Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 953
Filtrar
1.
J Stroke Cerebrovasc Dis ; 30(5): 105708, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33714073

RESUMO

BACKGROUND: Recent evidence indicates that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) may favorably affect the risk of stroke in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease. OBJECTIVES: This meta-analysis considered data from cardiovascular outcome trials (CVOTs) regarding the effect of SGLT2i treatment on stroke risk in T2DM patients with an emphasis on patients with impaired renal function. SELECTION CRITERIA: Double-blind randomized trials (RCTs) representing CVOTs were included if they compared SGLT2i add-on therapy with placebo, and reported stroke among primary or secondary endpoints. RESULTS: Six eligible multicenter RCTs were included. The pooled analysis of 5 RCTs (n = 40,393) showed a neutral effect on the risk of total stroke from treatment with SGLT2i vs. placebo (hazard ratio, HR 0.90, 95% CI: 0.74-1.09, p = 0.29, I2 = 58%). Subgroup analysis (4 RCTs) involving patients with impaired renal function (n = 17,072) demonstrated a significant benefit in favor of SGLT2i (HR: 0.66, 95% CI: 0.54-0.82, p<0.0001, I2 = 8%). The pooled analysis of 2 RCTs (n = 14,543) showed a significant reduction in the risk of hemorrhagic stroke in T2DM patients (HR: 0.46, 95% CI: 0.25-0.83, p = 0.01; I2 = 0). No differences were noticed regarding the risk of ischemic stroke (HR: 0.97, 95% CI: 0.85-1.12, p = 0.69; I2 = 0), non-fatal stroke (HR: 0.98, 95% CI: 0.83-1.16, p = 0.79, I2 = 28%), and fatal stroke (HR: 0.77, 95% CI: 0.50-1.17, p = 0.22, I2 = 0). CONCLUSIONS: Available data suggest that SGLT2i reduce the risk of total stroke in patients with T2DM and impaired renal function. Based on the findings of two RCTs, these drugs may offer a protection against hemorrhagic stroke.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/fisiopatologia , AVC Hemorrágico/prevenção & controle , Rim/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Idoso , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Feminino , AVC Hemorrágico/diagnóstico , AVC Hemorrágico/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Medição de Risco , Fatores de Risco , Resultado do Tratamento
2.
Int Immunopharmacol ; 93: 107413, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33524800

RESUMO

BACKGROUND: Growing evidence points to the pivotal role of inflammation in the pathogenesis of diabetic kidney disease (DKD). However, as an inflammation-based prognostic score, the significance of platelet-to-lymphocyte ratio (PLR) in biopsy-proven DKD remains uncertain. Therefore, the current study aimed to evaluate the association of PLR with the clinicopathological features and the progression of DKD. METHODS: In total, 167 patients with biopsy-proven T2DKD were retrospectively recruited. Clinicopathological characteristics were compared according to the tertiles of baseline PLR. Pearson's or Spearman correlations were used to examine the associations between PLR and baseline characteristics. Assessment of the prospective relationship of PLR with the kidney outcomes defined as a doubling of baseline serum creatinine or onset of end stage renal disease (ESRD), were investigated by Kaplan-Meier survival analysis. Moreover, a cubic spline curve was further calculated to explore the significance of PLR in DKD prognosis. On top of that, identification of the risk factors associated with DKD progression was executed by a model of Cox proportional hazards. RESULTS: Median follow-up period was 23.77 months, during which 92 (55.1%) patients confronted DKD progression. Pearson's correlation indicated that urinary protein increased along with PLR rising (r = 0.193, P = 0.012). Kaplan-Meier survival curves revealed a significantly increased probability of event-free survival in the lowest tertile of PLR compared to those in the highest tertile (P = 0.018). A statistical linear correlation between PLR and DKD development was demonstrated by a restricted cubic spline analysis (P for nonlinear = 0.784). In addition, the analyses of multivariate Cox regression indicated that elevated PLR had an association with a greater risk of DKD progression (HR 1.004, 95%CI [1.000-1.008], P = 0.035), which was verified to be an independent risk factor for renal outcomes. CONCLUSIONS: Our findings demonstrated that the PLR was associated with proteinuria and prognosis in DKD patients. It was an independent risk factor for kidney progression in biopsy-proven DKD.


