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1.
High Blood Press Cardiovasc Prev ; 27(1): 43-49, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31916208

RESUMO

INTRODUCTION: Albuminuria is an early marker of kidney disease and reduction of albuminuria translates into a decreased occurrence of cardiovascular and renal outcomes. AIMS: To evaluate the changes in the prevalence of albuminuria in diabetic hypertensive patients treated with several combinations of renin-angiotensin aldosterone system with calcium channel blockers. METHODS: We analysed data from 668 unselected patients from the PAIT survey (mean age 60.4 ± 10.2 years, prevalence of males 38%), with and without albuminuria, maintained for 6 months with the previous treatment with amlodipine-valsartan, amlodipine perindopril, lercanidipine-enalapril, verapamil-trandolapril, nitrendipine-enalapril and felodipine-ramipril Albuminuria was assessed, as urinary albumin-creatinine ratio, using a Multistic-Clinitek device analyzer. Microalbuminuria was defined as a loss of 3.4-33.9 mg albumin/mmol creatinine (30-300 mg/g) and macroalbuminuria as a loss of > 33.9 mg albumin/mmol creatinine (> 300 mg/g). Blood pressure was measured with a validated digital device. RESULTS: At baseline, albuminuria was present in 310 subjects (46.4%) (microalbuminuria in 263 (84.8%), macroalbuminuria in 15.2%), and normoalbuminuria in 53.6% 358. After 6 months, the prevalence of subjects with albuminuria was significantly lowered (p < 0.01) by 23.5% (microalbuminuria - 23.9%, p < 0.01 and macroalbuminuria - 21.3%). The prevalence of subjects with microalbuminuria was reduced with all treatments: amlodipine-valsartan - 15.6%, amlodipine-perindopril - 11.8%, lercanidipine-enalapril - 41.3% and verapamil-trandolapril - 19.2%. Data with nitrendipine-enalapril and felodipine-ramipril were not analyzed, due to the low number of patients. The frequency of patients with normoalbuminuria was significantly higher (p < 0.01) with lercanidipine-enalapril compared with any other treatment. Blood pressure was significantly (p < 0.01) reduced, with a similar effect between treatments. CONCLUSIONS: The treatments decrease the prevalence of subjects with albuminuria, showing a significant difference among the different drug combinations, favoring the use of new dihydropyridine calcium channel blockers, such as lercanidipine, combined with RAAS inhibitors, to control albuminuria in diabetic hypertensive patients.


Assuntos
Albuminúria/prevenção & controle , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Diabetes Mellitus/epidemiologia , Nefropatias Diabéticas/epidemiologia , Hipertensão/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Idoso , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Albuminúria/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Estudos Transversais , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/fisiopatologia , Quimioterapia Combinada , Europa (Continente)/epidemiologia , Feminino , Pesquisas sobre Serviços de Saúde , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
2.
Vasc Health Risk Manag ; 15: 365-373, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686830

RESUMO

Chronic kidney disease (CKD) has become a major public health problem in the USA and worldwide. A large majority of patients with CKD have mild to moderate disease and microalbuminuria. It has increasingly been noted that patients with CKD have a significantly higher risk of cardiovascular outcomes compared to patients with normal kidney function. Many studies have shown increased risk beginning at stage 3 CKD but risk has been elevated in patients with milder degrees of kidney dysfunction in some studies. This risk may be better predicted by the degree of albuminuria in the earlier stages of CKD. Data addressing interventions to improve outcomes in patients with mild to moderate CKD are scarce. In this paper, we examined data and post hoc analyses from the ORIGIN and ACCORD trials. Data indicate that intensive treatment of diabetes in patients with CKD actually may result in adverse outcomes. The mechanism by which CKD results in increased cardiovascular risk is not clear. Patients with CKD frequently have the traditional risk factors that cause cardiovascular disease and there are mechanisms that are unique to CKD that promote the development of cardiovascular disease. In this article, we describe in some detail traditional, newer and novel risk factors that play a role in the development of CKD and heart disease.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/mortalidade , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Humanos , Hipoglicemiantes/efeitos adversos , Prognóstico , Proteinúria/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Medição de Risco , Fatores de Risco
3.
Nutr Metab Cardiovasc Dis ; 29(11): 1127-1150, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31586514

