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1.
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
2.
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
3.
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
4.
Cardiovasc Diabetol ; 18(1): 99, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382965

RESUMO

BACKGROUND: To summarize the four recent sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials: Dapagliflozin Effect on CardiovascuLAR Events (DECLARE-TIMI 58), CANagliflozin CardioVascular Assessment Study (CANVAS) Program, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), and explore the potential determinants for their cardiovascular, renal, and safety outcomes. RESULTS: The composite renal outcome event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 3.7, 7.0, 47%; 5.5, 9.0, 40%; 6.3, 11.5, 46%; 43.2, 61.2, 30% for DECLARE-TIMI 58, CANVAS, EMPA-REG OUTCOME, and CREDENCE, respectively (event definitions varied across trials). The major adverse cardiovascular (CV) event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 22.6, 24.2, 7%; 26.9, 31.5, 14%; 37.4, 43.9, 14%; 38.7, 48.7, 20% for DECLARE-TIMI 58, CANVAS, EMPA-REG OUTCOME, and CREDENCE, respectively. DECLARE-TIMI 58 had the fewest cardiorenal events and CREDENCE the most. These differences were presumably due to varying inclusion criteria resulting in DECLARE-TIMI 58 having the best baseline renal filtration function and CREDENCE the worst (mean estimated glomerular filtration rate 85.2, 76.5, 74, 56.2 mL/min/1.73 m2 for DECLARE-TIMI 58, CANVAS, EMPA-REG OUTCOME, and CREDENCE, respectively). Additionally, CREDENCE had considerably higher rates of albuminuria (median urinary albumin-creatinine ratios (UACR) were 927, 12.3, and 13.1 mg/g for CREDENCE, CANVAS, and DECLARE-TIMI 58, respectively; EMPA-REG OUTCOME had 59.4% UACR < 30, 28.6% UACR > 30-300, 11.0% UACR > 300 mg/g). CONCLUSIONS: Dapagliflozin, empagliflozin, and canagliflozin have internally and externally consistent and biologically plausible class effects on cardiorenal outcomes. Baseline renal filtration function and degree of albuminuria are the most significant indicators of risk for both CV and renal events. Thus, these two factors also anticipate the greatest clinical benefit for SGLT2i.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Canagliflozina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Glucosídeos/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Canagliflozina/efeitos adversos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/fisiopatologia , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Glucosídeos/efeitos adversos , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
5.
Diabetes Care ; 42(9): 1760-1768, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31262950

RESUMO

OBJECTIVE: Patients with type 1 diabetes (T1D) have a higher risk of developing chronic kidney disease, cardiovascular events (CVEs), and mortality than the general population. We hypothesized that two previously published biomarkers, namely PRO-C6, a biomarker of collagen type VI formation, and C3M, a biomarker of collagen type III degradation, may be associated with impaired renal function and have prognostic value for adverse renal, CVE, and mortality in patients with T1D. RESEARCH DESIGN AND METHODS: PRO-C6 and C3M in serum (sPRO-C6, sC3M) and urine (uPRO-C6, uC3M) were measured by ELISA in 663 patients with T1D ranging from normoalbuminuric to macroalbuminuric. Association of the biomarkers with mortality, CVEs, heart failure, decline in estimated glomerular filtration rate (eGFR) ≥30%, and end-stage renal disease (ESRD) were tested in Cox proportional hazards models after log2 transformation and adjusted for relevant clinical characteristics. Hazard ratios (HRs) were reported per doubling of biomarker levels. RESULTS: High levels of sPRO-C6 were independently associated with a higher risk of all-cause mortality (HR 2.26 [95% CI 1.31-3.87], P < 0.0031). There was an association with higher risk of CVEs (n = 94) and heart failure (n = 28) but not after adjustment (P ≥ 0.58). In relation to renal outcomes, adjusted sPRO-C6 was associated with a higher risk of eGFR decline ≥30% in T1D, with eGFR >45 and >30 mL/min/1.73 m2, and with a higher risk of ESRD (all P ≤ 0.03). Higher uPRO-C6 was associated with a lower risk of decline in eGFR. CONCLUSIONS: In patients with T1D, higher sPRO-C6 was an independent predictor of both decline in eGFR and development of ESRD and of all-cause mortality. Higher uPRO-C6 was also associated with a lower risk of decline in eGFR.


