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1.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414764

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Several factors are known to contribute to the development and progression of diabetic nephropathy. Different microRNAs have been shown to contribute in the pathogenesis of DN. This study, aimed to evaluate the expression level of circulating miR-155 in patients with diabetic nephropathy. METHODS: In this case-control study, 83 diabetic patients and normal subjects were evaluated in four groups of normal healthy subjects without diabetes and nephropathy, diabetes without nephropathy, diabetes with microalbuminuria, and diabetes with macroalbuminuria. After RNA extraction from serum and cDNA synthesis, the expression of circulating miR-155 was evaluated by quantitative polymerase chain reaction (qPCR). RESULTS: Expression level of cell-free miR-155 was significantly lower in diabetics compared to the normal healthy controls (p < 0.05). However, no significant difference was found in miR-155 expression level between different diabetes groups with different conditions of kidney function. Furthermore, we detected a significant negative correlation between cell-free miR-155 expression and GFR only in patients with microalbuminuria (r = -0.70, p = 0.001). CONCLUSIONS: It seems that miR-155 can discriminate diabetic and nondiabetic status, but is not an appropriate biomarker for tracking of macroalbuminuria.


Assuntos
Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , MicroRNAs/sangue , Idoso , Albuminúria/sangue , Albuminúria/complicações , Albuminúria/diagnóstico , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/diagnóstico , Progressão da Doença , Feminino , Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Sensibilidade e Especificidade
2.
Ren Fail ; 41(1): 540-546, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31234687

RESUMO

Low serum 25 hydroxyvitamin D (25 OH D) is common among chronic kidney disease (CKD) patients. This cross-sectional study is looking for the different factors associated with serum 25 OH D among pre-dialysis CKD. 1624 adult stage 3-5 CKD patients were studied beside 200 normal control subjects. All candidates were tested for body mass index (BMI), estimated glomerular filtration rate (eGFR), calcium (Ca), phosphorus (P), parathormone (PTH), 25 OH D, albumin, and uric acid (UA), and urine albumin/creatinine ratio (ACR). Multivariate linear regression analysis was done to determine predictors of 25 OH D. 98.6% of CKD patients have inadequate level of 25 OH D vs 48% of normal subjects. Serum 25 OH D was significantly lower in CKD patients (mean ± S.D = 16.54 ± 5.8 vs 37.79 ± 3.58 ng/mL for CKD vs control group respectively, p < .001). Serum level of 25 OH D has significant positive correlation with Ca (r = 0.337, p < .001), and significant negative correlation with P, PTH, UA, and ACR (r = -0.440, -0. 679, -0.724, and -0.781respectively, p < .001 in all). The independent predictors of 25 OH D were Ca, P, UA, PTH, and ACR (R square = 0.7, ß = -0.087, -0.226, -0.313, -0.253, and -0.33 respectively, p < .001 in all). In conclusion, pre-dialysis CKD patients frequently suffer low 25 OH D. Among the different abnormalities related to CKD, urine albumin excretion rate and UA are the most important predictors of 25 OH D in these patients.


Assuntos
Albuminúria/urina , Insuficiência Renal Crônica/complicações , Ácido Úrico/sangue , Deficiência de Vitamina D/diagnóstico , Vitamina D/análogos & derivados , Adolescente , Adulto , Albuminas/análise , Albuminúria/sangue , Albuminúria/etiologia , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/urina , Vitamina D/sangue , Deficiência de Vitamina D/etiologia , Adulto Jovem
3.
Niger J Clin Pract ; 22(6): 750-753, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31187757

RESUMO

Objective: To study the role of hypoxia inducible factor-1α (HIF-1α) in patients with diabetic nephropathy (DN). Methods: In total, 133 participants were selected to conduct the investigation, parameters such as fasting blood sugar (FBS), blood urea nitrogen (BUN), and urine albumin-creatinine ratio (UACR) were tested and recorded. The biopsy assessment was conducted when renal function or urinary abnormalities. Western blotting was used to test the expression of serum HIF-1α in all patients and control group. Results: The values of FBS, BUN, and UACR were higher in DN and diabetes groups than in the healthy control. The values of FBG, BUN, and UACR were higher in DN patients than in the diabetes patients with no nephropathy. eGFR in DN patients was lower than the other two groups. The expression of HIF-1α was higher than both diabetes patients with no nephropathy and healthy control, P < 0.05. Patients with lots of albuminuria showed the highest expression of HIF-1α than the other groups. HIF-1α in normoalbuminuria and microalbuminuria groups showed no significant difference. Conclusions: HIF-1α was up-regulated in DN patients, which might give clinical basis to the role of HIF-1α in the development of DN.


