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1.
PLoS One ; 16(1): e0244779, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33400721

RESUMO

BACKGROUND: Currently, the SARS-CoV-2 promptly spread across China and around the world. However, there are controversies about whether preexisting chronic kidney disease (CKD) and acute kidney injury complication (AKI) are involved in the COVID-19 pandemic. MEASUREMENTS: Studies reported the kidney outcomes in different severity of COVID-19 were included in this study. Standardized mean differences or odds ratios were calculated by employing Review Manager meta-analysis software. RESULTS: Thirty-six trials were included in this systematic review with a total of 6395 COVID-19 patients. The overall effects indicated that preexisting CKD (OR = 3.28), complication of AKI (OR = 11.02), serum creatinine (SMD = 0.68), abnormal serum creatinine (OR = 4.86), blood urea nitrogen (SMD = 1.95), abnormal blood urea nitrogen (OR = 6.53), received continuous renal replacement therapy (CRRT) (OR = 23.63) were significantly increased in severe group than that in nonsevere group. Additionally, the complication of AKI (OR = 13.92) and blood urea nitrogen (SMD = 1.18) were remarkably elevated in the critical group than that in the severe group. CONCLUSIONS: CKD and AKI are susceptible to occur in patients with severe COVID-19. CRRT is applied frequently in severe COVID-19 patients than that in nonsevere COVID-19 patients. The risk of AKI is higher in the critical group than that in the severe group.


Assuntos
Lesão Renal Aguda/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Lesão Renal Aguda/sangue , Nitrogênio da Ureia Sanguínea , China/epidemiologia , Creatinina/sangue , Humanos , Razão de Chances , Pandemias , Insuficiência Renal Crônica/sangue , Resultado do Tratamento
2.
Yonsei Med J ; 62(1): 41-49, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33381933

RESUMO

PURPOSE: Oral adsorbents delay disease progression and improve uremic symptoms in patients with chronic kidney disease (CKD). DW-7202 is a newly developed oral adsorbent with high adsorptive selectivity for uremic toxins. We evaluated patient preference for and adherence to DW-7202 versus AST-120 therapy and compared treatment efficacy and safety in patients with pre-dialysis CKD. MATERIALS AND METHODS: A seven-center, randomized, open-label, two-way crossover, active-controlled, phase IV clinical trial was conducted. Patients with stable CKD were randomly assigned to receive DW-7202 (capsule type) or AST-120 (granule type) for 12 weeks. The groups then switched to the other adsorbent and took it for the next 12 weeks. Patient preference was the primary outcome. Secondary outcomes included changes in estimated glomerular filtration rate (eGFR) and serum creatinine, cystatin C, and indoxyl sulfate (IS) levels. RESULTS: Significantly more patients preferred DW-7202 than AST-120 (p<0.001). Patient adherence improved after switching from AST-120 to DW-7202; there was no apparent change in adherence after switching from DW-7202 to AST-120. Changes in eGFR and serum creatinine, cystatin C, and IS levels were not significantly different according to adsorbent type. There was also no significant difference in the incidences of adverse events during treatment with DW-7202 and AST-120. CONCLUSION: DW-7202 can be considered as an alternative to AST-120 in patients who cannot tolerate or show poor adherence to granule type adsorbents. Further studies to evaluate factors affecting patient preferences and improved adherence are warranted (Clinical trial registration No. NCT02681952).


Assuntos
Insuficiência Renal Crônica/tratamento farmacológico , Adsorção , Carbono/administração & dosagem , Carbono/uso terapêutico , Creatinina/sangue , Estudos Cross-Over , Cistatina C/sangue , Progressão da Doença , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Indicã/sangue , Masculino , Pessoa de Meia-Idade , Óxidos/administração & dosagem , Óxidos/uso terapêutico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Resultado do Tratamento
3.
Sci Rep ; 10(1): 20202, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33214633

RESUMO

Alterations in hemodialysis patients' serum trace metals have been documented. Early studies addressing associations levels of serum trace metals with erythropoietic responses and/or hematocrit generated mixed results. These studies were conducted prior to current approaches for erythropoiesis stimulating agent (ESA) drug dosing guidelines or without consideration of inflammation markers (e.g. hepcidin) important for regulation of iron availability. This study sought to determine if the serum trace metal concentrations of incident or chronic hemodialysis patients associated with the observed ESA response variability and with consideration to ESA dose response, hepcidin, and high sensitivity C-reactive protein levels. Inductively-coupled plasma-mass spectrometry was used to measure 14 serum trace metals in 29 incident and 79 prevalent dialysis patients recruited prospectively. We compared these data to three measures of ESA dose response, sex, and dialysis incidence versus dialysis prevalence. Hemoglobin was negatively associated with ESA dose and cadmium while positively associated with antimony, arsenic and lead. ESA dose was negatively associated with achieved hemoglobin and vanadium while positively associated with arsenic. ESA response was positively associated with arsenic. Vanadium, nickel, cadmium, and tin were increased in prevalent patients. Manganese was increased in incident patients. Vanadium, nickel, and arsenic increased with time on dialysis while manganese decreased. Changes in vanadium and manganese were largest and appeared to have some effect on anemia. Incident and prevalent patients' chromium and antimony levels exceeded established accepted upper limits of normal.