RESUMO

AIMS: This joint document of the Italian Diabetes Society and the Italian Society of Nephrology reviews the natural history of diabetic kidney disease (DKD) in the light of the recent epidemiological literature and provides updated recommendations on anti-hyperglycemic treatment with non-insulin agents. DATA SYNTHESIS: Recent epidemiological studies have disclosed a wide heterogeneity of DKD. In addition to the classical albuminuric phenotype, two new albuminuria-independent phenotypes have emerged, i.e., "nonalbuminuric renal impairment" and "progressive renal decline", suggesting that DKD progression toward end-stage kidney disease (ESKD) may occur through two distinct pathways, albuminuric and nonalbuminuric. Several biomarkers have been associated with decline of estimated glomerular filtration rate (eGFR) independent of albuminuria and other clinical variables, thus possibly improving ESKD prediction. However, the pathogenesis and anatomical correlates of these phenotypes are still unclear. Also the management of hyperglycemia in patients with type 2 diabetes and impaired renal function has profoundly changed during the last two decades. New anti-hyperglycemic drugs, which do not cause hypoglycemia and weight gain and, in some cases, seem to provide cardiorenal protection, have become available for treatment of these individuals. In addition, the lowest eGFR safety thresholds for some of the old agents, particularly metformin and insulin secretagogues, have been reconsidered. CONCLUSIONS: The heterogeneity in the clinical presentation and course of DKD has important implications for the diagnosis, prognosis, and possibly treatment of this complication. The therapeutic options for patients with type 2 diabetes and impaired renal function have substantially increased, thus allowing a better management of these individuals.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/terapia , Taxa de Filtração Glomerular , Hipoglicemiantes/uso terapêutico , Falência Renal Crônica/terapia , Rim/fisiopatologia , Biomarcadores/sangue , Glicemia/metabolismo , Tomada de Decisão Clínica , Consenso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Humanos , Hipoglicemiantes/efeitos adversos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/fisiopatologia , Seleção de Pacientes , Fatores de Risco , Resultado do Tratamento
5.
EBioMedicine ; 47: 446-456, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31542391

RESUMO

BACKGROUND: Senescent cells, which can release factors that cause inflammation and dysfunction, the senescence-associated secretory phenotype (SASP), accumulate with ageing and at etiological sites in multiple chronic diseases. Senolytics, including the combination of Dasatinib and Quercetin (D + Q), selectively eliminate senescent cells by transiently disabling pro-survival networks that defend them against their own apoptotic environment. In the first clinical trial of senolytics, D + Q improved physical function in patients with idiopathic pulmonary fibrosis (IPF), a fatal senescence-associated disease, but to date, no peer-reviewed study has directly demonstrated that senolytics decrease senescent cells in humans. METHODS: In an open label Phase 1 pilot study, we administered 3 days of oral D 100 mg and Q 1000 mg to subjects with diabetic kidney disease (N = 9; 68·7 ±â€¯3·1 years old; 2 female; BMI:33·9 ±â€¯2·3 kg/m2; eGFR:27·0 ±â€¯2·1 mL/min/1·73m2). Adipose tissue, skin biopsies, and blood were collected before and 11 days after completing senolytic treatment. Senescent cell and macrophage/Langerhans cell markers and circulating SASP factors were assayed. FINDINGS: D + Q reduced adipose tissue senescent cell burden within 11 days, with decreases in p16INK4A-and p21CIP1-expressing cells, cells with senescence-associated ß-galactosidase activity, and adipocyte progenitors with limited replicative potential. Adipose tissue macrophages, which are attracted, anchored, and activated by senescent cells, and crown-like structures were decreased. Skin epidermal p16INK4A+ and p21CIP1+ cells were reduced, as were circulating SASP factors, including IL-1α, IL-6, and MMPs-9 and -12. INTERPRETATION: "Hit-and-run" treatment with senolytics, which in the case of D + Q have elimination half-lives <11 h, significantly decreases senescent cell burden in humans. FUND: NIH and Foundations. ClinicalTrials.gov Identifier: NCT02848131. Senescence, Frailty, and Mesenchymal Stem Cell Functionality in Chronic Kidney Disease: Effect of Senolytic Agents.


