatment, unnecessary expenses and damage to the patient's quality of life.

Is screening for chronic kidney disease in patients with diabetes mellitus being properly conducted in primary care?

INTRODUCTION: Screening patients with diabetes mellitus (DM) for chronic kidney disease (CKD) enables early diagnosis and helps to establish adequate treatment and avoid possible damages to health associated with disease progression. This study aimed to verify whether screening for CKD has been properly conducted in populations with diabetes mellitus seen at primary care clinics. METHODS: This descriptive study included 265 individuals with DM seen at Basic Healthcare Clinics in Divinópolis, MG, Brazil. Clinical and laboratory data were collected from the Integrated Health System. Frequency of testing and kidney function evaluations performed within the last 12 months were calculated along with the proportion of patients with increased urinary albumin excretion (UAE) and decreased glomerular filtration rate (GFR) to determine the proportion of patient with kidney involvement. RESULTS: We found that 41.2% of the patients had kidney involvement and that 61.2% of the individuals with kidney involvement were on nephroprotective medication. Of the 21.9% tested for isolated albuminuria, 46.5% had increased UAE. The albumin-to-creatinine ratio (ACR) was measured in 12.1% of the patients, with 43.8% having an increased ACR. We found that 89.0% of the patients had their serum creatinine levels measured, and that 33.1% had a decreased GFR. CONCLUSION: CKD screening was more frequently performed via the GFR than UAE, a parameter analyzed only in a small proportion of patients. Therefore, CKD screening for patients with diabetes is not being performed properly in primary care.

Human papillomavirus infection and oral squamous cell carcinoma - a systematic review / Infecção por papilomavírus humano e carcinoma espinocelular oral - Uma revisão sistemática

Abstract Introduction The association between uterine cervix and anogenital carcinomas and human papillomavirus, HPV, is well established, however the involvement of this virus in the development of oral squamous cell carcinomas remains controversial. Objectives To evaluate the relationship between HPV infection and oral squamous cell carcinomas, and to estimate the incidence of this infection in these patients. Methods Four electronic databases were searched to find studies that met the following inclusion criteria: i) performed in humans; ii) were cohort, case-control or cross-sectional; iii) assessed the HPV oncogenic activity by the E6 and E7 mRNA; iv) included primary oral squamous cell carcinomas which; v) diagnosis had been confirmed by biopsy. Information about the country; study period; sample obtainment; sites of oral squamous cell carcinomas; number, gender and age range of the population; the prevalence of HPV infection and subtypes detected; use of tobacco or alcohol and oral sex practice were extracted. The methodological quality of included articles was assessed using 14 criteria. Results The search strategy retrieved 2129 articles. Assessment of the full text was done for 626 articles, but five were included. The total of participants included was 383, most of them male with mean age between 51.0 and 63.5 years old. Seventeen patients were HPV/mRNA-positive, being the subtypes 16 and 18 detected more frequently. Nine of the HPV/mRNA-positive oral squamous cell carcinomas occurred on the tongue. The quality score average of included articles was five points. Conclusions Among the 383 oral squamous cell carcinoma patients included, 17 (4.4%) were HPV/mRNA-positive, nevertheless it was not possible to assess if HPV infection was associated with oral squamous cell carcinomas because none of the studies included was longitudinal and cross-sectional investigations do not have control group.