Assuntos
Plaquetas/patologia , Nefropatias Diabéticas/diagnóstico , Rim/patologia , Linfócitos/patologia , Adulto , Idoso , Nefropatias Diabéticas/imunologia , Nefropatias Diabéticas/mortalidade , Progressão da Doença , Feminino , Seguimentos , Humanos , Rim/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida
3.
Ther Adv Cardiovasc Dis ; 14: 1753944720939383, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32715944

RESUMO

This review focuses on the pathogenic role of sodium glucose cotransporter (SGLT)-2 in the development of renal dysfunction and heart failure in patients with diabetes, by emphasizing the concept of reno-cardiac syndrome (kidney injury worsens cardiac condition) and by substantiating the deleterious effect of sympathetic overdrive in this context. Furthermore, the review proposes a mechanistic hypothesis to explain the benefits of SGLT2 inhibitors, specifically that SGLT-2 inhibitors reduce sympathetic activation at the renal level. To illustrate this point, several examples from both animal experiments and clinical observations are introduced. The bidirectional interaction of the heart and kidney were deeply implicated as an exacerbator of heart failure and renal failure without diabetes. Renal cortical ischemia and abnormal glucose metabolism of tubular epithelial cells are likely to exist as common pathologies in nondiabetic heart failure patients. It is no wonder why SGLT-2 inhibitors are specifically being studied even in the absence of diabetes, both for heart failure and also for renal failure.


Assuntos
Síndrome Cardiorrenal/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Coração/inervação , Rim/inervação , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Sistema Nervoso Simpático/efeitos dos fármacos , Animais , Síndrome Cardiorrenal/mortalidade , Síndrome Cardiorrenal/fisiopatologia , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/fisiopatologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Sistema Nervoso Simpático/fisiopatologia , Resultado do Tratamento
4.
Nutr Metab Cardiovasc Dis ; 30(10): 1622-1632, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32631704

RESUMO

AIMS: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have been proven to lead to relevant cardiovascular benefits, regardless of glycemic control function. SGLT2i have on the one hand led to reduction in cardiovascular events such as heart failure and on the other hand to renal protection. Blood pressure reduction and kidney function play a central role in these outcomes. This focused review describes the main mechanisms and clinical aspects of SGLT2i. DATA SYNTHESIS: These drugs act on the proximal renal tubule and behave as diuretics with a "hybrid" mechanism, as they can favour both natriuresis and enhanced diuresis due to an osmotic effect dependent on glycosuria, resulting in blood pressure decrease. The exclusive peculiarity of these "diuretics", which distinguishes them from loop and thiazide diuretics, lies also in the activation of the tubule-glomerular feedback. CONCLUSIONS: This mechanism, resulting in modulation of arterioles' tone and renin secretion, contributes to the favorable outcomes, suggesting a wider use of SGLT2i in internal medicine, nephrology and cardiology.


Assuntos
Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Diuréticos/uso terapêutico , Túbulos Renais Proximais/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/fisiopatologia , Diuréticos/efeitos adversos , Humanos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/fisiopatologia , Fatores de Proteção , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Resultado do Tratamento
5.
Cardiovasc Diabetol ; 19(1): 82, 2020 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-32534580

RESUMO

BACKGROUND: Reactive hyperemia-peripheral arterial tonometry (RH-PAT) is a noninvasive and simple test for evaluating the endothelial function. There has been sparse evidence on the usefulness of the RH-PAT index (RHI) in predicting future cardiovascular diseases among diabetic patients. METHODS: Asymptomatic diabetic patients with albuminuria were selected; their medical history and laboratory findings were evaluated every 3 to 4 months, respectively. The primary outcome was a composite of three-point major adverse cardiovascular events (3-point MACE): death from cardiovascular causes, acute coronary events, or nonfatal stroke. On the contrary, secondary outcomes included a composite of 3-point MACE, hospitalization for heart failure, or chronic kidney disease (CKD) progression. RHI was measured using the Endo-PAT2000 at the baseline. RHI < 1.67 was considered to indicate peripheral endothelial dysfunction (PED). RESULTS: In total, 149 subjects were included (mean age, 61.8 ± 9.2 years; duration of diabetes was 12 years). During the follow-up period (median, 49.7 months), of the 149 subjects, primary outcomes were detected in 12 (1 [2.3%] and 11 [10.5%] of those without and with PED, respectively). The presence of PED in baseline measurements significantly increased both primary and secondary outcomes, following adjustment for age, sex, hypertension, glycated hemoglobin, low-density lipoprotein cholesterol, triglyceride, systolic blood pressure, baseline estimated glomerular filtration rate, overt proteinuria, duration of diabetes, premedical history of ischemic events, anti-platelet agents, and smoking history (hazard ratio [HR]: 10.95; 95% confidence interval CI 1.00-119.91 for the primary outcome; HR, 4.12; 95% CI 1.37-12.41 for secondary outcome). In addition, PED could predict secondary outcomes independent of the risk score according to the American College of Cardiology/American Heart Association (HR: 3.24; 95% CI 1.14-9.17). CONCLUSIONS: PED can independently predict future cardiovascular events among diabetic patients with albuminuria.


