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1.
Am J Physiol Regul Integr Comp Physiol ; 320(3): R297-R306, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33407017

RESUMO

Recent evidence indicates a crucial role for G protein-coupled estrogen receptor 1 (GPER1) in the maintenance of cardiovascular and kidney health in females. The current study tested whether GPER1 activation ameliorates hypertension and kidney damage in female Dahl salt-sensitive (SS) rats fed a high-salt (HS) diet. Adult female rats were implanted with telemetry transmitters for monitoring blood pressure and osmotic minipumps releasing G1 (selective GPER1 agonist, 400 µg/kg/day ip) or vehicle. Two weeks after pump implantation, rats were shifted from a normal-salt (NS) diet (0.4% NaCl) to a matched HS diet (4.0% NaCl) for 2 wk. Twenty-four hour urine samples were collected during both diet periods and urinary markers of kidney injury were assessed. Histological assessment of kidney injury was conducted after the 2-wk HS diet period. Compared with values during the NS diet, 24-h mean arterial pressure markedly increased in response to HS, reaching similar values in vehicle-treated and G1-treated rats. HS also significantly increased urinary excretion of protein, albumin, nephrin (podocyte damage marker), and KIM-1 (proximal tubule injury marker) in vehicle-treated rats. Importantly, G1 treatment prevented the HS-induced proteinuria, albuminuria, and increase in KIM-1 excretion but not nephrinuria. Histological analysis revealed that HS-induced glomerular damage did not differ between groups. However, G1 treatment preserved proximal tubule brush-border integrity in HS-fed rats. Collectively, our data suggest that GPER1 activation protects against HS-induced proteinuria and albuminuria in female Dahl SS rats by preserving proximal tubule brush-border integrity in a blood pressure-independent manner.


Assuntos
Albuminúria/prevenção & controle , Ciclopentanos/farmacologia , Nefropatias/prevenção & controle , Glomérulos Renais/efeitos dos fármacos , Túbulos Renais Proximais/efeitos dos fármacos , Quinolinas/farmacologia , Receptores Acoplados a Proteínas-G/agonistas , Albuminúria/etiologia , Albuminúria/metabolismo , Albuminúria/patologia , Animais , Pressão Arterial , Moléculas de Adesão Celular/metabolismo , Modelos Animais de Doenças , Feminino , Hipertensão/etiologia , Hipertensão/fisiopatologia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Ratos Endogâmicos Dahl , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais , Cloreto de Sódio na Dieta
2.
Diab Vasc Dis Res ; 17(6): 1479164120971220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33371732

RESUMO

INTRODUCTION: Diabetes mellitus is a progressive disease with cardiovascular complications. We evaluated the impact of a glucagon like peptide-1 (GLP-1) receptor agonist and sodium glucose cotransporter 2 (SGLT-2) inhibitors dapagliflozin and empagliflozin on renal and cardiac function in type 2 diabetes patients with renal impairment. MATERIALS AND METHODS: A total of 156 patients referred with suboptimal glycemic control were assigned to Group G (GLP-1): n = 72 or Group S (SGLT-2 inhibitor)-dapagliflozin (n = 52) or empagliflozin (n = 32). Renal function was assessed every 3 months for 36 months. Cardiovascular parameters were evaluated every 12 months for 36 months. RESULTS: Compared with baseline, HbA1c and systolic blood pressure significantly decreased in both groups (p < 0.05). The estimated glomerular filtration rate decreased, but without significance. Albuminuria decreased significantly in both groups and then subsequently increased after 30 months in Group S. Diastolic cardiac function, assessed by E/e' or left atrial volume index, decreased only in Group G at 36 months. CONCLUSIONS: The GLP-1 receptor agonist and SGLT-2 inhibitors were effective for glycemic and blood pressure control and for maintaining renal function. The GLP-1 receptor agonist improved diastolic function at 36 months.


Assuntos
Albuminúria/tratamento farmacológico , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Glucosídeos/uso terapêutico , Incretinas/uso terapêutico , Rim/efeitos dos fármacos , Liraglutida/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Albuminúria/diagnóstico , Albuminúria/etiologia , Albuminúria/fisiopatologia , Compostos Benzidrílicos/efeitos adversos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Glucosídeos/efeitos adversos , Humanos , Incretinas/efeitos adversos , Rim/fisiopatologia , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Rigidez Vascular/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
3.
Rev. cuba. oftalmol ; 33(3): e900, tab
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1139087