Assuntos
Albuminúria/sangue , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Adulto , Idoso , Albuminúria/urina , Glicemia/metabolismo , Nitrogênio da Ureia Sanguínea , Estudos de Casos e Controles , Creatinina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regulação para Cima
4.
Ren Fail ; 41(1): 489-496, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31215304

RESUMO

Purpose: This meta-analysis aimed to determine the diagnostic performance of neutrophil gelatinase-associated lipocalin (NGAL) in diabetic nephropathy (DN). Methods: We searched the PubMed, Embase, Wanfang, and China National Knowledge Infrastructure databases for articles published up to 24 April 2019. The meta-analyses were conducted by Stata 11.0, and diagnostic accuracy, sensitivity, specificity, negative and positive likelihood ratios (NLR and PLR), diagnostic odds ratio (DOR), and receiver operating characteristic (ROC) curve data were pooled. Moreover, heterogeneity and small trials bias were evaluated. Results: Six cross-sectional studies were included in the meta-analysis. For the studies of microalbuminuria versus normoalbuminuria, the estimates (95% confidence interval) were as follows: sensitivity, 0.75 (0.51-0.89); specificity, 0.78 (0.70-0.84); PLR, 3.37 (2.49-4.56); NLR, 0.33 (0.16-0.69); DOR, 10.31 (4.05-26.25); and area under the ROC curve (AUC), 0.81 (0.77-0.84). For the studies of microalbuminuria + macroalbuminuria versus normoalbuminuria, the results were as follows: sensitivity, 0.83 (0.66-0.93); specificity, 0.88 (0.67-0.97); PLR, 7.20 (1.97-26.31); NLR, 0.19 (0.08-0.46); DOR, 37.83 (4.84-295.65); AUC, 0.92 (0.90-0.94). Deeks' funnel plot suggested that small trials bias was insignificant in this study. Conclusions: Our findings suggest that NGAL is a potential diagnostic marker for patients with DN and that its diagnostic value for microalbuminuria + macroalbuminuria is superior to that for microalbuminuria. Highlights The first meta-analysis to investigate NGAL diagnostic role in DN. NGAL is valuable for the early diagnosis of DN. The diagnostic value of NGAL in microalbuminuria + macroalbuminuria was much higher.


Assuntos
Albuminúria/diagnóstico , Nefropatias Diabéticas/diagnóstico , Lipocalina-2/análise , Adulto , Albuminúria/sangue , Albuminúria/urina , Biomarcadores/análise , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/urina , Humanos , Curva ROC
5.
J Diabetes Res ; 2019: 5204394, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31218232

RESUMO

Aims: MicroRNAs (miRNAs) stably and abundantly exist in body fluids and have been considered as novel and noninvasive biomarkers for several diseases. The present study is aimed at investigating the expression profiling and clinical significance of plasma miRNAs in the pathogenesis and progression of diabetic nephropathy (DN). Methods: Plasma samples were obtained from 66 DN patients (36 had microalbuminuria and 30 had macroalbuminuria), 36 diabetic patients with normoalbuminuria, and 40 healthy controls. The plasma miRNA profiles were obtained by miRNA low-density array chip and validated by quantitative real-time polymerase chain reaction. The correlations between the differential expression of plasma miRNAs and clinicopathological parameters were explored. Results: miR-150-5p, miR-155-5p, miR-30e, miR-320e, and miR-3196 were found to be differentially expressed in plasma samples among these three groups: diabetic patients with microalbuminuria, diabetic patients with normoalbuminuria, and healthy controls (P < 0.05). The expression levels of miR-150-5p and miR-155-5p in patients with macroalbuminuria were 2.3-fold (P = 0.001) and 1.5-fold (P = 0.033) higher than patients with microalbuminuria, respectively. However, the expression levels of miR-30e, miR-3196, miR-320, and let-7a-5p were not significantly different between these two groups (P > 0.05). Furthermore, plasma miR-150-5p (P = 0.016, r = -0.460) and miR-155-5p (P = 0.014, r = -0.467) were negatively correlated with the albuminuria excretion rate, while plasma miR-150-5p (P = 0.01, r = 0.318) and miR-155-5p (P = 0.030, r = 0.271) were positively correlated with the estimated glomerular filtration rate. Conclusion: miR-150-5p, miR-155-5p, miR-30e, miR-320e, and miR-3196 are potentially new diagnostic biomarkers for early DN. miR-150-5p and miR-155-5p may be involved in the pathogenesis and progression of DN. Further research is required to verify these findings and clarify the specific molecular mechanisms.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Perfilação da Expressão Gênica , MicroRNAs/sangue , Albuminúria/sangue , Biomarcadores/metabolismo , Líquidos Corporais/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/genética , Progressão da Doença , Feminino , Genótipo , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Curva ROC
6.
Clin Lab ; 65(4)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30969095

