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1.
Medicine (Baltimore) ; 100(1): e24208, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429812

RESUMO

OBJECTIVE: To explore the influence of the education of lifestyle in the type 2 diabetes mellitus (T2DM) patients with microalbuminuria as a part of the enhanced multifactorial intervention. METHODS: This study will be conducted from May 2021 to August 2022 at Ningbo No.6 hospital. The experiment was granted through the Research Ethics Committee of Ningbo No.6 hospital (539D035). The patients will be included if they are between 18 and 65 years old and are diagnosed with T2DM with microalbuminuria and the patients who have signed the written informed consent. While the patients will be excluded if they have serious physical comorbidities and patients who are unwilling to offer the informed consent to take part in this experiment. We measure the clinical examination (fasting blood-glucose, glycosylated hemoglobin and routine urine test) timely. Detail of daily dietary intake and lifestyle factors are also recorded. RESULTS: Table 1 reflects the comparison of the biochemical and clinical variables and the lifestyle factors. CONCLUSION: Lifestyle education is effective in facilitating the control of T2DM and reducing microalbuminuria. TRIAL REGISTRATION NUMBER: researchregistry6348.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Educação de Pacientes como Assunto , Assunção de Riscos , Albuminúria/complicações , Diabetes Mellitus Tipo 2/complicações , Humanos
2.
PLoS One ; 15(12): e0243638, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33332405

RESUMO

BACKGROUND: Albuminuria develops in ~40% of subjects with Type 2 Diabetes Mellitus (T2DM), and is often associated with malnutrition, severe comorbidities and decreased life expectancy. The association between albuminuria and altered whole body protein turnover in T2DM is currently unknown. OBJECTIVE: To assess whole body protein degradation and synthesis in type 2 diabetes with and without albuminuria. METHODS: Fourteen T2DM male subjects, with either increased [AER+] or normal [AER-] urinary albumin excretion rate, and eleven age-matched male healthy controls, were infused with phenylalanine [Phe] and tyrosine [Tyr] tracers. Post-absorptive rates of appearance (Ra) of Phe (= protein degradation) and Tyr, Phe hydroxylation to Tyr (Hy) (catabolic pathway), and Phe disposal to protein synthesis [PS], were determined. RESULTS: Phe and Tyr Ra were not different among the groups. However, in T2DM [AER+], the fraction of Phe disposal to hydroxylation was ~50% and ~25% greater than that of both controls and T2DM [AER-] (p<0.006 and p = 0.17, respectively). Conversely, as compared to controls, the fractional Phe disposal to PS was ~10% lower in T2DM [AER+] (p<0.006), and not different from that in T2DM [AER-]. As a consequence, in T2DM [AER+], the ratio between the fractional Phe disposal to hydroxylation and that to PS was ~70% greater (p = 0.005) than that in healthy controls, whereas in the T2DM [AER-] this ratio was ~30% greater than in controls (p = 0.19). CONCLUSIONS: On the basis of the kinetics of the essential amino acid phenylalanine, T2DM subjects with increased AER exhibit a catabolic pattern of whole body protein turnover.


Assuntos
Albuminúria/complicações , Diabetes Mellitus Tipo 2/complicações , Proteólise , Adulto , Albuminúria/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenilalanina/metabolismo , Biossíntese de Proteínas
3.
Clin Exp Hypertens ; 42(8): 743-747, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-32631160

RESUMO

AIMS: Circulating miR-29b and inflammatory process play a vital role in hypertension and hypertensive nephropathy. The aim of the present study was to investigate the association of circulating miR-29b and inflammatory markers with albuminuria and assess the predictive value of circulating miR-29b for albuminuria in essential hypertension. METHODS: This cross-sectional study was continuously enrolled 150 subjects and were divided into three groups based on random urinary albumin/creatinine ratio (UACR, mg/g), the patients with ACR<30 mg/g were classified as normal albuminuria, the values of 30< ACR<300 was defined as micro-albuminuria while the group with ACR over 300 mg/g are macro-albuminuria. Circulating miR-29b was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Multivariate logistic regression and area under the ROC curve (AUC) were used. RESULTS: We found miR-29b, C-reactive protein, and transforming growth factor-ß1 (TGF-ß1) in macro-albuminuria group were significantly higher than those in the micro-albuminuria and normal albuminuria group. The level of miR-29b was positively associated with TGF-ß1, C-reactive protein, and UACR, while negatively related to glomerular filtration rate. Circulating miR-29b was a significant independent determinant factor for albuminuria. CONCLUSION: Our results provided a clinical evidence of a positive association between circulating miR-29b, inflammatory markers, and UACR, and implied miR-29b was a significant independent determinant factor for albuminuria.