Assuntos
Anemia/sangue , Hematínicos/administração & dosagem , Falência Renal Crônica/sangue , Diálise Renal , Insuficiência Renal Crônica/sangue , Oligoelementos/sangue , Anemia/tratamento farmacológico , Anemia/etiologia , Feminino , Ferritinas/sangue , Hemoglobina A Glicada/análise , Hematínicos/uso terapêutico , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia
4.
Sci Rep ; 10(1): 17585, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067501

RESUMO

The relationship between serum uric acid (SUA) and cardiovascular (CV) mortality in patients with chronic kidney disease (CKD) has been described as either a J- or U-shaped function. However, its effect in non-diabetic CKD (and varying severities of CKD) remains unclear. We analyzed the database of the National Health and Nutrition Examination Survey, USA, from the years 1999 to 2010. We then grouped the subjects into 4 categories according to their SUA levels: (a) < 5 mg/dl, (b) 5-7 mg/dl, (c) 7-9 mg/dl and (d) ≥ 9 mg/dl. For mortality comparison purposes (CV related, cancer related and all-cause mortality), we set the SUA group of 5-7 mg/dl as the reference. We also separated this population into moderate (stage 3) and severe (stages 4 and 5) CKD. A total of 1860 participants were included in this study. Results showed that the group with the lowest SUA levels (< 5 mg/dl), were the least male gender (19.25%), had the lowest body mass index (26.41(95% CI = 25.66-27.16) kg/m2), highest systolic blood pressure (139.02 (95% CI 135.72-142.32) mmHg), highest high-density cholesterol (59.55 (95% CI 57.37-61.74) mg/dl), lowest blood glucose (95.46 (95% CI 93.16-97.76) mg/dl), highest total cholesterol (210.31 (95% CI 203.36-217.25) mg/dl), lowest serum albumin (4.09 (95% CI 4.04-4.14) g/dl), highest estimated glomerular filtration rate (eGFR) (47.91 (95% CI 45.45-50.49) ml/min/1.732m2), least history of hypertension (54.4%), and least total energy intake (1643.7 (95% CI 1536.13-1751.27) kcal/day). In the group with SUA ≥ 9 mg/dl, patients had higher all-cause mortality (HR = 2.15) whatever their baseline CVD status. In non-DM CKD patients with a CVD history, the group with SUA ≥ 9 mg/dl had the highest all-cause mortality (HR = 5.39), CVD mortality (HR = 8.18) and CVD or cancer (HR = 8.25) related mortality. In non-DM patients with severe CKD (eGFR < 30 ml/min/1.732m2), the group with SUA < 5 had a significantly increased all-cause mortality. On the contrary, in non-DM patients with moderate CKD (eGFR = 30-60 ml/min/1.832m2), the group with SUA ≥ 9 had a significantly increased all-cause mortality. In moderate non-DM CKD, SUA ≥ 9 mg/dl is associated with higher all-cause mortality. However, once progressing to severe non-DM CKD, SUA < 5 mg/dl is associated with higher all-cause mortality (even though it has the least risk factors for metabolic syndrome).


Assuntos
Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/mortalidade , Ácido Úrico/análise , Idoso , Índice de Massa Corporal , Doenças Cardiovasculares/metabolismo , Bases de Dados Factuais , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipertensão/metabolismo , Masculino , Síndrome Metabólica/metabolismo , Inquéritos Nutricionais , Insuficiência Renal Crônica/sangue , Fatores de Risco , Estados Unidos , Ácido Úrico/sangue
5.
PLoS One ; 15(10): e0240446, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33108385

RESUMO

The uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) accumulate in patients with chronic kidney disease (CKD) as a consequence of altered gut microbiota metabolism and a decline in renal excretion. Despite of solid experimental evidence for nephrotoxic effects, the impact of uremic toxins on the progression of CKD has not been investigated in representative patient cohorts. In this analysis, IS and pCS serum concentrations were measured in 604 pediatric participants (mean eGFR of 27 ± 11 ml/min/1.73m2) at enrolment into the prospective Cardiovascular Comorbidity in Children with CKD study. Associations with progression of CKD were analyzed by Kaplan-Meier analyses and Cox proportional hazard models. During a median follow up time of 2.2 years (IQR 4.3-0.8 years), the composite renal survival endpoint, defined as 50% loss of eGFR, or eGFR <10ml/min/1.73m2 or start of renal replacement therapy, was reached by 360 patients (60%). Median survival time was shorter in patients with IS and pCS levels in the highest versus lowest quartile for both IS (1.5 years, 95%CI [1.1,2.0] versus 6.0 years, 95%CI [5.0,8.4]) and pCS (1.8 years, 95%CI [1.5,2.8] versus 4.4 years, 95%CI [3.4,6.0]). Multivariable Cox regression disclosed a significant association of IS, but not pCS, with renal survival, which was independent of other risk factors including baseline eGFR, proteinuria and blood pressure. In this exploratory analysis we provide the first data showing a significant association of IS, but not pCS serum concentrations with the progression of CKD in children, independent of other known risk factors. In the absence of comorbidities, which interfere with serum levels of uremic toxins, such as diabetes, obesity and metabolic syndrome, these results highlight the important role of uremic toxins and accentuate the unmet need of effective elimination strategies to lower the uremic toxin burden and abate progression of CKD.