Assuntos
Senescência Celular/efeitos dos fármacos , Dasatinibe/farmacologia , Nefropatias Diabéticas/metabolismo , Quercetina/farmacologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Idoso , Biomarcadores , Biópsia , Ensaios Clínicos Fase I como Assunto , Dasatinibe/uso terapêutico , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Testes de Função Renal , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Quercetina/uso terapêutico
6.
Diabetes Res Clin Pract ; 156: 107865, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545979

RESUMO

AIMS: We investigated whether serum haptoglobin (Hp) levels play a role in the development and progression of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients in a Chinese Han population, which has not been previously investigated. METHODS: We recruited 233 participants who had suffered from T2DM for more than 10 years, including 118 subjects with DKD (case) and 115 subjects without DKD (control). Serum Hp levels were measured by an enzyme-linked immunosorbent assay. RESULTS: Serum Hp levels were significantly higher (P = 0.0258) in case group (2.74 (1.77, 3.48) g/L) than control (2.29 (0.98, 3.48) g/L). The serum Hp level was significantly positively associated with both logarithmically transformed (log-transformed) serum creatinine (r = 0.1663, P = 0.011) and albuminuria levels (r = 0.1793, P = 0.0062) and was negatively associated with the log-transformed estimated glomerular filtration rate (r = -0.1482, P = 0.0237). Multiple linear regression analysis revealed that serum Hp levels were significantly correlated with serum creatinine levels (P = 0.0088) after adjusting for confounding risk factors. CONCLUSIONS: Our findings suggest that serum Hp levels may be used as a potential biomarker for the early diagnosis and monitoring of DKD in T2DM patients.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Haptoglobinas/metabolismo , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
7.
Acta Diabetol ; 56(12): 1323-1331, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31494747

RESUMO

AIMS: Nephropathic patients show higher levels of advanced glycation end products (AGEs) and oxidized human serum albumin (HSAox) compared to healthy subjects. These two classes of compounds are formed as the result of oxidative insults; for this reason, they can be useful oxidative stress biomarkers. The present study examines the variation of AGEs and HSAox in hemodialysis (HD) patients before and after dialysis session, evaluating the impact of different dialytic techniques and filters on their removal. METHODS: A total of 50 healthy subjects (control group) and 130 HD patients were enrolled in the study. Hemodialysis patients were subdivided based on dialytic techniques: 109 in diffusive technique and 22 in convective technique. We monitored HSAox, AGEs and other laboratory parameters at early morning in healthy subjects and in HD patients before and after the dialysis procedures. RESULTS: The level of HSAox decreases after a single dialytic session (from 58.5 ± 8.8% to 41.5 ± 11.1%), but the concentration of total AGEs increases regardless of adopted dialytic techniques (from 6.8 ± 5.2 µg/ml to 9.2 ± 4.4 µg/ml). In our study, levels of HSAox and total AGEs are similar in diabetic and non-diabetic HD patients. The increase in total AGEs after dialysis was only observed using polysulfone filters but was absent with polymethacrylate filters. CONCLUSIONS: HSAox is a simple and immediate method to verify the beneficial effect of a single dialysis session on the redox imbalance, always present in HD patients. Total AGEs assayed by ELISA procedure seem to be a less reliable biomarker in this population.


Assuntos
Biomarcadores , Produtos Finais de Glicação Avançada/sangue , Diálise Renal , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Albumina Sérica Humana/metabolismo , Biomarcadores/análise , Biomarcadores/sangue , Estudos de Casos e Controles , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/terapia , Feminino , Produtos Finais de Glicação Avançada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Estresse Oxidativo/fisiologia , Polímeros/química , Ácidos Polimetacrílicos/química , Prognóstico , Diálise Renal/métodos , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Albumina Sérica Humana/análise , Sulfonas/química , Resultado do Tratamento
8.
Georgian Med News ; (292-293): 44-49, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31560661