Assuntos
Albuminúria/epidemiologia , Nefropatias Diabéticas/epidemiologia , Endotélio Vascular/fisiopatologia , Doença Arterial Periférica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Idoso , Albuminúria/diagnóstico , Albuminúria/mortalidade , Albuminúria/terapia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Feminino , Humanos , Hiperemia/fisiopatologia , Masculino , Manometria , Pessoa de Meia-Idade , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/terapia , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/terapia , Medição de Risco , Fatores de Risco , Seul/epidemiologia , Fatores de Tempo
6.
Cardiovasc Diabetol ; 19(1): 50, 2020 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-32359350

RESUMO

BACKGROUND: The prognostic importance of an increased visit-to-visit blood pressure variability (BP-VVV) for the future development of micro- and macrovascular complications in type 2 diabetes has been scarcely investigated and is largely unsettled. We aimed to evaluate it in a prospective long-term follow-up study with 632 individuals with type 2 diabetes. METHODS: BP-VVV parameters (systolic and diastolic standard deviations [SD] and variation coefficients) were measured during the first 24-months. Multivariate Cox analysis, adjusted for risk factors and mean BP levels, examined the associations between BP-VVV and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications (total cardiovascular events [CVEs], major adverse CVEs [MACE] and cardiovascular and all-cause mortality). Improvement in risk discrimination was assessed by the C-statistic and integrated discrimination improvement (IDI) index. RESULTS: Over a median follow-up of 11.3 years, 162 patients had a CVE (132 MACE), and 212 patients died (95 from cardiovascular diseases); 153 newly-developed or worsened diabetic retinopathy, 193 achieved the renal composite outcome (121 newly-developed microalbuminuria and 95 deteriorated renal function), and 171 newly-developed or worsened peripheral neuropathy. Systolic BP-VVV was an independent predictor of MACE (hazard ratio: 1.25, 95% CI 1.03-1.51 for a 1-SD increase in 24-month SD), but not of total CVEs, cardiovascular and all-cause mortality, and of any microvascular outcome. However, no BP-VVV parameter significantly improved cardiovascular risk discrimination (increase in C-statistic 0.001, relative IDI 0.9%). CONCLUSIONS: Systolic BP-VVV was an independent predictor of MACE, but it did not improve cardiovascular risk stratification. The goal of anti-hypertensive treatment in patients with type 2 diabetes shall remain in controlling mean BP levels, not on decreasing their visit-to-visit variability.


Assuntos
Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/epidemiologia , Nefropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/epidemiologia , Idoso , Brasil/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Causas de Morte , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/mortalidade , Angiopatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/mortalidade , Neuropatias Diabéticas/fisiopatologia , Progressão da Doença , Feminino , Humanos , Incidência , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Sístole , Fatores de Tempo
7.
Cardiovasc Diabetol ; 19(1): 68, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32429911

RESUMO

BACKGROUND: ABO blood groups have previously been associated with cardiovascular disease (CVD) in the general population. This study aimed to investigate the potential relationship between ABO blood groups and CVD in individuals with type 1 diabetes according to diabetic nephropathy (DN) status. METHODS: Adults with type 1 diabetes (4531 individuals) from the FinnDiane Study were evaluated. DN was determined by two out of three measurements of urinary albumin excretion rate. Albuminuria was defined as an excretion rate above 20 µg/min. CVD events were identified by linking the data with the Finnish Care Register for Health Care and the Finnish Cause of Death Register. Follow-up ranged from the baseline visit until a CVD event, death or the end of 2017. The impact of ABO blood groups on CVD risk was estimated by multivariable Cox-regression analyses adjusted for traditional risk factors. RESULTS: At baseline, the median age was 38.5 (IQR 29.2-47.9) years, 47.5% were female and median duration of diabetes was 20.9 (11.4-30.7) years. There were 893 incident ischemic heart disease (IHD) events, 301 ischemic strokes (IS), and 415 peripheral artery disease (PAD) events during a median follow up of 16.5 (IQR 12.8-18.6) years. The A blood group showed the highest risk of IHD versus the O blood group, when microalbuminuria was present. Comparing the population with microalbuminuria with those with normoalbuminuria, only the A blood group elevated the risk of IHD. This increased risk was neither explained by the FUT2 secretor phenotype nor by the A-genotype distribution. The risk of IS or PAD was no different among the ABO blood groups regardless of diabetic nephropathy stage. CONCLUSION: The A blood group is a risk factor for IHD in individuals with type 1 diabetes and microalbuminuria.