Assuntos
Biomarcadores/sangue , Indicã/sangue , Insuficiência Renal Crônica/sangue , Adolescente , Criança , Cresóis/sangue , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Insuficiência Renal Crônica/mortalidade , Ésteres do Ácido Sulfúrico/sangue , Análise de Sobrevida
7.
PLoS One ; 15(9): e0238421, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877465

RESUMO

BACKGROUND: Inflammation plays a pivotal role in the pathogenesis of chronic kidney disease (CKD). Significant association between serum albumin-to-globulin (AG) ratio and inflammation led us to investigate the prognostic value of serum AG ratio for incident CKD. METHODS: The predictive value of serum AG ratio, white blood cell (WBC), and C-reactive protein (CRP) for CKD development was assessed in 8,057 non-CKD participants from a community-based, prospective cohort in Korea. Serum AG ratio was calculated by following equation: serum albumin (g/L)/[serum total protein (g/L)-serum albumin (g/L)]. Incident CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 and/or proteinuria of more than 1+ on dipstick. RESULTS: Median serum AG ratio was 1.38 (interquartile range, 1.28-1.52). During a mean follow-up duration of 9.1±3.7 years, 1,732 participants (21.5%) developed CKD. In a multivariable Cox analysis, a low serum AG ratio was significantly associated with an increased risk of incident CKD (Q1, serum AG ratio <1.26: hazard ratio [HR] = 1.651, 95% confidence interval [CI] = 1.406-1.938, Q5 as reference; per 0.2 decrease, HR = 1.170, 95% CI = 1.109-1.234). Serum AG ratio was the only indicator to improve the predictability of CKD development (net reclassification index = 0.158, P <0.001; integrated discrimination improvement = 0.005, P <0.001), compared with WBC or CRP. CONCLUSIONS: This study demonstrates that low serum AG ratio is an independent predictor for CKD development and exhibits a stronger predictive value than other inflammatory markers. These findings suggest that determining serum AG ratio may be more valuable for predicting adverse kidney outcomes in non-CKD populations.


Assuntos
Insuficiência Renal Crônica/fisiopatologia , Albumina Sérica Humana/análise , Soroglobulinas/análise , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Creatinina/sangue , Progressão da Doença , Feminino , Globulinas/análise , Globulinas/metabolismo , Taxa de Filtração Glomerular , Humanos , Inflamação , Rim/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Proteinúria , Insuficiência Renal Crônica/sangue , República da Coreia , Medição de Risco , Fatores de Risco , Albumina Sérica
8.
J Urol ; 204(6): 1305-1311, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32924780

RESUMO

PURPOSE: Most international practice guidelines recommend screening for chronic kidney disease among older men with lower urinary tract symptoms. However, prior studies supporting these guidelines are insufficient due to incomplete assessments of kidney function and inadequate adjustment for confounding factors. MATERIALS AND METHODS: We conducted a cross-sectional study among 5,530 American men older than 65 years in the multicenter Osteoporotic Fractures in Men Study. Chronic kidney disease was defined per international guidelines as estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 based on serum creatinine or cystatin C, or urinary albumin-to-creatinine ratio 30 mg/gm or greater. Lower urinary tract symptoms were assessed with the American Urological Association Symptom Index. Associations were estimated using multivariable linear and modified Poisson regression models. RESULTS: Chronic kidney disease prevalence was 16% among 5,530 men with serum creatinine, 24% among 1,504 men with serum cystatin C and 14% among 1,487 men with urinary albumin-to-creatinine measurements. Lower urinary tract symptoms were not associated with lower estimated glomerular filtration rate based on serum creatinine or cystatin C. Although symptom severity was modestly associated with a higher prevalence of chronic kidney disease in age/site adjusted analyses, confidence intervals were wide and associations using all 3 definitions were not statistically significant after adjustment for important confounders, including cardiovascular disease and analgesic use. CONCLUSIONS: Lower urinary tract symptoms are not independently associated with multiple measures of kidney dysfunction or prevalence of chronic kidney disease among older community dwelling men. Our results do not support recommendations for kidney function testing among older men with lower urinary tract symptoms.


