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1.
Medicine (Baltimore) ; 99(2): e18626, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914044

RESUMO

Detection of the chronic kidney disease (CKD) progression can begin early intervention to improve the prognosis of severe non-alcoholic fatty liver disease (NAFLD). This bi-directional cross-sectional study evaluates the roles of fatty acid-binding protein (FABP) and retinol binding protein (RBP4), which are produced from inflamed liver, adipose tissue and immune cells, for the prediction of CKD progression in severe NAFLD. Ninety severe NAFLD patients with hypertension and proteinuria (NAFLDHTN) were enrolled and divided into CKD (n = 39) and non-CKD groups (n = 51). Among 39 NAFLDHTN patients, 18 cases were categorized as CKD progression group. In comparison with CKD stable group (n = 21), the positive correlation between fold change values of hepatic fibrotic score (KPa), urinary FABP4 or urinary RBP4 versus severity of albuminuria were noted among CKD progression group. On multivariate analysis, high body mass index (BMI, >25 kg/m), high hepatic fibrosis score (>9.5 KPa), high urinary level of vascular cell adhesion molecule-1 (VCAM-1, >2239 µg/g cr), high urinary level of FABP4 (>115 ng/g cr) and high urinary level of RBP4 (>33.5 mg/g cr) are 5 independent predictors for progressive CKD during 24 months of follow-up. Synergetic effect was noted among these 5 risk factors for the prediction of CKD progression in NAFLDHTN patients. The in vitro experiments revealed that both FABP4 and RBP4 directly enhanced albumin-induced ER stress and apoptosis of human renal tubular epithelial cell line HK-2 cells and human podocytes cell lines. Through clinical and experimental approaches, this study revealed new 5 synergetic predictors including high BMI, hepatic fibrosis score, urinary level of VCAM-1, urinary level of FABP4 and RBP4, for the CKD progression in severe NAFLD patients with hypertension and proteinuria.


Assuntos
Ácidos Graxos/urina , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Proteínas de Ligação ao Retinol/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/epidemiologia , Índice de Massa Corporal , Linhagem Celular Transformada , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Índice de Gravidade de Doença , Molécula 1 de Adesão de Célula Vascular/urina , Adulto Jovem
2.
Clin Sci (Lond) ; 134(2): 239-259, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31943002

RESUMO

Mitochondrial stress has been widely observed in diabetic kidney disease (DKD). Cyclophilin D (CypD) is a functional component of the mitochondrial permeability transition pore (mPTP) which allows the exchange of ions and solutes between the mitochondrial matrix to induce mitochondrial swelling and activation of cell death pathways. CypD has been successfully targeted in other disease contexts to improve mitochondrial function and reduced pathology. Two approaches were used to elucidate the role of CypD and the mPTP in DKD. Firstly, mice with a deletion of the gene encoding CypD (Ppif-/-) were rendered diabetic with streptozotocin (STZ) and followed for 24 weeks. Secondly, Alisporivir, a CypD inhibitor was administered to the db/db mouse model (5 mg/kg/day oral gavage for 16 weeks). Ppif-/- mice were not protected against diabetes-induced albuminuria and had greater glomerulosclerosis than their WT diabetic littermates. Renal hyperfiltration was lower in diabetic Ppif-/- as compared with WT mice. Similarly, Alisporivir did not improve renal function nor pathology in db/db mice as assessed by no change in albuminuria, KIM-1 excretion and glomerulosclerosis. Db/db mice exhibited changes in mitochondrial function, including elevated respiratory control ratio (RCR), reduced mitochondrial H2O2 generation and increased proximal tubular mitochondrial volume, but these were unaffected by Alisporivir treatment. Taken together, these studies indicate that CypD has a complex role in DKD and direct targeting of this component of the mPTP will likely not improve renal outcomes.