Assuntos
Colágeno Tipo III/sangue , Colágeno Tipo VI/sangue , Diabetes Mellitus Tipo 1/sangue , Nefropatias Diabéticas/mortalidade , Pró-Colágeno/sangue , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/mortalidade , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/mortalidade , Nefropatias Diabéticas/etiologia , Feminino , Taxa de Filtração Glomerular , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Humanos , Rim/fisiopatologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco
6.
Medicine (Baltimore) ; 98(27): e16333, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277183

RESUMO

The prognostic utility of histologic features in patients with diabetic nephropathy (DN) classified according to the Renal Pathology Society (RPS) classification is controversial. Therefore, we aimed to evaluate the relationship between histologic changes and renal outcome in DN patients.We examined the renal outcome at November 30, 2017 of 74 adult patients (median age of 54.6 years, 69% male, 81% diabetes mellitus (DM) type 2, estimated GFR (eGFR) 29.6 mL/min) with biopsy proven DN between 2010 and 2015. The primary endpoint was renal replacement therapy (RRT) initiation.Half of the patients progressed to end stage renal disease (ESRD) during follow-up; they had lower eGFR, increased proteinuria, hematuria and serum cholesterol. Regarding the pathologic features, they were more frequently in class III and IV, had higher interstitial fibrosis and tubular atrophy score (IFTA), increased interstitial inflammation, more frequent arteriolar hyalinosis and higher glomerular basement membrane (GBM) thickness. The mean kidney survival time was 2.7 (95%CI 2.1, 3.3) years. In univariate time-dependent analyses, higher RPS DN class, increased IFTA, the presence of arteriolar hyalinosis and arteriosclerosis were associated with RRT initiation.In the fully adjusted model, the clinical characteristics associated with poor renal survival were longer duration of DM, lower eGFR, increased proteinuria and higher hematuria and the only pathologic lesions to remain significant were the GBM thickness and the IFTA.In conclusion, in this European cohort, the severity of glomerular lesions evaluated with the RPS DN classification had limited utility in predicting RRT initiation. However, IFTA and GBM thickness were significantly associated with renal survival.


Assuntos
Nefropatias Diabéticas/patologia , Falência Renal Crônica/etiologia , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/terapia , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Valor Preditivo dos Testes , Terapia de Substituição Renal , Estudos Retrospectivos , Taxa de Sobrevida
7.
Ren Fail ; 41(1): 521-531, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31216914

RESUMO

Aim: Renal replacement therapy was primary treatment for end stage kidney (ESRD) patients. Numbers of studies comparing peritoneal dialysis (PD) and hemodialysis (HD) yielded inconsistent results. The aim of this study was to assess the mortality risk between diabetic PD patients and those in HD. Methods: We included cohort studies comparing the risk of death among diabetic ESRD patients who receiving peritoneal dialysis or hemodialysis by searching Medline and Embase. Overall estimates were calculated using the random-effects model. Results: Seventeen studies were included in the meta-analyses. Mortality comparison between PD and HD in the diabetic ESRD patients showed PD significantly increased mortality rate (hazard ratio (HR) 1.20; 95% confidence interval (CI) 1.10-1.30; I2 = 89.1%). The overall HR using an intention-to-treat analysis was 1.23 with 95% CI (1.13 to 1.34). Meta-regression demonstrated PD patients from Asian country were associated with increase in mortality risk (coefficient = 0.270, SE = 0.112, p = .033). Limitation: The high heterogeneity in our meta-analyses undermined the robustness of the findings. Conclusion: ESRD patients with diabetes may benefit more from HD than PD.


Assuntos
Nefropatias Diabéticas/terapia , Falência Renal Crônica/terapia , Diálise Peritoneal , Diálise Renal , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/patologia , Progressão da Doença , Humanos , Falência Renal Crônica/mortalidade , Falência Renal Crônica/patologia , Resultado do Tratamento
8.
Diabetes Care ; 42(8): 1512-1520, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31123156

