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1.
Diab Vasc Dis Res ; 17(7): 1479164120945910, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32746630

RESUMO

BACKGROUND: The effect of interarm blood pressure difference on the development of diabetic retinopathy, proteinuria and chronic kidney disease remains unknown. We investigated to determine the impact of interarm blood pressure difference on the prevalence of diabetic retinopathy, proteinuria and chronic kidney disease in patients with type 2 diabetes. METHODS: The study included 563 patients with diabetes, who were evaluated with a simultaneous bilateral blood pressure measurement. The cutoff values for interarm blood pressure difference were 5, 10 and 15 mmHg. Logistic regression analysis was used to explore the relation between interarm blood pressure difference and diabetic retinopathy, proteinuria and chronic kidney disease. RESULTS: Diabetic patients with systolic interarm blood pressure difference ⩾5, ⩾10 and ⩾15 mmHg showed an increased risk of diabetic retinopathy [adjusted odds ratio = 1.48 (95% confidence interval = 1.01-2.18), odds ratio = 1.80 (95% confidence interval = 0.99-3.22), odds ratio = 2.29 (95% confidence interval = 1.00-5.23)] after adjustment. There were significant associations between interarm blood pressure difference ⩾5 and ⩾10 mmHg and proteinuria [odds ratio = 1.68 (95% confidence interval = 1.15-2.44), 1.89 (95% confidence interval = 1.05-3.37)]. CONCLUSION: The association between interarm blood pressure difference and the presence of diabetic retinopathy emerged even for systolic interarm blood pressure difference ⩾5 mmHg without interaction of systolic blood pressure. Systolic interarm blood pressure difference should be considered a surrogate marker for vascular complication in patients with type 2 diabetes.


Assuntos
Pressão Sanguínea , Diabetes Mellitus Tipo 2/fisiopatologia , Retinopatia Diabética/fisiopatologia , Extremidade Superior/irrigação sanguínea , Idoso , Índice Tornozelo-Braço , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/fisiopatologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Proteinúria/diagnóstico , Proteinúria/epidemiologia , Proteinúria/fisiopatologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Seul/epidemiologia
2.
PLoS Med ; 17(8): e1003255, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32797043

RESUMO

BACKGROUND: Hypertensive disorders of pregnancy (HDP) (preeclampsia, gestational hypertension) are associated with an increased risk of end-stage kidney disease (ESKD). Evidence for associations between HDP and chronic kidney disease (CKD) is more limited and inconsistent. The underlying causes of CKD are wide-ranging, and HDP may have differential associations with various aetiologies of CKD. We aimed to measure associations between HDP and maternal CKD in women who have had at least one live birth and to identify whether the risk differs by CKD aetiology. METHODS AND FINDINGS: Using data from the Swedish Medical Birth Register (MBR), singleton live births from 1973 to 2012 were identified and linked to data from the Swedish Renal Register (SRR) and National Patient Register (NPR; up to 2013). Preeclampsia was the main exposure of interest and was treated as a time-dependent variable. Gestational hypertension was also investigated as a secondary exposure. The primary outcome was maternal CKD, and this was classified into 5 subtypes: hypertensive, diabetic, glomerular/proteinuric, tubulointerstitial, and other/nonspecific CKD. Cox proportional hazard regression models were used, adjusting for maternal age, country of origin, education level, antenatal BMI, smoking during pregnancy, gestational diabetes, and parity. Women with pre-pregnancy comorbidities were excluded. The final sample consisted of 1,924,409 women who had 3,726,554 singleton live births. The mean (±SD) age of women at first delivery was 27.0 (±5.1) years. Median follow-up was 20.7 (interquartile range [IQR] 9.9-30.0) years. A total of 90,917 women (4.7%) were diagnosed with preeclampsia, 43,964 (2.3%) had gestational hypertension, and 18,477 (0.9%) developed CKD. Preeclampsia was associated with a higher risk of developing CKD during follow-up (adjusted hazard ratio [aHR] 1.92, 95% CI 1.83-2.03, p < 0.001). This risk differed by CKD subtype and was higher for hypertensive CKD (aHR 3.72, 95% CI 3.05-4.53, p < 0.001), diabetic CKD (aHR 3.94, 95% CI 3.38-4.60, p < 0.001), and glomerular/proteinuric CKD (aHR 2.06, 95% CI 1.88-2.26, p < 0.001). More modest associations were observed between preeclampsia and tubulointerstitial CKD (aHR 1.44, 95% CI 1.24-1.68, p < 0.001) or other/nonspecific CKD (aHR 1.51, 95% CI 1.38-1.65, p < 0.001). The risk of CKD was increased after preterm preeclampsia, recurrent preeclampsia, or preeclampsia complicated by pre-pregnancy obesity. Women who had gestational hypertension also had increased risk of developing CKD (aHR 1.49, 95% CI 1.38-1.61, p < 0.001). This association was strongest for hypertensive CKD (aHR 3.13, 95% CI 2.47-3.97, p < 0.001). Limitations of the study are the possibility that cases of CKD were underdiagnosed in the national registers, and some women may have been too young to have developed symptomatic CKD despite the long follow-up time. Underreporting of postpartum hypertension is also possible. CONCLUSIONS: In this study, we found that HDP are associated with increased risk of maternal CKD, particularly hypertensive or diabetic forms of CKD. The risk is higher after preterm preeclampsia, recurrent preeclampsia, or preeclampsia complicated by pre-pregnancy obesity. Women who experience HDP may benefit from future systematic renal monitoring.