RESUMO

BACKGROUND: This study is to investigate the protective effects of vitamin D in T2DM, as well as the associations between serum calcifediol level and ß-cell function, and risk of CRC, in Chinese type 2 diabetes mellitus (T2DM) patients with albuminuria. METHODS: Serum calcifediol levels were analyzed and compared among healthy individuals and T2DM patients stratified by albumin/creatinine ratio (ACR). Relative correlation analyses were performed with ß-cell function (BCF) and risk of CRC. RESULTS: Patients' ACR was positively associated with fasting plasma glucose and insulin, homeostasis model assessment (HOMA) of insulin resistance (IR), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA)199, CA125, and Septin9 methylation, but inversely associated with HOMA-BCF and insulin secretion. Serum calcifediol level in the healthy controls was significantly higher than T2DM patients. In T2DM patients, calcifediol level was inversely associated with ACR, HOMA-IR, AFP, CEA, and Septin9 methylation, but positively associated with HOMA-BCF and insulin secretion. Multivariate stepwise principal component regression analysis indicated that calcifediol, hemoglobin A1c, and serum creatinine were independent risk factors for elevated CEA in T2DM. CONCLUSIONS: Higher serum calcifediol level is correlated with better ß-cell function, lower insulin resistance, and decreased risk of CRC. Vitamin D may have suppressive effects on T2DM-associated complications and therefore represents a potential prophylactic treatment against ß-cell dysfunction and cancer development in T2DM patients with albuminuria.


Assuntos
Albuminúria/sangue , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Diabetes Mellitus Tipo 2/sangue , Células Secretoras de Insulina/citologia , Vitamina D/sangue , Idoso , Albuminúria/urina , Antígenos Glicosídicos Associados a Tumores/sangue , Biomarcadores Tumorais/urina , Antígeno Ca-125/sangue , Calcifediol/sangue , Antígeno Carcinoembrionário , China , Neoplasias Colorretais/urina , Diabetes Mellitus Tipo 2/urina , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Resistência à Insulina , Luminescência , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Análise Multivariada , Análise de Componente Principal , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Fatores de Risco , Septinas/sangue , alfa-Fetoproteínas/química
7.
Nat Commun ; 10(1): 1835, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015435

RESUMO

Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.


Assuntos
Albuminúria/etiologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/sangue , Microbioma Gastrointestinal/fisiologia , Ésteres do Ácido Sulfúrico/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/sangue , Albuminúria/tratamento farmacológico , Albuminúria/patologia , Animais , Animais Geneticamente Modificados , Estudos de Coortes , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/urina , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/patologia , Cães , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Células Madin Darby de Rim Canino , Masculino , Metabolômica/métodos , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Transportadores de Ânions Orgânicos/genética , Podócitos/metabolismo , Podócitos/patologia , Ratos , Estreptozocina/toxicidade , Ésteres do Ácido Sulfúrico/sangue , Tirosina Fenol-Liase/antagonistas & inibidores , Tirosina Fenol-Liase/metabolismo , Adulto Jovem
8.
Neurol Res ; 41(6): 498-503, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30931822

RESUMO

OBJECTIVE: Microalbuminuria could be detected in patients with acute stroke. However, the association between microalbuminuria and the severity of ischemic stroke has not been systematically investigated. This study aimed to systematically explore the prevalence of microalbuminuria in ischemic stroke patients, and the association of microalbuminuria with the severity of ischemic stroke, as well as the prognostic value of microalbuminuria in cerebral infarction patients. METHODS: 160 ischemic stroke patients and 54 controls were enrolled and clinical characteristics were recorded. Severity of stroke was assessed by NIHSS score at admission, and outcome was measured using mRS score. The concentration of urinary microalbumin was collected for each participant. Multiple linear regression analysis was performed to evaluate the relationship between microalbuminuria and the severity of ischemic stroke, and logistic regression analysis was employed to identify the prognostic value of microalbuminuria in ischemic stroke patients. RESULTS: The incidence of microalbuminuria in ischemic stroke patients was 36.88%. The concentration of urinary microalbumin increased with the increasing of cerebral infarction size, and was independently correlated with NIHSS score at admission and mRS score at 3 months after onset. In multivariate logistic regression analyses, microalbuminuria was one of the independent risk factors for poor prognosis of cerebral infarction patients. CONCLUSIONS: MAU was found in approximately one-third of patients with acute ischemic stroke. It was correlated with the severity of cerebral infarction at admission and clinical outcomes at 3 months after onset and could be used as a potential indicator of poor prognosis in ischemic stroke patients.