RESUMO

OBJECTIVE: Trimethylamine N-oxide (TMAO) is suggested as an independent gut microbiota-derived risk factor for cardiovascular and renal disease. We investigated associations between plasma TMAO concentrations and cardio-renal outcomes in a prospective study of individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: Plasma TMAO was measured at baseline in 1,159 individuals with type 1 diabetes (58% male, mean ± SD age 46 ± 13 years). End points were all-cause and cardiovascular mortality, cardiovascular disease (CVD), and renal events tracked from national registries. Associations between TMAO and end points were tested using Cox regression models. RESULTS: After 15.0 (6.7-19.3) (median [interquartile range]) years of follow-up, we recorded all-cause and cardiovascular mortality (n = 363 and 120, respectively), combined CVD (n = 406), coronary outcome (myocardial infarction and coronary intervention) (n = 163), stroke (n = 115), hospitalization for heart failure (n = 81), and end-stage renal disease (n = 144). In univariate analyses, higher TMAO concentrations were associated with all end points (P ≤ 0.005). Except for stroke and heart failure, all end points remained significantly associated with higher TMAO concentrations after adjustment for conventional cardiovascular risk factors (P ≤ 0.003). After further adjustment for baseline estimated glomerular filtration rate (eGFR), results became insignificant for all end points. TMAO was inversely associated with baseline eGFR (R 2 = 0.29; P < 0.001). CONCLUSIONS: In individuals with type 1 diabetes, higher concentrations of plasma TMAO were associated with mortality, CVD events, and poor renal outcome, independent of conventional risk factors. However, the association became insignificant after further adjustment for baseline eGFR. This could reflect TMAO as a renal function marker or a risk factor for micro- and macrovascular complications mediated through impaired renal function.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/mortalidade , Cardiomiopatias Diabéticas/mortalidade , Nefropatias Diabéticas/mortalidade , Metilaminas/sangue , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 1/complicações , Cardiomiopatias Diabéticas/etiologia , Nefropatias Diabéticas/etiologia , Feminino , Microbioma Gastrointestinal , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Insuficiência Renal/etiologia , Insuficiência Renal/mortalidade , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade
9.
BMC Complement Altern Med ; 19(1): 81, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943956

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) that imposes an enormous burden on the healthcare system. Although some studies show that traditional Chinese medicine (TCM) treatments confer a protective effect on DN, the long-term impact remains unclear. This study aims to examine end-stage renal disease (ESRD) and mortality rates among TCM users with DN. METHODS: A total of 125,490 patients with incident DN patients from 2004 to 2006 were identified from the National Health Insurance Research Database in Taiwan and followed until 2012. The landmark method was applied to avoid immortal time bias, and propensity score matching was used to select 1:1 baseline characteristics-matched cohort. The Kaplan-Meier method and competing-risk analysis were used to assess mortality and ESRD rates separately. RESULTS: Among all eligible subjects, about 60% of patients were classified as TCM users (65,812 TCM users and 41,482 nonusers). After 1:1 matching, the outcomes of 68,882 patients were analyzed. For the ESRD rate, the 8-year cumulative incidence was 14.5% for TCM users [95% confidence interval (CI): 13.9-15.0] and 16.6% for nonusers (95% CI: 16.0-17.2). For the mortality rate, the 8-year cumulative incidence was 33.8% for TCM users (95% CI: 33.1-34.6) and 49.2% for nonusers (95% CI: 48.5-49.9). After adjusting for confounding covariates, the cause-specific hazard ratio of ESRD was 0.81 (95% CI: 0.78-0.84), and the hazard ratio of mortality for TCM users was 0.48 (95% CI: 0.47-0.50). The cumulative incidence of mortality increased rapidly among TCM users with ESRD (56.8, 95% CI: 54.6-59.1) when compared with TCM users without ESRD (30.1, 95% CI: 29.4-30.9). In addition, TCM users who used TCM longer or initiated TCM treatments after being diagnosed with DN were associated with a lower risk of mortality. These results were consistent across sensitivity tests with different definitions of TCM users and inverse probability weighting of subjects. CONCLUSIONS: The lower ESRD and mortality rates among patients with incident DN correlates with the use of TCM treatments. Further studies about specific TCM modalities or medications for DN are still needed.


Assuntos
Nefropatias Diabéticas , Medicamentos de Ervas Chinesas/uso terapêutico , Falência Renal Crônica , Adulto , Estudos Transversais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/mortalidade , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Taiwan/epidemiologia , Adulto Jovem
10.
Diabetes Care ; 42(6): 1112-1119, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30885954

RESUMO

OBJECTIVE: Soluble urokinase plasminogen activator receptor (suPAR) is an important inflammatory biomarker implicated in endothelial and podocyte dysfunction. However, suPAR's predictive qualities for complications in type 1 diabetes have yet to be determined. We investigated the prognostic value of suPAR for the development of cardiovascular events, decline in renal function, and mortality in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: We included 667 patients with type 1 diabetes with various degrees of albuminuria in a prospective study. End points were cardiovascular events (cardiovascular death, nonfatal acute myocardial infarction, nonfatal stroke, or coronary or peripheral arterial interventions), estimated glomerular filtration rate (eGFR) decline ≥30%, progression from lower to higher albuminuric state, development of end-stage renal disease (ESRD), and mortality. Follow-up was 5.2-6.2 years. Results were adjusted for known risk factors. Hazard ratios (HRs) are presented per doubling of suPAR with 95% CI. Relative integrated discrimination improvement (rIDI) was calculated. RESULTS: Quantification of suPAR was available in all participants; median (interquartile range) was 3.4 ng/mL (2.7-4.5). The adjusted HR (95% CI) for cardiovascular events (n = 94), progression in albuminuria (n = 36), eGFR decline (n = 93), ESRD (n = 23), and mortality (n = 58) were 3.13 (1.96-5.45, P < 0.001), 1.27 (0.51-3.19, P = 0.61), 2.93 (1.68-5.11, P < 0.001), 2.82 (0.73-11.9, P = 0.13), and 4.13 (1.96-8.69, P < 0.001), respectively. rIDI was significant for cardiovascular events (22.6%, P < 0.001), eGFR decline (14.4%, P < 0.001), and mortality (23.9%, P < 0.001). CONCLUSIONS: In patients with type 1 diabetes and a broad range of albuminuria, a higher level of suPAR is a significant and independent risk factor for cardiovascular events, decline in eGFR ≥30%, and mortality. In addition, suPAR contributes significantly to discrimination for the end points.