Resumo Introdução A associação entre os carcinomas de colo uterino e anogenitais e o papilomavírus humano (HPV) está bem estabelecida; entretanto, o envolvimento desse vírus no desenvolvimento de carcinomas espinocelulares orais permanece controverso. Objetivos Avaliar a relação entre a infecção pelo HPV e os carcinomas espinocelulares orais e estimar a proporção dessa infecção nesses pacientes. Método Quatro bases de dados eletrônicas foram pesquisadas para encontrar estudos que atendessem aos seguintes critérios de inclusão: i) feitos em humanos; ii) estudos do tipo coorte, caso-controle ou transversal; iii) avaliaram a atividade oncogênica do HPV pelo mRNA E6 e E7; iv) incluíram CECOs primários, cujo diagnóstico foi confirmado por biópsia; v) o diagnóstico foi confirmado por biópsia. Informações sobre o país; período do estudos; obtenção da amostra; locais dos carcinomas espinocelulares orais; número, sexo e faixa etária da população; prevalência de infecção por HPV e subtipos detectados; informações sobre o uso de tabaco ou álcool e a prática de sexo oral foram obtidas. A qualidade metodológica dos artigos incluídos foi avaliada através de 14 critérios. Resultados A estratégia de busca recuperou 2.129 artigos. A avaliação de texto completo foi feita em 626 artigos, mas apenas cinco foram incluídos. O total de participantes incluídos foi de 383, a maioria do sexo masculino e com média de idade entre 51,0 e 63,5 anos. Dezessete pacientes eram HPV/mRNA-positivos, os subtipos 16 e 18 foram detectados com maior frequência. Nove dos carcinomas espinocelulares orais HPV/mRNA-positivos ocorreram na língua. A média do escore de qualidade dos artigos incluídos foi de cinco pontos. Conclusões Entre os 383 pacientes incluídos com carcinomas espinocelulares orais, 17 (4,4%) eram HPV/mRNA-positivos; entretanto, não foi possível avaliar se a infecção por HPV estava associada com carcinomas espinocelulares orais porque nenhum dos estudos incluídos era longitudinal e as investigações transversais não têm grupo controle.

Human papillomavirus infection and oral squamous cell carcinoma - a systematic review.

INTRODUCTION: The association between uterine cervix and anogenital carcinomas and human papillomavirus, HPV, is well established, however the involvement of this virus in the development of oral squamous cell carcinomas remains controversial. OBJECTIVES: To evaluate the relationship between HPV infection and oral squamous cell carcinomas, and to estimate the incidence of this infection in these patients. METHODS: Four electronic databases were searched to find studies that met the following inclusion criteria: i) performed in humans; ii) were cohort, case-control or cross-sectional; iii) assessed the HPV oncogenic activity by the E6 and E7 mRNA; iv) included primary oral squamous cell carcinomas which; v) diagnosis had been confirmed by biopsy. Information about the country; study period; sample obtainment; sites of oral squamous cell carcinomas; number, gender and age range of the population; the prevalence of HPV infection and subtypes detected; use of tobacco or alcohol and oral sex practice were extracted. The methodological quality of included articles was assessed using 14 criteria. RESULTS: The search strategy retrieved 2129 articles. Assessment of the full text was done for 626 articles, but five were included. The total of participants included was 383, most of them male with mean age between 51.0 and 63.5 years old. Seventeen patients were HPV/mRNA-positive, being the subtypes 16 and 18 detected more frequently. Nine of the HPV/mRNA-positive oral squamous cell carcinomas occurred on the tongue. The quality score average of included articles was five points. CONCLUSIONS: Among the 383 oral squamous cell carcinoma patients included, 17 (4.4%) were HPV/mRNA-positive, nevertheless it was not possible to assess if HPV infection was associated with oral squamous cell carcinomas because none of the studies included was longitudinal and cross-sectional investigations do not have control group.

Association between reduced serum levels of magnesium and the presence of poor glycemic control and complications in type 1 diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the association between reduced serum magnesium levels and poor glycemic control and/or complications in patients with type 1 diabetes mellitus through a systematic review and meta-analysis. METHODS: The articles were selected using the Medline/PubMed, Web of Science, Scopus and Scielo databases. Eligibility criteria were cross-sectional, cohort or case-control observational studies that assessed the association between reduced magnesium levels and poor glycemic control and/or complications in patients with type 1 diabetes mellitus. RESULTS: Nine articles were included in the systematic review and two in the meta-analysis, all articles being cross-sectional. Among the seven studies that were designed to evaluate glycemic control, five showed an association between reduced levels of magnesium and poor glycemic control, and these findings were corroborated by the meta-analysis. Among the two studies in which dyslipidemia was evaluated, both showed higher levels of triglycerides, total cholesterol and LDL cholesterol, and lower levels of HDL cholesterol in patients with lower levels of magnesium as compared to those with higher magnesium levels. The three studies that evaluated diabetes kidney disease and the two studies that evaluated diabetic retinopathy found divergent results. CONCLUSION: There is an association between reduced levels of magnesium and poor glycemic control in patients with type 1 diabetes mellitus, however, this needs further studies.