Assuntos
Vida Independente/estatística & dados numéricos , Sintomas do Trato Urinário Inferior/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Albuminúria/diagnóstico , Fatores de Confusão Epidemiológicos , Creatinina/sangue , Creatinina/urina , Estudos Transversais , Cistatina C/sangue , Taxa de Filtração Glomerular/fisiologia , Humanos , Sintomas do Trato Urinário Inferior/complicações , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Prevalência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/etiologia , Índice de Gravidade de Doença , Micção/fisiologia
9.
Sci Rep ; 10(1): 15557, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968161

RESUMO

In end-stage renal disease (ESRD) patients receiving dialysis, anemia is common and related to a higher mortality rate. Erythropoietin (EPO) resistance and iron refractory anemia require red blood cell transfusions. Myelodysplastic syndrome (MDS) is a disease with hematopoietic dysplasia. There are limited reports regarding ESRD patients with MDS. We aim to assess whether, for ESRD patients, undergoing dialysis is a predictive factor of MDS by analyzing data from the Taiwan National Health Insurance Research Database. We enrolled 74,712 patients with chronic renal failure (ESRD) who underwent dialysis and matched 74,712 control patients. In our study, we noticed that compared with the non-ESRD controls, in ESRD patients, undergoing dialysis (subdistribution hazard ratio [sHR] = 1.60, 1.16-2.19) and age (sHR = 1.03, 1.02-1.04) had positive predictive value for MDS occurrence. Moreover, more units of red blood cell transfusion (higher than 4 units per month) was also associated with a higher incidence of MDS. The MDS cumulative incidence increased with the duration of dialysis in ESRD patients. These effects may be related to exposure to certain cytokines, including interleukin-1, tumor necrosis factor-α, and tumor growth factor-ß. In conclusion, we report the novel finding that ESRD patients undergoing dialysis have an increased risk of MDS.


Assuntos
Anemia/epidemiologia , Falência Renal Crônica/epidemiologia , Síndromes Mielodisplásicas/epidemiologia , Diálise Renal/efeitos adversos , Adulto , Idoso , Anemia/sangue , Anemia/etiologia , Anemia/patologia , Transfusão de Eritrócitos/efeitos adversos , Eritropoetina/sangue , Feminino , Humanos , Interleucina-1/sangue , Ferro/metabolismo , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/patologia , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Fator de Crescimento Transformador beta/sangue , Fator de Necrose Tumoral alfa/sangue
10.
Medicine (Baltimore) ; 99(31): e21492, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756181

RESUMO

Activation of the renin angiotensin system and renal oxidative stress (OS) are critical contributors in the progression of chronic kidney disease(CKD). Recent studies have confirmed that the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas(ACE2/Ang(1-7)/Mas) axis, the important components of renin angiotensin system, protected kidneys against damage by antagonizing angiotensin II and attenuating OS in rats with several nephropathy models, but its effect needs to be further evaluated in clinic. In this study, we aimed to detected serum ACE2/Ang (1-7)/Mas axis, OS conditions and described its clinical associations in patients with CKD at different stages.A total of 48 patients with CKD and 6 healthy controls (CT) were enrolled, and serum angiotensin converting enzyme (ACE), ACE2, Ang (1-7), 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined by ELISA. Serum extracellular glutathione peroxidase(eGSH-Px) activity and renal functions were determined by the biochemical method.Serum ACE and ACE2 levels in CKD stages 3 to 5 and serum Ang(1-7) levels in CKD stages 4 to 5 without Ang II receptor blockers treatment significantly increased compared to those in the CT group. However, ACE2 was decreased and Ang(1-7) level increased in early CKD stage with Ang II receptor blockers treatment. Higher serum 8-OHdG levels and lower eGSH-Px activity were noted in CKD stages 4 to 5. Serum 8-OHdG level was correlated with serum ACE2, Ang(1-7) expression. Estimated glomerular filtration rate (eGFR) was correlated with serum ACE, ACE2, Ang(1-7), 8-OHdG, Hcy levels and serum eGSH-Px activity. Multiple-regression analysis eGFR was predicted by ACE, Hcy, eGSH-Px, and also can be predicted by ACE2, Ang(1-7), Hcy in CT subgroup.The ACE2/Ang(1-7)/Mas axis is associated with OS, and both them were associated with eGFR in the progression of CKD. Activation of ACE2/Ang(1-7)/Mas axis may have renoprotective effect and can be a potential therapeutic target in patients with early CKD stages.