Assuntos
Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/epidemiologia , Sistema de Registros , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Hipertensão Induzida pela Gravidez/fisiopatologia , Pessoa de Meia-Idade , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Suécia/epidemiologia , Adulto Jovem
3.
Lancet ; 396(10246): 277-287, 2020 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711803

RESUMO

Acute and chronic kidney disease encompasses a complex set of diseases that can both lead to, and result from, cancer. In particular, kidney disease can arise from the use of chemotherapeutic agents. Many of the current and newly developed cancer chemotherapeutic agents are nephrotoxic and can promote kidney dysfunction, which frequently manifests during the terminal stages of cancer. Given the link between kidney disease and cancer development and treatment, the aim of this Review is to highlight the importance of multidisciplinary collaboration between oncologists and nephrologists to predict and prevent chemotherapeutic-induced nephrotoxicity. As new therapies are introduced to treat cancer, new renal toxicities require proper diagnosis and management. We anticipate that multidisciplinary collaborations will lead to the development and implementation of guidelines for clinicians to improve the therapeutic management of patients with both cancer and renal impairment.


Assuntos
Antineoplásicos/efeitos adversos , Nefropatias/induzido quimicamente , Neoplasias/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Lesão Renal Aguda/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Humanos , Comunicação Interdisciplinar , Nefropatias/patologia , Nefrologistas , Oncologistas , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia
4.
PLoS One ; 15(7): e0235135, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32628733

RESUMO

BACKGROUND: In patients on hemodialysis (HD), the various chemical elements in the dialysate may influence survival rates. In particular, calcium modifies mineral and bone metabolism and the vascular calcification rate. We studied the influence of the dialysate calcium concentration and the treatments prescribed for mineral bone disease (MBD) on survival. METHODS: All patients in REIN having initiated HD from 2010 to 2013 were classified according to their exposure to the different dialysate calcium concentrations in their dialysis unit. Data on the individual patients' treatments for MBD were extracted from the French national health database. Cox proportional hazard models were used to estimate mortality hazard ratios (HR) associated with time-dependent exposure to dialysate calcium concentrations and MBD therapies, adjusted for comorbidities, laboratory and technical data. RESULTS: Dialysate calcium concentration of 1.5 mmol/L was used by 81% of the dialysis centers in 2010 and in 83% in 2014. Most centers were using several formulas in up to 78% for 3 formulas in 2010 to 86% in 2014. In full adjusted Cox survival analyses, the percentage of calcium >1.5 mmol/L and <1.5 mmol/l by center and the number of formula used per center were not associated with survival. Depending on the daily dose used, the MBD therapies were associated with survival improvement for calcium, native vitamin D, active vitamin D, sevelamer, lanthanum and cinacalcet in the second and third tertiles of dose. CONCLUSION: No influence of the dialysate calcium concentration was evidenced on survival whereas all MBD therapies were associated with a survival improvement depending on the daily dose used.


Assuntos
Osso e Ossos/efeitos dos fármacos , Cálcio/análise , Soluções para Hemodiálise/análise , Sistema de Registros , Diálise Renal , Insuficiência Renal Crônica/terapia , Idoso , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiopatologia , Osso e Ossos/metabolismo , Osso e Ossos/fisiopatologia , Calcinose/epidemiologia , Calcinose/metabolismo , Calcinose/fisiopatologia , Cálcio/administração & dosagem , Cálcio/metabolismo , Cinacalcete/análise , Feminino , França/epidemiologia , Soluções para Hemodiálise/administração & dosagem , Soluções para Hemodiálise/química , Humanos , Lantânio/análise , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Sevelamer/análise , Vitamina D/análise , Vitamina D/metabolismo
5.
Rev Cardiovasc Med ; 21(2): 157-162, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32706205

RESUMO

Cardiovascular disease, and in particular coronary artery disease (CAD), remains an important contributor of morbidity and mortality among patients with chronic kidney disease (CKD). Classic symptomatology of CAD and effectiveness of established therapeutic measures is less frequent in patients with CKD. This suggests unique characteristics of CAD among patients with CKD. Two important features of CAD in CKD include increased calcific density of atherosclerotic plaques and of the vessels themselves (coronary artery calcification -- CAC), as well as a decrease in microcirculatory function -- or coronary microcirculatory dysfunction. A multitude of pathophysiologic pathways have been identified that contribute to CAC in CKD; less is known about the pathophysiology of microcirculatory dysfunction. It is not well established if these two processes are directly related to each other, but the combination results in a greater severity of effect on overall myocardial function and may in part explain the greater preponderance of silent myocardial infarction. Further investigation is needed to better understand these unique aspects of CAD in CKD as well as the role they play in overall CVD in this group, and ultimately therapeutics that may lessen the burden of disease.