Assuntos
Albuminúria/sangue , Isquemia Encefálica/complicações , Infarto Cerebral/complicações , Acidente Vascular Cerebral/complicações , Idoso , Isquemia Encefálica/cirurgia , Infarto Cerebral/cirurgia , Feminino , Humanos , Isquemia/complicações , Isquemia/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/cirurgia
9.
PLoS One ; 14(2): e0212973, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30817774

RESUMO

BACKGROUND: Marinobufagenin (MBG) is an endogenous cardiotonic steroid (CTS) that inhibits the Na+/K+-ATPase. Human MBG is significantly increased in end-stage renal disease and immunization against MBG attenuates cardiovascular fibrosis in a rat model of uremic cardiomyopathy. Mineralocorticoid antagonists (MRA) block MBG binding sites and decrease proteinuria in chronic kidney disease (CKD) patients. We therefore aimed to investigate the association of MBG and albuminuria, as a marker of renal damage, as well as MBG and decline of glomerular filtration rate (GFR). METHODS: The Graz endocrine causes of hypertension (GECOH) study is a single center study of adults routinely referred for screening of endocrine hypertension. Plasma MBG was measured by an enzyme-linked immunoassay, and in a post-hoc analysis, follow-up creatinine levels were obtained. Patients with proteinuria >3.5g/day at baseline were excluded from further evaluation. RESULTS: We measured MBG concentrations in 40 hypertensive subjects and excluded one patient due to pre-existing proteinuria. Plasma MBG was significantly correlated with albuminuria (Spearman ρ = .357; p = .028) and proteinuria (ρ = .336; p = .039). In linear regression analysis, the association remained significant after adjustment for age, sex, and BMI (ß = .306; p = .036), and for mean systolic blood pressure (ß = .352; p = .034). In follow-up analyses (N = 30), MBG was significantly associated with decline in GFR after adjustment for time-to-follow-up (ß = -.374; p = .042). CONCLUSION: The findings suggest that MBG plasma concentrations were associated with albuminuria as well as decline in kidney function. Whether MBG predicts hard renal endpoints warrants further investigations.


Assuntos
Bufanolídeos/sangue , Taxa de Filtração Glomerular/fisiologia , Hipertensão/sangue , Hipertensão/fisiopatologia , Adulto , Idoso , Albuminúria/sangue , Albuminúria/fisiopatologia , Animais , Biomarcadores/sangue , Cardiotônicos/sangue , Inibidores Enzimáticos/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Proteinúria/sangue , Proteinúria/fisiopatologia , Ratos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia
10.
Med Sci Monit ; 25: 1699-1708, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30835718

RESUMO

BACKGROUND Diabetic kidney disease (DKD) can result in end-stage kidney disease and renal failure. This study aimed to examine the expression of serum microRNAs (miRNAs), miR-20a, miR-99b, miR-122-5p, and miR-486-5p, and to use bioinformatics data to investigate the pathways involved in DKD. MATERIAL AND METHODS Serum miRNAs were obtained from 25 healthy volunteers, 50 patients with non-complicated type 2 diabetes mellitus (T2DM), and 42 patients with T2DM and DKD. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of serum miRNAs. Specificity and sensitivity of the association between serum miRNAs in DKD were evaluated by analysis of the receiver operating characteristic (ROC) area under the curve (AUC). Serum miRNAs and clinical parameters of the patients were compared. Bioinformatics data analysis accessed the miRNA targets involved in the pathways related to the pathogenesis of DKD. RESULTS Serum levels of miR-99b and miR-122 significantly increased, and mir-20a and miR-486 decreased in the DKD group compared with healthy controls. Serum levels of miR-20a, miR-99b, miR-486-5p, and miR-122-5p were significantly correlated with albuminuria, estimated glomerular filtration rate (eGFR), blood glucose and lipid profiles. ROC curve analysis showed that diagnostic accuracy of serum levels of miR-99b for DKD was superior to miR-486-5p, miR-122-5p, and miR-20a, resulting in AUCs of 0.895, 0.853, 0.80, and 0.697, respectively. These four miRNAs regulate several genes affecting oxidative stress, inflammation, and apoptosis. CONCLUSIONS Serum miR-99b, miR-486-5p, miR-122-5p, and miR-20a were differentially expressed in patients with T2DM and DKD and should be evaluated further as potential biomarkers for DKD.