Assuntos
Sistema ABO de Grupos Sanguíneos , Albuminúria/sangue , Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 1/sangue , Nefropatias Diabéticas/sangue , Adulto , Albuminúria/diagnóstico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Causas de Morte , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/mortalidade , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo
8.
J Stroke Cerebrovasc Dis ; 29(4): 104657, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32037266

RESUMO

OBJECTIVE: Dialysis patients have a higher incidence of stroke, and outcomes are often poor. Diabetic nephropathy (DN) is a stroke risk-factor, but the importance is unclear in dialysis patients. This study investigated the stroke features and risk factors in hemodialysis (HD) patients. METHODS: All end-stage renal disease patients undergoing HD at Teraoka Memorial Hospital dialysis center were identified, with 195 recruited. Baseline clinical characteristics were collected, and the clinical outcomes and related factors of stroke in HD patients were retrospectively analyzed. The incidence rate of stroke and mortality were calculated using Kaplan-Meier survival analysis. Factors potentially related to stroke were analyzed by the log-rank test and Cox proportional hazards model for univariate and multivariate analysis. RESULTS: In total, 21.0% (41 of 195) patients developed stroke. The incidence rates of stroke per 1000 patient-years were 53.6, 65.2, and 34.0 in all HD patients, DN patients, and non-DN patients, respectively. The cumulative incidence rates of stroke in all HD patients, DN patients, and non-DN patients per 5 years, and per 10 years were 22.6%, 43.5%; 28.8%, 59.6%; and 17.6%, 31.1%, respectively. The incidence rate of stroke in the DN patients was significantly higher than in the non-DN patients (P = .013). DN was the significant risk factor for stroke by multivariate analysis (hazard ratio 2.63, 95% confidence interval 1.08-7.85; P = .032). CONCLUSIONS: This study revealed the trends of stroke in HD patients at a single institution in Japan. DN was shown to be a significant risk factor for stroke in HD patients.


Assuntos
Nefropatias Diabéticas/terapia , Falência Renal Crônica/terapia , Diálise Renal , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Feminino , Humanos , Incidência , Japão/epidemiologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo
9.
Diabetes Care ; 43(2): 321-328, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31801788

RESUMO

OBJECTIVE: In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients. RESEARCH DESIGN AND METHODS: We included all 2,796 patients with type 1 diabetes in the Netherlands who started renal replacement therapy between 1986 and 2016. We used multivariable Cox regression analyses adjusted for recipient age and sex, dialysis modality and vintage, transplantation era, and donor age to compare all-cause mortality between deceased- or living-donor kidney and SPK transplant recipients. Separately, we analyzed mortality between regions where SPK transplant was the preferred intervention (80% SPK) versus regions where a kidney transplant alone was favored (30% SPK). RESULTS: Of 996 transplanted patients, 42%, 16%, and 42% received a deceased- or living-donor kidney or SPK transplant, respectively. Mean (SD) age at transplantation was 50 (11), 48 (11), and 42 (8) years, respectively. Median (95% CI) survival time was 7.3 (6.2; 8.3), 10.5 (7.2; 13.7), and 16.5 (15.1; 17.9) years, respectively. SPK recipients with a functioning pancreas graft at 1 year (91%) had the highest survival (median 17.4 years). Compared with deceased-donor kidney transplant recipients, adjusted hazard ratios (95% CI) for 10- and 20-year all-cause mortality were 0.79 (0.49; 1.29) and 0.98 (0.69; 1.39) for living-donor kidney and 0.67 (0.46; 0.98) and 0.79 (0.60; 1.05) for SPK recipients, respectively. A treatment strategy favoring SPK over kidney transplantation alone showed 10- and 20-year mortality hazard ratios of 0.56 (0.40; 0.78) and 0.69 (0.52; 0.90), respectively. CONCLUSIONS: Compared with living- or deceased-donor kidney transplantation, SPK transplant was associated with improved patient survival, especially in recipients with a long-term functioning pancreatic graft, and resulted in an almost twofold lower 10-year mortality rate.