Assuntos
Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Vasos Coronários/fisiopatologia , Rim/fisiopatologia , Microcirculação , Insuficiência Renal Crônica/fisiopatologia , Calcificação Vascular/fisiopatologia , Animais , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/terapia , Vasos Coronários/diagnóstico por imagem , Progressão da Doença , Taxa de Filtração Glomerular , Hemodinâmica , Humanos , Placa Aterosclerótica , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Calcificação Vascular/terapia
6.
Cardiovasc Ther ; 2020: 1807941, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670409

RESUMO

Nephropathic patients show elevated cardiovascular morbidity and mortality compared to the general population. In order to delve deeper into the understanding of this phenomenon, it is necessary to recognize risk factors that are distinctive to the uremic state, such as oxidative stress and chronic low-grade inflammation. Moreover, gender differences have been reported in nephrology, as it has been observed that chronic kidney disease has higher prevalence in males than in females. The use of an oral food supplement (OFS) containing natural active compounds from Capsicum annuum L., Garcinia cambogia, Centella asiatica L., artichoke, and Aesculus hippocastanum L. which are virtually devoid from side effects, but rich in antioxidant and antiradical properties, could represent a valid therapeutic adjunct in the clinical management of nephropathic patients. Moreover, quantitative analysis performed in vitro on such compounds showed that they expressed good total antioxidant (7.28 gallic acid equivalents) and antiradical activity (above 80%). In this study, 23 male nephropathic patients and 10 age and body composition parameter matched healthy males (control group) were enrolled and took 3 cps/day of OFS for 5 weeks. At the end of the study, the nephropathic patient group showed a statistically significant reduction in the following laboratory parameters: total cholesterol (TC) (p = 0.044), atherogenic index TC/high-density lipoprotein cholesterol (p = 0.010), inflammatory parameters (C-reactive protein, p = 0.048, and erythrocyte sedimentation rate, p = 0.019), systolic (p = 0.044), and diastolic arterial blood pressure (p = 0.003). Regarding body composition, there was an increase in total body water % (p = 0.035) with redistribution of extracellular water % (p = 0.030) and intracellular water % (p = 0.049). In the control group, there was a reduction in fat mass % (p = 0.017) and extracellular water % (p = 0.047). Therefore, this OFS may represent a valid adjunct therapy to counteract comorbidities related to uremia.


Assuntos
Antioxidantes/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais , Extratos Vegetais/administração & dosagem , Insuficiência Renal Crônica/dietoterapia , Idoso , Idoso de 80 Anos ou mais , Antioxidantes/efeitos adversos , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Suplementos Nutricionais/efeitos adversos , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento
7.
Diabetes Metab Syndr ; 14(5): 1017-1025, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32634716

RESUMO

BACKGROUND AND AIMS: Currently there is limited knowledge on medical comorbidities and COVID-19; we conducted a systematic review and meta-analysis to evaluate the impact of various morbidities on serious events in COVID 19. METHODS: PubMed, Cochrane Central Register of Clinical Trials were searched on April 28, 2020, to extract published articles that reported the outcomes of COVID-19 patients. The search terms were "coronavirus" and "clinical characteristics". ICU admission, mechanical ventilation, ARDS, Pneumonia, death was considered serious events. The comorbidities assessed in the study were Hypertension (HTN), Diabetes mellitus (DM), Cardiovascular diseases (CVD), Chronic obstructive pulmonary disease (COPD) and Chronic Kidney disease (CKD). Subsequently, comparisons between comorbidity patient group and the non-comorbidity patient groups, in terms of serious events were made using the pooled estimates of odd's ratio (OR) RESULTS: We identified 688 published results and 16 studies with 3994 patients were included in the systematic review. Serious events were seen in 526(13.16%) patients. Presence of hypertension with OR 2.95, diabetes mellitus with OR 3.07, Cardio vascular disease with OR 4.58, COPD with OR 6.66 and Chronic kidney disease with OR 5.32 had significant association in patients with COVID 19 on having serious events. Presence of diabetes mellitus (OR 2.78)) had a significant impact on death in COVID 19 patients with a p-value 0.004. CONCLUSIONS: Presence of medical comorbidities in COVID-19 leads to higher risk of developing serious events i.e. ICU admission, mechanical intubation and mortality. The presence of Diabetes mellitus has a significant impact on mortality rate in COVID-19 patients.