Assuntos
/metabolismo , Diabetes Mellitus Experimental/metabolismo , Nefropatias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Albuminúria/genética , Albuminúria/metabolismo , Animais , /genética , Ciclosporina/farmacologia , Diabetes Mellitus Experimental/genética , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Peróxido de Hidrogênio/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/genética , ATPases Translocadoras de Prótons/metabolismo
3.
Nat Med ; 25(11): 1753-1760, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31700174

RESUMO

Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models and adjusting for atherosclerotic risk factors (per relevant risk scores), and the predictive utility was determined by the C-statistic and categorical net reclassification index. We show that eGFRcys is most strongly associated with CVD and mortality, and, along with albuminuria, adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment.


Assuntos
Doenças Cardiovasculares/diagnóstico , Taxa de Filtração Glomerular/fisiologia , Falência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/diagnóstico , Adulto , Idoso , Albuminúria/complicações , Albuminúria/diagnóstico , Albuminúria/fisiopatologia , Albuminúria/urina , Bancos de Espécimes Biológicos , Biomarcadores/sangue , Biomarcadores/urina , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/fisiopatologia , Creatinina/metabolismo , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco
4.
High Blood Press Cardiovasc Prev ; 26(5): 361-373, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31650516

RESUMO

High blood pressure (BP) is becoming a growing health issue even in children and adolescents. Moreover, BP elevation in youth frequently translates into children and adult hypertension contributing to the development of cardiovascular disease. The detection of early markers of vascular damage, potentially leading to overt cardiovascular disease, is important for clinical decisions about if and how to treat hypertension and can be useful in monitoring the effectiveness of the treatment. The purpose of this review is to summarize the actual knowledge about subclinical organ damage (SOD) in hypertensive children and adolescents and its association with cardiovascular disease in children and young adults. Our focus is especially put on left ventricular mass, pulse wave velocity, carotid intima-media thickness and microalbuminuria. We also want to address the scientific evidence about possible regression of SOD and cardiovascular risk with the use of behavioural and specific anti-hypertensive therapy. Indications from current guidelines are critically discussed.


Assuntos
Albuminúria/epidemiologia , Pressão Sanguínea , Cardiopatias/epidemiologia , Hipertensão/epidemiologia , Nefropatias/epidemiologia , Doenças Vasculares/epidemiologia , Adolescente , Fatores Etários , Albuminúria/diagnóstico , Albuminúria/fisiopatologia , Doenças Assintomáticas , Criança , Feminino , Cardiopatias/diagnóstico , Cardiopatias/fisiopatologia , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Masculino , Fatores de Risco , Doenças Vasculares/diagnóstico , Doenças Vasculares/fisiopatologia , Remodelação Vascular , Rigidez Vascular
5.
Bratisl Lek Listy ; 120(7): 532-535, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31602990

RESUMO

AIM: The aim of this study is to evaluate the association between urinary megalin, renal function, blood pressure, lipid profile, vitamin D and glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: . This was a cross-sectional study which recruited 209 patients with T2DM. Urinary megalin was positively associated with systolic blood pressure (SBP) (r=0.218, p=0.04) but negatively with glomerular filtration rate (GFR) (r=-0.16, p=0.023). The levels of urinary albumin, triglycerides (TGs) and glycosylated hemoglobin (HbA1c) were higher in the "high-megalin" group, compared to those in "low-megalin" group. Moreover, there was a significant inverse association between vitamin D3 levels and megalin levels in urine (OR=0.281, p=0.047). CONCLUSION: Our study showed for the first time that megalin is associated with progression factors of diabetic nephropathy as well as vitamin D deficiency (Tab. 3, Fig. 1, Ref. 15).