Assuntos
Albuminúria/complicações , Hipertensão Essencial/complicações , Inflamação/genética , MicroRNAs/genética , Idoso , Área Sob a Curva , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos Transversais , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Fator de Crescimento Transformador beta1/sangue
4.
BMC Neurol ; 20(1): 170, 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32359353

RESUMO

BACKGROUND AND PURPOSE: Albuminuria is a marker for endothelial dysfunction and knowledge on its association with stroke and stroke subtypes are limited. METHODS: Corresponding data from 7261 participants of the population-based HUNT2 study (1995-1997) was linked with hospital records, identified all patients registered and diagnosed with a first-time stroke. Each diagnosis was validated by reviewal of the medical record appertaining to the individual. We then applied Cox proportional hazard models to estimate the hazard ratios (HRs) for the association between albuminuria (measured as albumin-to-creatinine-ratio, ACR) and diagnosis of stroke and stroke subtypes. RESULTS: 703 (9.7%) participants developed a first ischemic stroke during a median follow-up of 15 years. Higher albuminuria was associated with a higher rate for ischemic stroke and the risk rose steadily with increasing ACR (15% increment per unit increase in ACR concentration in mg/mmol). In the fully adjusted model, the HR for all ischemic strokes was 1.56 (95% CI 1.24-1.95) for those with an ACR ≥3 mg/mmol compared to participants with an ACR < 1 mg/mmol. Overall, increasing ACR was associated with a higher risk of all ischemic stroke subtypes. This was seen to be strongest for lacunar stroke (HR 1.75, CI 1.12-2.72, p = 0.019), and also for stroke of undetermined etiology (HR 1.53, CI 1.11-2.11, p = 0.009) and those caused by atherosclerosis in the large arteries (HR 1.51, CI 0.78-2.94, p = 0.186) than for cardio-embolic stroke (HR 1.22, CI 0.64-2.3, p = 0.518). CONCLUSIONS: Albuminuria is an important risk factor, potentially already at low grade, for ischemic stroke especially for lacunar subtype. Measuring albuminuria is both cheap and readily available. This offers the opportunity to evaluate the risk for endothelial dysfunction and thus the subsequent risk for stroke and cerebral small vessel disease.


Assuntos
Albuminúria , Acidente Vascular Cerebral , Albuminúria/complicações , Albuminúria/epidemiologia , Estudos de Coortes , Humanos , Noruega/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/classificação , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia
5.
Int J Clin Pract ; 74(7): e13505, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32239620

RESUMO

BACKGROUND: We aimed to investigate the effect of a low-protein intake on all-cause mortality in subjects with an estimated glomerular filtration rate (eGFR) ≧60 mL/min/1.73 m2 with or without albuminuria using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: We analysed participants in the NHANES from 2003 to 2010. We excluded participants with an eGFR less than 60 mL/min/1.73 m2 from the analyses. Low-protein intake was defined as a protein intake of less than 0.8 g/kg/day. The Healthy Eating Index 2010 was used to assess diet quality. The vital status of all participants in the NHANES was determined by linking to the National Death Index through the end of 2011. The hazard ratios (HRs) for the association of low-protein intake and mortality were determined using weighted Cox proportional hazards regression models. RESULTS: A total of 7730 participants were included in the analyses. After a median follow up of 4.7 years, 462 participants died. A low-protein intake was associated with a higher risk of mortality (HRs 1.394, 95% CI 1.121-1.734, P = .004) with adjustment for diet quality and relevant risk factors. The higher risk of mortality associated with a low-protein intake was consistent in subjects with or without albuminuria (P interaction .280). CONCLUSION: A protein intake of less than 0.8 g/kg/day was associated with a higher risk of mortality in subjects with an eGFR ≧60 mL/min/1.73 m2 , irrespective of whether they had albuminuria.