Assuntos
Betacoronavirus/isolamento & purificação , Doenças Cardiovasculares/mortalidade , Infecções por Coronavirus/mortalidade , Diabetes Mellitus/mortalidade , Hipertensão/mortalidade , Pneumonia Viral/mortalidade , Doença Pulmonar Obstrutiva Crônica/mortalidade , Insuficiência Renal Crônica/mortalidade , Doenças Cardiovasculares/fisiopatologia , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Diabetes Mellitus/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Hipertensão/fisiopatologia , Incidência , Índia , Unidades de Terapia Intensiva/estatística & dados numéricos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Taxa de Sobrevida
8.
Ren Fail ; 42(1): 733-739, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32718215

RESUMO

BACKGROUND: Patients with chronic kidney disease (CKD) require specialized management. However, the current situation of CKD management is unclear during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to investigate the influence of the COVID-19 on kidney patients' follow-ups. METHODS: In April 2020, we included patients who underwent kidney biopsy from January 2017 to December 2019 in a referral center of China, and then initiated a survey via telephone on different aspects of follow-up during the COVID-19 pandemic. We collected and analyzed demographic data, diagnoses, follow-up conditions, and telemedicine experience. RESULTS: We reached 1190 CKD patients with confirmed kidney biopsies, and included 1164 patients for analysis after excluding those on dialysis. None of our patients have had COVID-19, although more than 50% of them were complicated with other comorbidities, and over 40% were currently using immunosuppressive treatments. Face-to-face clinic visits were interrupted in 836 (71.82%) participants. Medicine adjustments and routine laboratory examinations were delayed or made irregular in about 60% of patients. To continue their follow-ups, 255 (21.90%) patients utilized telemedicine, and about 80% of them were satisfied with the experience. The proportion of telemedicine users was significantly higher in patients with immunosuppressive treatments than those without (31.88% vs. 17.12%, p < 0.001). CONCLUSION: The risk of COVID-19 was mitigated in patients with CKD and other co-existing risk factors when proper protection was utilized. The routine medical care was disrupted during the pandemic, and telemedicine could be a reasonable alternative method.


Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Infecções por Coronavirus/epidemiologia , Controle de Infecções/métodos , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/patologia , Adulto , Biópsia por Agulha , China/epidemiologia , Comorbidade , Infecções por Coronavirus/diagnóstico , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Incidência , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Inquéritos e Questionários
9.
Life Sci ; 257: 118061, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32652137

RESUMO

Obesity is an independent risk factor for the development of chronic kidney disease. The pathophysiology of the obesity-induced kidney injury is complex, but evidence suggests the involvement of reduced adiponectin levels and signaling. We investigated the extent by which adiponectin contributes to the establishment and progression of renal disease in wild type (WT) and adiponectin null (adipoKO) mice fed a control or a high-fat diet (HFD) for 16 weeks. HFD induced obesity, kidney hypertrophy, albuminuria, renal lipid accumulation and decreased nephrin expression in both mice genotypes. Notably, HFD in adipoKO mice exacerbated progression of albuminuria in comparison to WT mice. In addition, lack of adiponectin per se increased kidney weight, reduced nephrin levels, up-regulated Fabp4 expression, reduced Cpt1a expression and increased miR-130 levels in kidney. Our results demonstrate that lack of adiponectin combined with a HFD contributes to accelerated kidney dysfunction.


Assuntos
Adiponectina/genética , Albuminúria/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Obesidade/complicações , Insuficiência Renal Crônica/fisiopatologia , Albuminúria/genética , Animais , Carnitina O-Palmitoiltransferase/genética , Modelos Animais de Doenças , Progressão da Doença , Proteínas de Ligação a Ácido Graxo/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética , Insuficiência Renal Crônica/genética
10.
Medicine (Baltimore) ; 99(21): e20234, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481298

RESUMO

BACKGROUND: The prevalence of chronic kidney disease (CKD) has been rapidly increasing and has become one of the most concerned global health problems. It is of good importance to improve therapeutic efficiency of CKD and delay disease progression to end stage renal disease (ESRD). Traditional Chinese Medicine (TCM) is a widely used complementary therapy for patients with CKD. The aim of this study is to evaluate whether basic treatment combined with Chinese herbs mixture Qi Gui Yi Shen decoction could achieve better therapeutic effect on CKD patients. METHODS: To determine whether traditional Chinese medicine Qi Gui Yi Shen decoction could achieve better therapeutic effect, we will conduct a randomized controlled trial. A total of 100 CKD patients that meet the inclusion criteria will be enrolled and divided into 2 groups: Qi Gui Yi Shen group (QGYS group) and placebo group. Each group will receive 6-monthly basic treatment in combination with TCM or placebo 3 times per day. Efficacy of Qi Gui Yi Shen decoction is evaluated by analyzing renal function and TCM symptoms, other efficacy assessments include serum level of PAI-I, expression of transforming growth factor beta1 (TGF-beta1). Routine blood count, plasma albumin (ALB), and alanine transaminase (ALT) are evaluated as side effect and safety profile. DISCUSSION: The results from the clinical trial will provide evidence for the effectiveness and safety of Qi Gui Yi Shen Decoction as a treatment for CKD patients. Furthermore, this will propose a new theory and method for CKD treatment. TRIAL REGISTRATION: Registered with Chinese Clinical Trials Registry at www.chictr.org. (Registration number: ChiCTR1900021622) on 1 March 2019.