RESUMO

RESUMEN Objetivo: Identificar la relación de la hemoglobina glicosilada y la albuminuria con la progresión de la retinopatía diabética. Métodos: Se realizó un estudio descriptivo y transversal en el Centro Oftalmológico de Santiago de Cuba desde octubre del año 2017 hasta octubre de 2019. La muestra fue de 42 pacientes diabéticos tipo 2. Resultados: Predominaron los pacientes con tiempo de diabetes mellitus mayor de 10 años y las edades de 55 años o más con el 60,0 por ciento. El color de piel negra fue mayor con 66,7 por ciento; la agudeza visual mayor de 0,6 se presentó en el 49,4 por ciento y la retinopatía diabética proliferativa fue la más presentada con 55,9 por ciento. Predominaron además valores de hemoglobina glicosilada mayores de 7 por ciento en ambos grupos y la normoalbuminuria fue la que predominó en ambos grupos con 46,7 y 66,7 por ciento. Conclusiones: Los valores elevados de hemoglobina glicosilada y la normoalbuminuria se asocian de forma clínica a retinopatía diabética proliferativa(AU)


ABSTRACT Objective: Identify the relationship of glycosylated hemoglobin and albuminuria to progression of diabetic retinopathy. Methods: A descriptive cross-sectional study was conducted at Santiago de Cuba Ophthalmology Center from October 2017 to October 2019. The sample was 42 type 2 diabetic patients. Results: A predominance was found of patients with diabetes mellitus for more than 10 years and the 55 years and over age group (60.0 percent). Black skin color prevailed with 66.7 percent, visual acuity above 0.6 was present in 49.4 percent, and proliferative diabetic retinopathy was the most common type (55.9 percent). In both groups glycosylated hemoglobin values above 7 percent prevailed and normal albuminuria was predominant with 46.7 percent and 66.7 percent. Conclusions: High glycosylated hemoglobin and normal albuminuria values are clinically associated to proliferative diabetic retinopathy(AU)


Assuntos
Humanos , Pessoa de Meia-Idade , Hemoglobina A Glicada/efeitos adversos , Acuidade Visual , Retinopatia Diabética/diagnóstico , Albuminúria/etiologia , Epidemiologia Descritiva , Estudos Transversais
4.
West Afr J Med ; 37(4): 412-417, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32835405

RESUMO

BACKGROUND: Sickle cell anaemia (SCA), one of the causes of morbidity and mortality in children is associated with a large spectrum of systemic complications including sickle cell nephropathy (SCN). Microalbuminuria has been used as a marker of preclinical glomerular damage in these patients. This study aimed at detecting early, renal injury in children with SCA aged 1-17 years, highlighting associations and predictors of microalbuminuria in these children. METHODS: 102 known HbSS children aged 1-17yrears in steady state were recruited into a cross-sectional study. Socio-demographic and clinical findings were recorded. Albuminuria was assayed with spot urine using a quantitative method. Urine creatinine concentration was estimated using the Roche reflotron test strips for quantitative determination of creatinine in blood, serum, plasma and urine. Albumin to creatinine ratio (ACR) was then calculated. Microalbuminuria was defined as ACR of 30-300mg/g. RESULTS: Microalbuminuria was detected in 22.5% of SCA patients in our cohort. Age (p=0.001), gender (p=0.000), packed cell volume (p=0.047) showed a significant relationship with the occurrence of microalbuminuria in this study. Increasing age (OR=1.72, CI=1.22-2.44, p=0.002), female gender (OR=0.09, CI=0.01-0.95, p=0.04) and lower packed cell volume (OR=0.49, CI=0.26-0.90, p=0.02) emerged as independent risk factors associated with the occurrence of microalbuminuria in the study population. CONCLUSION: Renal injury occurs in a high proportion of patients with SCA. Routine screening of all patients with SCA as part of their follow up is therefore recommended to identify patients with early renal injury for proper management.


Assuntos
Albuminúria , Anemia Falciforme , Adolescente , Albuminúria/etiologia , Anemia Falciforme/complicações , Criança , Pré-Escolar , Creatinina , Estudos Transversais , Feminino , Humanos , Lactente , Rim , Masculino , Nigéria
5.
Cardiovasc Diabetol ; 19(1): 90, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539802

