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INTRODUCTION: Elevated levels of fibroblast growth factor-23 (FGF23) in chronic kidney disease (CKD) are associated with progression of CKD. FGF23 inhibits proximal tubular phosphate reabsorption, raising phosphate concentrations in the tubular fluid of functioning nephrons, predisposing to spontaneous precipitation of calcium phosphate crystals and resultant tubular injury. Calciprotein monomers (CPM) form spontaneously in biological fluids when clusters of calcium phosphate ions are bound by the liver-derived glycoprotein fetuin-A. Serum CPM are elevated in CKD and are postulated to trigger FGF23 secretion. CPM are also readily filtered at the glomerulus into the tubular fluid, suggesting that higher CPM levels could be associated with progression of CKD via FGF23-mediated increased phosphate load but also through direct effects in the proximal tubule. METHODS: ACADEMIC was a prospective observational study of 200 stable outpatients with CKD stages 3 and 4. Participants were followed until commencement of dialysis or death. In this study, we examined a sub-cohort of 189 participants who had baseline serum available for measurement of CPM. Cox proportionate hazard regression models were used to examine the association between CPM and a composite kidney disease outcome (commencement of dialysis or reduction in estimated glomerular filtration rate [eGFR] >30%). Linear regression models were used to examine the association between CPM and annualized eGFR slope. RESULTS: Relative to the lowest tertile, the highest tertile of CPM was associated with increased risk of the composite kidney disease outcome in univariate models and after sequential adjustment for conventional risk factors for progression of CKD (adjusted hazard ratio 4.22; 95% confidence interval [CI] 1.91, 9.33, p < 0.001). Natural log-transformed CPM was also inversely associated with eGFR slope in univariate and multivariate adjusted models (adjusted ß-coefficient -1.66, 95% CI: -3.10, -0.22, p = 0.024). In exploratory mediation analysis, the association between serum CPM and eGFR slope was partially mediated by iFGF23; however, the majority of the association was direct and independent of the iFGF23 pathway. CONCLUSION: Elevated levels of CPM are associated with the progression of CKD. This association was partially mediated via FGF23, consistent with recent evidence that FGF23 predisposes to spontaneous precipitation of calcium phosphate crystals leading to tubular injury. However, serum CPM also appeared to have a direct association with eGFR slope, raising the possibility that CPM may also be associated with progression of CKD through additional pathways.
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Insuficiência Renal Crônica , Humanos , Rim/metabolismo , Fosfatos , Diálise Renal , Fatores de Risco , Taxa de Filtração Glomerular , Fatores de Crescimento de Fibroblastos , Progressão da DoençaRESUMO
BACKGROUND: Sodium zirconium cyclosilicate (SZC) is an effective and well-tolerated treatment for hyperkalemia in maintenance hemodialysis patients. In post-hoc analyses of the phase 3b DIALIZE study, we examined the spectrum of potassium responses to SZC. METHODS: Post-hoc analyses with SZC and placebo included: the number of long interdialytic interval (LIDI) visits during the 4-week evaluation period where patients attained pre-dialysis serum potassium (sK+) concentrations of 4.0-5.0 and 4.0-5.5 mmol/L; potassium gradient (the difference between pre-dialysis sK+ and dialysate potassium) at days 36, 43, 50, and 57, and change from baseline to the end of treatment (EOT) using categories of potassium gradient (1 to < 2, 2 to < 3, 3 to < 4, and ≥ 4 mmol/L). RESULTS: A greater proportion of patients achieved the ranges of pre-dialysis sK+ concentration with SZC versus placebo for ≥1, ≥ 2, ≥ 3, and 4 LIDI visits over 4 weeks; 23.7 and 48.5% of patients in the SZC group achieved pre-dialysis sK+ concentrations of 4.0-5.0 and 4.0-5.5 mmol/L, respectively, at all 4 LIDI visits. Baseline mean potassium gradient was similar with SZC and placebo. At day 57, mean (standard deviation) potassium gradient was 2.78 (0.08) mmol/L with SZC and 3.52 (0.08) mmol/L with placebo; mean difference (95% confidence interval) was - 0.74 mmol/L (- 0.97 to - 0.52). A greater reduction in potassium gradient category from baseline towards lower-risk categories at EOT was observed with SZC versus placebo. CONCLUSIONS: These analyses expand our knowledge of the spectrum of potassium responses with SZC in hyperkalemic hemodialysis patients. TRIAL REGISTRATION: NCT03303521 .