Assuntos
Angiotensina II/sangue , Angiotensina I/sangue , Estresse Oxidativo/fisiologia , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Insuficiência Renal Crônica/sangue , 8-Hidroxi-2'-Desoxiguanosina/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sistema Renina-Angiotensina/fisiologia
11.
Sci Rep ; 10(1): 14175, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843714

RESUMO

Patients with chronic kidney disease (CKD) are often 25(OH)D3 and 1,25(OH)2D3 insufficient. We studied whether vitamin D repletion could correct aberrant adipose tissue and muscle metabolism in a mouse model of CKD-associated cachexia. Intraperitoneal administration of 25(OH)D3 and 1,25(OH)2D3 (75 µg/kg/day and 60 ng/kg/day respectively for 6 weeks) normalized serum concentrations of 25(OH)D3 and 1,25(OH)2D3 in CKD mice. Vitamin D repletion stimulated appetite, normalized weight gain, and improved fat and lean mass content in CKD mice. Vitamin D supplementation attenuated expression of key molecules involved in adipose tissue browning and ameliorated expression of thermogenic genes in adipose tissue and skeletal muscle in CKD mice. Furthermore, repletion of vitamin D improved skeletal muscle fiber size and in vivo muscle function, normalized muscle collagen content and attenuated muscle fat infiltration as well as pathogenetic molecular pathways related to muscle mass regulation in CKD mice. RNAseq analysis was performed on the gastrocnemius muscle. Ingenuity Pathway Analysis revealed that the top 12 differentially expressed genes in CKD were correlated with impaired muscle and neuron regeneration, enhanced muscle thermogenesis and fibrosis. Importantly, vitamin D repletion normalized the expression of those 12 genes in CKD mice. Vitamin D repletion may be an effective therapeutic strategy for adipose tissue browning and muscle wasting in CKD patients.


Assuntos
Adipócitos Bege/efeitos dos fármacos , Caquexia/tratamento farmacológico , Calcifediol/uso terapêutico , Calcitriol/uso terapêutico , Insuficiência Renal Crônica/complicações , Adipócitos Bege/metabolismo , Adipócitos Marrons/metabolismo , Adipócitos Brancos/metabolismo , Animais , Caquexia/etiologia , Caquexia/fisiopatologia , Calcifediol/sangue , Calcifediol/deficiência , Calcifediol/farmacologia , Calcitriol/sangue , Calcitriol/deficiência , Calcitriol/farmacologia , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Fibrose/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Força da Mão , Camundongos , Camundongos Endogâmicos C57BL , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Nefrectomia , Hormônio Paratireóideo/sangue , RNA Mensageiro/biossíntese , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/tratamento farmacológico , Teste de Desempenho do Rota-Rod , Análise de Sequência de RNA , Termogênese/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos
12.
Life Sci ; 260: 118295, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32822720

RESUMO

Advanced chronic kidney disease is associated with high rates of cardiovascular disease. Considering the crucial role of capillaries in renal function, our study aimed to evaluate microparticles related to vascular physiology examining the link between stages of chronic kidney disease with circulating endothelial (EMP), platelet (PMP) and monocytic (MMP) microparticles. Cross-sectional study with blinded endpoints included subjects of both sexes, aged 40-75 years (n = 247), with established cardiovascular disease (coronary heart disease, ischemic stroke, or peripheral artery disease). They were stratified 1:1 by the presence or absence of decreased glomerular filtration rate (GFR < 60 mL/min/1.73 m2) estimated by the CKD-EPI criteria, and according to the stages of CKD. Microparticles were quantified by flow-cytometry using specific antibodies to identify endothelial, platelet, and monocytic derived microparticles. Higher percentages of circulating MMP (p = 0.036), but not for EMP or PMP, were observed in subjects with reduced GFR. Circulating MMP were also related to the stages of chronic kidney disease (trend analysis across renal stages, p = 0.038). Higher percentages of circulating MMP were found in subjects with reduced GFR, and their percentages were progressively higher according to the stage of chronic renal function.


Assuntos
Micropartículas Derivadas de Células , Monócitos/ultraestrutura , Insuficiência Renal Crônica/sangue , Adulto , Idoso , Plaquetas/ultraestrutura , Doenças Cardiovasculares/sangue , Estudos Transversais , Progressão da Doença , Células Endoteliais/ultraestrutura , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia
13.
PLoS One ; 15(8): e0237086, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764782