Assuntos
Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 1/diagnóstico , Angiopatias Diabéticas/diagnóstico , Nefropatias Diabéticas/diagnóstico , Falência Renal Crônica/diagnóstico , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Adulto , Idoso , Biomarcadores/análise , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Dinamarca/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 1/fisiopatologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/mortalidade , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Receptores de Ativador de Plasminogênio Tipo Uroquinase/análise , Fatores de Risco
11.
Iran J Kidney Dis ; 13(1): 56-66, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30851720

RESUMO

INTRODUCTION: This study aimed to investigate the influence of peritoneal transport characteristics on clinical outcome in nondiabetic and diabetic nephropathy peritoneal dialysis (PD) patients. MATERIALS AND METHODS: All 112 patients were from the PD Center. Peritoneal transport characteristic was assessed by peritoneal equilibration test. The patients were divided into 2 groups of high-transport group (HT) and non-high-transport group (non-HT) and followed-up till December 31st, 2010. The primary outcomes were all-cause death and technique failure. RESULTS: The patients were followed-up for 65.9 ± 23.9 months. Diabetic nephropathy patients with HT had a higher all-cause mortality (P = .04) and technique failure (P = .04) than those with non-HT. There were no differences in outcomes between HT and non-HT subgroups without diabetic nephropathy. Cox regression demonrtrated that high peritoneal transport (HR, 2.369; 95% CI, 1.056 to 5.311), diabetic nephropathy (HR, 2.499; 95% CI, 1.134 to 5.508), age (HR, 1.081; 95% CI, 1.032 to 1.133), and peritoneal creatinine clearance (HR, 0.962; 95% CI, 0.929 to 0.997) independently predicted all-cause mortality in continuous ambulatory PD patients. Moreover, high peritoneal transport (HR, 2.299; 95% CI, 1.079 to 4.899) and age (HR, 1.070; 95% CI, 1.026 to 1.116) predicted technique failure in continuous ambulatory PD patients. CONCLUSIONS: Diabetic nephropathy PD patients with HT had a higher all-cause mortality and technique failure than those with non-HT, but we did not find the correlation between peritoneal transport and outcome in nondiabetic patients. The peritoneal transport was an independent predictor for outcomes in continuous ambulatory PD patients.


Assuntos
Nefropatias Diabéticas/terapia , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Diálise Peritoneal Ambulatorial Contínua/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Pequim/epidemiologia , Transporte Biológico , Pressão Sanguínea , Causas de Morte , Nefropatias Diabéticas/mortalidade , Impedância Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Albumina Sérica , Análise de Sobrevida
12.
Diabetologia ; 62(4): 633-643, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30649599

RESUMO

AIMS/HYPOTHESIS: The role of burden and duration of multiple microvascular complications on mortality rate has not been explored in detail in type 1 diabetes. Taking complication burden and time-updated duration into account we aimed to quantify mortality rate in individuals with and without microvascular complications. METHODS: This observational clinical cohort included 3828 individuals with type 1 diabetes attending the Steno Diabetes Center Copenhagen in 2001-2013. We used information on mortality and detailed clinical measures of microvascular complications from electronic patient records. Poisson models were used to model mortality rates according to complication burden. RESULTS: During 26,665 person-years of follow-up, 503 deaths occurred. Compared with individuals without microvascular complications, the mortality rate ratio was 2.20 (95% CI 1.79, 2.69) for individuals with diabetic kidney disease, 1.72 (95% CI 1.39, 2.12) for individuals with neuropathy and 1.02 (95% CI 0.77, 1.37) for individuals with retinopathy, all adjusted for calendar time (year/month/day), age, duration of diabetes, sex, HbA1c, LDL-cholesterol, BMI, smoking status, systolic blood pressure, use of antihypertensive and lipid-lowering medication, and cardiovascular disease status. In individuals with two complications or more, the risk of mortality did not exceed the combined risk from each individual complication. Mortality rate ratios increased immediately after diagnosis of neuropathy and diabetic kidney disease. Mortality rate ratios were independent of the duration of neuropathy and retinopathy, while the mortality rate associated with diabetic kidney disease reached a stable level after approximately 3 years. CONCLUSIONS/INTERPRETATION: Neuropathy and diabetic kidney disease are strong and independent risk markers of mortality in type 1 diabetes, whereas no evidence of higher mortality rate was found for retinopathy. We found no indication that the mortality risk with multiple complications exceeds the risk conferred by each complication separately. The duration spent with microvascular complications had only a marginal effect on mortality.