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Hiperpotassemia/sangue , Hiperpotassemia/tratamento farmacológico , Resinas de Troca Iônica/uso terapêutico , Potássio/sangue , Silicatos/uso terapêutico , Soluções para Diálise/análise , Método Duplo-Cego , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Potássio/análise , Diálise RenalRESUMO
Hyperkalemia (serum K+ >5.0 mmol/L) is commonly observed among patients receiving maintenance hemodialysis and associated with increased risk of cardiac arrhythmias. Current international guidelines may not reflect the latest evidence on managing hyperkalemia in patients undergoing hemodialysis, and there is a lack of high-quality published studies in this area. This consensus guideline aims to provide recommendations in relation to clinical practice. Available published evidence was evaluated through a systematic literature review, and the nominal group technique was used to develop consensus recommendations from a panel of experienced nephrologists, covering monitoring, dietary restrictions, prescription of K+ binders, and concomitant prescription of renin-angiotensin-aldosterone system inhibitors. Recent studies have shown that K+ binders reduce the incidence of hyperkalemia, but further evidence is needed in areas including whether reduced-K+ diets or treatment with K+ binders improve patient-centered outcomes. Treatment of hyperkalemia in the hemodialysis setting is complex, and decisions need to be tailored for individual patients.
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Hiperpotassemia , Humanos , Hiperpotassemia/tratamento farmacológico , Potássio , Diálise Renal , Sistema Renina-AngiotensinaRESUMO
We report a case of intravascular hemolysis and methemoglobinemia, precipitated by severe acute respiratory syndrome coronavirus 2 infection, in a patient with undiagnosed glucose-6-phosphate dehydrogenase deficiency. Clinicians should be aware of this complication of coronavirus disease as a cause of error in pulse oximetry and a potential risk for drug-induced hemolysis.
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Betacoronavirus , Infecções por Coronavirus/complicações , Deficiência de Glucosefosfato Desidrogenase/virologia , Metemoglobinemia/virologia , Pneumonia Viral/complicações , COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Deficiência de Glucosefosfato Desidrogenase/sangue , Humanos , Masculino , Metemoglobinemia/sangue , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/virologia , SARS-CoV-2RESUMO
BACKGROUND: Patients with ESRD have minimal renal potassium excretion and, despite hemodialysis, often have persistent predialysis hyperkalemia. The DIALIZE study (NCT03303521) evaluated sodium zirconium cyclosilicate (SZC) in the management of hyperkalemia in hemodialysis patients. METHODS: In the DIALIZE study, a double-blind, placebo-controlled, phase 3b multicenter study, we randomized adults with ESRD who were managed by three-times weekly hemodialysis and had predialysis hyperkalemia to receive placebo or SZC 5 g once daily on non-dialysis days, and titrated towards maintaining normokalemia over 4 weeks, in 5 g increments to a maximum of 15 g. The primary efficacy outcome was proportion of patients during the 4-week stable-dose evaluation period who maintained predialysis serum potassium of 4.0-5.0 mmol/L during at least three of four hemodialysis treatments after the long interdialytic interval and did not require urgent rescue therapy to reduce serum potassium. RESULTS: In total, 196 patients (mean [standard deviation (SD)] age =58.1 [13.7] years old) were randomized to sodium zirconium cyclosilicate or placebo. Of 97 patients receiving sodium zirconium cyclosilicate, 41.2% met the primary end point and were deemed treatment responders compared with 1.0% of 99 patients receiving placebo (P<0.001). Rescue therapy to reduce serum potassium during the treatment period was required by 2.1% of patients taking sodium zirconium cyclosilicate versus 5.1% taking placebo. Serious adverse events occurred in 7% and 8% of patients in sodium zirconium cyclosilicate and placebo groups, respectively. The two groups displayed comparable interdialytic weight gain. There were few episodes of hypokalemia. CONCLUSIONS: Sodium zirconium cyclosilicate is an effective and well-tolerated treatment for predialysis hyperkalemia in patients with ESRD undergoing adequate hemodialysis.
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Hiperpotassemia/tratamento farmacológico , Resinas de Troca Iônica/uso terapêutico , Falência Renal Crônica/complicações , Silicatos/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Hiperpotassemia/etiologia , Hiperpotassemia/prevenção & controle , Resinas de Troca Iônica/efeitos adversos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Diálise Renal , Silicatos/efeitos adversos , Adulto JovemRESUMO
Medial arterial calcification is accelerated in patients with CKD and strongly associated with increased arterial rigidity and cardiovascular mortality. Recently, a novel in vitro blood test that provides an overall measure of calcification propensity by monitoring the maturation time (T50) of calciprotein particles in serum was described. We used this test to measure serum T50 in a prospective cohort of 184 patients with stages 3 and 4 CKD, with a median of 5.3 years of follow-up. At baseline, the major determinants of serum calcification propensity included higher serum phosphate, ionized calcium, increased bone osteoclastic activity, and lower free fetuin-A, plasma pyrophosphate, and albumin concentrations, which accounted for 49% of the variation in this parameter. Increased serum calcification propensity at baseline independently associated with aortic pulse wave velocity in the complete cohort and progressive aortic stiffening over 30 months in a subgroup of 93 patients. After adjustment for demographic, renal, cardiovascular, and biochemical covariates, including serum phosphate, risk of death among patients in the lowest T50 tertile was more than two times the risk among patients in the highest T50 tertile (adjusted hazard ratio, 2.2; 95% confidence interval, 1.1 to 5.4; P=0.04). This effect was lost, however, after additional adjustment for aortic stiffness, suggesting a shared causal pathway. Longitudinally, serum calcification propensity measurements remained temporally stable (intraclass correlation=0.81). These results suggest that serum T50 may be helpful as a biomarker in designing methods to improve defenses against vascular calcification.