MicroRNAs: new biomarkers and promising therapeutic targets for diabetic kidney disease / MicroRNAs: novos biomarcadores e alvos terapêuticos promissores da doença renal do diabetes

Abstract Diabetic kidney disease (DKD) is a chronic complication of diabetes mellitus associated with significant morbidity and mortality regarded as a global health issue. MicroRNAs - small RNA molecules responsible for the post-transcriptional regulation of gene expression by degradation of messenger RNA or translational repression of protein synthesis - rank among the factors linked to the development and progression of DKD. This study aimed to offer a narrative review on investigations around the use of microRNAs in the diagnosis, monitoring, and treatment of DKD. Various microRNAs are involved in the pathogenesis of DKD, while others have a role in nephroprotection and thus serve as promising therapeutic targets for DKD. Serum and urine microRNAs levels have also been considered in the early diagnosis and monitoring of individuals with DKD, since increases in albuminuria, decreases in the glomerular filtration rate, and progression of DKD have been linked to changes in the levels of some microRNAs.

Resumo A doença renal do diabetes (DRD) é uma complicação crônica do diabetes mellitus associada à elevada morbidade e mortalidade, considerada um problema de saúde mundial. Dentre os fatores associados ao desenvolvimento e à progressão da DRD, destacam-se os microRNAs, que consistem em pequenas moléculas de RNA que regulam a expressão gênica por meio da degradação pós-transcricional do RNA mensageiro ou inibição translacional da síntese proteica. Este estudo teve como objetivo realizar uma revisão narrativa buscando investigar os microRNAs como auxiliares no diagnóstico, monitoramento e tratamento da DRD. Vários microRNAs estão envolvidos na patogênese da DRD, enquanto que outros têm papel nefroprotetor, consistindo assim em alvos terapêuticos promissores para o tratamento da DRD. A dosagem laboratorial dos microRNAs no soro e na urina também é muito promissora para o diagnóstico precoce e o monitoramento da DRD, já que os níveis de alguns microRNAs se alteram antes do aumento da albuminúria e da diminuição da taxa de filtração glomerular e podem ainda se alterar com a progressão da DRD.

MicroRNAs: new biomarkers and promising therapeutic targets for diabetic kidney disease.

Diabetic kidney disease (DKD) is a chronic complication of diabetes mellitus associated with significant morbidity and mortality regarded as a global health issue. MicroRNAs - small RNA molecules responsible for the post-transcriptional regulation of gene expression by degradation of messenger RNA or translational repression of protein synthesis - rank among the factors linked to the development and progression of DKD. This study aimed to offer a narrative review on investigations around the use of microRNAs in the diagnosis, monitoring, and treatment of DKD. Various microRNAs are involved in the pathogenesis of DKD, while others have a role in nephroprotection and thus serve as promising therapeutic targets for DKD. Serum and urine microRNAs levels have also been considered in the early diagnosis and monitoring of individuals with DKD, since increases in albuminuria, decreases in the glomerular filtration rate, and progression of DKD have been linked to changes in the levels of some microRNAs.

The role of C-peptide in the attenuation of outcomes of diabetic kidney disease: a systematic review and meta-analysis / Emprego do peptídeo C na atenuação dos desfechos da doença renal do diabetes: uma revisão sistemática e meta-análise

ABSTRACT Introduction: Preclinical trials have shown that C-peptide may contribute to the treatment of diabetic kidney disease (DKD). This systematic review and meta-analysis aimed to assess the use of C-peptide in attenuating the outcomes of DKD. Methods: Searches were made on databases PubMed, Web of Science, and Scielo for in vivo clinical and preclinical trials written in English, Portuguese or Spanish that looked into the use of C-peptide in the attenuation of the outcomes of DKD. Results: Twelve papers were included in this review, one clinical and eleven preclinical trials. In the clinical trial, DKD patients given C-peptide had lower levels of albuminuria than the subjects in the control group, but glomerular filtration rates were not significantly different. The main parameters assessed in the preclinical trials were glomerular filtration rate (six trials) and albuminuria (five trials); three trials described less hyperfiltration and three reported lower levels of albuminuria in the groups offered C-peptide. The meta-analysis revealed that the animals given C-peptide had lower glomerular volumes and lower urine potassium levels than the groups not given C-peptide. Conclusion: The results of the studies included in the systematic review diverged. However, the meta-analysis showed that the animals given C-peptide had lower glomerular volumes and lower urine potassium levels.