Assuntos
Nefropatias Diabéticas/genética , MicroRNAs/genética , Adulto , Albuminúria/sangue , Albuminúria/genética , Área Sob a Curva , Biomarcadores/sangue , Glicemia/análise , Estudos de Casos e Controles , Biologia Computacional/métodos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/sangue , Feminino , Perfilação da Expressão Gênica/métodos , Taxa de Filtração Glomerular/genética , Humanos , Lipídeos/análise , Lipídeos/sangue , Masculino , MicroRNAs/análise , MicroRNAs/sangue , Pessoa de Meia-Idade , Curva ROC
11.
Appl Biochem Biotechnol ; 188(3): 854-867, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30706418

RESUMO

Altered plasma levels of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) may predict the development of insulin resistance and other type 2 diabetes mellitus (T2DM) associated comorbidities. To elucidate the role of plasma free amino acids (PFAAs) profile as a biomarker for early detection of diabetic kidney disease, quantitative measurement of PFAAs profile was determined for 90 T2DM subjects, 30 were free of nephropathy, 30 with microalbuminuria, 30 with macroalbuminuria, and in addition to 30 healthy controls. The plasma levels of valine, leucine, isoleucine, phenylalanine, citrulline, and total BCAAs were significantly increased in diabetic normoalbuminuria group when compared to controls. However, the total BCAAs level was significantly decreased in diabetic patients with micro and macroalbuminuria. Other amino acid plasma levels as tyrosine, arginine, ornithine, glycine, and the total AAAs level were significantly decreased in all diabetic subgroups compared to controls. Significant positive correlations between total BCAAs, valine, leucine, isoleucine, serum insulin, glucose, and HOMA-IR values in the diabetic normoalbuminuria group were found. The use of altered PFAAs profile as a prognostic factor in T2DM patients at risk for microalbuminuria or macroalbuminuria might reduce or prevent the incidence of end-stage diabetic renal disease.


Assuntos
Albuminúria/sangue , Aminoácidos/sangue , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/complicações , Resistência à Insulina , Adulto , Albuminúria/classificação , Glicemia/análise , Estudos de Casos e Controles , Creatinina/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade
12.
Nat Commun ; 10(1): 403, 2019 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-30679422

RESUMO

Albuminuria affects millions of people, and is an independent risk factor for kidney failure, cardiovascular morbidity and death. The key cell that prevents albuminuria is the terminally differentiated glomerular podocyte. Here we report the evolutionary importance of the enzyme Glycogen Synthase Kinase 3 (GSK3) for maintaining podocyte function in mice and the equivalent nephrocyte cell in Drosophila. Developmental deletion of both GSK3 isoforms (α and ß) in murine podocytes causes late neonatal death associated with massive albuminuria and renal failure. Similarly, silencing GSK3 in nephrocytes is developmentally lethal for this cell. Mature genetic or pharmacological podocyte/nephrocyte GSK3 inhibition is also detrimental; producing albuminuric kidney disease in mice and nephrocyte depletion in Drosophila. Mechanistically, GSK3 loss causes differentiated podocytes to re-enter the cell cycle and undergo mitotic catastrophe, modulated via the Hippo pathway but independent of Wnt-ß-catenin. This work clearly identifies GSK3 as a critical regulator of podocyte and hence kidney function.


Assuntos
Albuminúria/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Nefropatias/metabolismo , Rim/fisiologia , Podócitos/metabolismo , Albuminúria/sangue , Albuminúria/patologia , Albuminúria/urina , Animais , Ciclo Celular , Linhagem Celular , Modelos Animais de Doenças , Drosophila , Deleção de Genes , Inativação Gênica , Quinase 3 da Glicogênio Sintase/genética , Glicogênio Sintase Quinase 3 beta/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Estimativa de Kaplan-Meier , Rim/patologia , Nefropatias/sangue , Nefropatias/patologia , Nefropatias/urina , Masculino , Camundongos , Podócitos/enzimologia , Podócitos/patologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteômica , Ratos Wistar , Insuficiência Renal , Verteporfina/farmacologia , beta Catenina/metabolismo
13.
Diabetes Metab Syndr ; 13(1): 496-499, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30641752