RESUMO

Paramylon is a novel ß-glucan that is stored by Euglena gracilis Z, which is a unicellular photosynthesizing green alga with characteristics of both animals and plants. Recent studies have indicated that paramylon functions as an immunomodulator or a dietary fiber. Currently, chronic kidney disease (CKD) is a global health problem, and there is no effective preventive treatment for CKD progression. However, paramylon may suppress the progression of CKD via the elimination of uremic toxins or modulation of gut microbiota, leading to the alleviation of inflammation. The aim of this study was to evaluate the effect of paramylon in CKD rat model. Eight-week-old male Wistar rats with a 5/6 nephrectomy were given either a normal diet or a diet containing 5% paramylon for 8 weeks. Proteinuria was measured intermittently. Serum and kidney tissues were harvested after sacrifice. We performed a renal molecular and histopathological investigation, serum metabolome analysis, and gut microbiome analysis. The results showed that paramylon attenuated renal function, glomerulosclerosis, tubulointerstitial injury, and podocyte injury in the CKD rat model. Renal fibrosis, tubulointerstitial inflammatory cell infiltration, and proinflammatory cytokine gene expression levels tended to be suppressed with paramylon treatment. Further, paramylon inhibited the accumulation of uremic toxins, including tricarboxylic acid (TCA) cycle-related metabolites and modulated a part of CKD-related gut microbiota in the CKD rat model. In conclusion, we suggest that paramylon mainly inhibited the absorption of non-microbiota-derived uremic solutes, leading to protect renal injury via anti-inflammatory and anti-fibrotic effects. Paramylon may be a novel compound that can act against CKD progression.


Assuntos
Glucanos/farmacologia , Rim/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Proteinúria/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Administração Oral , Animais , Ciclo do Ácido Cítrico/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Euglena gracilis/química , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Glucanos/isolamento & purificação , Glucanos/uso terapêutico , Humanos , Mediadores da Inflamação/metabolismo , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Rim/imunologia , Rim/patologia , Masculino , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/uso terapêutico , Proteinúria/sangue , Proteinúria/patologia , Ratos , Ratos Wistar , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/urina , Toxinas Biológicas/sangue , Toxinas Biológicas/metabolismo
14.
Psychopharmacology (Berl) ; 237(9): 2739-2752, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32601991

RESUMO

RATIONALE: Although a growing body of evidence indicates that the scores of cognitive function in hemodialysis patients are significantly lower than those of healthy individuals, underlying mechanisms have not been fully elucidated. OBJECTIVES: To investigate the roles of gut microbiota and serum metabolites in hemodialysis patients with mild cognitive decline (MCD). METHODS: A total of 30 healthy individuals and 77 hemodialysis patients were enrolled and were classified into healthy control (HC), normal cognitive function (NCF), and MCD groups by evaluation of Montreal Cognitive Assessment. Fecal samples were analyzed by 16S rRNA and serum samples were analyzed by gas chromatography-mass spectrometry from all subjects. RESULTS: The 16S rRNA study demonstrated that the gut microbiota profiles, including α- and ß-diversity, and a number of 16 gut bacteria were significantly altered in the MCD group compared with those in HC or those with NCF. A metabonomics study showed that a total of 29 serum metabolites were altered in the MCD group. Receiver operating characteristic curves showed that Genus Bilophila and serum putrescine might be sensitive biomarkers to indicate MCD in patients with hemodialysis. CONCLUSIONS: These findings demonstrate gut microbiota and serum metabolites were probably involved in the pathogenesis of hemodialysis-related MCD. Therapeutic strategies targeting abnormalities in gut microbiota and serum metabolites may facilitate the beneficial effects for hemodialysis patients with MCD.


Assuntos
Disfunção Cognitiva/sangue , Microbioma Gastrointestinal/fisiologia , Metabolômica/tendências , Diálise Renal/tendências , Insuficiência Renal Crônica/sangue , Adulto , Biomarcadores/sangue , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/genética , Fezes/microbiologia , Feminino , Humanos , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , RNA Ribossômico 16S/sangue , RNA Ribossômico 16S/genética , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/terapia
15.
Sci Rep ; 10(1): 12749, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32728174

RESUMO

Dyslipidemia is common in patients with chronic kidney disease (CKD), however the relationship between dyslipidemia and mortality in patients with moderate to severe CKD remains controversial. Non-high-density lipoprotein (HDL) cholesterol has been reported to be a more accurate predictor of clinical outcomes than conventional lipid measurements. Hence, the aim of this study was to investigate associations between non-HDL cholesterol and the risk of overall and cardiovascular mortality in patients with CKD stage 3-5. We enrolled 429 pre-dialysis patients with stage 3 to 5 CKD from May 2006 to January 2010. The patients were divided into four groups according to quartiles of non-HDL cholesterol. The patients were followed until death or until January 2020. During a median 11.6 years of follow-up, there were 78 (18.2%) deaths overall and 32 (7.5%) cardiovascular deaths. In adjusted models, the patients in quartile 1 (hazard ratio [HR] 3.368; 95% confidence interval [CI] 1.388-8.176; p = 0.007), quartile 3 (HR 3.666; 95% CI 1.486-9.044; p = 0.005), and quartile 4 (HR 2.868; 95% CI 1.136-7.240; p = 0.026) of non-HDL cholesterol had a higher risk of overall mortality (vs. quartile 2). In addition, the patients in quartile 1 (HR 19.503; 95% CI 2.185-174.0925 p = 0.008), quartile 3 (HR 28.702; 95% CI 2.990-275.559; p = 0.004), and quartile 4 (HR 11.136; 95% CI 1.126-110.108; p = 0.039) had a higher risk of cardiovascular mortality (vs. quartile 2). Our study showed a U-shaped relationship between non-HDL cholesterol and the risk of overall and cardiovascular mortality in patients with CKD stage 3-5. Assessing non-HDL cholesterol may help to identify subjects at high-risk of adverse outcomes.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Colesterol/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/mortalidade , Idoso , Biomarcadores/sangue , HDL-Colesterol , LDL-Colesterol/sangue , Dislipidemias/sangue , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Resultado do Tratamento , Triglicerídeos/sangue
16.
Sci Rep ; 10(1): 12675, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32728058