RESUMO

BACKGROUND: Exercise induced albuminuria (EiA) is elevated in patients with metabolic dysfunction and diabetes, and may serve as an early biomarker for endothelial dysfunction and "kidney reserve". However, the change in EiA levels over time and its interaction with metabolic dysfunction and glucose metabolism has never been studied. Therefore, we sought to determine EiA levels over time in a cohort of individuals attending a routine annual health survey. METHODS: We prospectively enrolled 412 patients attending an annual healthy survey at our Medical Center. We collected urine samples for albumin and creatinine measurements before and immediately after completing an exercise stress test, along with multiple physiologic and metabolic parameters. Participants returned to a second follow up visit after a mean follow up period of 3 years (± 1.7 SD). RESULTS: Patients with diagnosed diabetes and subjects with HbA1c ≥ 6.5% significantly increased their EiA over time (median [IQR] change between visits = 19.5 [- 10.4-56.1] vs. - 1.1 [- 12.7-4.9] (p = 0.049) for diabetics vs non-diabetics respectively). Moreover, a diabetes diagnosis was significantly associated with a high increase in EiA over time (top 10th percentile) even after adjusting for age, BMI, eGFR, METs, self-reported history of heart disease, systolic and diastolic blood pressure; OR = 4.4 (1.01-19.3 95% CI) (p = 0.049). Finally, elevated fasting blood glucose (≥ 100 mg/dl) was the strongest and only significant predictor for a greater increase in EiA over time after adjusting for all five metabolic syndrome components; blood glucose, waist circumference, blood triglycerides, HDL cholesterol, and BP criteria; OR = 4.0 (1.6-9.8 95% CI) (p < 0.01). CONCLUSIONS: Patients with diabetes and/or elevated fasting blood glucose increase their exercise-induced urinary albumin excretion over time. The ability of EiA to predict major clinical outcomes in patients with and without diabetes needs to be determined in future studies.


Assuntos
Albuminúria/etiologia , Glicemia/metabolismo , Diabetes Mellitus/sangue , Exercício Físico , Jejum/sangue , Síndrome Metabólica/sangue , Idoso , Albuminúria/diagnóstico , Albuminúria/urina , Biomarcadores/sangue , Pressão Sanguínea , Diabetes Mellitus/diagnóstico , Teste de Esforço , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Lipídeos/sangue , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Circunferência da Cintura
6.
Am J Physiol Renal Physiol ; 318(5): F1229-F1236, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32249610

RESUMO

Metformin, an AMP-activated protein kinase (AMPK) activator, has been shown in previous studies to reduce kidney fibrosis in different models of experimental chronic kidney disease (CKD). However, in all of these studies, the administration of metformin was initiated before the establishment of renal disease, which is a condition that does not typically occur in clinical settings. The aim of the present study was to investigate whether the administration of metformin could arrest the progression of established renal disease in a well-recognized model of CKD, the subtotal kidney nephrectomy (Nx) model. Adult male Munich-Wistar rats underwent either Nx or sham operations. After the surgery (30 days), Nx rats that had systolic blood pressures of >170 mmHg and albuminuria levels of >40 mg/24 h were randomized to a no-treatment condition or to a treatment condition with metformin (300 mg·kg-1·day-1) for a period of either 60 or 120 days. After 60 days of treatment, we did not observe any differences in kidney disease parameters between Nx metformin-treated and untreated rats. However, after 120 days, Nx rats that had been treated with metformin displayed significant reductions in albuminuria levels and in markers of renal fibrosis. These effects were independent of any other effects on blood pressure or glycemia. In addition, treatment with metformin was also able to activate kidney AMPK and therefore improve mitochondrial biogenesis. It was concluded that metformin can arrest the progression of established kidney disease in the Nx model, likely via the activation of AMPK.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Ativadores de Enzimas/farmacologia , Rim/efeitos dos fármacos , Metformina/farmacologia , Nefrectomia , Insuficiência Renal Crônica/prevenção & controle , Albuminúria/etiologia , Albuminúria/metabolismo , Albuminúria/prevenção & controle , Animais , Modelos Animais de Doenças , Progressão da Doença , Ativação Enzimática , Fibrose , Hipertensão/etiologia , Hipertensão/metabolismo , Hipertensão/prevenção & controle , Rim/enzimologia , Rim/patologia , Rim/cirurgia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Biogênese de Organelas , Ratos Wistar , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Fatores de Tempo
7.
Sci Rep ; 10(1): 2970, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32076062