RESUMO

The aim of the present study was to establish the disorders of mineral metabolism and production of monocyte chemoattractant protein type 1 (MCP-1) and plasminogen activator inhibitor type 1 (PAI-1) in patients with diabetic nephropathy (DN) at different stages of the disease. We examined 78 patients with DN aged from 57 to 76 years. Fibroblast growth factor 23 (FGF23), MCP-1 and PAI-1 levels in blood serum were determined by ELISA. The levels of calcium and phosphorus in the serum were established by biochemical method. Our results showed the progressive elevation of FGF-23 level in serum depending on the stage of the DN (p <0.05). High levels of FGF23 were determined already in the early stages of nephropathy. FGF23 levels in DN patients twice exceeded control group level. The highest FGF23 concentrations were detected in the late stages of the disease. Hyperphosphatemia was found in the late stages of the DN when compared with controls and early preclinical stages. We found a significant increase of MCP-1 and PAI-1 levels in patients with DN. These changes may be involved in inflammatory and fibrotic processes in the kidneys. FGF23 elevation in the peripheral blood of DN patients was associated with an increase of inflammatory and fibrosis mediators MCP-1 and PAI-1. We conclude that FGF23 increase may be considered as an important risk factor of DN progression.


Assuntos
Quimiocina CCL2/sangue , Nefropatias Diabéticas/diagnóstico , Fatores de Crescimento de Fibroblastos/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Nefropatias Diabéticas/sangue , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Fibrose , Humanos , Hiperfosfatemia/sangue , Inflamação/sangue , Pessoa de Meia-Idade
9.
Diabetes Res Clin Pract ; 155: 107807, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31394129

RESUMO

AIM: This study examined the association among the onset of diabetic kidney disease (DKD), blood glucose levels (HbA1C), and body mass index (BMI) in Japanese patients with type 2 diabetes mellitus. METHODS: Patients eligible for this study included those with type 2 diabetes who visited the outpatient clinic at Kawasaki Medical School Hospital between 2000 and 2018 and were followed up for more than two years. The Cox proportional hazards model was used in four categories of subjects: at the beginning of the follow-up period, "controlled" or "uncontrolled" glycemic control based on HbA1c and "overweight" or "non-overweight" based on BMI. RESULTS: After dividing the participants into four categories according to HbA1c (lower than 7.0% (C) or higher (U)), and BMI (25 kg/m2 or higher (O) or lower (N)), hazard ratios for groups CO, UN, and UO were 1.40 (95% CI 1.03-1.90, P = 0.030), 1.40 (1.04-1.88, P = 0.027), and 1.54 (1.12-2.11, P = 0.008), respectively, compared with the CN reference group, after adjustment was made for age, sex, duration of diabetes, and medication for hypertension or dyslipidemia. CONCLUSION: Maintenance of both an HbA1c level lower than 7.0% and a BMI lower than 25 kg/m2 was important for the prevention of DKD in Japanese patients with type 2 diabetes mellitus. Both factors had a similar effect on DKD in this study.


Assuntos
Índice de Massa Corporal , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/prevenção & controle , Hemoglobina A Glicada/análise , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/patologia , Feminino , Humanos , Japão , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Retrospectivos
10.
BMC Endocr Disord ; 19(1): 84, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382952

RESUMO

BACKGROUND: In patients with diabetes mellitus, the urinary microalbumin-to-urine creatinine ratio (UACR) can not only predict the occurrence of diabetic nephropathy but also can be a risk factor for cardiovascular disease and renal function damage. Current studies on subclinical hypothyroidism (SCH) and UACR are mainly cross-sectional studies, and the results suggest that SCH is an independent risk factor for UACR. To further explore the longitudinal effect of SCH on UACR, we carried out this study. METHODS: This was a retrospective cohort study including 46 patients with type 2 diabetes mellitus and SCH in the Department of Endocrinology, The Affiliated Huai'an Hospital of Xuzhou Medical University from January 2013 to April 2018. At the same time, 96 patients with type 2 diabetes mellitus and euthyroid were chosen according to 1:2 approximately matched with age, sex and duration of diabetes mellitus. Univariate analysis, stratified analysis, and multiple linear regression analysis were used to investigate the effect of SCH on ΔUACR(ΔUACR = UACR after 1 year - baseline UACR) in patients with type 2 diabetes mellitus. RESULTS: There was no significant difference between the baseline UACR, (p > 0.05). However, the ΔUACR was significantly higher in SCH group than euthyroid group, as shown by univariate analysis, stratified analysis and multiple linear regression analysis (ß:-1.071, 95% CI: - 1.713--0.428), and the difference was statistically significant (all p < 0.05). CONCLUSION: SCH is associated with an increased UACR in type 2 diabetes mellitus patients. It is necessary to screen for thyroid function in type 2 diabetes mellitus and increase the follow-up frequency of UACR in patients with SCH.