Assuntos
Terapia Combinada/métodos , Medicina Tradicional Chinesa/métodos , Insuficiência Renal Crônica/tratamento farmacológico , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/prevenção & controle , Masculino , Medicina Tradicional Chinesa/efeitos adversos , Pessoa de Meia-Idade , Placebos/administração & dosagem , Prevalência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Segurança , Albumina Sérica/análise , Fator de Crescimento Transformador beta1/sangue , Adulto Jovem
11.
Clin Nephrol ; 94(2): 70-77, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32567541

RESUMO

AIMS: Seven theories address the evolution of secondary hyperparathyroidism (SHPT) as chronic kidney disease (CKD) progresses. The tradeoff-in-the-nephron hypothesis states that the plasma parathyroid hormone ([PTH]) concentration rises because an increased phosphate concentration in the cortical distal nephron ([P]CDN) reduces the ionized calcium concentration in that segment. In the present study, we compared this hypothesis to its predecessors. MATERIALS AND METHODS: We studied 30 patients with estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73m2 (mean 29.5). To examine historic theories, we performed regressions of [PTH] on plasma concentrations of ionized calcium, phosphorus, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and fibroblast growth factor 23, and on calcium excreted per volume of filtrate (ECa/Ccr). To assess the tradeoff-in-the-nephron hypothesis, we examined regressions of [PTH] on 100/eGFR and phosphorus excreted per volume of filtrate (EP/Ccr). RESULTS: Regressions pertinent to historic theories yielded significant direct relationships between [PTH] and both ECa/Ccr and [FGF23], but neither association supported the theory to which it pertained. [PTH] varied directly with 100/eGFR and with EP/Ccr, a surrogate for [P]CDN. EP/Ccr correlated strongly with 100/eGFR. CONCLUSIONS: The only theory of SHPT that our data support is the tradeoff-in-the-nephron hypothesis. Other theories are not supported.


Assuntos
Hiperparatireoidismo Secundário , Insuficiência Renal Crônica , Taxa de Filtração Glomerular , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/complicações , Hiperparatireoidismo Secundário/fisiopatologia , Néfrons/fisiopatologia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia
12.
PLoS One ; 15(6): e0234825, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32542048

RESUMO

BACKGROUND: Few studies examined the individual and conjoint associations of accelerometer-measured physical activity (PA) and sedentary times with the prevalence of chronic kidney disease (CKD) among older adults. METHODS: We evaluated 1,268 Framingham Offspring Study participants (mean age 69.2 years, 53.8% women) between 2011 and 2014. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.732 and/or urine albumin-to-creatinine ratio (UACR) ≥25/35 µg/mg (men/women). We used multivariable logistic regression models to relate time spent being sedentary and active with the odds of CKD. We then performed compositional data analysis to estimate the change in the eGFR and UACR when a fixed proportion of time in one activity behavior (among the following: moderate to vigorous physical activity [MVPA], light intensity physical activity [LIPA], and sedentary) is reallocated to another activity behavior. RESULTS: Overall, 258 participants had prevalent CKD (20.4%; 120 women). Higher total PA ([MVPA+LIPA], adjusted-odds ratio [OR] per 30 minutes/day increase, 0.86; 95% CI, 0.78-0.96) and higher LIPA (OR per 30 minutes/day increase, 0.87; 95% CI, 0.76-0.99) were associated with lower odds of CKD. Additionally, higher sedentary time (OR per 30 minutes/day increase, 1.16; 95% CI, 1.04-1.29) was associated with higher odds of CKD. Reallocating 5% of the time from LIPA to sedentary was associated with the largest predicted difference in eGFR (-1.06 ml/min/1.73m2). Reallocating 1% of time spent in MVPA to sedentary status predicted the largest difference in UACR (14.37 µg/mg). CONCLUSION: The findings suggest that increasing LIPA and maintaining MVPA at the expense of sedentary time may be associated with a lower risk of CKD in community-based older adults.


Assuntos
Acelerometria/instrumentação , Exercício Físico , Estudos Longitudinais , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Comportamento Sedentário , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino
13.
Lancet Gastroenterol Hepatol ; 5(10): 918-926, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32531259