RESUMO Introdução: Estudos pré-clínicos demonstraram que o peptídeo C pode contribuir para a terapia da doença renal do diabetes (DRD). Esta revisão sistemática e meta-análise teve como objetivo avaliar a utilidade do peptídeo C na atenuação dos desfechos da DRD. Métodos: Foram utilizadas as bases de dados PubMed, Web of Science e Scielo, e definidos como critérios de elegilibilidade ensaios clínicos e pré-clínicos in vivo, redigidos em inglês, português ou espanhol, que avaliaram a utilidade do peptídeo C na atenuação dos desfechos da DRD. Resultados: Doze artigos foram incluídos nesta revisão: onze ensaios pré-clínicos e um ensaio clínico. No ensaio clínico, os pacientes com DRD que receberam peptídeo C apresentaram menor albuminúria do que os do grupo controle, contudo não houve diferença significativa em relação à taxa de filtração glomerular. Os principais parâmetros avaliados pelos estudos pré-clínicos foram taxa de filtração glomerular (seis estudos) e albuminúria (cinco estudos), dos quais três encontraram menor hiperfiltração e três verificaram menor albuminúria no grupo que recebeu peptídeo C. A meta-análise demonstrou que os animais que receberam peptídeo C apresentaram menor volume glomerular e menor excreção urinária de potássio em comparação com aqueles que não o receberam. Conclusão: Os resultados dos estudos incluídos nesta revisão sistemática foram divergentes. Contudo, a meta-análise demonstrou que a administração do peptídeo C em animais resultou em menor volume glomerular e menor excreção urinária de potássio.

Associação entre a presença de anemia ferropriva com variáveis socioeconômicas e rendimento escolar / Association between the occurence of iron-deficiency anemia with socioeconomic variables and school performance

Modelo do estudo: Observacional transversal. Objetivo: Avaliar a associação entre a presença de anemia ferropriva com variáveis socioeconômicas e rendimento escolar. Método: Foram incluídas no estudo 124 crianças com idade entre seis e oito anos, estudantes do ensino fundamental de escolas municipais, as quais foram divididas em dois grupos de acordo com a presença (n=32) ou ausência de anemia (n=92). Os níveis de hemoglobina e ferro sérico foram determinados por método colorimétrico, a contagem de hemácias foi realizada utilizando a câmara de Neubauer, o hematócrito foi avaliado utilizando centrífuga de microhematócrito, e foram calculados os índices hematimétricos volume corpuscular médio, hemoglobina corpuscular média e concentração de hemoglobina corpuscular média. O desempenho escolar das crianças foi fornecido pelas escolas participantes e as variáveis socioeconômicas foram obtidas através de preenchimento de ficha clínica e do questionário socioeconômico da Associação Brasileira das Empresas de Pesquisa pelos pais ou responsáveis. Resultados: A prevalência de anemia ferropriva nos escolares foi de 25,8% que é considerada pelos parâmetros da OMS uma prevalência moderada. Foi observada uma maior proporção de crianças sem anemia que apresentaram melhores conceitos escolares e que pertencem aos níveis socioeconômicos mais altos do que de crianças com anemia. Contudo, não foram observadas diferenças estatisticamente significativas entre os grupos com relação ao rendimento escolar e as variáveis socioeconômicas. Conclusão: Uma prevalência moderada de anemia ferropriva foi encontrada nas crianças com idade entre seis e oitos anos, entretanto, não foi observada uma associação significativa entre a anemia ferropriva com variáveis socioeconômicas e o rendimento escolar. (AU)

Study design: Cross-sectional observational. Objective: Evaluate the association between the occurence of iron-deficiency anemia with socioeconomic variables and school performance. Method: They were included in the study 124 children aged between six and eight years old, municipal elementary school students, which were divided in two groups according to the presence (n=32) or absence of anemia (n=92). Hemoglobin and serum iron levels were determined by colorimetric method, red blood cells count was performed using Neubauer chamber, hematocrit was evaluated using microhematocrit centrifuge, and mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration hematimetric indexes were calculated. The school performance of children was provided by participating schools and socioeconomic variables were obtained by filling out the clinic file and the socioeconomic questionnaire of Brazilian Association of Research Companies by parents or guardians. Results: The prevalence of iron-deficiency anemia in school children was 25.8%, which is considered to be moderate. The proportion of better school grades was higher in children without anemia and in those belonging to the upper socioeconomic levels. However, it was not observed statistically differences between groups regarding school performance and socioeconomic variables. Conclusion: A moderate prevalence of iron-deficiency anemia was found in children aged between six and eight years old, however, it was not observed a significant association between irondeficiency anemia with socioeconomic variables and school performance. (AU)

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.