Assuntos
Albuminúria/mortalidade , Proteínas na Dieta/uso terapêutico , Taxa de Filtração Glomerular , Inquéritos Nutricionais , Deficiência de Proteína/prevenção & controle , Adulto , Idoso , Albuminúria/complicações , Albuminúria/prevenção & controle , Dieta/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Deficiência de Proteína/etiologia , Risco , Fatores de Risco , Fatores de Tempo
6.
Medicine (Baltimore) ; 99(11): e19284, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176052

RESUMO

High levels of albuminuria have been demonstrated to associate with hearing loss in non-diabetic people, while the clinical impact of low-grade albuminuria has attracted less attention. This cross-sectional population-based study aimed to examine whether hearing loss in non-diabetic United States (US) adults is independently associated with low-grade albuminuria or reduced estimated glomeruli filtration rate (eGFR).A total of 2518 participants aged 20 to 69 years were selected from the US National Health and Nutritional Examination Survey database. Participants with diabetes or high-grade albuminuria were excluded. Hearing loss was assessed using low-frequency pure-tone average (LFPTA) thresholds (0.5, 1.0, 2.0 kHz) and high-frequency pure-tone average (HFPTA) thresholds (3.0, 4.0, 6.0, 8.0 kHz). Logistic and linear regression analyses were used to evaluate associations between renal function indicators and hearing loss.The median age of included participants was 37.4 years, and 55% of them were female. Multivariate analysis revealed that participants with urinary albumin-to-creatinine ratio (UACR) in the highest tertile had a significantly higher risk of hearing loss (OR, 1.79; 95% CI, 1.01-3.19) and higher HFPTA thresholds (ß: 2.23; SE: 0.77). Participants with eGFR <60 mL/min/1.73 m had higher LFPTA thresholds (ß: 4.31; SE: 1.79). After stratification by sex, a significant risk remained only for males in the highest UACR tertile, with 2.18 times the risk of hearing loss (95% CI, 1.06-4.48).Non-diabetic US males with low-grade albuminuria are at increased risk of hearing loss, independent of eGFR.


Assuntos
Albuminúria/complicações , Albuminúria/diagnóstico , Comorbidade , Perda Auditiva/epidemiologia , Perda Auditiva/etiologia , Adulto , Distribuição por Idade , Idoso , Audiometria/métodos , Glicemia/análise , Estudos Transversais , Diabetes Mellitus , Taxa de Filtração Glomerular , Perda Auditiva/diagnóstico , Humanos , Incidência , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Inquéritos Nutricionais , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Estados Unidos , Urinálise/métodos
7.
Biomed Res Int ; 2020: 5240153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32076606

RESUMO

Several studies show that even a level of urine albumin/creatinine ratio (UACR) within the normal range (below 30 mg/g) increases the risk of cardiovascular diseases. We speculate that mildly increased UACR is related to left ventricular hypertrophy (LVH) in patients with type 2 diabetes mellitus (T2DM). In this retrospective study, 317 patients with diabetes with normal UACR, of whom 62 had LVH, were included. The associations between UACR and laboratory indicators, as well as LVH, were examined using multivariate linear regression and logistic regression, respectively. The diagnostic efficiency and the optimal cutoff point of UACR for LVH were evaluated using the area under the receiver operating characteristic curve (AUC) and Youden index. Our results showed that patients with LVH had significantly higher UACR than those without LVH (P < 0.001). The prevalence of LVH presented an upward trend with the elevation of UACR. UACR was independently and positively associated with hemoglobin A1c (P < 0.001). UACR can differentiate LVH (AUC = 0.682, 95% CI (0.602-0.760), P < 0.001). The optimal cutoff point determined with the Youden index was UACR = 10.2 mg/g. When categorized by this cutoff point, the odds ratio (OR) for LVH in patients in the higher UACR group (10.2-30 mg/g) was 3.104 (95% CI: 1.557-6.188, P=0.001) compared with patients in the lower UACR group (<10.2 mg/g). When UACR was analyzed as a continuous variable, every double of increased UACR, the OR for LVH was 1.511 (95% CI: 1.047-2.180, P=0.028). Overall, UACR below 30 mg/g is associated with LVH in patients with T2DM. The optimal cutoff value of UACR for identifying LVH in diabetes is 10 mg/g.