Assuntos
Nefropatias Diabéticas/urina , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/análise , Albuminúria , Colecalciferol/urina , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Taxa de Filtração Glomerular , Hemoglobina A Glicada/urina , Humanos , Triglicerídeos/urina , Deficiência de Vitamina D
6.
F1000Res ; 82019.
Artigo em Inglês | MEDLINE | ID: mdl-31583081

RESUMO

Since the association of microalbuminuria (MAU) with cardiovascular (CV) risk was described, a huge number of reports have emerged. MAU is a specific integrated marker of CV risk and targets organ damage in patients with hypertension, chronic kidney disease (CKD), and diabetes and its recognition is important for identifying patients at a high or very high global CV risk. The gold standard for diagnosis is albumin measured in 24-hour urine collection (normal values of less than 30 mg/day, MAU of 30 to 300 mg/day, macroalbuminuria of more than 300 mg/day) or, more practically, the determination of urinary albumin-to-creatinine ratio in a urine morning sample (30 to 300 mg/g). MAU screening is mandatory in individuals at risk of developing or presenting elevated global CV risk. Evidence has shown that intensive treatment could turn MAU into normoalbuminuria. Intensive treatment with the administration of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, in combination with other anti-hypertensive drugs and drugs covering other aspects of CV risk, such as mineralocorticoid receptor antagonists, new anti-diabetic drugs, and statins, can diminish the risk accompanying albuminuria in hypertensive patients with or without CKD and diabetes.


Assuntos
Albuminúria/diagnóstico , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Hipertensão/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Diabetes Mellitus , Humanos , Hipertensão/complicações , Insuficiência Renal Crônica/complicações , Fatores de Risco
7.
BMC Womens Health ; 19(1): 117, 2019 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590639

RESUMO

BACKGROUND: Women with a higher number of pregnancies have a higher risk of developing cardiovascular diseases. Subtle fluctuations in albumin excretion could be related to pathophysiologic changes in the vascular system. We aimed to investigate the possible association of parity with low-grade albuminuria. METHODS: We conducted a community-based study in 6495 women aged 40 years or older. Low-grade albuminuria was defined according to the highest quartile of urine albumin-to-creatinine ratio in participants free of micro- or macro-albuminuria. RESULTS: Parous women with a higher number of pregnancies had increased age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), fasting plasma glucose (FPG), and fasting insulin, as well as decreased high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR) levels, and proportion of menopause. The prevalence of low-grade albuminuria in parous women gradually increased with parity number. Compared with women with one childbirth, those with more than two childbirths were independently associated with a higher prevalent low-grade albuminuria (odds ratios [ORs] 1.41, 95% confidence interval [CI], 1.09-1.81) after multiple adjustments. In subgroup analysis after multiple adjustments, significant relation between parity number and prevalent low-grade albuminuria was detected in subjects age 55 years or older. CONCLUSION: Number of parity is associated with prevalent low-grade albuminuria in middle-aged and elderly Chinese women without micro- or macro-albuminuria.


Assuntos
Albuminúria/epidemiologia , Paridade , Adulto , Idoso , Albuminúria/etiologia , Pressão Sanguínea , Índice de Massa Corporal , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Prevalência , Circunferência da Cintura
8.
Medicine (Baltimore) ; 98(39): e17297, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574853

RESUMO

As a modifiable risk factor for cardiovascular disease, presence of hypertension (HT) necessitates the awareness of asymptomatic organ damage (AOD). The aim of this study was to measure plasma micro RNA-21 (miR-21) and the parameters that reflect AOD such as carotid intima-media thickness (CIMT), microalbuminuria (MAU) in hypertensive patients compared with healthy controls. In addition, the aim of this study was to evaluate plasma miR-21 levels in HT patients with AOD.This study was designed as a cross-sectional observational study. The study includes 2 groups: 32 patients with HT and 32 healthy controls. First, we compared these 2 groups. Then, to underline the relationship between plasma miR-21 and HT, hypertensive patients were divided into 2 groups: with AOD and without AOD.Sixteen patients with HT had AOD. MiR-21 levels significantly correlated with clinical systolic and diastolic blood pressure, MAU, C-reactive protein, and CIMT. CIMT, miR-21, and MAU levels were significantly higher in patients with AOD.Our study showed increased miR-21 levels in HT patients with AOD.