Association Between Increased Levels of Cystatin C and the Development of Cardiovascular Events or Mortality: A Systematic Review and Meta-Analysis.

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.

The role of C-peptide in the attenuation of outcomes of diabetic kidney disease: a systematic review and meta-analysis.

INTRODUCTION: Preclinical trials have shown that C-peptide may contribute to the treatment of diabetic kidney disease (DKD). This systematic review and meta-analysis aimed to assess the use of C-peptide in attenuating the outcomes of DKD. METHODS: Searches were made on databases PubMed, Web of Science, and Scielo for in vivo clinical and preclinical trials written in English, Portuguese or Spanish that looked into the use of C-peptide in the attenuation of the outcomes of DKD. RESULTS: Twelve papers were included in this review, one clinical and eleven preclinical trials. In the clinical trial, DKD patients given C-peptide had lower levels of albuminuria than the subjects in the control group, but glomerular filtration rates were not significantly different. The main parameters assessed in the preclinical trials were glomerular filtration rate (six trials) and albuminuria (five trials); three trials described less hyperfiltration and three reported lower levels of albuminuria in the groups offered C-peptide. The meta-analysis revealed that the animals given C-peptide had lower glomerular volumes and lower urine potassium levels than the groups not given C-peptide. CONCLUSION: The results of the studies included in the systematic review diverged. However, the meta-analysis showed that the animals given C-peptide had lower glomerular volumes and lower urine potassium levels.

Utilidade clínica da Cistatina C para avaliação do prognóstico das Síndromes Coronarianas Agudas: uma revisão sistemática e metanálise / Clinical usefulness of Cystatin C to assess the prognostic of Acute Coronary Syndrome: a systematic review and meta-analysis

A cistatina C é utilizada como marcador de função renal e tem se mostrado promissora para avaliação do prognóstico das síndromes coronarianas agudas (SCAs). Avaliar o valor prognóstico da cistatina C em pacientes com SCAs. A busca dos artigos foi realizada empregando as bases de dados PubMed, Web of Science e Scielo. Foram incluídos na revisão sistemática estudos observacionais de coorte que avaliaram a associação entre níveis elevados de cistatina C e o desenvolvimento de eventos cardiovasculares e mortalidade nos pacientes com SCAs. Somente os estudos que avaliaram desfechos semelhantes, que compararam o maior com o menor quartil de cistatina C e que realizaram análise multivariada, na qual foram incluídas a taxa de filtração glomerular ou a creatinina sérica, foram incluídos na metanálise. A qualidade metodológica dos artigos foi avaliada através do questionário Newcastle­Ottawa Scale para estudos de coorte. Após aplicação dos critérios de elegibilidade, 17 artigos foram incluídos na revisão sistemática. Todos os estudos incluídos encontraram uma associação significativa entre níveis maiores de cistatina C e os desfechos. A meta-análise demonstrou que níveis elevados de cistatina C estão associados com um maior risco de morte cardiovascular ou infarto do miocárdio não fatal nos pacientes com SCAs, e que esta associação é independente da função renal [OR = 1,65 (1,464 ­ 1,861), p < 0,001]. Dentre os estudos a revisão sistemática e meta-análise demonstrou que há uma associação significativa entre níveis elevados de cistatina C e o desenvolvimento de eventos cardiovasculares e mortalidade nos pacientes com SCAs

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).

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.

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.