Assuntos
Albuminúria/complicações , Creatinina/urina , Diabetes Mellitus Tipo 2/complicações , Hipertrofia Ventricular Esquerda/complicações , Adulto , Idoso , Albuminas , Albuminúria/sangue , Doenças Cardiovasculares/epidemiologia , China , Creatinina/sangue , Feminino , Hemoglobina A Glicada , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos
8.
Biomed Res Int ; 2020: 7462158, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32047814

RESUMO

Background: Glycemic variability is associated with higher risk of microvascular complications in patients with type 2 diabetes. Aim: To test the hypothesis that glycemic variability can contribute to progression to macroalbuminuria in normal or microalbuminuria in patients with type 2 diabetes. Design: This prospective study enrolled 193 patients with type 2 diabetes at a tertiary medical center. Methods: For each patient, the intrapersonal glycemic variability (mean, SD, and coefficient of variation of HbA1c) was calculated using all measurements obtained three years before the study. Patients were divided into four groups stratified by both urine albumin/creatinine ratio and HbA1c-SD. The presence of macroalbuminuria was assessed with Kaplan-Meier plots and compared by log-rank test. Results: Of the 193 patients, 83 patients were in the macroalbuminuria state. Patients in the initial macroalbuminuria group after enrollment had the highest diabetes duration, mean, CV-HbA1c and HbA1c-SD, and uric acid level, and the lowest estimate glomerular filtration rate, followed by subsequent macroalbuminuria and without macroalbuminuria groups. Patients with microalbuminuria and high HbA1c-SD showed the highest progression rate to macroalbuminuria, after a six-year follow-up study by Kaplan-Meier Plots and compared by log-rank test. Conclusions: Higher HbA1C variability is more likely to progress to macroalbuminuria in those patients who are already in a microalbuminuria state. We recommend that clinicians should aggressively control blood glucose to an acceptable range and avoid blood glucose fluctuations by individualized treatment to prevent renal status progression.


Assuntos
Albuminúria/complicações , Albuminúria/metabolismo , Diabetes Mellitus Tipo 2/complicações , Hemoglobina A Glicada/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas , Glicemia , Creatinina/urina , Progressão da Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Rim , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Taiwan
9.
Acta Diabetol ; 57(6): 725-732, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32025877

RESUMO

AIMS: Type 2 diabetes mellitus is a major cause of death and disability due to its long-term macro- and microvascular diseases. Although women with type 2 diabetes have more macrovascular diseases, it is unclear whether there are sex differences in the occurrence of microvascular disease. The aim of our study was to investigate sex differences in the incidence of microvascular complications in type 2 diabetes. METHODS: Analyses were performed in the DiaGene study, a prospective cohort study for complications of type 2 diabetes, collected in the city of Eindhoven, the Netherlands (n = 1886, mean follow-up time = 6.93 years). Cox proportional hazard models adjusted for risk factors for complications (age, smoking, hypertension, dyslipidemia, HbA1c and duration of type 2 diabetes) were used to analyze the incidence of microvascular complications in men and women. RESULTS: The incidence of microalbuminuria was significantly higher in men (HR microalbuminuria 1.64 [CI 1.21-2.24], p = 0.002). Additionally, men are more likely to develop two or three microvascular complications compared to women (OR 2.42 [CI 1.69-3.45], p < 0.001). CONCLUSIONS: This study shows that men with type 2 diabetes are more likely to develop microvascular complications, especially microalbuminuria. Furthermore, men seem to have a higher chance of developing multiple microvascular complications. Our results highlight that men and women may not benefit to a similar extent from current treatment approaches to prevent diabetes-related microvascular diseases.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/epidemiologia , Caracteres Sexuais , Idoso , Albuminúria/complicações , Albuminúria/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Dislipidemias/complicações , Dislipidemias/epidemiologia , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Incidência , Masculino , Microcirculação/fisiologia , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Fatores de Risco
10.
Diabetes Res Clin Pract ; 161: 108011, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31991151