RESUMO

Altered circulatory asymmetric and symmetric dimethylarginines have been independently reported in patients with end-stage renal failure suggesting their potential role as mediators and early biomarkers of nephropathy. These alterations can also be reflected in urine. Herein, we aimed to evaluate urinary asymmetric to symmetric dimethylarginine ratio (ASR) for early prediction of diabetic nephropathy (DN). In this cross-sectional study, individuals with impaired glucose tolerance (IGT), newly diagnosed diabetes (NDD), diabetic microalbuminuria (MIC), macroalbuminuria (MAC), and normal glucose tolerance (NGT) were recruited from Dr. Mohans' Diabetes Specialties centre, India. Urinary ASR was measured using a validated high-throughput MALDI-MS/MS method. Significantly lower ASR was observed in MIC (0.909) and MAC (0.741) in comparison to the NGT and NDD groups. On regression models, ASR was associated with MIC [OR: 0.256; 95% CI: 0.158-0.491] and MAC [OR 0.146; 95% CI: 0.071-0.292] controlled for all the available confounding factors. ROC analysis revealed ASR cut-point of 0.95 had C-statistic of 0.691 (95% CI: 0.627-0.755) to discriminate MIC from NDD with 72% sensitivity. Whereas, an ASR cut-point of 0.82 had C-statistic of 0.846 (95% CI: 0.800 - 0.893) had 91% sensitivity for identifying MAC. Our results suggest ASR as a potential early diagnostic biomarker for DN among the Asian Indians.


Assuntos
Albuminúria/diagnóstico , Arginina/análogos & derivados , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Adulto , Idoso , Albuminúria/etiologia , Albuminúria/urina , Arginina/urina , Cromatografia Líquida de Alta Pressão , Estudos Transversais , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/urina , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Espectrometria de Massas em Tandem
8.
Biochem Biophys Res Commun ; 525(2): 319-325, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32089264

RESUMO

To examine the cell-protective role of podocyte autophagy against glomerular endothelial dysfunction in diabetes, we analyzed the renal phenotype of tamoxifen (TM)-inducible podocyte-specific Atg5-deficient (iPodo-Atg5-/-) mice with experimental endothelial dysfunction. In both control and iPodo-Atg5-/- mice, high fat diet (HFD) feeding induced glomerular endothelial damage characterized by decreased urinary nitric oxide (NO) excretion, collapsed endothelial fenestrae, and reduced endothelial glycocalyx. HFD-fed control mice showed slight albuminuria and nearly normal podocyte morphology. In contrast, HFD-fed iPodo-Atg5-/- mice developed massive albuminuria accompanied by severe podocyte injury that was observed predominantly in podocytes adjacent to damaged endothelial cells by scanning electron microscopy. Although podocyte-specific autophagy deficiency did not affect endothelial NO synthase deficiency-associated albuminuria, it markedly exacerbated albuminuria and severe podocyte morphological damage when the damage was induced by intravenous neuraminidase injection to remove glycocalyx from the endothelial surface. Furthermore, endoplasmic reticulum stress was accelerated in podocytes of iPodo-Atg5-/- mice stimulated with neuraminidase, and treatment with molecular chaperone tauroursodeoxycholic acid improved neuraminidase-induced severe albuminuria and podocyte injury. In conclusion, podocyte autophagy plays a renoprotective role against diabetes-related structural endothelial damage, providing an additional insight into the pathogenesis of massive proteinuria in diabetic nephropathy.


Assuntos
Autofagia/fisiologia , Diabetes Mellitus Experimental/patologia , Células Endoteliais/patologia , Glomérulos Renais/patologia , Podócitos/patologia , Albuminúria/etiologia , Animais , Proteína 5 Relacionada à Autofagia/deficiência , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/complicações , Dieta Hiperlipídica , Camundongos , Proteinúria/etiologia
9.
Diabetes Res Clin Pract ; 161: 107992, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32032675

RESUMO

AIMS: Poor glycaemic control elevates the risk for vascular complications. Biomarkers for predicting susceptibility to glycaemic worsening are lacking. This 3-year prospective analysis assessed the utility of several circulating diabetes-related biomarkers for predicting loss of glycaemic control, and their contribution to albuminuria progression in type 2 diabetes mellitus (T2DM). METHODS: T2DM subjects with adequately-controlled diabetes (HbA1c < 8%) at initial recruitment were analysed (N = 859). Baseline plasma levels of osteoprotegerin (OPG), C-reactive protein (CRP), adiponectin, intercellular-cell adhesion molecule-1, and vascular-cell adhesion molecule-1 were quantified using immunoassay. Definitions for development of uncontrolled diabetes and albuminuria progression were HbA1c ≥ 8.0% and increase in albuminuria category at follow-up, respectively. RESULTS: At follow-up, 185 subjects developed uncontrolled diabetes. Higher baseline CRP and OPG levels were observed in the high-risk individuals, and predicted increased risk for developing uncontrolled diabetes. OPG, but not CRP, was associated with albuminuria progression after multivariable adjustment. The relationship was attenuated following adjustment for development of uncontrolled diabetes, which emerged as a significant associate. Mediation analysis revealed that loss of glycaemic control explained 64.5% of the relationship between OPG and albuminuria progression. CONCLUSIONS: OPG outperformed other diabetes-related biomarkers to be a potentially useful biomarker for predicting loss of glycaemic control and its associated albuminuria deterioration.