Associação entre doença celíaca e complicações do diabetes em pacientes com diabetes mellitus tipo 1: revisão sistemática / Association of celiac disease and complications of diabetes in type 1 diabetes mellitus patients: sistematic review

Devido à genética comum e à interação entre fatores ambientais e imunológicos, os pacientes com diabetes mellitus tipo 1 possuem um maior risco de desenvolverem outras doenças autoimunes, como a doença celíaca. O objetivo do trabalho foi avaliar a associação entre a doença celíaca e a presença de complicações do diabetes em pacientes com diabetes mellitus tipo 1. Foi realizada uma revisão sistemática da literatura, empregando as bases de dados PubMed, Web of Science, SciELO e LILACS. Foram estabelecidos como critérios de elegibilidade: estudos observacionais originais redigidos em português, inglês ou espanhol, que avaliaram a associação entre a doença celíaca e a presença de complicações do diabetes em pacientes com diabetes mellitus tipo 1. O processo de busca resultou em 3.651 artigos, e 13 foram incluídos no estudo. As principais complicações do diabetes avaliadas nos estudos selecionados foram nefropatia (34,8%) e retinopatia (26,1%), seguidas de hipoglicemia (13,0%), níveis reduzidos de HDL-colesterol (8,7%), neuropatia periférica (4,3%), aterosclerose subclínica (4,3%), doença cardiovascular (4,3%) e cetoacidose (4,3%). Para os níveis reduzidos de HDL-colesterol, doença cardiovascular, aterosclerose subclínica e neuropatia periférica, 100% dos estudos encontraram associação entre a doença celíaca e a presença destas complicações do diabetes. Com relação à retinopatia, nefropatia e hipoglicemia, 50%, 37,5% e 33,3% dos estudos encontraram associação, respectivamente, enquanto que nenhum estudo encontrou associação entre a doença celíaca e a cetoacidose. Portanto, foi verificada associação entre a doença celíaca e a presença de complicações do diabetes em pacientes com diabetes mellitus tipo 1.(AU)

Due to common genetics, and to interaction between environmental and immunologic factors, patients with type 1 diabetes mellitus have a higher risk to develop other autoimmune diseases, such as celiac disease. The aim of this study was to evaluate the association between celiac disease and the presence of complications of diabetes in patients with type 1 diabetes mellitus. A systematic review of literature was performed, using PubMed, Web of Science, Scielo and Lilacs databases. Eligibility criteria were: original observational studies written in Portuguese, English or Spanish, which evaluated the association between celiac disease and the presence of diabetes complications in patients with type 1 diabetes mellitus. The research resulted in 3651 papers, and from these, 13 were included in the study. The main complications of diabetes evaluated in the studies selected were nephropathy (34.8%) and retinopathy (26.1%), followed by hypoglycemia (13.0%), lower levels of HDL cholesterol (8.7%), peripheral neuropathy (4.3%), subclinical atherosclerosis (4.3%), cardiovascular disease (4.3%), and ketoacidosis (4.3%). Regarding lower levels of HDL cholesterol, cardiovascular disease, subclinical atherosclerosis, and peripheral neuropathy, 100% of the studies found an association between celiac disease and the presence of these complications of diabetes. Regarding retinopathy, nephropathy and hypoglycemia, 50%, 37.5% and 33.3% of the studies found some association, respectively, while none of the studies detected any association between celiac disease and ketoacidosis. Therefore, an association between celiac disease and the presence of diabetes complications in patients with type 1 diabetes mellitus was observed.(AU)

Avaliação da função renal na doença renal crônica / Evaluation of renal function in chronic kidney disease

O diagnóstico precoce da doença renal crônica (DRC) e a avaliação precisa do risco de progressão do declínio da função renal e do desenvolvimento de complicações cardiovasculares possuem extrema importância, já que o estabelecimento precoce de terapias reno e cardioprotetoras pode evitar ou retardar a ocorrência destes desfechos indesejáveis. Vários biomarcadores podem ser utilizados para a avaliação da função renal, como a creatinina, a proteinúria, a albuminúria, a cistatina C e o ritmo de filtração glomerular (RFG), o qual pode ser estimado através de equações baseadas na creatinina ou na cistatina C. Apesar de todos estes biomarcadores apresentarem limitações, a identificação da DRC e o monitoramento da função renal por meio da determinação da albuminúria associada à estimativa do RFG são muito importantes e úteis para a avaliação do prognóstico da doença renal e o estabelecimento de um tratamento adequado de acordo com a sua evolução

Early diagnosis of chronic kidney disease (CKD) and the accurate evaluation of the risk of progression of renal function decline and development of cardiovascular complications are extremely relevant, since the early establishment of reno- and cardioprotective therapies may prevent or delay the occurrence of these undesirable outcomes. Several biomarkers can be used to assess renal function, such as creatinine, proteinuria, albuminuria, cystatin C and glomerular filtration rate (GFR), which can be estimated using equations based on creatinine or cystatin C. Despite all of these biomarkers present limitations, the identification of CKD and the monitoring of the renal function through determination of albuminuria associated with GFR estimative are very important and useful for assessing the prognosis of renal disease and establish the appropriate treatment according to its evolution

Biomarcadores da função renal: do que dispomos atualmente? / Biomarkers of renal function: what is currently available?