Assuntos
Albuminúria , Doenças Cardiovasculares , Hipertensão , MicroRNAs/sangue , Adulto , Albuminúria/diagnóstico , Albuminúria/etiologia , Doenças Assintomáticas/epidemiologia , Pressão Sanguínea/fisiologia , Proteína C-Reativa/análise , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Espessura Intima-Media Carotídea , MicroRNA Circulante/análise , Correlação de Dados , Estudos Transversais , Feminino , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/genética , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Turquia/epidemiologia
9.
Rev Assoc Med Bras (1992) ; 65(9): 1155-1160, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618330

RESUMO

OBJECTIVE: In this study, we aimed to analyze the relationship between serum uric acid (UA) and microalbuminuria as a marker of renal injury in type 2 diabetes mellitus. METHODS: A total of 100 patients with type 2 diabetes mellitus were enrolled in the study. Participants were divided into two groups according to the urinary microalbumin/creatinine ratio: diabetic nephropathy and non-nephropathy group. UA and microalbuminuria were compared between the study groups. RESULTS: Serum UA levels of diabetic nephropathy patients were significantly higher than those in the non-nephropathy group (UA in patients with diabetic nephropathy groups: 6.3 (1.82) mg/dl, UA in patients of the non-nephropathic group: 4.85 (1.92) mg/dl) (p<0.001). There was a correlation between microalbuminuria and UA (r=0.238). This correlation was statistically significant (p=0.017). CONCLUSION: UA levels may be an important predictor of nephropathy in diabetic patients.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Hiperuricemia/complicações , Ácido Úrico/sangue , Idoso , Albuminúria/urina , Biomarcadores/sangue , Creatinina/urina , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
10.
Med. clín (Ed. impr.) ; 153(7): 263-269, oct. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-185334

RESUMO

Antecedentes y objetivo: El objetivo del estudio fue comprobar la validez de la clasificación de riesgo KDIGO 2012 para predecir mortalidad total (MT) y cardiovascular (MCV) en diabetes mellitus tipo 2 (DM2). Materiales y métodos: Estudio de cohortes prospectivo incluyendo pacientes con DM2. Los puntos finales clínicos fueron MT y MCV. La principal variable predictora fue la clasificación KDIGO, una variable que recoge 4 niveles de riesgo en dependencia de una combinación de la tasa de filtración glomerular y la excreción de albúmina urinaria. La evaluación del poder predictivo se realizó con el índice de mejora de discriminación integrada (IDI). Resultados: Se incluyeron 453 pacientes (39,3% varones, edad 64,9 [DE 9,3] años y evolución de DM2 de 10,4 [DE 7,5] años). Durante una mediana de 13 años de seguimiento, hubo incremento significativo de la tasa/1000 pacientes-año de MT (26,5 vs. 45,1 vs. 79,2 vs. 109,8; p<0,001) y de MCV (8,1 vs. 17,4 vs. 24,7 vs. 57,5; p<0,001) en las sucesivas categorías de riesgo KDIGO. En análisis multivariante también hubo incremento de riesgo de MT (HR[riesgo moderado]=1,29; HR[riesgo alto]=1,83; HR[riesgo muy alto]=2,15; p=0,016) y MCV (HR[riesgo moderado]=1,73; HR[riesgo alto]=2,27; HR[riesgo muy alto]=4,22; p=0,007) en las sucesivas categorías. La clasificación KDIGO mejoró la predicción de MT (IDI=0,00888; p=0,047) y MCV (IDI=0,01813; p=0,035). Conclusiones: La clasificación de riesgo según guías KDIGO 2012 puede estratificar eficazmente el riesgo de MT y MCV en pacientes con DM2