RESUMO

Blood metabolites of the tryptophan pathway were found to be associated with kidney function and disease in observational studies. In order to evaluate causal relationship and direction, we designed a study using a bidirectional Mendelian randomization approach. The analyses were based on published summary statistics with study sizes ranging from 1,960 to 133,413. After correction for multiple testing, results provided no evidence of an effect of metabolites of the tryptophan pathway on estimated glomerular filtration rate (eGFR). Conversely, lower eGFR was related to higher levels of four metabolites: C-glycosyltryptophan (effect estimate = - 0.16, 95% confidence interval [CI] (- 0.22; - 0.1); p = 9.2e-08), kynurenine (effect estimate = - 0.18, 95% CI (- 0.25; - 0.11); p = 1.1e-06), 3-indoxyl sulfate (effect estimate = - 0.25, 95% CI (- 0.4; - 0.11); p = 6.3e-04) and indole-3-lactate (effect estimate = - 0.26, 95% CI (- 0.38; - 0.13); p = 5.4e-05). Our study supports that lower eGFR causes higher blood metabolite levels of the tryptophan pathway including kynurenine, C-glycosyltryptophan, 3-indoxyl sulfate, and indole-3-lactate. These findings aid the notion that metabolites of the tryptophan pathway are a consequence rather than a cause of reduced eGFR. Further research is needed to specifically examine relationships with respect to chronic kidney disease (CKD) progression among patients with existing CKD.


Assuntos
Biomarcadores/sangue , Insuficiência Renal Crônica/fisiopatologia , Triptofano/química , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Indicã/sangue , Indóis/sangue , Cinurenina/sangue , Análise da Randomização Mendeliana , Insuficiência Renal Crônica/sangue , Triptofano/sangue
17.
Am J Kidney Dis ; 76(6): 765-774, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32682697

RESUMO

RATIONALE & OBJECTIVE: In prior research and in practice, the difference between estimated glomerular filtration rate (eGFR) calculated from cystatin C level and eGFR calculated from creatinine level has not been assessed for clinical significance and relevance. We evaluated whether these differences contain important information about frailty. STUDY DESIGN: A cohort analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS: 9,092 hypertensive SPRINT participants who had baseline measurements of serum creatinine, cystatin C, and frailty. EXPOSURE: eGFRs calculated using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations (eGFRcys and eGFRcr), and eGFRDiff, calculated as eGFRcys-eGFRcr. OUTCOMES: A validated 35-item frailty index that included questionnaire data for general and physical health, limitations of activities, pain, depression, sleep, energy level, self-care, and smoking status, as well as medical history, cognitive assessment, and laboratory data. We defined frailty as frailty index score>0.21 (range, 0-1). The incidence of injurious falls, hospitalizations, cardiovascular events, and mortality was also recorded. ANALYTICAL APPROACH: We used logistic regression to model the cross-sectional association of baseline eGFRDiff with frailty among all SPRINT participants. Adjusted proportional hazards regression was used to evaluate the association of eGFRDiff with adverse outcomes and mortality. RESULTS: Mean age was 68±9 (SD) years, mean eGFRcys and eGFRcr were 73±23 and 72±20mL/min/1.73m2, and mean eGFRDiff was 0.5±15mL/min/1.73m2. In adjusted models, each 1-SD higher eGFRDiff was associated with 24% lower odds of prevalent frailty (OR, 0.76; 95% CI, 0.71-0.81), as well as with lower incidence rate of injurious falls (HR, 0.84; 95% CI, 0.77-0.92), hospitalization (HR, 0.91; 95% CI, 0.88-0.95), cardiovascular events (HR, 0.89; 95% CI, 0.81-0.97), and all-cause mortality (HR, 0.71; 95% CI, 0.63-0.82); P<0.01. LIMITATIONS: Gold-standard measure of kidney function and assessment of muscle mass were not available. CONCLUSIONS: The difference between eGFRcys and eGFRcr is associated with frailty and health status. Positive eGFRDiff is strongly associated with lower risks for longitudinal adverse outcomes and mortality, even after adjusting for chronic kidney disease stage and baseline frailty.