RESUMO

AIMS: Recent studies have implicated possible contribution of adipocytokines in development and progression of microvascular complications in patients with type 1 diabetes (T1DM). The aim of our study was to investigate relationship between adipocytokines, namely leptin, resistin, adiponectin and dipeptidyl peptidase-4 (DPP-4) activity, with albuminuria in T1DM. METHODS: This study included 202 T1DM without or with incipient microvascular complications. Urinary albumin excretion rate (UAE) was measured from at least two 24-h urine samples. Serum DPP-4 activity was measured by a colorimetric assay, and the level of adiponectin, leptin, and resistin was determined by the ELISA method. RESULTS: Serum DPP-4 activity and adiponectin were significantly higher in patients with normoalbuminuria compared to patients with microalbuminuria (47 vs 36 U/L, and 10.9 vs 7.3 µg/mL, respectively, p ≤ 0.02). In multivariate logistic regression analysis adiponectin and serum DPP-4 activity were significantly associated with risk of microalbuminuria in our subjects (p ≤ 0.04), with odds ratios of 0.72-0.99. However, after adjustment for age, sex, HbA1c, duration of diabetes and BMI, only serum DPP-4 activity was significantly associated with risk of microalbuminuria (p = 0.008). CONCLUSION: The results of our study suggest that serum DPP-4 activity is lower in T1DM with microalbuminuria. Prospective studies are warranted to evaluate the relationship between serum DPP-4 activity and progression and development of albuminuria and nephropathy in T1DM.


Assuntos
Adipocinas/sangue , Albuminúria/sangue , Biomarcadores/sangue , Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/sangue , Adiponectina/sangue , Adolescente , Adulto , Idoso , Albuminúria/diagnóstico , Albuminúria/etiologia , Estudos de Casos e Controles , Doença Crônica , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/etiologia , Dipeptidil Peptidase 4/sangue , Feminino , Seguimentos , Humanos , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Resistina/sangue , Adulto Jovem
14.
Diabetes Metab Syndr ; 13(1): 548-552, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30641763

RESUMO

AIM: The aim of this study was to investigate the role of elevated glycated LDL (low-density lipoprotein) in the progression of diabetic kidney disease among type 2 diabetes (T2D) subjects. MATERIALS AND METHODS: This case-control observational study is a part of Saudi Diabetes Kidney Disease (SAUDI-DKD) study conducted during the period from April 2014 to June 2015. This study cohort is divided into two groups; the first group was T2D patients without diabetic nephropathy (DN) (n = 24) and the second group was T2D with DN (n = 45). Serum glycated LDL levels were determined by ELISA. Pearson's correlation analysis was performed, and the diagnostic accuracy was assessed using the area under the ROC curve. RESULTS: There was a threefold increase of serum glycated LDL level among diabetic subjects when compared with non-diabetic subjects and this level progressively increased with the progression of DN. The glycated LDL was found to have a significant diagnostic accuracy with AUC of 0.685 and 0.775 for cases with microalbuminuria and macroalbuminuria respectively. CONCLUSION: The glycated LDL could play a significant role in predicting diabetic patients who are susceptible to develop DN among T2D patients.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Progressão da Doença , Lipoproteínas LDL/sangue , Adulto , Albuminúria/sangue , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Arábia Saudita/epidemiologia
15.
Diabetes Metab Syndr ; 13(1): 830-843, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30641817

RESUMO

BACKGROUND & AIM: Previous studies have explored the relation of metabolic syndrome (MetS), its components and the risk of albuminuria/proteinuria but their results are inconsistent. Then, we aimed to conduct a meta-analysis in order to resolve these controversies. METHOD: PubMed and Scopus were systematically searched from their inception to 1 march 2018. Risk estimates and their 95% confidence intervals were extracted and pooled using the random-effects approach. RESULT: A total of 57 studies, 44 studies on albuminuria and 13 studies on proteinuria, with a total sample size of 10,603,067 participants, were included in this meta-analysis. Overall, MetS was contributed to higher risks of proteinuria (OR = 2.08, 95%CI = 1.85-2.34) and albuminuria (OR = 1.92, 95%CI = 1.71-2.15), independent of diabetes status; although, this relationship was more noticeable in studies that used the WHO definition of MetS and in non-East Asian populations. Also, the relationship between MetS and proteinuria was sex independent, while, for albuminuria was significant only in men. MetS components such as obesity, impaired fasting glucose, elevated blood pressure and hypertriglyceridemia were associated with significant increases in proteinuria and albuminuria risk, while lower HDL-Cholesterol was only linked to greater risk of proteinuria. Moreover, the total impact of MetS on proteinuria was more remarkable than each component of the syndrome and an escalating dose-response association was found between the number of MetS components and albuminuria risk. CONCLUSION: MetS and its components are potential risk factors for albuminuria and proteinuria.