Assuntos
Albuminúria/etiologia , Biomarcadores/análise , Creatinina/urina , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/etiologia , Hipotireoidismo/complicações , Adolescente , Adulto , Idoso , Albuminúria/diagnóstico , China/epidemiologia , Nefropatias Diabéticas/diagnóstico , Feminino , Seguimentos , Humanos , Hipotireoidismo/epidemiologia , Hipotireoidismo/patologia , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
11.
Prog Cardiovasc Dis ; 62(4): 298-302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31377223

RESUMO

The prevalence of Type 2 diabetes mellitus (T2DM) has reached pandemic proportions. T2DM frequently causes macrovascular and/or microvascular pathologic changes and thereby increases the risks for the development of myocardial infarction, heart failure, stroke, renal failure, and reduced survival. This article describes the important interactions between T2DM, heart failure, and renal dysfunction, forming vicious circles. The interruption of these circles represents important therapeutic goals.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Cardiomiopatias Diabéticas/epidemiologia , Nefropatias Diabéticas/epidemiologia , Insuficiência Cardíaca/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Comorbidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Cardiomiopatias Diabéticas/diagnóstico , Cardiomiopatias Diabéticas/terapia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/terapia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Masculino , Prevalência , Prognóstico , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Índice de Gravidade de Doença , Análise de Sobrevida , Estados Unidos/epidemiologia
12.
Ann Biol Clin (Paris) ; 77(4): 407-414, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31418702

RESUMO

Like all proteins, plasma albumin can undergo glycation to produce glycated albumin. This glycation will change the structure and therefore functionalities of albumin. Because of its accessibility, its high concentration and its half-life the glycation of albumin is greater than that of haemoglobin. Laboratory measurement of glycated albumin is possible. The value of glycated albumin reflects the glycaemic balance over a period of 3 weeks, and shows its interest in cases where the determination of HbA1c is impossible or deficient. It also seems that the glycated albumin has a prognostic interest in the chronic kidney disease patients dialyzed or not. In some patients, the assay of glycated albumin could replace measurement of fructosamines and provide additional information to HbA1c values.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Monitorização Fisiológica/métodos , Albumina Sérica/análise , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/metabolismo , Humanos , Valor Preditivo dos Testes , Prognóstico , Diálise Renal , Albumina Sérica/metabolismo
13.
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
14.
Diabetes Metab Syndr ; 13(4): 2365-2373, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31405645

RESUMO

AIMS: Diabetes patients with renal impairment commonly have a degree of hematological abnormalities than those non-diabetics with chronic kidney disease. The present study aimed to clarify the association between oxidative stress and hematological abnormalities with the progression of diabetic nephropathy. METHODS: A total of 20 healthy subjects and 100 patients were enrolled in the study. Eligible renal dysfunction patients were classified according to biochemical markers into five groups (20 patients); diabetic patients, pre-renal failure patients, diabetic pre-renal failure patients, renal failure patients, and diabetic renal failure patients. RESULTS: Erythrocytes and platelets count, hemoglobin and hematocrit levels revealed a significant decrease in all renal dysfunction groups, while leukocytes count, red cell distribution width, platelet distribution width, and mean platelet volume showed significant increases in diabetic and renal dysfunction groups as compared to the healthy control. Nitric oxide level increased significantly, while reduced glutathione showed a marked decrease in diabetic and all renal dysfunction groups compared to the healthy control. CONCLUSION: Nitric oxide and reduced glutathione were associated with the inflammatory status in diabetic renal dysfunction patients which reflected by elevation in leukocytes and neutrophils count, red cell distribution width as well as the reduction in values of erythrocytes, platelets count, hemoglobin and hematocrit. Therefore, hematological indices can play a role in predict the progression of diabetic nephropathy.