RESUMO

AIMS: The association of blood glucose in advanced diabetic kidney disease (DKD) is unclear. This study investigated the association between blood glucose and renal endpoints in DKD patients. METHODS: This retrospective cohort study enrolled type 2 diabetic patients with advanced DKD with an estimated glomerular filtration rate (eGFR) between 30 and 90 ml/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g. We classified patients into 2 groups according to their 1-year average HbA1c: <7% and >7%. We followed up the patients until the occurrence of primary renal endpoints. RESULTS: A total of 345 patients were included in the analysis for the period 2012-2018. Mean baseline eGFR was 58 ml/min/1.73 m2 and mean albuminuria levels were 1146 and 1313 mg/g, respectively. Median study duration was 3 years. The risk of primary renal endpoints was not decreased in patients with HbA1c less than 7% with an adjusted hazard ratio (aHR) of 0.62, 95% CI 0.26-1.45. The risks of persistent eGFR lower than 15 ml/min/1.73 m2 and doubling of serum creatinine level were similar between 2 group with aHR of 0.58 (95% CI 0.19-1.83) and 0.61 (95% CI 0.26-1.44), respectively. CONCLUSIONS: Intensive blood sugar control did not prevent renal failure in advanced DKD.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Rim/fisiopatologia , Idoso , Albuminúria/sangue , Albuminúria/complicações , Albuminúria/fisiopatologia , Biomarcadores/análise , Biomarcadores/sangue , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Renal/sangue , Insuficiência Renal/complicações , Insuficiência Renal/diagnóstico , Estudos Retrospectivos
11.
Can J Cardiol ; 36(4): 527-534, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31926740

RESUMO

BACKGROUND: Urinary albumin to creatinine ratio (UACR) is common in patients with heart failure (HF) and may have an impact on clinical outcome. We evaluated the effect of UACR on clinical outcome in a real-world cohort of patients with HF. METHODS: All patients with HF at a health maintenance organization were followed for cardiac-related hospitalizations and death. RESULTS: The study cohort included 4668 patients with HF and was divided into 3 groups based on UACR: normal-range albuminuria (2085 patients; 45%), microalbuminuria (1769 patients; 38%), and macroalbuminuria (814 patients; 17%). Microalbuminuria and macroalbuminuria were both associated with increasing age, diabetes mellitus, hypertension, peripheral vascular disease, atrial fibrillation, and New York Heart Association class III/IV. Microalbuminuria and macroalbuminuria were directly associated with decreased event-free survival from death and death and cardiovascular hospitalizations. Cox regression analysis after adjustment for significant predictors demonstrated that microalbuminuria was associated with increase in mortality (hazard ratio, 1.18; 95% confidence interval, 1.18-1.38; P = 0.03) and macroalbuminuria (hazard ratio, 1.33; 95% confidence interval, 1.10-1.61; P < 0.001). Albuminuria was also an independent predictor of death and cardiovascular hospitalizations. Analysis of albuminuria as a continuous parameter (natural logarithm transformed) showed that UACR was an independent predictor of mortality, and cardiovascular hospitalizations. Subclinical albuminuria (UACR 12-29 µg/mg) was directly associated with reduced survival. Cox regression analysis using restricted cubic splines demonstrated an independent continuous increase in mortality with increasing albuminuria (P < 0.0001 adjusted linear model). CONCLUSION: Albuminuria provides important information regarding several detrimental processes in HF and is a significant predictor of a worse outcome.


Assuntos
Albuminúria/complicações , Albuminúria/urina , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/urina , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Creatinina/urina , Feminino , Humanos , Masculino , Índice de Gravidade de Doença
12.
Metabolism ; 103: 154013, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31734275