Assuntos
Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 1/terapia , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Transplante de Pâncreas/mortalidade , Adulto , Idoso , Estudos de Coortes , Terapia Combinada/mortalidade , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/terapia , Feminino , Seguimentos , Sobrevivência de Enxerto/fisiologia , Humanos , Falência Renal Crônica/terapia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Transplante de Pâncreas/métodos , Diálise Renal , Análise de Sobrevida , Sobreviventes/estatística & dados numéricos
10.
Rev Med Interne ; 41(1): 67-68, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31812446
11.
Clin Exp Nephrol ; 24(2): 119-125, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31587125

RESUMO

BACKGROUND: The difficulty of adhering to a low-protein diet is a serious limitation of randomized controlled trials aimed at validating the efficacy of this therapy. In this observational study of patients with diabetic nephropathy, we examined the association of dietary protein intake (DPI) with renal outcome and mortality, taking into account the nutritional status. METHODS: We conducted a single-center historical cohort study of 449 adult Japanese patients with type 2 diabetes and the urinary albumin-to-creatinine ratio of ≥ 300 mg/g or estimated glomerular filtration rate of < 30 mL/min/1.73 m2. DPI was estimated with a formula using nitrogen levels in spot urine and body mass index. Malnutrition was defined as the Geriatric Nutritional Risk Index of ≤ 98. The primary and secondary endpoints were renal replacement therapy (RRT) initiation and mortality before RRT initiation, respectively. The Fine and Gray subdistribution hazard model was used to determine the relative effects of DPI on the respective endpoint. RESULTS: Decreased DPI was associated with lower incidence of RRT with an adjusted hazard ratio of 0.81 (95% confidence interval: 0.72-0.92, p < 0.001). The interaction between DPI and nutritional status with respect to mortality was significant (p interaction = 0.047). Decreased DPI was a risk factor for mortality in patients with malnutrition (p = 0.009) but not in those without malnutrition (p = 0.559). CONCLUSIONS: In patients with type 2 diabetic nephropathy, lower DPI was associated with lower incidence of RRT initiation, suggesting beneficial effects of a low-protein diet on kidneys. Conversely, lower DPI might lead to increased mortality in patients with malnutrition.


Assuntos
Nefropatias Diabéticas/dietoterapia , Dieta com Restrição de Proteínas/mortalidade , Desnutrição/mortalidade , Estado Nutricional , Idoso , Bases de Dados Factuais , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/fisiopatologia , Dieta com Restrição de Proteínas/efeitos adversos , Progressão da Doença , Feminino , Humanos , Japão , Masculino , Desnutrição/diagnóstico , Desnutrição/fisiopatologia , Pessoa de Meia-Idade , Terapia de Substituição Renal/mortalidade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
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
14.
BMJ Open Diabetes Res Care ; 7(1): e000735, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798896

RESUMO

Objective: To derive, and externally validate, a risk score for cardiovascular death among patients with type 2 diabetes and newly diagnosed diabetic nephropathy (DN). Research design and methods: Two independent prospective cohorts with type 2 diabetes were used to develop and externally validate the risk score. The derivation cohort comprised 2282 patients with an incident, clinical diagnosis of DN. The validation cohort includes 950 patients with incident, biopsy-proven diagnosis of DN. The outcome was cardiovascular death within 2 years of the diagnosis of DN. Logistic regression was applied to derive the risk score for cardiovascular death from the derivation cohort, which was externally validated in the validation cohort. The score was also estimated by applying the United Kingdom Prospective Diabetes Study (UKPDS) risk score in the external validation cohort. Results: The 2-year cardiovascular mortality was 12.05% and 11.79% in the derivation cohort and validation cohort, respectively. Traditional predictors including age, gender, body mass index, blood pressures, glucose, lipid profiles alongside novel laboratory test items covering five test panels (liver function, serum electrolytes, thyroid function, blood coagulation and blood count) were included in the final model.C-statistics was 0.736 (95% CI 0.731 to 0.740) and 0.747 (95% CI 0.737 to 0.756) in the derivation cohort and validation cohort, respectively. The calibration slope was 0.993 (95% CI 0.974 to 1.013) and 1.000 (95% CI 0.981 to 1.020) in the derivation cohort and validation cohort, respectively.The UKPDS risk score substantially underestimated cardiovascular mortality. Conclusions: A new risk score based on routine clinical measurements that quantified individual risk of cardiovascular death was developed and externally validated. Compared with the UKPDS risk score, which underestimated the cardiovascular disease risk, the new score is a more specific tool for patients with type 2 diabetes and DN. The score could work as a tool to identify individuals at the highest risk of cardiovascular death among those with DN.