Assuntos
Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 1/terapia , Microcirculação , Adolescente , Adulto , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , Dinamarca , Angiopatias Diabéticas/mortalidade , Nefropatias Diabéticas/mortalidade , Neuropatias Diabéticas/mortalidade , Retinopatia Diabética/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
13.
Diabetes Res Clin Pract ; 148: 144-151, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30641169

RESUMO

AIMS: Diabetic nephropathy (DMN) is usually diagnosed clinically without pathology, and the prognosis of which compared to non-diabetic renal diseases has rarely been investigated especially in ethnic Chinese population. Here we reported the outcome of patients with biopsy-proved DMN compared to those with isolated crescentic glomerulonephritis (GN) or lupus nephritis (LN). METHODS: This retrospective observational study included patients with DMN (n = 55), crescentic GN (n = 48) and LN (n = 82) from an original cohort of 987 adult patients who underwent kidney biopsy. The median follow-up period was 8.3 years. The Cox regression model was used to identify factors associated with the outcome measures of end-stage renal disease (ESRD) and all-cause mortality. RESULTS: Patients with DMN and crescentic GN exhibited higher rates of ESRD than LN group (65.5%, 66.7% versus 32.9%, p < 0.001). After accounting for the competing risk of death, DMN versus LN, along with lower hemoglobin values, lower estimated glomerular filtration rates and severe proteinuria were independent predictors for ESRD. Patients with DMN and crescentic GN displayed higher mortality rates than LN patients following the development of ESRD (38.2% and 29.2% versus 9.8%, p < 0.001). Multivariate analysis showed old age (≧65 years) and lower serum albumin levels were independently associated with overall death. CONCLUSIONS: Patients with biopsy-proved DMN, but not crescentic GN, showed a greater risk of ESRD than LN counterparts. Given the grave renal prognosis of DMN, more meticulous follow-up is critical to ensure that best therapeutic strategies are used to avert progression to ESRD.


Assuntos
Nefropatias Diabéticas/diagnóstico , Glomerulonefrite/diagnóstico , Rim/patologia , Nefrite Lúpica/diagnóstico , Doença Aguda , Adulto , Idoso , Biópsia , Estudos de Coortes , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/patologia , Progressão da Doença , Feminino , Seguimentos , Glomerulonefrite/complicações , Glomerulonefrite/mortalidade , Glomerulonefrite/patologia , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Falência Renal Crônica/patologia , Nefrite Lúpica/complicações , Nefrite Lúpica/mortalidade , Nefrite Lúpica/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
14.
Am J Nephrol ; 49(2): 146-155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30677760

RESUMO

BACKGROUND: Overt albuminuria (urinary albumin-creatinine ratio [ACR] > 300 mg/g) is an established risk factor for progression of nephropathy and total mortality. However, whether a reduction in ACR translates into a reduction in mortality and/or cardiovascular (CV) events among insulin-treated patients with type 2 diabetes (T2D) in routine practice is currently not known. METHODS: We obtained data on a large cohort of insulin users with T2D and nephropathy (baseline ACR ≥300 mg/g) from UK general practices between 2007 and 2014. Their corresponding ACR values after 1year of follow-up were thereafter categorized into: (1) < 300 mg/g (i.e., albuminuria regression) or (2) > 300 mg/g (i.e., nonregression of albuminuria), and the cohort was followed-up for 5 years for all-cause mortality and CV events. Cox proportional hazard models were fitted to estimate the risk of all-cause death. RESULTS: A total of 11,074 patients with insulin-treated T2D met the inclusion criteria. Their mean age was 62.3 (13.6) years; mean HbA1c: 8.7 (1.8) and 53% were male. A total of 682 deaths occurred after a follow-up period of 43,393 person-years with a mortality rate of 16 per 1,000 person-years. Five-year survival was markedly reduced in the group whose proteinuria persisted or progressed (91 vs. 95%; log-rank p value < 0.001). Compared to patients whose ACR levels remained above 300 mg/g, all-cause mortality and CV events were 31 and 27% lower in those whose albuminuria regressed to < 300 mg/g (adjusted hazard ratio [aHR] 0.69; 95% CI 0.52-0.91; p = 0.008 and aHR 0. 73; 95% CI 0.54-0.98; p = 0.041), respectively. CONCLUSION: In patients with insulin-treated T2D and nephropathy in routine practice, a regression in albuminuria (e.g., via better BP or glycemic control) is associated with a significant reduction in all-cause mortality. Thus, albuminuria is not only simply a risk marker of renal and CV disease but also an independent target for therapy. Albuminuria reduction should be viewed as a goal for renal and CV protection.