RESUMO

BACKGROUND: There is a medical need for highly effective, safe, and well tolerated treatments for patients infected with hepatitis C virus (HCV) with severe renal impairment. We investigated the safety and efficacy of sofosbuvir with ribavirin or ledipasvir combined with sofosbuvir in a prospective study of patients with genotype 1 or 3 HCV infection and stage 4-5 chronic kidney disease (creatinine clearance by Cockcroft-Gault ≤30 mL/min) who were not on dialysis. METHODS: This phase 2b, open-label, non-randomised, multicentre study in the USA and New Zealand investigated three sequentially enrolled cohorts of patients. Patients were recruited from ten hospitals and clinical research centres and were included if they had genotype 1 or 3 HCV infection, a creatinine clearance less than or equal to 30 mL/min, and were not on dialysis. In cohorts 1 and 2, patients received sofosbuvir (200 mg in cohort 1 and 400 mg in cohort 2) plus ribavirin 200 mg once per day for 24 weeks. In cohort 3, 18 patients received ledipasvir combined with sofosbuvir (90 mg ledipasvir and 400 mg sofosbuvir) once per day for 12 weeks. The primary efficacy endpoint was the proportion of patients achieving sustained virological response 12 weeks after the end of treatment (SVR12). Safety and pharmacokinetic data were also collected. The trial is registered with ClinicalTrials.gov, number NCT01958281, and is completed. FINDINGS: This study was done between Oct 7, 2013, and Oct 29, 2017. In the sofosbuvir plus ribavirin cohorts, 32 patients were screened, of whom 20 were enrolled and assessed for efficacy and safety (ten patients in each cohort). In the ledipasvir plus sofosbuvir cohort, 33 patients were screened, of whom 18 were enrolled and assessed for treatment efficacy and safety. Four (40%, 95% CI 12-74) of ten patients in cohort 1 and six (60%, 26-88) of ten patients in cohort 2 achieved SVR12. All 18 (100%, 82-100) patients in cohort 3 achieved SVR12. Adverse events were mostly mild or moderate in severity. The most commonly reported adverse events overall were headache (eight [21%] of 38 patients), anaemia (seven [18%] of 38 patients), and fatigue (six [16%] of 38 patients). Eight patients had serious adverse events, none of which were treatment related. There were no treatment-related cardiac events or clinically significant changes in echocardiographic parameters or creatinine clearance by Cockcroft-Gault. INTERPRETATION: In this phase 2b study, ledipasvir combined with sofosbuvir for 12 weeks was safe and effective in patients with genotype 1 HCV infection and stage 4-5 chronic kidney disease who were not on dialysis. FUNDING: Gilead Sciences.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepatite C/tratamento farmacológico , Ensaios Clínicos Controlados não Aleatórios como Assunto/métodos , Insuficiência Renal Crônica/complicações , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Uridina Monofosfato/análogos & derivados , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/farmacocinética , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Benzimidazóis/farmacocinética , Quimioterapia Combinada/métodos , Feminino , Fluorenos/administração & dosagem , Fluorenos/efeitos adversos , Fluorenos/farmacocinética , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Insuficiência Renal Crônica/classificação , Insuficiência Renal Crônica/fisiopatologia , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Ribavirina/farmacocinética , Segurança , Sofosbuvir/administração & dosagem , Sofosbuvir/efeitos adversos , Sofosbuvir/farmacocinética , Resultado do Tratamento , Estados Unidos/epidemiologia , Uridina Monofosfato/administração & dosagem , Uridina Monofosfato/efeitos adversos , Uridina Monofosfato/farmacocinética , Uridina Monofosfato/uso terapêutico , Carga Viral/efeitos dos fármacos
14.
N Engl J Med ; 382(26): 2504-2513, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32579811

RESUMO

BACKGROUND: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known. METHODS: In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULTS: Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m2; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m2 per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group. CONCLUSIONS: In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932.).


Assuntos
Alopurinol/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Supressores da Gota/uso terapêutico , Ácido Úrico/sangue , Xantina Oxidase/antagonistas & inibidores , Idoso , Alopurinol/efeitos adversos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Feminino , Supressores da Gota/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Sistema Renina-Angiotensina , Falha de Tratamento
15.
PLoS One ; 15(6): e0235077, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32569271

RESUMO

Proteinuria and hyperphosphatemia are risk factors for cardiovascular disease in patients with chronic kidney disease (CKD). Although the interaction between proteinuria and the serum phosphate level is well established, the mechanistic link between the two, particularly the extent to which this interaction is mediated by phosphate-regulating factors, remains poorly understood. In this study, we examined the association between proteinuria and the serum phosphate level, as well as potential mediators, including circulating fibroblast growth factor (FGF23)/klotho, the 24-h urinary phosphate excretion rate to glomerular filtration rate ratio (EP/GFR), and the 24-h tubular phosphate reabsorption rate to GFR ratio (TRP/GFR). The analyses were performed with data from 1793 patients in whom 24-h urine protein and phosphate, serum phosphate, FGF23, and klotho levels were measured simultaneously, obtained from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Multivariable linear regression and mediation analyses were performed. Total, direct, and indirect effects were also estimated. Patients with high serum phosphate levels were found to be more likely to exhibit greater proteinuria, higher FGF23 levels, and lower klotho levels. The 24-h EP/GFR increased and the 24-h TRP/GFR decreased with increasing proteinuria and CKD progression. Simple mediation analyses showed that 15.4% and 67.9% of the relationship between proteinuria and the serum phosphate level were mediated by the FGF23/klotho ratio and 24-h EP/GFR, respectively. Together, these two factors accounted for 73.1% of the relationship between serum markers. These findings suggest that proteinuria increases the 24-h EP/GFR via the FGF23/klotho axis as a compensatory mechanism for the increased phosphate burden well before the reduction in renal function is first seen.