Background and aims: Our aim was to assess the usefulness of KDIGO 2012 risk classification to predict total and cardiovascular mortality in type 2 diabetes mellitus (DM2). Material and methods: Prospective cohort study that included DM2 patients. Clinical end-points were total and cardiovascular mortality. The main predictive variable was KDIGO risk classification, which is a combination of urinary albumin excretion and glomerular filtration rate. The predictive value was evaluated by the integrated discrimination improvement (IDI) index. Results: 453 patients (39.3% males, aged 64.9 [SD 9.3] and with a mean diabetes duration of 10.4 [SD 7.5] years) were included. During a median follow-up of 13 years, mortality rates per 1000 patients/year (26.5 vs. 45.1 vs. 79,2 vs. 109,8; p<0,001) and cardiovascular mortality (8.1 vs. 17.4 vs. 24.7 vs. 57.5; p<0,001) were progressively increased in successive KDIGO categories. In the multivariate analysis, there was also a progressive increase of mortality risk (HR[moderate risk]=1.29; HR[high risk])=1.83; HR[very high risk]=2.15; p=.016) and cardiovascular mortality risk (HR[moderate risk]=1.73; HR[high risk]=2.27; HR[very high risk]=4.22; p=.007) in the successive categories. KDIGO classification was able to improve the mortality risk prediction (IDI=0.00888; p=.047) and cardiovascular mortality risk prediction (IDI=0.01813; p=.035). Conclusions: KDIGO risk classification can effectively stratify total and cardiovascular mortality risk in DM2 patients


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Diabetes Mellitus Tipo 2/complicações , Taxa de Filtração Glomerular , Albuminúria , Medição de Risco , Prognóstico , Estudos de Coortes , Estudos Prospectivos , Análise Multivariada , Diabetes Mellitus Tipo 2/mortalidade
12.
Int J Mol Sci ; 20(18)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505904

RESUMO

: Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of kidney disease in adults and children. However, it is uncertain whether this association is influenced by major NAFLD susceptibility genes. In a sample of 230 overweight/obese children, 105 with NAFLD (hepatic fat fraction ≥5% by magnetic resonance imaging) and 125 without NAFLD, rs738409 in PNPLA3, rs58542926 in TM6SF2, rs1260326 in GCKR, and rs641738 in MBOAT7 were genotyped. Abnormal kidney function was defined as estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 and/or the presence of microalbuminuria (24 h urinary albumin excretion between 30 and 300 mg). In comparison with children without NAFLD, those with NAFLD showed increased prevalence of reduced eGFR (13.3% vs. 1.6%; p < 0.001) and microalbuminuria (8.6% vs. 3.4%, p = 0.025). TM6SF2, GCKR, and MBOAT7 risk alleles did not show any impact on kidney function, while the PNPLA3 G allele was associated with lower eGFR, but only in children with NAFLD (p = 0.003). After adjustment for confounders, NAFLD (OR, 4.7; 95% CI, 1.5-14.8; padj = 0.007), but not the PNPLA3 gene variant, emerged as the main independent predictor of renal dysfunction. Overall, our findings suggest that NAFLD remains the main determinant of decline in kidney function in overweight/obese children, while the PNPLA3 rs738409 prosteatogenic variant has a small impact, if any.


Assuntos
Albuminúria , Variação Genética , Nefropatias , Lipase/genética , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica , Obesidade Pediátrica , Adolescente , Albuminúria/genética , Albuminúria/urina , Criança , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/genética , Nefropatias/urina , Masculino , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/urina , Obesidade Pediátrica/genética , Obesidade Pediátrica/urina
14.
J Assoc Physicians India ; 67(9): 24-26, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31561683

RESUMO

Introduction: Hypertension is one of the most challenging health problems in the world. Hypertension is closely related to kidney diseases. Microalbuminuria is a reflection of early kidney dysfunction and a marker of asymptomatic preclinical disease which precedes and predicts the occurrence of major morbid events. Aims and objectives: To investigate the relationship between microalbuminuria and LVH in patients with primary hypertension. To establish microalbuminuria as an independent risk factor for increased Left Ventricular Mass Index in patients with Primary Hypertension. Methods: This was a cross-sectional prevalence, analytical study conducted for a period of two years in a tertiary care teaching hospital in Western India. 126 patients diagnosed as primary hypertension, according to JNC 7 criteria were included in the study. Left ventricular Mass Index was measured using 2 D Echo Machine using the formula of Left ventricular mass. Multiple logistic regression was conducted to find out independent correlation of Left Ventricular Hypertrophy. Results: Mean age was 64.32 years in patients without LVH while it was 63.85 years in patients with LVH. Serum creatinine, albumin-creatinine ration and Microalbuminuria were independently correlated with the Left Ventricular hyper trophy. Multiple logistic regression concluded that presence of microalbuminuria increases risk of LVH 2.04 times more as compared to absence of microalbuminuria. Serum creatinine level was higher in patients with LVH compare to patients without LVH. patients with Microalbuminuria were higher in LVH group compare to non LVH group and this difference was statistically significant. Conclusion: This study demonstrates that microalbuminuria has an independent correlation with Left Ventricular Mass Index and hence an independent risk factor for increased cardiovascular morbidity and mortality.