A avaliação da função renal é de extrema importância na prática clínica, tanto para o diagnóstico quanto para e prognóstico e monitoração das doenças renais. Neste contexto, aparticipação do laboratório é de grande importância, uma vez que a maior parte das doenças renais só se manifesta clinicamente quando mais de 50% a 75% da função renal estácomprometida. O desenvolvimento de novos biomarcadores para diagnóstico precoce, estratificação de risco, prognóstico de lesão renal tem sido um dos principais alvos das pesquisas envolvendo o sistema renal. Dessa forma, diversos novos biomarcadores, tais como lipocalina associada à gelatinase de neutrófilos (NGAL), cistatina C, molécula-1 de lesão renal (KIM-1), interleucina-18 (IL-18), enzimas urinárias tubulares e proteínas de baixo peso molecular, dentre outros, têm sido propostos para diagnosticar /monitorar as doenças renais agudas e crônicas. Este estudo visa discutir aspectos associados aos principais biomarcadores utilizados na rotina laboratorial para diagnóstico, prognóstico e acompanhamento do paciente com disfunção renal, bem como apresentar novos marcadores que se destacam na literatura recente e que podem ser promissores na prática clínica

The assessment of renal function is very important in clinical practice, both for diagnosis and for prognosis and monitoring of renal diseases. In this context, the role of the laboratory is of great importance, since most of the kidney disease manifests itself clinically only when more than 50 to 75% of kidney function is compromised. The development of new biomarkers for early diagnosis, risk stratification, prognosis of renal injury has been a major focus of research involving the renal system. Thus, several new biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL18) and low-molecular weight proteins and enzymes, and others, have been proposed to diagnose/monitoring acute and chronic renal diseases. The aim of this study is to discuss aspects related to the main biomarkers used in routine laboratory tests for diagnosis, prognosis and monitoring of patients with renal dysfunction, as well as provide new markers that stand out in the recent literature, and that may be promising in clinical practice

Papel das citocinas inflamatórias na nefropatia diabética / Role of inflammatory cytokines in diabetic nephropathy

A nefropatia diabética consiste na principal causa de doença renal terminal e está associada a um risco aumentado de doença cardiovascular. O estudo dos mecanismos responsáveis pelo desenvolvimento da nefropatia diabética possui extrema importância, já que pode contribuir para o desenvolvimento de terapias mais eficazes para a prevenção e o tratamento dessa complicação. Alguns estudos têm demonstrado que os processos inflamatórios devem desempenhar um papel significativo no desenvolvimento e na progressão da nefropatia diabética. Citocinas inflamatórias, como interleucina 1, fator de necrose tumoral alfa e interleucina 6, têm sido associadas com o desenvolvimento e a evolução da disfunção renal em pacientes diabéticos tipos 1 e 2. O reconhecimento das citocinas inflamatórias como fatores patogênicos significativos da nefropatia diabética pode fornecer novos alvos terapêuticos. Neste contexto, o uso de anti-inflamatórios para o tratamento da doença renal no diabetes tem se mostrado estratégia bastante promissora

Diabetic nephropathy is the most important cause of endstage renal disease, and is associated with an increased risk of cardiovascular disease. The study of the mechanisms involved with the development of diabetic nephropathy is extremely relevant, since it can contribute to the development of more effective therapies for the prevention and treatment of this complication. Some studies have demonstrated that the inflammatory processes play a significant role in the development and progression of diabetic nephropathy. Inflammatory cytokines, such as interleukin-1, tumor necrosis factor alpha and interleukin-6, have been associated with the development and evolution of renal dysfunction in type 1 and type 2 diabetic patients. The recognition of inflammatory cytokines as significant pathogenic factors of diabetic nephropathy can provide new therapeutic targets. In this context, the use of antiinflammatories for the treatment of renal disease in diabetes has been shown to be a very promising strategy