Assuntos
Pressão Sanguínea/fisiologia , Creatinina/sangue , Cistatina C/sangue , Fragilidade/sangue , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/sangue , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Fragilidade/complicações , Humanos , Masculino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Sístole
18.
Clin Appl Thromb Hemost ; 26: 1076029620943671, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702995

RESUMO

Severe acute respiratory syndrome coronavirus 2 infection (COVID-19) is known to induce severe inflammation and activation of the coagulation system, resulting in a prothrombotic state. Although inflammatory conditions and organ-specific diseases have been shown to be strong determinants of morbidity and mortality in patients with COVID-19, it is unclear whether preexisting differences in coagulation impact the severity of COVID-19. African Americans have higher rates of COVID-19 infection and disease-related morbidity and mortality. Moreover, African Americans are known to be at a higher risk for thrombotic events due to both biological and socioeconomic factors. In this review, we explore whether differences in baseline coagulation status and medical management of coagulation play an important role in COVID-19 disease severity and contribute to racial disparity trends within COVID-19.


Assuntos
Afro-Americanos , Betacoronavirus , Infecções por Coronavirus/etnologia , Pandemias , Pneumonia Viral/etnologia , Trombofilia/etnologia , Tromboembolia Venosa/etnologia , Afro-Americanos/genética , Anemia Falciforme/sangue , Anemia Falciforme/etnologia , Anticoagulantes/uso terapêutico , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/genética , Ensaios Clínicos como Assunto , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Fator VIII/análise , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Estudos de Associação Genética , Predisposição Genética para Doença , Disparidades em Assistência à Saúde , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Seleção de Pacientes , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Polimorfismo de Nucleotídeo Único , Prevalência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etnologia , Fatores de Risco , Determinantes Sociais da Saúde , Fatores Socioeconômicos , Trombofilia/sangue , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
19.
PLoS One ; 15(6): e0234712, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32603378

RESUMO

Chronic kidney disease is a common disease in dogs, and factors such as serum concentrations of creatinine, albumin, and phosphorus at the moment of diagnosis may influence the survival of these patients. The present retrospective study aimed to evaluate the relationship between survival in dogs with chronic kidney disease and laboratory parameters (creatinine, phosphorus, albumin, and hematocrit) and nutritional parameters (body condition score, muscle mass score, type of food, appetite and feeding method). A total of 116 dogs with chronic kidney disease stages 2 to 4 were included, and survival was calculated considering the time between diagnosis and death. Survival curves were configurated by Kaplan-Meier analysis and a comparison between survival curves was performed by the log-rank test. Factors related to survival were disease stage (p<0.0001), serum phosphorus concentration (p = 0.0005), hematocrit (0.0001), body condition score (p = 0.0391), muscle mass score (p = 0.0002), type of food (p = 0.0009), feeding method (p<0.0001) and appetite (p = 0.0007). Based on data obtained in this study, it is possible to conclude that early diagnosis, as well as nutritional evaluation and renal diet intake, are determinant strategies to increase survival in dogs with chronic kidney disease.


Assuntos
Doenças do Cão/metabolismo , Laboratórios , Estado Nutricional , Insuficiência Renal Crônica/veterinária , Animais , Doenças do Cão/sangue , Cães , Feminino , Estimativa de Kaplan-Meier , Masculino , Fósforo/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/metabolismo , Análise de Sobrevida
20.
Rev Cardiovasc Med ; 21(2): 191-203, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32706208

RESUMO

Acute myocardial infarction (MI) represents one of the most common hospital encounters, with significant short-term and long-term morbidity and mortality, and frequently occurs in patients with chronic kidney disease (CKD). Cardiac troponin is an exquisitely sensitive biomarker for myocardial injury and plays an essential role in the diagnosis, risk-stratification, and management of MI. In 2017, the United States Food and Drug Administration approved Roche Diagnostics' 5th generation high-sensitivity cardiac troponin (hs-cTn) for clinical use. Whilst the improved analytical sensitivity of these new high-sensitivity troponin assays facilitate early diagnosis of MI, it also frequently identifies troponin elevations above the conventional reference threshold in the context of non-coronary conditions such as renal dysfunction, and can represent a major diagnostic challenge to clinicians. Furthermore, the optimal management strategy of patients with troponin elevation and high comorbidity burden, a common issue in patients with CKD, remains undefined. In recent years, there has been substantial research and progress undertaken in this rapidly evolving area. In this review, we aim to provide clinicians with an overview of hs-cTn in the setting of CKD as well as an update on its application and the particular considerations involved in the management of myocardial infarction, stable coronary artery disease and myocardial injury in this high risk population.


Assuntos
Infarto do Miocárdio/diagnóstico , Insuficiência Renal Crônica/diagnóstico , Troponina/sangue , Animais , Biomarcadores/sangue , Comorbidade , Humanos , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Valor Preditivo dos Testes , Prognóstico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Regulação para Cima
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