Assuntos
Albuminúria/microbiologia , Hipertensão/epidemiologia , Idoso , Estudos Transversais , Humanos , Hipertrofia Ventricular Esquerda , Índia/epidemiologia , Prevalência
15.
Nat Commun ; 10(1): 4130, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511532

RESUMO

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.


Assuntos
Albuminúria/genética , Mapeamento Cromossômico , Estudo de Associação Genômica Ampla , Metanálise como Assunto , Animais , Creatinina/urina , Diabetes Mellitus/genética , Diabetes Mellitus/urina , Drosophila melanogaster/genética , Regulação da Expressão Gênica , Loci Gênicos , Predisposição Genética para Doença , Humanos , Fatores de Risco
16.
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
17.
Nat Commun ; 10(1): 3605, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399600

RESUMO

Microalbuminuria is an important clinical marker of several cardiovascular, metabolic, and other diseases such as diabetes, hypertension, atherosclerosis, and cancer. The accurate detection of microalbuminuria relies on albumin quantification in the urine, usually via an immunoturbidity assay; however, like many antibody-based assessments, this method may not be robust enough to function in global health applications, point-of-care assays, or wearable devices. Here, we develop an antibody-free approach using synthetic molecular recognition by constructing a polymer to mimic fatty acid binding to the albumin, informed by the albumin crystal structure. A single-walled carbon nanotube, encapsulated by the polymer, as the transduction element produces a hypsochromic (blue) shift in photoluminescence upon the binding of albumin in clinical urine samples. This complex, incorporated into an acrylic material, results in a nanosensor paint that enables the detection of microalbuminuria in patient samples and comprises a rapid point-of-care sensor robust enough to be deployed in resource-limited settings.


Assuntos
Albuminas/química , Albuminúria/diagnóstico , Técnicas Biossensoriais/métodos , Albuminas/isolamento & purificação , Albuminúria/urina , Biomarcadores/sangue , Biomarcadores/urina , Proteínas Sanguíneas/análise , Ácidos Graxos , Humanos , Imobilização , Nanoestruturas/química , Pintura , Espectrometria de Fluorescência , Urina/química
18.
Anal Chim Acta ; 1080: 146-152, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31409464

RESUMO

Field-amplified stacking (FAS) is a commonly used method for enhancing the sensitivity of charged species from low conductive media in capillary electrophoresis. FAS also showed significant sensitivity enhancement effect on a uniform paper fluidic channel by proper design of the electrolyte. In this paper, a novel method of introducing electric field gradient is proposed by geometry design of a 2D paper fluidic channel, and field amplification effect was successfully demonstrated with reduced requirement on the sample's conductivity. Sensitive colorimetric detection of microalbuminuria (MAU) from urine samples was demonstrated by mobile phone camera. Experimental results showed that, with active electric field motivation, up to 93.5% of the loaded protein probe could be effectively transferred and stacked into a narrow band on the newly designed paper fluidic channel. A limit of detection (LOD) of 6.5 mg‧L-1 HSA was achieved with a dynamic range of 10-300 mg‧L-1 (linear in the range of 10-100 mg‧L-1, R2 = 0.991). Combined with selective staining of albumin with bromophenol blue (BPB), the established method was applied to the detection of MAU from clinical urine samples, and consistent results with that of the clinical method were obtained. With this paper-based analytical device (PAD), MAU from highly conductive urine samples can be directly loaded and detected without any pretreatment. This method provides a way to develop highly sensitive point-of-care test (POCT) for rapid screening of some diseases.