Assuntos
Albuminúria/diagnóstico , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Osteoprotegerina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/sangue , Albuminúria/etiologia , Proteína C-Reativa/metabolismo , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/sangue , Progressão da Doença , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
11.
Diab Vasc Dis Res ; 17(1): 1479164119879039, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31726864

RESUMO

BACKGROUND: Multiple studies demonstrate an albuminuria-lowering impact of Roux-en-Y gastric bypass surgery, but neither evaluation of its penetrance across different baseline levels of albuminuria nor its association with alterations in podocyte phenotype has previously been reported. METHODS: We profiled changes in body weight, glycaemic control and urinary albumin excretion following Roux-en-Y gastric bypass surgery in 105 patients with type 2 diabetes, albuminuria of varying degrees of severity and classified as being at moderate or high risk of chronic kidney disease progression according to the Kidney Disease: Improving Global Outcomes 2012 criteria. In parallel pre-clinical studies, the impact of Roux-en-Y gastric bypass surgery on markers of podocyte injury was assessed in the Zucker diabetic fatty rat model of diabetic kidney disease. RESULTS: At 12- to 18-month post-operative follow-up in patients at moderate or high risk of chronic kidney disease, significant reductions in albuminuria were observed across all tertiles of baseline albumin-creatinine ratio, with remission of albuminuria occurring in 78% of patients. Relative to sham-operated control animals, weight loss and improvements in glycaemia following Roux-en-Y gastric bypass surgery in Zucker diabetic fatty rats were paralleled by normalisation of glomerular tuft-size, reductions in podocyte expression of desmin, and preservation of podocyte foot process morphology. CONCLUSION: Improvements in podocyte differentiation likely underpin the reductions in albuminuria observed following Roux-en-Y gastric bypass surgery.


Assuntos
Albuminúria/etiologia , Diferenciação Celular , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Derivação Gástrica , Obesidade/cirurgia , Podócitos/patologia , Idoso , Albuminúria/sangue , Albuminúria/patologia , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Obesidade/complicações , Obesidade/diagnóstico , Estudos Prospectivos , Ratos Zucker , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Perda de Peso
12.
Nephrol Dial Transplant ; 35(1): 115-121, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30007296

RESUMO

BACKGROUND: The progression trajectory of renal filtration function has not been well characterized in patients with early-onset type 2 diabetes mellitus (T2DM) although albuminuria is often reported in this population. We aim to study the risk of progressive chronic kidney disease (CKD) in individuals with early-onset T2DM. METHODS: In total, 1189 T2DM participants were followed for 3.9 (interquartile range 3.2-4.7) years. Progressive CKD was defined as estimated glomerular filtration rate (eGFR) decline of ≥5 mL/min/1.73 m2 per year. Early-onset T2DM was defined as age at T2DM diagnosis between 18 and 30 years. RESULTS: Compared with later-onset counterparts (N = 1032), participants with early-onset T2DM (N = 157) were more obese and had poorer glycaemic control at baseline. In the follow-up, 24.2% and 15.6% experienced progressive CKD in early-onset and later-onset participants, respectively (P = 0.007). Logistic regression suggested that participants with early-onset T2DM had 2.63-fold [95% confidence interval (CI) 1.46-4.75] higher risk of progressive CKD after accounting for multiple traditional risk factors. Furthermore, the excess risk of progressive CKD associated with early-onset T2DM mainly occurred in participants with preserved renal function [eGFR ≥60 mL/min/1.73 m2, odds ratio (OR) 2.85, 95% CI 1.50-5.42] and was more pronounced in those with diabetes duration <10 years (OR 3.67, 95% CI 1.51-8.90). CONCLUSIONS: Individuals with early-onset T2DM have a higher risk of progressive CKD. The excess risk mainly exhibits in early stage of CKD and cannot be solely attributed to traditional risk factors and a longer diabetes duration.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Insuficiência Renal Crônica/etiologia , Adulto , Idade de Início , Albuminúria/etiologia , Albuminúria/patologia , Nefropatias Diabéticas/patologia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/patologia , Fatores de Risco
13.
Endocrinol Metab (Seoul) ; 34(4): 398-405, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31884740