RESUMO

BACKGROUND: Transforming growth factor (TGF)-ß/Smad3 signaling is highly activated in kidneys of patients with type 2 diabetic nephropathy (T2DN), however, the precise role of Smad3 in the pathogenesis of diabetic nephropathy remains unclear. METHODS: Smad3 knockout (KO)-db/db mice were generated by intercrossing of male and female double-heterozygous Smad3+/- db/m mice. Renal functions including urinary albumin excretion and serum creatinine were determined. Renal histological injury including renal fibrosis and inflammation were examined by periodic acid Schiff (PAS), periodic acid-silver methenamine (PASM), and immunohistochemistry (IHC) staining. RESULTS: Smad3 knockout (KO)-db/db mice were protected from the development of diabetic kidney injury, characterized by the normal levels of urinary albumin excretion and serum creatinine without any evidence for renal fibrosis and inflammation. In contrast, Smad3 wild-type (WT) db/db and Smad3+/- db/db mice developed progressively decline in renal function over the 12 to 32-week time course, including increased microalbuminuria and elevated levels of serum creatinine. Pathologically, Smad3 WT db/db and Smad3+/- db/db mice exhibited a marked deposition of collagen-I (colI), collagen-IV(col-IV), and an increased infiltration of F4/80+ macrophages in kidney. Mechanistically, Smad3 deficiency decreased the lncRNA Erbb4-IR transcription, while increased miR-29b transcription and therefore protected the kidney from progressive renal injury in db/db mice. CONCLUSION: Results from this study imply that Smad3 may represent as a novel and effective therapeutic target for T2DN.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/prevenção & controle , Rim/patologia , Proteína Smad3/genética , Albuminúria/complicações , Albuminúria/genética , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Feminino , Fibrose/genética , Fibrose/prevenção & controle , Deleção de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
13.
Biochem Biophys Res Commun ; 521(3): 660-667, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31679688

RESUMO

Podocyte injury is an important factor in the pathogenesis of diabetic nephropathy. Podocytes are characterized by large numbers of mitochondria. However, mitochondrial dysfunction as it relates to kidney pathology remains poorly understood. The present study found that podocyte mitochondria in different animal models of diabetes mellitus became elongated with the development of albuminuria, suggesting a change in mitochondrial dynamics. We then treated cells with a combination of glucose, fatty acids, and angiotensin II (GFA) to mimic the diabetic milieu. Cultured podocytes exposed to GFA showed megamitochondria formation and decreased autophagosome degradation. We also found that GFA treatment decreased the binding of the autophagosome to the lysosome. Our results suggest that megamitochondria are common in podocytes during diabetic nephropathy and that insufficient autophagy flux may underlie this effect. These findings have expanded our understanding of the pathogenesis of diabetic nephropathy and identified a potential pharmacological target for treatment.


Assuntos
Autofagia , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/patologia , Mitocôndrias/patologia , Podócitos/patologia , Albuminúria/complicações , Albuminúria/patologia , Animais , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/complicações , Modelos Animais de Doenças , Rim/patologia , Masculino , Ratos Long-Evans , Ratos Sprague-Dawley
14.
Nephrol Dial Transplant ; 35(3): 458-464, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30085245

RESUMO

BACKGROUND: Current classification systems do not specify a healthy normal range for urinary albumin excretion. Occult microvascular disease induced by a Western lifestyle may mean that normal values for apparently healthy adults exceed optimal levels defined by mortality risk. METHODS: Using a national population sample [the US Third National Health and Nutrition Examination Survey (NHANES III) cohort; n = 11 887], the distributions of albumin:creatinine ratio (ACR) and fractional excretion of albumin (FEalb) were studied in healthy young adults [ages 20-40 years, without cardiovascular disease (CVD) or risk factors]. The threshold for mortality risk prediction in the whole adult population sample was then studied across ACR/FEalb categories corresponding to quartiles for healthy young adults. RESULTS: ACR quartiles for healthy young adults were 2.7, 4.2 and 5.9 mg/g in men and 3.8, 6.2 and 9.8 mg/g in women. Increases in ACR below the medians for healthy young adults were not associated with increased mortality or with cardiovascular risk factors when tested in the whole adult population. Increases above this threshold were independently associated with mortality risk [hazard ratio 1.2 (95% confidence interval 1.1-1.4) and 1.8 (1.6-2.0) for Quartiles 3 and 4, respectively]. The prevalence of an optimal ACR below the mortality risk threshold was <25% in the setting of diabetes, hypertension, age >70 years or CVD. Using FEalb to define quartiles of albuminuria gave the same findings. CONCLUSION: Based on mortality risk in the whole adult population, there is an optimal range of albumin excretion (ACR < 6 mg/g and 4 mg/g for women and men, respectively). However, only half of even apparently healthy young US adults fall within this range.