Assuntos
Albuminúria/diagnóstico , Colorimetria/métodos , Eletroforese Capilar/métodos , Papel , Albumina Sérica Humana/urina , Azul de Bromofenol/química , Colorimetria/instrumentação , Corantes/química , Eletroforese Capilar/instrumentação , Humanos , Limite de Detecção
19.
Nat Commun ; 10(1): 3656, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409793

RESUMO

In this work we model the glomerular filtration barrier, the structure responsible for filtering the blood and preventing the loss of proteins, using human podocytes and glomerular endothelial cells seeded into microfluidic chips. In long-term cultures, cells maintain their morphology, form capillary-like structures and express slit diaphragm proteins. This system recapitulates functions and structure of the glomerulus, including permselectivity. When exposed to sera from patients with anti-podocyte autoantibodies, the chips show albuminuria proportional to patients' proteinuria, phenomenon not observed with sera from healthy controls or individuals with primary podocyte defects. We also show its applicability for renal disease modeling and drug testing. A total of 2000 independent chips were analyzed, supporting high reproducibility and validation of the system for high-throughput screening of therapeutic compounds. The study of the patho-physiology of the glomerulus and identification of therapeutic targets are also feasible using this chip.


Assuntos
Glomérulos Renais/metabolismo , Dispositivos Lab-On-A-Chip , Nefrite Hereditária/metabolismo , Albuminas/metabolismo , Albuminúria/tratamento farmacológico , Albuminúria/metabolismo , Células Imobilizadas/química , Células Imobilizadas/metabolismo , Células Endoteliais/química , Células Endoteliais/metabolismo , Humanos , Glomérulos Renais/química , Glomérulos Renais/efeitos dos fármacos , Masculino , Nefrite Hereditária/tratamento farmacológico , Podócitos/química , Podócitos/metabolismo
20.
Diabetes Metab Syndr ; 13(4): 2633-2639, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31405687

RESUMO

BACKGROUND&AIM: Mean platelet volume (MPV) is suggested as a marker of platelet reactivity and tendency for thrombosis and microvascular complications like albuminuria in patients with type 2 DM. We aimed to measure the MPV in patients with type 2 DM and its correlation with albuminuria, body mass index (BMI), duration of DM, hypertension (HTN), stroke, ischemic heart disease (IHD), and HbA1c level. METHODS: A cross sectional study included 100 patients with type 2 DM ≥ 18 y of both genders who were randomly selected from the medical units of Baghdad Teaching Hospital. After taking verbal consents; MPV was measured&correlated with aimed variables. Diabetics with HbA1c ≤ 7% were considered as having adequate control while those with (HbA1c) > 7% as having poor control. Albumin creatinine ratio (ACR) in urine was measured and classified into normal, moderately and severely increased. Odds ratios with 95% CI were calculated and P ≤ 0.05 was considered as statistically significant. RESULTS: The mean MPV was 7.7 fl ±â€¯1.2. Regarding ACR, 42% had normal level, 37% with moderately increased and 21% had severely increased level. Regarding HbA1c, 68% were having poorly controlled DM. Mean platelets' count and MPV were higher in the uncontrolled group with a statistically significant association. There was a statistically significant positive correlation between MPV and albuminuria, duration of DM, HTN, IHD, Stroke, BMI, HbA1c, and platelets count. CONCLUSIONS: The mean MPV was statistically significantly higher in the uncontrolled DM group and there was a statistically significant positive correlation between MPV and albuminuria.


Assuntos
Albuminúria/diagnóstico , Biomarcadores/análise , Diabetes Mellitus Tipo 2/complicações , Hipertensão/diagnóstico , Volume Plaquetário Médio , Acidente Vascular Cerebral/diagnóstico , Albuminúria/etiologia , Glicemia/análise , Índice de Massa Corporal , Estudos Transversais , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Acidente Vascular Cerebral/etiologia
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