Assuntos
Albuminúria/mortalidade , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/mortalidade , Insulina/uso terapêutico , Idoso , Albuminúria/diagnóstico , Albuminúria/etiologia , Albuminúria/patologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/urina , Creatinina/urina , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/urina , Progressão da Doença , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Albumina Sérica Humana/urina , Análise de Sobrevida , Reino Unido/epidemiologia
15.
Diabetes Obes Metab ; 21(2): 340-348, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30207040

RESUMO

AIM: To assess the possible risk of acute kidney injury (AKI) with the use of sodium-glucose co-transporter-2 inhibitors (SGLT2-i) as well as changes in estimated glomerular filtration rate (eGFR), hospitalizations and mortality in a real-world setting. MATERIALS AND METHODS: Included in this historical cohort study were patients with type 2 diabetes in a large health organization in Israel who initiated therapy with SGLT2-i or dipeptidyl peptidase-4 inhibitors (DPP-4i) during 1 April 2015 to 30 June 2017. We collected data on serum creatinine measurements taken between 180 days prior to and 24 weeks after therapy initiation. Study endpoints included ≥30% reduction in eGFR, hospitalization with AKI, any hospitalization and all-cause mortality. RESULTS: Overall 6418 and 5604 patients initiated SGLT2-i and DPP-4i, respectively. Baseline mean (SD) eGFR was higher among the SGLT2-i group compared with the DPP-4i group (88.3 [17.4] and 82.8 [23.7], respectively) but were similar when stratifying by chronic kidney disease (CKD) stages. The adjusted odds ratio (OR) (95% confidence interval [CI]) for ≥30% reduction in eGFR with SGLT2-i versus DPP4-i was 0.70 (0.49-1.00) and ORs ranged from 1.97 (0.62-6.26) to 0.45 (0.21-0.99) in patients with baseline eGFR 30 to 45 and ≥90 mL/min/1.73 m2 , respectively. Risks of AKI (OR = 0.47, 95% CI 0.27-0.80), hospitalization (OR = 0.66, 95% CI 0.56-0.78) or all-cause mortality (OR = 0.43, 95% CI 0.20-0.95) were lower in patients initiating SGLT2-i versus DPP-4i. CONCLUSIONS: This real-world data analysis supports reassuring findings from previous randomized clinical trials showing no increased AKI risk among SGLT2-i users. Nevertheless, because of the more prominent decrease in eGFR in patients with moderate CKD, cautious use of SGLT2-i in patients with reduced eGFR is advised.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/terapia , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/fisiopatologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Hospitalização/estatística & dados numéricos , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/mortalidade , Fatores de Risco
16.
Catheter Cardiovasc Interv ; 93(4): E217-E224, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30467952

RESUMO

BACKGROUND: The aim of this study was to examine the relationship of albuminuria to cardiovascular disease outcomes in diabetic patients undergoing treatment for stable coronary artery disease. METHODS AND RESULTS: We analyzed data from 2176 participants of the Bypass Angioplasty Revascularization Investigation in type-2 diabetes (BARI-2D) trial, a randomized clinical trial comparing Percutaneous coronary intervention/Coronary artery bypass grafting (PCI/CABG) to medical therapy for people with diabetes. The population was stratified by baseline spot urine albumin-creatinine ratio (uACR) into normal (uACR <10 mg/g), mildly (uACR ≥10 mg/g < 30 mg/g), moderately (uACR ≥30 mg/g < 300 mg/g) and severely increased (uACR ≥300 mg/g) groups, and outcomes compared between groups. Death, myocardial infarction (MI) and/or stroke were experienced by 489 patients at a mean follow-up of 4.3 ± 1.5 years. Compared with normal uACR, mildly increased uACR was associated with a 1.4 times (P = 0.042) increase in all-cause mortality. Additionally, nonwhites with type-II diabetes and stable coronary artery disease who had mildly increased albuminuria had a Hazard ratio (HR) of 3.3 times (P = 0.028) for cardiovascular death, 3.1 times for (P = 0.002) all-cause mortality, and two times for (P = 0.015) MI during follow-up. CONCLUSIONS: Mildly increased albuminuria is a significant predictor of all-cause mortality in those with type-II diabetes mellitus and stable coronary artery disease, as well as for cardiovascular events those who are nonwhites.