Assuntos
Fosfatos/sangue , Proteinúria/sangue , Insuficiência Renal Crônica/sangue , Estudos de Coortes , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Taxa de Filtração Glomerular , Glucuronidase/sangue , Humanos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Insuficiência Renal Crônica/fisiopatologia , República da Coreia , Resultado do Tratamento
16.
Am J Physiol Renal Physiol ; 319(1): F106-F114, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32508113

RESUMO

Thirty-seven million people in the United States are estimated to have chronic kidney disease (CKD). Hypertension (HTN) is the second leading risk factor for developing kidney disease. A recent study reported that increasing levels of ß-hydroxybutyrate levels by administration of its precursor, 1,3-butanediol, decreased salt-induced HTN in male Dahl salt-sensitive (S) rats. The effect of 1,3-butanediol on hypertensive kidney disease in female rats or the absence of high salt has not been investigated. This study tested the hypothesis that 1,3-butanediol attenuates HTN and the progression of CKD in female S-SHR(11) rats. The S-SHR(11) strain is a congenic rat strain generated from genetic modification of the Dahl S rat, previously characterized as a model of accelerated renal disease. Rats received 1,3-butanediol (20% via drinking water) or control for 10 wk and were maintained on a 0.3% NaCl rodent diet (n = 12-14 rats/group). Blood pressure was measured after 6 and 9 wk of treatment by tail-cuff plethysmography; after 10 wk, urine and tissues were collected. Activity of the treatment was confirmed by measuring plasma ß-hydroxybutyrate levels, which were greater in the treated group. The 1,3-butanediol-treated group had lower systolic blood pressure, proteinuria, plasma creatinine, and renal fibrosis after 9 wk of treatment compared with controls. The treated group had significantly smaller spleens and increased the renal anti-inflammatory molecules interleukin-10 and granulocyte-macrophage colony-stimulating factor, suggesting reduced inflammation. The present data demonstrate that 1,3-butanediol lowers blood pressure and renal injury in female rats and could be a novel nutritional intervention for the treatment of CKD.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Butileno Glicóis/uso terapêutico , Hipertensão/tratamento farmacológico , Rim/efeitos dos fármacos , Insuficiência Renal Crônica/tratamento farmacológico , Animais , Butileno Glicóis/farmacologia , Progressão da Doença , Feminino , Hipertensão/fisiopatologia , Rim/fisiopatologia , Ratos , Ratos Endogâmicos SHR , Insuficiência Renal Crônica/fisiopatologia
17.
Clin Sci (Lond) ; 134(12): 1333-1356, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32542397

RESUMO

Chronic kidney disease (CKD) is a relentlessly progressive disease with a very high mortality mainly due to cardiovascular complications. Endothelial dysfunction is well documented in CKD and permanent loss of endothelial homeostasis leads to progressive organ damage. Most of the vast endothelial surface area is part of the microcirculation, but most research in CKD-related cardiovascular disease (CVD) has been devoted to macrovascular complications. We have reviewed all publications evaluating structure and function of the microcirculation in humans with CKD and animals with experimental CKD. Microvascular rarefaction, defined as a loss of perfused microvessels resulting in a significant decrease in microvascular density, is a quintessential finding in these studies. The median microvascular density was reduced by 29% in skeletal muscle and 24% in the heart in animal models of CKD and by 32% in human biopsy, autopsy and imaging studies. CKD induces rarefaction due to the loss of coherent vessel systems distal to the level of smaller arterioles, generating a typical heterogeneous pattern with avascular patches, resulting in a dysfunctional endothelium with diminished perfusion, shunting and tissue hypoxia. Endothelial cell apoptosis, hypertension, multiple metabolic, endocrine and immune disturbances of the uremic milieu and specifically, a dysregulated angiogenesis, all contribute to the multifactorial pathogenesis. By setting the stage for the development of tissue fibrosis and end organ failure, microvascular rarefaction is a principal pathogenic factor in the development of severe organ dysfunction in CKD patients, especially CVD, cerebrovascular dysfunction, muscular atrophy, cachexia, and progression of kidney disease. Treatment strategies for microvascular disease are urgently needed.


Assuntos
Doenças Cardiovasculares/epidemiologia , Microvasos/patologia , Insuficiência Renal Crônica/epidemiologia , Animais , Doenças Cardiovasculares/fisiopatologia , Comorbidade , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Microcirculação , Microvasos/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia
18.
Vasc Health Risk Manag ; 16: 167-180, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32494148

RESUMO

Vascular calcification (VC) is a life-threatening state in chronic kidney disease (CKD). High cardiovascular mortality and morbidity of CKD cases may root from medial VC promoted by hyperphosphatemia. Vascular calcification is an active, highly regulated, and complex biological process that is mediated by genetics, epigenetics, dysregulated form of matrix mineral metabolism, hormones, and the activation of cellular signaling pathways. Moreover, gut microbiome as a source of uremic toxins (eg, phosphate, advanced glycation end products and indoxyl-sulfate) can be regarded as a potential contributor to VC in CKD. Here, an update on different cellular and molecular processes involved in VC in CKD is discussed to elucidate the probable therapeutic pathways in the future.