Assuntos
Biomarcadores/sangue , Diabetes Mellitus/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Índices de Eritrócitos , Hemoglobinas/análise , Estresse Oxidativo , Glicemia/análise , Estudos de Casos e Controles , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/epidemiologia , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Hematócrito , Humanos , Incidência , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico
15.
Diabetes Metab Syndr ; 13(4): 2457-2461, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31405660

RESUMO

AIM: To evaluate the role of advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) expression levels as predictors of vascular complications in uncontrolled type 2 diabetes mellitus (T2DM). METHODS: Cross-sectional study was conducted on T2DM adults of both sexes who attended the outpatient service of Al-Karak Teaching Hospital, Jordan during the period from June 2017 to August 2018. Participants were categorized in two groups according to their glycemic control and the presence of reno-vascular complications. Twenty healthy subjects were recruited as control group. Blood sample was obtained from all participants and used for the assessment of FBG, HbA1c, serum AGEs and sRAGE, serum urea and creatinine; 24 h urine was also collected for the determination of urinary albumin. RESULTS: Diabetic subjects with vascular complication had a significantly higher serum AGEs 50.3 ±â€¯13 vs. 28.9 ±â€¯8 pg/ml) and AGEs/sRAGE ratio (0.058 ±â€¯0.02 vs. 0.037 ±â€¯0.02) associated with significantly lower serum sRAGE (868.7 ±â€¯50.8 vs. 912.8 ±â€¯294.3) compared to those with no complications. Serum AGEs and sRAGE showed weak negative and non-significant association in both groups of patients. However, the AGEs/sRAGE ration was inversely and significantly associated with the urinary albumin/creatinine ratio (r = - 0.51, P = 0.009) only in DM patients with reno-vascular complications. CONCLUSION: We found an association between AGEs/sRAGE ratio and urinary albumin/serum creatinine ratio in T2DM patients with reno-vascular complications; providing evidence that serum AGEs and sRAGE can be considered as predictors of vascular complications in uncontrolled T2DM patients.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Produtos Finais de Glicação Avançada/sangue , Receptor para Produtos Finais de Glicação Avançada/sangue , Glicemia/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Estudos Transversais , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
16.
Diabetes Res Clin Pract ; 155: 107809, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31401150

RESUMO

AIMS: Both clinical and pathogenetic markers for accurate prediction of end-stage renal disease in diabetic nephropathy (DN) are lacking. This study aimed to establish an effective prognostic nomogram and a score for renal survival (RS) in biopsy-proven DN. METHODS: Analyses were derived from 110 DN patients who underwent renal biopsy at China-Japan Friendship Hospital between January 2006 and May 2018 with DN as the only glomerular disease diagnosis. The prognostic ability of 34 baseline clinicopathologic parameters was evaluated using univariate and multivariate Cox regression analyses. The predictive accuracy and discriminative ability of the final model were measured using the calibration curve and concordance index (C-index). Internal validation of the model was assessed using bootstrap resampling. RESULTS: Urinary proteinuria excretion, stages of chronic kidney disease, glomerular hyalinosis, and extracapillary hypercellularity were independent prognostic factors for RS, and all were selected into the nomogram. The calibration curve for the probability of survival showed good agreement between the prediction by nomogram and actual observation. The C-index for predicting survival was 0.79 (95% confidence interval (CI) 0.72-0.86). A high C-index value of 0.76 indicated good internal validation. The prognostic score had the potential to delineate two prognosis groups with median RS of 24 and 70 months, respectively. CONCLUSIONS: The proposed nomogram and score provide a useful individualized risk estimate of renal prognosis in patients with DN.


Assuntos
Nefropatias Diabéticas/diagnóstico , Nomogramas , Adulto , Idoso , Nefropatias Diabéticas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
17.
Saudi J Kidney Dis Transpl ; 30(4): 989-994, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31464262

RESUMO

Mammalian target of rapamycin (mTOR) inhibitors are used in renal sparing protocols and transplant immunosuppression in patients with solid organ and stem cell transplants. They cause various side effects, including proteinuria, which is mediated by blockade of the vascular endothelial growth factor receptor pathway. There have been various reports of mTOR inhibitors causing proteinuria or worsening proteinuria form preexisting renal glomerulo-pathies. We report a 73-year old male with diabetic glomerulosclerosis, acute liver failure due to Budd-Chiari syndrome, chronic low platelets, and worsening proteinuria from 0.46 g protein/g creatinine to 2.2 g protein/g creatinine. Workup revealed no thrombotic microangiopathy through skin biopsy, and a renal biopsy confirmed only clinically suspected diabetic and hypertensive glomerulosclerosis and possible calcineurin inhibitors. On discontinuation of everolimus urine protein decreased back to 0.6 g/g creatinine. We review the mechanism of mTOR-induced proteinuria and how this may affect diabetic nephropathy secondarily. We also consider the clinical implications of this in transplant patients receiving these agents.


