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.

Plasminogen activator inhibitor-1 4G/5G promoter polymorphism and PAI-1 plasma levels in young patients with ischemic stroke.

The 4G/5G polymorphism in the plasminogen activator inhibitor-1 (PAI-1) gene, has been associated with arterial disease. In this study, we investigated the association of IS in young patients with CRP and PAI-1 levels and frequency of insertion-deletion polymorphism of PAI-1 gene. The plasma levels of PAI-1 and CRP and the frequency of 4G/5G polymorphism were analyzed in 127 Brazilian young patients that presented IS and in 201 healthy and unrelated control subjects. The levels of CRP (P < 0.001) and PAI-1 (P < 0.001) were significantly higher in patients when compared with control group. Only PAI-1 plasma levels were independently associated with risk of IS (OR 3.40; 95% CI 1.49-7.74; P = 0.001) after adjustments for lifestyles covariates. The 4G/4G genotype was significantly more frequent among control subjects as compared to patients (OR 0.41; 95% CI 0.24-0.68; P < 0.001). Although increased PAI-1 plasma levels are associated with development of IS in Brazilian young patients, they are not influenced by the 4G/5G PAI-1 polymorphism.

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.

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.

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.

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.

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? / 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.

Association between Von Willebrand factor, disintegrin and metalloproteinase with thrombospondin type 1 motif member 13, d-Dimer and cystatin C levels with retinopathy in type 1 diabetes mellitus.

BACKGROUND: We evaluated the association between plasma levels of VWF, ADAMTS13 and d-Dimer, which consist on endothelial dysfunction and hypercoagulability biomarkers, and cystatin C with retinopathy in type 1 diabetic patients. METHODS: Patients were classified according to presence (n=55) or absence (n=70) of retinopathy. Plasma levels of VWF, ADAMTS13, d-Dimer and cystatin C were evaluated by ELISA and ADAMTS13 activity was evaluated by FRET. RESULTS: Plasma levels of VWF (p=0.033), ADAMTS13 activity (p=0.014), d-Dimer (p=0.002) and cystatin C (p<0.001) were elevated in diabetic patients with retinopathy compared to those without this complication. The multivariate logistic regression analysis showed that ADAMTS13 activity (p=0.031) d-Dimer (p=0.015) and cystatin C (p=0.001) remained associated with retinopathy after adjustment for age, diabetes duration, use of statin, use of ACEi or angiotensin antagonist, use of acetylsalicylic acid and glomerular filtration rate. CONCLUSION: ADAMTS13 activity, d-Dimer and cystatin C are associated with retinopathy in type 1 diabetic patients and are promising biomarkers for the diagnosis and monitoring of diabetic retinopathy.

Diabetes mellitus: The linkage between oxidative stress, inflammation, hypercoagulability and vascular complications.

BACKGROUND: Vascular complications are the leading cause of morbidity and mortality among patients with type 1 and type 2 diabetes mellitus. These vascular abnormalities result of a chronic hyperglycemic state, which leads to an increase in oxidative stress and inflammatory responses. AIM: This review addresses the relationships among endothelial dysfunction, hypercoagulability and inflammation and their biomarkers in the development of vascular complications in type 1 and type 2 diabetes. RESULTS: Inflammation, endothelial dysfunction, and hypercoagulability are correlated to each other, playing an important role in the development of vascular complications in diabetic patients. Moreover, it has been observed that several endothelial, inflammatory and pro-coagulant biomarkers, such as VWF, IL-6, TNF-α, D-dimer and PAI-1, are increased in diabetic patients who have microvascular and macrovascular complications, including nephropathy or cardiovascular disease. CONCLUSION: It is promising the clinical and laboratory use of endothelial, inflammatory and pro-coagulant biomarkers for predicting the risk of cardiovascular and renal complications in diabetic patients and for monitoring these patients.

Association of Haemostatic and Inflammatory Biomarkers with Nephropathy in Type 1 Diabetes Mellitus.

This study aimed at investigating the association between haemostatic biomarkers, proinflammatory, and anti-inflammatory cytokines with chronic kidney disease in type 1 diabetic patients. Patients were divided into two groups: with nephropathy (albuminuria ≥ 30 mg/g and/or GFR < 60 mL/min/1.73 m(2)), n = 65; and without nephropathy (albuminuria < 30 mg/g and GFR ≥ 60 mL/min/1.73 m(2)), n = 60. INF-γ, IL-6, IL-10, and TNF-α plasma levels were determined by flow cytometry. VWF, ADAMTS13 antigen, and D-Dimer plasma levels were determined by enzyme-linked immunosorbent assay and ADAMTS13 activity was assessed by fluorescence resonance energy transfer assay. Elevated levels of INF-γ, VWF, ADAMTS13 antigen, D-Dimer, and reduced ADAMTS13 activity/antigen ratio were observed in patients with nephropathy as compared to those without nephropathy (P = 0.001, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, resp.). Cytokines and haemostatic biomarkers remained associated with nephropathy after adjustments (use of statin, acetylsalicylic acid, angiotensin converting enzyme inhibitor, and angiotensin antagonist). INF-γ, TNF-α, and IL-10 significantly correlated with haemostatic biomarkers. Inflammatory and hypercoagulability status are associated with nephropathy in type 1 diabetes mellitus and an interrelationship between them may play an important role in pathogenesis of diabetic nephropathy.

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.

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

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.

Von Willebrand Factor, ADAMTS13 and D-Dimer Are Correlated with Different Levels of Nephropathy in Type 1 Diabetes Mellitus.

We have investigated whether von Willebrand factor, ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), and D-Dimer were associated with different levels of renal function in patients with type 1 diabetes. Patients were classified according to level of renal function through estimated glomerular filtration rate: ≥90 and <130mL/min/1,73m2, n=52 (control group), ≥60 and <90mL/min/1,73m2, n=29 (mild renal dysfunction group), <60mL/min/1,73m2, n=28 (severe renal dysfunction group); and through urinary albumin excretion: normoalbuminuria, microalbuminuria and macroalbuminuria. Von Willebrand factor, ADAMTS13, and D-Dimer plasma levels were determined by enzyme-linked immunosorbent assay. ADAMTS13 activity was determined by fluorescence resonance energy transfer assay. Von Willebrand factor levels were increased in patients with mild (P=0.001) and severe (P<0.001) renal dysfunction as compared to the control group. ADAMTS13 levels were also increased in mild (P=0.029) and severe (P=0.002) renal dysfunction groups in comparison to the control group, while ADAMTS13 activity was increased only in the severe renal dysfunction group as compared to the control group (P=0.006). No significant differences were observed among the groups regarding von Willebrand factor/ADAMTS13 ratio. ADAMTS13 activity/ADAMTS13 levels ratio was reduced in patients with mild (P=0.013) and severe (P=0.015) renal dysfunction as compared to the control group. D-Dimer levels were increased in patients with mild (P=0.006) and severe (P<0.001) renal dysfunction as compared to the control group; it was also higher in patients with severe renal dysfunction as compared to the mild renal dysfunction group (P=0.019). Similar results were found for albuminuria classification. Increased von Willebrand factor, ADAMTS13, and D-Dimer levels and decreased ADAMTS13 activity/ADAMTS13 levels ratio are associated with renal dysfunction in patients with type 1 diabetes, suggesting that endothelial dysfunction and hypercoagulability are associated with nephropathy in type 1 diabetes.

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.

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.

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

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.