RESUMO

BACKGROUND: To evaluate the changes in cardiovascular risk markers including pulse wave velocity (PWV), microalbuminuria, inflammatory cytokines, and adhesion molecules after treatment with beraprost sodium (BPS) in patients with diabetic nephropathy. METHODS: This was a multicenter, prospective, randomized, double-blind, placebo-controlled trial. Type 2 diabetes mellitus patients with microalbuminuria were included. The primary endpoints were changes in microalbuminuria in spot urine and PWV after BPS or placebo (PCB) treatment for 24 weeks. The secondary endpoints were changes in clinical and metabolic parameters. RESULTS: A total of 52 patients completed the 24-week trial. Changes in PWV were not different significantly in the BPS and PCB groups (right, P=0.16; left, P=0.11). Changes in microalbuminuria were 14.2±157.0 and 34.5±146.6 (µg/mg Cr) in the BPS and PCB groups, respectively (P=0.63). Subgroup analysis in the high blood pressure (BP) group (baseline systolic BP >120 mm Hg and diastolic BP >80 mm Hg), showed that microalbuminuria decreased by ?47.6 in the BPS group compared with an increase by 116.4 (µg/mg Cr) in the PCB group (P=0.04). Also, in the large waist circumference group (>95 cm), microalbuminuria decreased significantly in the BPS group (P=0.04). CONCLUSION: Short-term treatment of BPS for patients with diabetic nephropathy did not show significant improvement in various cardiovascular risk factors. However, BPS significantly decreased microalbuminuria in study subjects with higher cardiovascular risk such as high BP or large waist circumference.


Assuntos
Albuminúria/tratamento farmacológico , Biomarcadores/análise , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/tratamento farmacológico , Epoprostenol/análogos & derivados , Hipertensão/tratamento farmacológico , Adulto , Idoso , Albuminúria/etiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Nefropatias Diabéticas/epidemiologia , Método Duplo-Cego , Epoprostenol/uso terapêutico , Feminino , Seguimentos , Humanos , Hipertensão/etiologia , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Análise de Onda de Pulso , República da Coreia/epidemiologia , Vasodilatadores/uso terapêutico
14.
J Diabetes Res ; 2019: 8712979, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886287

RESUMO

Introduction: The development of metabolic syndrome-associated renal dysfunction is exacerbated by a number of factors including dyslipidemia, ectopic deposition of lipids and their toxic metabolites, impairment of lipid metabolism, and insulin resistance. Renal dysfunction is also affected by the production of proinflammatory and profibrotic factors secreted from adipose tissue, which can in turn directly impair kidney cells and potentiate insulin resistance. In this study, we investigated the manifestation of renal lipid accumulation and its effect on renal dysfunction in a model of metabolic syndrome-the hereditary hypertriglyceridemic rat (HHTg)-by assessing microalbuminuria and targeted urinary proteomics. Male Wistar control rats and HHTg rats were fed a standard diet and observed over the course of ageing at 3, 12, and 20 months of age. Results: Chronically elevated levels of triglycerides in HHTg rats were associated with increased levels of NEFA during OGTT and over a period of 24 hours (+80%, P < 0.01). HHTg animals exhibited qualitative changes in NEFA fatty acid composition, represented by an increased proportion of saturated fatty acids (P < 0.05) and a decreased proportion of n-3 PUFA (P < 0.01). Ectopic lipid deposition in the kidneys of HHTg rats-triglycerides (+30%) and cholesterol (+10%)-was associated with markedly elevated microalbuminuria as ageing increased, despite the absence of microalbuminuria at the young age of 3 months in these animals. According to targeted proteomic analysis, 3-month-old HHTg rats (in comparison to age-matched controls) exhibited increased urinary secretion of proinflammatory parameters (MCP-1, IL-6, IL-8, P < 0.01) and decreased urinary secretion of epidermal growth factor (EGF, P < 0.01) before manifestation of microalbuminuria. Elevation in the urinary secretion of inflammatory cytokines can be affected by increased relative expression of MCP-1 in the renal cortex (P < 0.05). Conclusions: Our results confirm dyslipidemia and ectopic lipid accumulation to be key contributors in the development of metabolic syndrome-associated renal dysfunction. Assessing urinary secretion of proinflammatory cytokines and epidermal growth factor can help in detecting early development of metabolic syndrome-associated renal dysfunction.