Assuntos
Albuminas/análise , Albuminúria/complicações , Biomarcadores/urina , Doenças Cardiovasculares/mortalidade , Urinálise/métodos , Adulto , Albuminúria/diagnóstico , Albuminúria/urina , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos Nutricionais , Prevalência , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
16.
Diabetes Care ; 43(1): 122-129, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31796570

RESUMO

OBJECTIVE: We aimed to investigate the rate of progression of nonalbuminuric chronic kidney disease (CKD) to end-stage kidney disease (ESKD) or death or major cardiovascular events (MACE) compared with albuminuric and nonalbuminuric phenotypes. RESEARCH DESIGN AND METHODS: We included 10,185 participants with type 2 diabetes enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Based on baseline albuminuria and estimated glomerular filtration rate (eGFR), participants were classified as having no kidney disease (no CKD), albuminuria only (albuminuric non-CKD), reduced eGFR only (nonalbuminuric CKD), or both albuminuria and reduced eGFR (albuminuric CKD). The rate of eGFR decline and hazard ratios (HRs) for ESKD or death or MACE were calculated. RESULTS: For individuals with no CKD and those with nonalbuminuric CKD, the rates of eGFR decline were -1.31 and -0.60 mL/min/year, respectively (P < 0.001). In competing-risks analysis (no CKD as the reference), HRs for ESKD indicated no increased risk for nonalbuminuric CKD (0.76 [95% CI 0.34, 1.70]) and greatest risk for albuminuric CKD (4.52 [2.91, 7.01]). In adjusted Cox models, HRs for death and MACE were highest for albumuniuric CKD (2.38 [1.92, 2.90] and 2.37 [1.89, 2.97], respectively) and were higher for albuminuric non-CKD (1.82 [1.59, 2.08] and 1.88 [1.63, 2.16], respectively) than for those with nonalbuminuric CKD (1.42 [1.14, 1.78] and 1.44 [1.13, 1.84], respectively). CONCLUSIONS: Those with nonalbuminuric CKD showed a slower rate of decline in eGFR than did any other group; however, these individuals still carry a greater risk for death and MACE than do those with no CKD.


Assuntos
Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Angiopatias Diabéticas/mortalidade , Nefropatias Diabéticas/mortalidade , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/complicações , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Causas de Morte , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/complicações , Angiopatias Diabéticas/patologia , Angiopatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/mortalidade , Falência Renal Crônica/patologia , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia , Fatores de Risco
17.
Egypt J Immunol ; 27(2): 81-92, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33548980

RESUMO

Modulation of the immune inflammatory system has been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN); nevertheless, many of the underlying mechanisms are still unknown. A possible role of micro-RNA 152-3p in T2DM and DN has been suggested due to its immunomodulatory effect on the innate immunity. This case control study aimed, first, to determine the possible role of micro-RNA 152-3p in the pathogenesis of T2DM and DN by evaluating its serum expression in T2DM and DN patients. Second, to assess the performance of serum micro-RNAs 16 and 24 as endogenous control in TaqMan assays of micro-RNA analysis by real time PCR in such disease. Quantification of the expression of micro-RNA 152-3p by qRT-PCR was performed using serum of 70 subjects enrolled in this study and grouped into 20 apparently healthy non-diabetic participants (control group), 15 patients with T2DM without nephropathy (DM group) and 35 diabetic patients with nephropathy (DN group). In diabetic patients with nephropathy (DN) (P<0.001), or without nephropathy (DM) (P 0.004), the expression of micro-RNA 152-3p demonstrated a significant elevation in comparison to the controls. Also, the level of micro-RNA 152-3p showed a positive correlation with HbA1c and the duration of diabetes mellitus. The severity of nephropathy as evaluated by markers of renal disease progression; estimated (e)GFR and albumin/creatinine ratio (ACR) revealed a significant correlation with the level of micro-RNA 152-3p. In the same context, serum level of micro-RNA 152-3p was elevated in diabetics with advanced stage of nephropathy (macroalbuminuria) versus the rest of diabetics (without albuminuria and with microalbuminuria). Two one sided T procedure provided a strong statistical support for equivalence of both micro-RNA s 16 and 24. In conclusion, such findings may indicate a pathologic role of micro-RNA 152-3p in Type 2 diabetes mellitus and in the progression of diabetic nephropathy.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas/sangue , MicroRNAs/sangue , Albuminúria/complicações , Biomarcadores/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Humanos
18.
Turk Kardiyol Dern Ars ; 47(8): 657-661, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31802772