Assuntos
Nefropatias Diabéticas/complicações , Everolimo/efeitos adversos , Imunossupressores/efeitos adversos , Falência Hepática Aguda/cirurgia , Transplante de Fígado/efeitos adversos , Proteinúria/etiologia , Idoso , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/urina , Progressão da Doença , Humanos , Falência Hepática Aguda/complicações , Falência Hepática Aguda/diagnóstico , Masculino , Proteinúria/diagnóstico , Proteinúria/urina , Fatores de Risco , Resultado do Tratamento
18.
Diabetes Metab Syndr ; 13(5): 2849-2854, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31425946

RESUMO

INTRODUCTION: Podocyte injury and subsequent excretion in urine play a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). Quantification of messenger RNA expression in urinary sediment by real-time PCR is emerging as a noninvasive method of screening DN-associated biomarkers. We aimed to study the expression of podocyte-associated genes in urinary sediment and their relation to disease severity in type 2 diabetic Egyptian patients with diabetic nephropathy. METHOD: ology: Sixty patients with type 2 diabetes mellitus were recruited in addition to twenty non diabetic healthy volunteers. Relative mRNA abundance of nephrin, podocalyxin, and podocin were quantified, and correlations between target mRNAs and clinical parameters were examined. RESULTS: The urinary mRNA levels of all genes studied were significantly higher in diabetics compared with controls (p < 0.001), and mRNA levels increased with DN progression. Urinary mRNA levels of all target genes positively correlated with both UAE and HbA1c. The expression of nephrin, podocalyxin, and podocin mRNA correlated with serum creatinine {(r = 0.397, p value = 0.002), (r = 0.431, p value = 0.001), (r = 0.433, p value = 0.001) respectively}. CONCLUSION: The urinary mRNA profiles of nephrin, podocalyxin, and podocin were found to increase with the progression of DN, which suggested that quantification of podocyte-associated molecules will be useful biomarkers of DN.


Assuntos
Biomarcadores/urina , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Podócitos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/urina , Estudos de Casos e Controles , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/urina , Egito , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
19.
Ophthalmic Res ; 62(2): 68-79, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256153

RESUMO

AIMS: To conduct an evidence-based evaluation of diabetic retinopathy (DR) for the diagnosis of diabetic nephropathy (DN) in type 2 diabetics with kidney disease. METHODS: We systematically searched PubMed, EMBASE, and the Cochrane Library from inception to June 27, 2018, including the reference lists of identified primary studies. A study was included if it (1) used DR as a diagnostic test for DN; and (2) used histological evaluation of renal tissues as the reference standard. RESULTS: The analysis included 45 studies (4,561 patients). A bivariate analysis yielded a sensitivity of 0.67 (95% CI 0.61-0.74) and a specificity of 0.78 (95% CI 0.73-0.82). The summary receiver operating characteristic curve analysis provided an area under the curve (AUC) of 0.79 (95% CI 0.76-0.83). In a setting of 41% prevalence of DN, the probability of DN would be 68% if the test of DR was positive, and the probability of DN would be 23% if it was negative. In addition, although the mean specificity of proliferative DR for the detection of DN was 0.99 (95% CI 0.45-1.00), the mean sensitivity was 0.34 (95% CI 0.24-0.44), and the AUC was 0.58 (95% CI 0.53-0.62). CONCLUSIONS: DR is helpful in diagnosing DN in persons with type 2 diabetes and kidney disease, but the severity of DR may not parallel the presence of DN.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Retinopatia Diabética/diagnóstico , Área Sob a Curva , Humanos , Curva ROC , Sensibilidade e Especificidade
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