Assuntos
Albuminúria/etnologia , Fármacos Cardiovasculares/uso terapêutico , Ponte de Artéria Coronária , Doença da Artéria Coronariana/terapia , Diabetes Mellitus Tipo 2/etnologia , Nefropatias Diabéticas/etnologia , Intervenção Coronária Percutânea , Idoso , Albuminúria/diagnóstico , Albuminúria/mortalidade , Brasil/epidemiologia , Fármacos Cardiovasculares/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etnologia , Doença da Artéria Coronariana/mortalidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etnologia , Infarto do Miocárdio/mortalidade , América do Norte/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Resultado do Tratamento
17.
Diabetes Metab Res Rev ; 35(1): e3081, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30261555

RESUMO

AIM: Current evidence relating testosterone to cardiovascular disease and mortality is inconclusive. Cellular effects of testosterone are mediated by androgen receptor and longer receptor gene CAG repeat length correlates with reduced transcriptional activity. We investigated the independent and interactive association of total testosterone and CAG repeat length with incident cardiovascular disease (CVD), chronic kidney disease (CKD) and mortality in Chinese men with type 2 diabetes. MATERIALS AND METHODS: From March 2008 and February 2009, 474 men with diabetes underwent structured clinical assessment including genotyping for CAG repeat length. Patients were followed for new-onset CVD, CKD defined by estimated glomerular filtration rate <60 mL/min/1.73m2 , and death until 31 May 2015. RESULTS: In this cohort (mean age: 58.6 years, disease duration: 15.4 years), CAG repeat number ranged from 11 to 32 with median of 23, and 9.3% had low testosterone. Over follow-up of 5.8 years, 49 (10.3%) men had CVD, 139 (29.3%) had CKD, and 43 (9.1%) died. In multivariate Cox regression adjusted for age, duration of diabetes, and cardiometabolic risk factors, both total testosterone and interaction term of total testosterone × CAG repeat were associated with all-cause death with respective hazard ratios 1.63 (P = 0.002) and 0.98 (P = 0.004). Total testosterone and CAG repeat were not related to incident CVD or CKD. CONCLUSIONS: Among men with type 2 diabetes, high total testosterone was associated with increased mortality in the presence of shorter CAG repeat length but decreased mortality in those with long CAG repeats.


Assuntos
Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/genética , Receptores Androgênicos/genética , Testosterona/sangue , Repetições de Trinucleotídeos , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/mortalidade , Genótipo , Hong Kong/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Sistema de Registros , Fatores de Risco , Taxa de Sobrevida
18.
Clin Exp Nephrol ; 23(3): 409-414, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30255261

RESUMO

BACKGROUND: Although peritoneal dialysis (PD) is becoming more widespread, PD among diabetic patients carries some concerns, such as worsened glycemic control due to constant exposure to glucose and operational errors due to diabetic complications. However, several technical advances could overcome these disadvantages. We, therefore, aimed to compare technical and patient survival between diabetic and non-diabetic PD patients. METHODS: We conducted a historical cohort study of 103 patients (mean age, 57 ± 16 years; 75 males, 32 diabetic patients) who started PD between January 2011 and January 2016. Kaplan-Meier survival analysis was used to compare technical and patient survivals between diabetic and non-diabetic patients. Multivariate Cox regression analysis was used to estimate the effects of the presence of diabetes on these outcomes. RESULTS: Technical and patient survivals did not differ significantly between groups (P = 0.62, P = 0.34, respectively). In addition, presence of diabetes affected neither technical nor patient survival in multivariate analysis (hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.58-2.82 and HR 0.80; 95% CI 0.22-2.68, respectively). CONCLUSIONS: Technical and patient survivals of diabetic PD patients were not inferior to those of non-diabetic PD patients. These results suggest that no hesitation is warranted in initiating PD for diabetic patients with end-stage renal disease.