Assuntos
Vasos Sanguíneos/metabolismo , Rim/metabolismo , Eliminação Renal , Insuficiência Renal Crônica/complicações , Calcificação Vascular/etiologia , Remodelação Vascular , Animais , Vasos Sanguíneos/patologia , Vasos Sanguíneos/fisiopatologia , Humanos , Rim/fisiopatologia , Prognóstico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Calcificação Vascular/metabolismo , Calcificação Vascular/mortalidade , Calcificação Vascular/fisiopatologia
19.
Eur J Endocrinol ; 183(3): 233-244, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32508317

RESUMO

Background: Patients with chronic kidney disease (CKD) have a high risk of premature cardiovascular diseases (CVD) and show increased mortality. Pro-neurotensin (Pro-NT) was associated with metabolic diseases and predicted incident CVD and mortality. However, Pro-NT regulation in CKD and its potential role linking CKD and mortality have not been investigated, so far. Methods: In a central lab, circulating Pro-NT was quantified in three independent cohorts comprising 4715 participants (cohort 1: patients with CKD; cohort 2: general population study; and cohort 3: non-diabetic population study). Urinary Pro-NT was assessed in part of the patients from cohort 1. In a 4th independent cohort, serum Pro-NT was further related to mortality in patients with advanced CKD. Tissue-specific Nts expression was further investigated in two mouse models of diabetic CKD and compared to non-diabetic control mice. Results: Pro-NT significantly increased with deteriorating renal function (P < 0.001). In meta-analysis of cohorts 1-3, Pro-NT was significantly and independently associated with estimated glomerular filtration rate (P ≤ 0.002). Patients in the middle/high Pro-NT tertiles at baseline had a higher all-cause mortality compared to the low Pro-NT tertile (Hazard ratio: 2.11, P = 0.046). Mice with severe diabetic CKD did not show increased Nts mRNA expression in different tissues compared to control animals. Conclusions: Circulating Pro-NT is associated with impaired renal function in independent cohorts comprising 4715 subjects and is related to all-cause mortality in patients with end-stage kidney disease. Our human and rodent data are in accordance with the hypotheses that Pro-NT is eliminated by the kidneys and could potentially contribute to increased mortality observed in patients with CKD.


Assuntos
Neurotensina/metabolismo , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos Transversais , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Rim/metabolismo , Rim/fisiopatologia , Estudos Longitudinais , Masculino , Metanálise como Assunto , Camundongos , Pessoa de Meia-Idade , Neurotensina/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia
20.
Am J Physiol Renal Physiol ; 319(2): F215-F228, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32463727

RESUMO

Nitric oxide synthase inhibition by Nω-nitro-l-arginine methyl ester (l-NAME) plus a high-salt diet (HS) is a model of chronic kidney disease (CKD) characterized by marked hypertension and renal injury. With cessation of treatment, most of these changes subside, but progressive renal injury develops, associated with persistent low-grade renal inflammation. We investigated whether innate immunity, and in particular the NF-κB system, is involved in this process. Male Munich-Wistar rats received HS + l-NAME (32 mg·kg-1·day-1), whereas control rats received HS only. Treatment was ceased after week 4 when 30 rats were studied. Additional rats were studied at week 8 (n = 30) and week 28 (n = 30). As expected, HS + l-NAME promoted severe hypertension, albuminuria, and renal injury after 4 wk of treatment, whereas innate immunity activation was evident. After discontinuation of treatments, partial regression of renal injury and inflammation occurred, along with persistence of innate immunity activation at week 8. At week 28, glomerular injury worsened, while renal inflammation persisted and renal innate immunity remained activated. Temporary administration of the NF-κB inhibitor pyrrolidine dithiocarbamate, in concomitancy with the early 4-wk HS + l-NAME treatment, prevented the development of late renal injury and inflammation, an effect that lasted until the end of the study. Early activation of innate immunity may be crucial to the initiation of renal injury in the HS + l-NAME model and to the autonomous progression of chronic nephropathy even after cessation of the original insult. This behavior may be common to other conditions leading to CKD.


Assuntos
Arginina/análogos & derivados , Glomérulos Renais/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Insuficiência Renal Crônica/tratamento farmacológico , Animais , Arginina/metabolismo , Inibidores Enzimáticos/farmacologia , Rim/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Nefrite/fisiopatologia , Ratos Wistar , Insuficiência Renal Crônica/fisiopatologia , Cloreto de Sódio/farmacologia , Cloreto de Sódio na Dieta/farmacologia
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