Assuntos
Albuminúria/etiologia , Citocinas/urina , Fator de Crescimento Epidérmico/urina , Hipertrigliceridemia/complicações , Mediadores da Inflamação/urina , Nefropatias/etiologia , Lipídeos/sangue , Síndrome Metabólica/complicações , Proteômica , Albuminúria/urina , Animais , Biomarcadores/sangue , Biomarcadores/urina , Modelos Animais de Doenças , Diagnóstico Precoce , Hipertrigliceridemia/sangue , Hipertrigliceridemia/genética , Hipertrigliceridemia/urina , Nefropatias/sangue , Nefropatias/urina , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/genética , Síndrome Metabólica/urina , Valor Preditivo dos Testes , Ratos Transgênicos , Ratos Wistar , Fatores de Tempo , Urinálise
15.
Physiol Rep ; 7(24): e14302, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31872559

RESUMO

Chymase released from mast cells produces pro-fibrotic, inflammatory, and vasoconstrictor agents. Studies were performed to test the hypothesis that chronic chymase inhibition provides a renal protective effect in type 2 diabetes. Diabetic (db/db) and control mice (db/m) were chronically infused with a chymase-specific inhibitor or vehicle for 8 weeks. Baseline urinary albumin excretion (UalbV) averaged 42 ± 3 and 442 ± 32 microg/d in control (n = 22) and diabetic mice (n = 27), respectively (p < .05). After administration of chymase inhibitor to diabetic mice, the change in UalbV was significantly lower (459 ± 57 microg/d) than in vehicle-treated diabetic mice (645 ± 108 microg/d). UNGAL V was not different at baseline between diabetic mice that would receive the chymase inhibitor (349 ± 56 ng/d, n = 6) and vehicle (373 ± 99 ng/d, n = 6) infusions, but increased significantly only in the vehicle-treated diabetic mice (p < .05). Glomeruli of diabetic kidneys treated chronically with chymase inhibition demonstrated reduced mesangial matrix expansion compared to glomeruli from untreated diabetic mice. Plasma angiotensin II levels were not altered by chymase inhibitor treatment. In summary, chronic chymase inhibition slowed the progression of urinary albumin excretion in diabetic mice. In conclusion, renal chymase may contribute to the progression of albuminuria in type 2 diabetes renal disease.


Assuntos
Albuminúria/tratamento farmacológico , Quimases/antagonistas & inibidores , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Oligopeptídeos/uso terapêutico , Albuminúria/etiologia , Animais , Quimases/metabolismo , Nefropatias Diabéticas/etiologia , Inibidores Enzimáticos/farmacologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Masculino , Camundongos , Oligopeptídeos/farmacologia
16.
Cardiovasc Ther ; 2019: 4183781, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772610

RESUMO

This study aimed to investigate the correlation between complement C1q tumor necrosis factor-related protein 1 (CTRP1) and subclinical target organ damage (STOD) in essential hypertension (EH). 720 patients were enrolled in this study, including 360 healthy subjects and 360 patients with EH. The EH group included 183 patients complicated with STOD and 177 patients without STOD. In the STOD group, there were 87 patients with left ventricular hypertrophy (LVH), 32 patients with microalbuminuria (MAU), and 58 patients with complication of LVH and MAU. Enzyme-linked immunosorbent assay (ELISA) was used to detect the CTRP1, adiponectin (APN), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). We found that CTRP1 levels were higher in patients with EH than those in healthy subjects; moreover, the level of CTRP1 of patients in the group complicated with EH and STOD was increased compared with EH patients without STOD. CTRP1 levels in the group complicated with LVH and MAU were significantly higher than those in the LVH group and the MAU group. Furthermore, APN, CTRP1, and IL-6 were three factors that influenced the STOD of EH patients, among which CTRP1 and IL6 were positively related with the complication of hypertension and STOD. In conclusion, CTRP1 levels are increased and associated with the STOD (heart and kidney) in essential hypertension, which can be regarded as a novel biomarker in the prediction of prognosis for patients with essential hypertension.


Assuntos
Albuminúria/sangue , Pressão Sanguínea , Hipertensão Essencial/sangue , Hipertrofia Ventricular Esquerda/sangue , Proteínas/análise , Adiponectina/sangue , Adulto , Idoso , Albuminúria/etiologia , Albuminúria/fisiopatologia , Biomarcadores/sangue , Estudos de Casos e Controles , China , Progressão da Doença , Hipertensão Essencial/complicações , Hipertensão Essencial/fisiopatologia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fator de Necrose Tumoral alfa/sangue , Regulação para Cima , Função Ventricular Esquerda , Remodelação Ventricular
17.
Clin Lab ; 65(11)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31710443