Assuntos
Albuminúria/diagnóstico , Albuminúria/epidemiologia , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Proteinúria/diagnóstico , Proteinúria/epidemiologia , Albuminúria/sangue , Estudos de Casos e Controles , Estudos Transversais , Humanos , Síndrome Metabólica/sangue , Estudos Prospectivos , Proteinúria/sangue , Fatores de Risco
16.
Blood Purif ; 47(1-3): 205-213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30517931

RESUMO

BACKGROUND: Compared to the past, patients with sickle cell disease (SCD) currently live longer due to improvements in diagnosis and comprehensive care. Due to these advances, long-term chronic complications pose a greater challenge in the management of patients with SCD. In particular, sickle cell nephropathy (SCN) is associated with significant morbidity and mortality across all age groups. Furthermore, SCN is an understudied condition with relatively few symptoms and therefore requires close surveillance. In this review, we sought to explore the epidemiology, natural history, and treatment options for SCN with an emphasis on the pediatric population. SUMMARY: SCN invariably begins in childhood with evidence of structural changes detected as early as infancy. These indolent changes can progress undetected to advanced chronic kidney disease by late adolescence or early adulthood. The risk factors for progression are not well defined, but significant albuminuria (which is also the most common presentation in childhood) is a key factor in progression. One of the main challenges in understanding SCN in children is the poor correlation between estimated and measured glomerular filtration rates. Another challenge is the lack of large-scale longitudinal studies that track the clinical outcomes of pediatric patients over time. Several studies aim to identify early biomarkers of SCN in children, as albuminuria presents only following significant chronic damage. The utility of angiotensin converting enzyme inhibitors and hydroxyurea in treating albuminuria is addressed here as well as novel treatments that may be of benefit.


Assuntos
Albuminúria , Anemia Falciforme , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Hidroxiureia/uso terapêutico , Nefropatias , Adolescente , Adulto , Albuminúria/sangue , Albuminúria/tratamento farmacológico , Albuminúria/etiologia , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Biomarcadores , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Nefropatias/sangue , Nefropatias/tratamento farmacológico , Nefropatias/etiologia , Masculino
17.
Br J Haematol ; 184(2): 253-262, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30467843

RESUMO

Growth failure (GF) in children with sickle cell disease (SCD) tends to decline in high-income countries, but data are lacking in sub-Saharan Africa. We performed a cross-sectional study nested in the CADRE (Cœur, Artères et DREpanocytose) cohort in Mali, Senegal, Cameroon, Gabon and the Ivory Coast. SCD patients and healthy controls aged 5-21 years old were recruited (n = 2583). Frequency of GF, defined as a height, weight or body mass index below the 5th percentile on World health Organization growth charts, was calculated. We assessed associations between GF and SCD phenotypic group, clinical and biological characteristics and history of SCD-related complications. GF was diagnosed in 51% of HbSS, 58% of HbSß0 , 44% of HbSC, 38% of HbSß+ patients and 32% of controls. GF in patients was positively associated with parents' lower education level, male sex, age 12-14 years, lower blood pressure, HbSS or HbSß0 phenotypes, icterus, lower haemoglobin level, higher leucocyte count and microalbuminuria. No association was found between GF and clinical SCD-related complications. In sub-Saharan Africa, GF is still frequent in children with SCD, especially in males and during adolescence. GF is associated with haemolysis and microalbuminuria, but not with the history of SCD-related clinical complications.


Assuntos
Albuminúria/epidemiologia , Anemia Falciforme/epidemiologia , Transtornos do Crescimento/epidemiologia , Hemólise , Adolescente , África Ocidental/epidemiologia , Grupo com Ancestrais do Continente Africano , Albuminúria/sangue , Albuminúria/etiologia , Albuminúria/fisiopatologia , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Anemia Falciforme/fisiopatologia , Pressão Sanguínea , Criança , Estudos Transversais , Feminino , Transtornos do Crescimento/sangue , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/fisiopatologia , Hemoglobina Falciforme/metabolismo , Humanos , Masculino
18.
Br J Haematol ; 184(2): 246-252, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30460977

RESUMO

Although renin-angiotensin-aldosterone system (RAAS) blocking agents decrease albuminuria in short-term studies, there is no evidence confirming their long-term efficacy in sickle cell disease (SCD). In a single-centre, retrospective study, we evaluated the long-term effect of RAAS blocking agents on proteinuria and declining estimated glomerular filtration rates (eGFR). Eighty-six patients on RAAS blocking agents for proteinuria, followed for a median of 2·28 years, were compared with 68 patients with proteinuria followed for 2·24 years who were not receiving such treatment. The log odds of proteinuria decreased over time in patients on RAAS blocking agents (ß: -0·23, P = 0·03) and in the non-treatment group (ß: -0·54, P < 0·0001), but was not statistically different between both groups (ß: 0·31, P = 0·063). The eGFR declined over time in patients on RAAS blocking agents (ß: -2·78, P < 0·0001) and in those not on such treatment (ß: -4·7, P < 0·0001), and was statistically different between both groups (ß: 1·9, P = 0·0002). Baseline eGFR was associated with mortality (Hazard rato: 0·97, P < 0·0001), but RAAS blocking agents had no significant effect on mortality. These data suggest that RAAS blockade may slow the loss of kidney function in SCD.