Assuntos
Algoritmos , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2 , Angiopatias Diabéticas/mortalidade , Nefropatias Diabéticas/mortalidade , Idoso , Biópsia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/patologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/patologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/patologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco
15.
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
16.
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
17.
BMC Public Health ; 19(1): 1498, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706298

RESUMO

BACKGROUND: The prevalence of type 2 diabetes has grown significantly in China. However, little is known about the survival outcome of people with type 2 diabetes and diabetic kidney disease (DKD). The purpose of this study is to examine the survival of this population and the risk factors for mortality in one suburb cohort of Beijing, China. METHODS: Four hundred and forty-five people with DKD (48.8% male, age at onset of diabetes 48.8 ± 11.0 years, age at enrollment 57.5 ± 11.6 years) were enrolled in one suburb of Beijing, China between January 1st, 2003 and December 31st, 2015. Mortality ascertainment was censored by December 31st, 2015. Survival analysis was performed by Kaplan-Meier analysis, and Cox proportional hazards regression models were served for risk factor analysis of mortality. The Chiang method was used to estimate life expectancy by age. RESULTS: A total of 78 deaths were identified during the 3232 person-years of follow-up. Multivariate Cox regression analysis showed significantly higher risks of mortality with respect to older age, higher systolic blood pressure (SBP), lower body mass index (BMI) and lower estimated glomerular filtration rate (eGFR). The life expectancy at age of 50 was estimated to be 12.3 (95%, CI: 9.0-16.1) years. Circulatory disease was the leading cause of death in this population (accounting for 43.6% of all deaths), followed by diabetic complications (33.3%) and respiratory disease (6.4%). CONCLUSIONS: Data from one Chinese cohort from 2003 through 2015 showed that people with DKD faced higher risk of death and shorter life expectancy. Factors significantly increasing risk of death included older age, higher SBP, lower BMI and lower eGFR. There is an urgent need to early detection, closely monitoring and effective intervention on DKD.


Assuntos
Complicações do Diabetes/mortalidade , Diabetes Mellitus Tipo 2/mortalidade , Nefropatias Diabéticas/mortalidade , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Índice de Massa Corporal , China/epidemiologia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de Sobrevida
18.
Cardiovasc Diabetol ; 18(1): 159, 2019 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-31733651

RESUMO

BACKGROUND: Microvascular complications (MC) have been claimed to increase the risk for cardiovascular disease in diabetic subjects. However, the effect of MC burden on the risk of major vascular outcomes and all-cause mortality in type 1 diabetes is still poorly explored. We evaluated the relationship between microvascular complications burden and incidence of major cardiovascular events and all-cause mortality in subjects with type 1 diabetes. METHODS: We recruited 774 participants with type 1 diabetes in a single-center observational study over a follow-up of 10.8 ± 2.5 years. Hazard ratios (HR) for cardiovascular outcomes and all-cause death associated with microvascular complications were determined by unadjusted and adjusted Cox regression analysis. RESULTS: Out of 774 individuals, 54.9% had no-MC, 32.3% 1 MC, 9.7% 2 MC and 3.1% 3 MC. A total of 54 deaths (7.0%) occurred. Death rate increased from no-MC 2.1% (Ref) to 1 MC 7.2% (HR 3.54 [95% CI 1.59-7.87]), 2 MC 14.7% (HR 6.41 [95% CI 2.65-15.49]) and 3 MC 66.7% (HR 41.73 [95% CI 18.42-94.57], p < 0.0001). After adjustments, HRs were: 1 MC 2.05 (95% CI 0.88-4.76), 2 MC 1.98 (95% CI 0.75-5.21), 3 MC 7.02 (95% CI 2.44-20.20, p = 0.002). Forty-nine subjects (6.7%) had at least one cardiovascular event, and cumulative incidence went from no-MC 2.2% (Ref) to 1 MC 5.0%; (HR 2.27 [95% CI 0.96-5.38]), 2 MC 26.8% (HR 12.88 [95% CI 5.82-28.50]) and 3 MC 40.9% (HR 29.34 [95% CI 11.59-74.25], p < 0.0001). Upon adjustments, HRs were: 1 MC 1.59 (95% CI 0.65-3.88), 2 MC 4.33 (95% CI 1.75-10.74), 3 MC 9.31 (95% CI 3.18-27.25, p < 0.0001). Thirty-five individuals (4.8%) had at least one coronary event, which cumulative incidence increased with MC burden (p < 0.0001). CONCLUSIONS: In type 1 diabetes, microvascular complications burden increases in an independent dose-dependent manner the risk of major cardiovascular outcomes and all-cause mortality. The presence and number of microvascular complications should be considered in stratifying overall cardiovascular risk in type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/mortalidade , Nefropatias Diabéticas/mortalidade , Neuropatias Diabéticas/mortalidade , Retinopatia Diabética/mortalidade , Adulto , Idoso , Causas de Morte , Estudos Transversais , Diabetes Mellitus Tipo 1/diagnóstico , Nefropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/diagnóstico , Retinopatia Diabética/diagnóstico , Feminino , Seguimentos , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo
19.
Pharmacoeconomics ; 37(12): 1451-1468, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31571136