RESUMO

BACKGROUND: This study investigated the association between urinary levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) with estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (uACR), and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in patients with type 2 diabetes (T2D). METHODS: Urinary concentrations of IL-6, IL-10, TNF-α, ACR, and NGAL were measured in 121 patients with T2D. RESULTS: Urinary IL-6 and TNF-α increased 45.5% and 49.4% in the highest uACR quartile compared to lowest quartile. Urinary IL-10 levels decreased 40.9% in the highest uACR quartile compared to the lowest quartile. Urinary IL-6 and TNF-α were 75.3% and 81.6%, higher in the highest uNGAL quartile compared to the lowest quartile. Urinary IL-10 concentration was 69.8% lower in patients from the highest uNGAL quartile compared to lowest quartile. CONCLUSIONS: Urinary IL-6, IL-10, and TNF-α were associated with indicators of glomerular and tubular injuries in patients with T2D.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/urina , Interleucina-10/urina , Interleucina-6/urina , Fator de Necrose Tumoral alfa/urina , Idoso , Albuminúria/etiologia , Albuminúria/fisiopatologia , Albuminúria/urina , Biomarcadores/urina , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Humanos , Glomérulos Renais/fisiopatologia , Túbulos Renais/fisiopatologia , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes
18.
Sci Rep ; 9(1): 16398, 2019 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705008

RESUMO

There is an urgent need for a better molecular understanding of the pathophysiology underlying development and progression of diabetic nephropathy. The aim of the current study was to identify novel associations between serum lipidomics and diabetic nephropathy. Non-targeted serum lipidomic analyses were performed with mass spectrometry in 669 individuals with type 1 diabetes. Cross-sectional associations of lipid species with estimated glomerular filtration rate (eGFR) and urinary albumin excretion were assessed. Moreover, associations with register-based longitudinal follow-up for progression to a combined renal endpoint including ≥30% decline in eGFR, ESRD and all-cause mortality were evaluated. Median follow-up time was 5.0-6.4 years. Adjustments included traditional risk factors and multiple testing correction. In total, 106 lipid species were identified. Primarily, alkyl-acyl phosphatidylcholines, triglycerides and sphingomyelins demonstrated cross-sectional associations with eGFR and macroalbuminuria. In longitudinal analyses, thirteen lipid species were associated with the slope of eGFR or albuminuria. Of these lipids, phosphatidylcholine and sphingomyelin species, PC(O-34:2), PC(O-34:3), SM(d18:1/24:0), SM(d40:1) and SM(d41:1), were associated with lower risk of the combined renal endpoint. PC(O-34:3), SM(d40:1) and SM(d41:1) were associated with lower risk of all-cause mortality while an SM(d18:1/24:0) was associated with lower risk of albuminuria group progression. We report distinct associations between lipid species and risk of renal outcomes in type 1 diabetes, independent of traditional markers of kidney function.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Fosfatidilcolinas/sangue , Esfingomielinas/sangue , Adulto , Idoso , Albuminúria/sangue , Albuminúria/etiologia , Estudos Transversais , Dinamarca/epidemiologia , Diabetes Mellitus Tipo 1/mortalidade , Nefropatias Diabéticas/mortalidade , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/etiologia , Lipidômica , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fosfatidilcolinas/química , Fatores de Risco , Esfingomielinas/química , Análise de Sobrevida
19.
Curr Heart Fail Rep ; 16(6): 240-249, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31741232

RESUMO

PURPOSE OF REVIEW: To provide insight into the role of urine biomarkers and electrolytes for the management of heart failure. RECENT FINDINGS: The age-dependent decrease in glomerular filtration rate due to loss of functional nephrons occurs at a faster pace in heart failure, potentially exacerbated by episodes of acute kidney injury. Urine biomarkers have not convincingly demonstrated to improve detection of irreversible renal damage and predict long-term renal trajectories, compared with serial creatinine measurements. Recent data show that natriuresis and diuretic response track poorly with glomerular filtration, but strongly with prognosis. Urine sodium concentration > 50-70 mmol/L was recently put forward through expert consensus as an adequate diuretic response. The value of urine biomarkers to detect structural renal damage in heart failure remains unsure and the latter is probably uncommon, especially over short-term follow-up. Urine electrolytes on the other hand predict diuretic response accurately and may allow better diuretic titration.


Assuntos
Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/etiologia , Biomarcadores/urina , Insuficiência Cardíaca/complicações , Lesão Renal Aguda/fisiopatologia , Albuminúria/diagnóstico , Albuminúria/etiologia , Diuréticos/uso terapêutico , Monitoramento de Medicamentos/métodos , Taxa de Filtração Glomerular , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/patologia , Humanos , Falência Renal Crônica/patologia , Falência Renal Crônica/fisiopatologia , Néfrons/patologia , Sódio/urina
20.
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
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