RESUMO

OBJECTIVE: The pathophysiology of coronary slow flow phenomenon (CSFP) is poorly understood. Evidence suggesting endothelial dysfunction in patients with slow coronary flow (SCF) led to this evaluation of a possible correlation between microalbuminuria (MAU), as an indicator of endothelial dysfunction, and CSFP in order to investigate a mutual pathophysiology. METHODS: In this case-control study, 15786 patients who presented between September 2016 and April 2018 were screened. All patients with CSFP had chest pain and coronary angiography was indicated due to a positive noninvasive test. All cases had a Thrombosis in Myocardial Infarction (TIMI) flow grade of 2 or a corrected TIMI frame count of >27 without any evidence of obstructive coronary artery disease. The patients used as controls had completely normal coronary angiograms. Fasting mid-stream urine samples were analyzed using an immunoturbidimetric assay to determine the albumin-creatinine ratio (ACR) as a surrogate of microalbuminuria (MAU) (ACR: 30-300 mg/g). The prevalence of MAU in the case and control groups was analyzed. RESULTS: A total of 154 individuals with a normal coronary angiogram and 46 patients with SCF were enrolled in the study. The prevalence of MAU was greater in patients with SCF than in the control group (8.7% vs 1.9%, respectively; p=0.048). Even after adjustment for major risk factors, the association between MAU and CSPF remained significant. CONCLUSION: The results of this study indicated that there was a relationship between MAU and CSFP and confirmed that endothelial dysfunction is a contributing factor to CSFP. These findings are of utmost importance due to the prognostic value of MAU for both all-cause and cardiovascular mortality rates.


Assuntos
Albuminúria , Fenômeno de não Refluxo , Adulto , Idoso , Albuminúria/complicações , Albuminúria/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio , Fenômeno de não Refluxo/complicações , Fenômeno de não Refluxo/epidemiologia , Fatores de Risco , Trombose
19.
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
20.
Tohoku J Exp Med ; 249(2): 127-133, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31666446

RESUMO

Systemic lupus erythematosus (SLE) is characterized by the production of autoantibodies, which causes multi-organ injury such as lupus nephritis. SLE is associated with hypercoagulability. Activated coagulation factors such as tissue factor and VIIa complex and factor Xa activate protease-activated receptor 2 (PAR2). PAR2 promotes cytokine production through mitogen-activated protein kinase or nuclear factor kappa B signaling, and previous reports demonstrated that inhibition of PAR2 alleviated kidney injuries such as diabetic kidney disease and renal fibrosis in animal models. However, the involvement of PAR2 in the pathogenesis of SLE remains unclear. We therefore administered a selective PAR2 peptide antagonist, FSLLRY-NH2, to SLE-prone 4-month-old MRL-Faslpr mice for 4 weeks. Treatment with FSLLRY-NH2 caused the significant increases in the glomerular mesangial proliferation, glomerular deposition of both immunoglobulin G and complement factor C3d, and glomerular infiltration of Mac2-positive macrophages and CD3-positive T cells, compared with MRL-Faslpr mice treated with saline. In addition, the treatment with the PAR2 antagonist increased renal expression levels of tumor necrosis factor-α (Tnfa) and monocyte chemoattractant protein 1 (Mcp1) mRNA. Collectively, these results suggest that inhibition of PAR2 may increase the severity of inflammation in lupus nephritis; namely, opposite to previous observations, PAR2 has anti-inflammatory properties. We propose that activation of PAR2 could serve as a potential therapeutic option for patients with SLE.


Assuntos
Progressão da Doença , Glomérulos Renais/lesões , Glomérulos Renais/patologia , Lúpus Eritematoso Sistêmico/patologia , Receptor PAR-2/antagonistas & inibidores , Albuminúria/complicações , Animais , Anticorpos Antinucleares/metabolismo , Complexo CD3/metabolismo , Complemento C3/metabolismo , Citocinas/metabolismo , Feminino , Imunoglobulina G/metabolismo , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Testes de Função Renal , Macrófagos/metabolismo , Camundongos Endogâmicos MRL lpr , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor PAR-2/genética , Receptor PAR-2/metabolismo
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