Assuntos
Albuminúria , Anemia Falciforme , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Nefropatias , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Albuminúria/sangue , Albuminúria/tratamento farmacológico , Albuminúria/etiologia , Albuminúria/mortalidade , Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/mortalidade , Anemia Falciforme/patologia , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Intervalo Livre de Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/sangue , Nefropatias/tratamento farmacológico , Nefropatias/etiologia , Nefropatias/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
19.
J Clin Endocrinol Metab ; 104(4): 1171-1180, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30398516

RESUMO

CONTEXT: Despite sex differences in chronic kidney disease (CKD) onset and progression, it is unclear whether endogenous sex hormones are associated with kidney function in persons without CKD. DESIGN AND METHODS: We conducted a secondary analysis of the Diabetes Prevention Program (DPP) and its follow-up observational study, the DPP Outcomes Study, over 11 years. Participants included overweight and glucose-intolerant men (n = 889) and pre- and postmenopausal women (n = 1281) not using exogenous sex hormones and whose urine albumin-to-creatinine ratio (ACR) was <30 mg/g and normal estimated glomerular filtration ratio (eGFR) was ≥60 mL/min/1.73 m2 at randomization. We examined the association between sex hormone levels and incidence of low eGFR and/or ACR ≥30 mg/g on at least one measurement. RESULTS: At randomization, the mean (SD) eGFR was 94 (15) mL/min/1.73 m2; the median ACR (interquartile range) was 4.5 (3.3 to 7.6) mg/g. During follow-up, 187 men (24.6%) and 263 women (24.2%) had incident albuminuria and 136 men (17.9%) and 123 women (11.3%) had incident low eGFR. Among men, higher baseline sex hormone-binding globulin (SHBG) level was associated with reduced low eGFR risk (hazard ratio per SD, 0.80; 95% CI, 0.57 to 0.90) in adjusted analyses. No significant associations were observed among women. There were significant interactions between sex steroid levels and low eGFR by randomization arm. CONCLUSION: Sex steroids were not associated with development of low eGFR or albuminuria. Among men, higher SHBG level was associated with reduced risk of low eGFR on at least one measurement.


Assuntos
Albuminúria/epidemiologia , Nefropatias Diabéticas/epidemiologia , Estradiol/sangue , Taxa de Filtração Glomerular , Globulina de Ligação a Hormônio Sexual/análise , Adulto , Albuminúria/sangue , Albuminúria/urina , Creatinina/urina , Estudos Transversais , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Diabetes Mellitus/prevenção & controle , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Sobrepeso/complicações , Fatores Sexuais
20.
Diabetologia ; 62(1): 169-177, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30267180

RESUMO

AIMS/HYPOTHESIS: Elevated circulating adipocyte fatty acid-binding protein (AFABP) levels have been found to correlate with diabetic nephropathy staging in cross-sectional studies. However, it remains unclear whether these higher serum levels reflect a role of AFABP in the development of diabetic kidney disease (DKD), or simply result from its impaired renal clearance in DKD. Here we investigated prospectively the prognostic importance of serum AFABP level in the development of adverse renal outcomes in a large clinic-based cohort of participants with type 2 diabetes. METHODS: Baseline serum AFABP levels were measured in 5454 Chinese participants from the Hong Kong West Diabetes Registry. The association between circulating AFABP levels and incident adverse renal outcomes-defined as a composite endpoint of a sustained 40% decline in eGFR, end-stage renal disease requiring renal replacement therapy or kidney transplantation, or renal deaths-was evaluated using multivariable Cox regression analysis. RESULTS: Over a median follow-up of 5 years, 754 of the 5454 participants developed incident adverse renal outcomes. Elevated circulating AFABP levels were independently associated with incident adverse renal outcomes (HR 1.43, 95% CI 1.31, 1.57, p < 0.001) after adjustments for conventional risk factors for DKD progression. Importantly, the prognostic role of serum AFABP was independent of the baseline albuminuria status or eGFR levels of the study participants. CONCLUSIONS/INTERPRETATION: Circulating AFABP levels were predictive of incident adverse renal outcomes, even in participants with relatively well-preserved kidney function at baseline, suggesting its potential to be a useful marker for early risk stratification in DKD.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Proteínas de Ligação a Ácido Graxo/sangue , Adulto , Idoso , Albuminúria/sangue , Albuminúria/patologia , Estudos Transversais , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/patologia , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos
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