Assuntos
Nefropatias Diabéticas/mortalidade , Diálise Peritoneal/mortalidade , Adulto , Idoso , Nefropatias Diabéticas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos
19.
Nephrology (Carlton) ; 24(9): 943-950, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30407693

RESUMO

AIM: Advanced glycation end products and their precursors cause vascular damage through oxidative stress. We investigated the hypothesis that methylglyoxal (MG), 3-deoxyglucosone (3-DG) and pentosidine influence outcomes of chronic kidney disease (CKD) patients. METHODS: We conducted a 3 years prospective observational study involving 150 outpatients at CKD stages 3-5. At enrolment, MG, 3-DG and pentosidine plasma concentrations were measured; patients were divided into tertiles according to the concentration of each substance. The primary endpoint was death, a cardiovascular event or end-stage renal disease. Survival analysis was performed using the Cox regression model. RESULTS: The patients' mean age was 62 ± 12 years, 97 were men, and 20 had diabetic nephropathy. The mean estimated glomerular filtration rate was 25.0 ± 12.1 mL/min per 1.73 m2 , which negatively correlated with MG but not with 3-DG and pentosidine. Forty-eight patients reached the primary endpoint. Compared with the lowest MG tertile, the hazard ratio for the primary endpoint was 7.57 (95% confidence interval (CI): 1.71-33.54) in the middle tertile and 27.00 (CI: 6.46-112.82) in the highest tertile. When adjusted for characteristics at baseline, the corresponding hazard ratio decreased to 2.09 (CI: 0.37-11.96) and 6.13 (CI: 0.97-38.82), but MG tertile remained an independent risk factor for the primary endpoint. However, 3-DG and pentosidine were not related to the primary outcome. CONCLUSION: Methylglyoxal has a close clinical association with CKD. Higher MG concentrations may contribute renal function deterioration in CKD. In CKD patients, MG concentration might be useful when determining the prognosis.


Assuntos
Nefropatias Diabéticas/sangue , Falência Renal Crônica/sangue , Aldeído Pirúvico/sangue , Insuficiência Renal Crônica/sangue , Idoso , Arginina/análogos & derivados , Arginina/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Desoxiglucose/análogos & derivados , Desoxiglucose/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Progressão da Doença , Feminino , Humanos , Japão , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Lisina/análogos & derivados , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Fatores de Risco , Fatores de Tempo , Regulação para Cima
20.
Diabetes Care ; 42(1): 93-101, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30455333

RESUMO

OBJECTIVE: Patients with type 1 diabetes and diabetic nephropathy are targets for intervention to reduce high risk of end-stage renal disease (ESRD) and deaths. This study compares risks of these outcomes in four international cohorts. RESEARCH DESIGN AND METHODS: In the 1990s and early 2000s, Caucasian patients with type 1 diabetes with persistent macroalbuminuria in chronic kidney disease stages 1-3 were identified in the Joslin Clinic (U.S., 432), Finnish Diabetic Nephropathy Study (FinnDiane) (Finland, 486), Steno Diabetes Center Copenhagen (Denmark, 368), and INSERM (France, 232) and were followed for 3-18 years with annual creatinine measurements to ascertain ESRD and deaths unrelated to ESRD. RESULTS: During 15,685 patient-years, 505 ESRD cases (rate 32/1,000 patient-years) and 228 deaths unrelated to ESRD (rate 14/1,000 patient-years) occurred. Risk of ESRD was associated with male sex; younger age; lower estimated glomerular filtration rate (eGFR); higher albumin/creatinine ratio, HbA1c, and systolic blood pressure; and smoking. Risk of death unrelated to ESRD was associated with older age, smoking, and higher baseline eGFR. In adjusted analysis, ESRD risk was highest in Joslin versus reference FinnDiane (hazard ratio [HR] 1.44, P = 0.003) and lowest in Steno (HR 0.54, P < 0.001). Differences in eGFR slopes paralleled risk of ESRD. Mortality unrelated to ESRD was lowest in Joslin (HR 0.68, P = 0.003 vs. the other cohorts). Competing risk did not explain international differences in the outcomes. CONCLUSIONS: Despite almost universal renoprotective treatment, progression to ESRD and mortality in patients with type 1 diabetes with advanced nephropathy are still very high and differ among countries. Finding causes of these differences may help reduce risk of these outcomes.


Assuntos
Diabetes Mellitus Tipo 1/mortalidade , Nefropatias Diabéticas/mortalidade , Falência Renal Crônica/mortalidade , Adulto , Albuminúria/urina , Pressão Sanguínea , Colesterol/sangue , Creatinina/sangue , Dinamarca , Diabetes Mellitus Tipo 1/sangue , Nefropatias Diabéticas/sangue , Progressão da Doença , Feminino , Finlândia , Seguimentos , França , Taxa de Filtração Glomerular , Hemoglobina A Glicada/metabolismo , Humanos , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
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