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a progressive condition that leads to irreversible damage to the kidneys and is associated with an increased incidence of cardiovascular events and mortality. As novel interventions become available, estimates of economic and clinical outcomes are needed to guide payer reimbursement decisions. OBJECTIVE: The aim of the present study was to systematically review published economic models that simulated long-term outcomes of kidney disease to inform cost-effectiveness evaluations of CKD treatments. METHODS: The review was conducted across four databases (MEDLINE, Embase, the Cochrane library and EconLit) and health technology assessment agency websites. Relevant information on each model was extracted. Transition and mortality rates were also extracted to assess the choice of model parameterisation on disease progression by simulating patient's time with end-stage renal disease (ESRD) and time to ESRD/death. The incorporation of cardiovascular disease in a population with CKD was qualitatively assessed across identified models. RESULTS: The search identified 101 models that met the criteria for inclusion. Models were classified into CKD models (n = 13), diabetes models with nephropathy (n = 48), ESRD-only models (n = 33) and cardiovascular models with CKD components (n = 7). Typically, published models utilised frameworks based on either (estimated or measured) glomerular filtration rate (GFR) or albuminuria, in line with clinical guideline recommendations for the diagnosis and monitoring of CKD. Generally, two core structures were identified, either a microsimulation model involving albuminuria or a Markov model utilising CKD stages and a linear GFR decline (although further variations on these model structures were also identified). Analysis of parameter variability in CKD disease progression suggested that mean time to ESRD/death was relatively consistent across model types (CKD models 28.2 years; diabetes models with nephropathy 24.6 years). When evaluating time with ESRD, CKD models predicted extended ESRD survival over diabetes models with nephropathy (mean time with ESRD 8.0 vs. 3.8 years). DISCUSSION: This review provides an overview of how CKD is typically modelled. While common frameworks were identified, model structure varied, and no single model type was used for the modelling of patients with CKD. In addition, many of the current methods did not explicitly consider patient heterogeneity or underlying disease aetiology, except for diabetes. However, the variability of individual patients' GFR and albuminuria trajectories perhaps provides rationale for a model structure designed around the prediction of individual patients' GFR trajectories. Frameworks of future CKD models should be informed and justified based on clinical rationale and availability of data to ensure validity of model results. In addition, further clinical and observational research is warranted to provide a better understanding of prognostic factors and data sources to improve economic modelling accuracy in CKD.


Assuntos
Doenças Cardiovasculares/economia , Atenção à Saúde/economia , Nefropatias Diabéticas/economia , Modelos Econômicos , Insuficiência Renal Crônica/economia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Análise Custo-Benefício , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/mortalidade , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Cadeias de Markov , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/mortalidade , Resultado do Tratamento
20.
Am J Nephrol ; 50(5): 345-356, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31665733

RESUMO

BACKGROUND: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. PATIENTS AND METHODS: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. CONCLUSIONS: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. TRIAL REGISTRATION: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Naftiridinas/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/urina , Progressão da Doença , Método Duplo-Cego , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/mortalidade , Projetos de Pesquisa , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...