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Arteriosclerose/sangue , Calcinose/sangue , Fosfatos de Cálcio/sangue , Mortalidade , Fosfatos/sangue , Insuficiência Renal Crônica/sangue , Albumina Sérica/análise , alfa-2-Glicoproteína-HS/análise , Idoso , Idoso de 80 Anos ou mais , Arteriosclerose/epidemiologia , Biomarcadores , Calcinose/epidemiologia , Doenças Cardiovasculares/epidemiologia , Causalidade , Comorbidade , Diabetes Mellitus/epidemiologia , Difosfatos/sangue , Suscetibilidade a Doenças , Feminino , Seguimentos , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Osteoclastos/metabolismo , Estudos Prospectivos , Análise de Onda de Pulso , Diálise Renal , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Risco , Fumar/epidemiologia , Resistência Vascular , alfa-2-Glicoproteína-HS/químicaRESUMO
BACKGROUND: Chronic kidney disease (CKD) is an increasing public health issue. It is therefore potentially highly advantageous to identify patients at risk of accelerated renal progression and death. Neutrophil gelatinase-associated lipocalin (NGAL) is an established urinary biomarker for acute kidney injury, but it is not known whether adding urinary NGAL (uNGAL) measurements to conventional risk factors will improve risk assessment in the setting of chronic disease. METHODS: This is a prospective observational cohort study of 158 patients with Stage 3 or 4 CKD. The ability of baseline uNGAL to improve prediction of outcome was assessed by multivariate modelling and a number of metrics including net reclassification analysis. A primary composite endpoint of all-cause mortality or progression to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT) at 2 years and a secondary endpoint of ≥5 mL/min/1.73 m(2) decline in the estimated glomerular filtration rate (eGFR) after 1 year were considered. RESULTS: Forty patients (25%) reached the primary composite endpoint, 20 of whom died. Twenty-seven patients (19%) reached the secondary endpoint of a ≥5 mL/min/1.73 m(2) decline in the eGFR. The baseline uNGAL-to-creatinine ratio (uNCR) was associated with the combined endpoint of death or initiation of RRT (HR per 5 µg/mmol increase 1.27, 95% CI: 1.01-1.60, P = 0.036) independent of conventional cardiovascular and renal risk factors, including proteinuria. In separate analysis of these two competing endpoints, however, uNCR only remained associated with increased risk of progression to ESRD requiring RRT. Higher baseline uNCR was also independently predictive of rapid renal decline over 1 year (HR per 5 µg/mmol increase 1.47, 95% CI: 1.06-2.06, P = 0.022). Addition of uNCR to the base model resulted in a significant increase in discrimination for the secondary (C-statistic 0.76-0.85, P = 0.001) but not the primary endpoint (P = 0.276). Reclassification analysis on the other hand, demonstrated an improvement in risk predication of both primary and secondary endpoints by incorporating uNCR into the base model, but only in those with low-level urine protein excretion (<28 mg/mmol), with category-free net reclassification improvement (NRI) scores of 64% (95% CI: 8-70; P = 0.019) and 79% (95% CI: 12-83; P = 0.009), respectively. CONCLUSION: The utilization of uNCR in addition to conventional established cardiovascular and renal risk factors may improve the prediction of disease progression in elderly Caucasian pre-dialysis CKD patients with low-grade proteinuria.
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Proteínas de Fase Aguda/urina , Biomarcadores/urina , Falência Renal Crônica/diagnóstico , Lipocalinas/urina , Proteinúria/diagnóstico , Proteínas Proto-Oncogênicas/urina , Insuficiência Renal Crônica/complicações , Terapia de Substituição Renal , Idoso , Creatinina/sangue , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Lipocalina-2 , Masculino , Prognóstico , Estudos Prospectivos , Proteinúria/etiologia , Proteinúria/mortalidade , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/terapia , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Extra-skeletal calcification and disordered phosphate metabolism are hallmarks of chronic kidney disease-mineral bone disorder (CKD-MBD). Osteoprotegerin (OPG) and fibroblast growth factor 23 (FGF-23) are increased in chronic kidney disease (CKD) and have been associated with arterial and cardiac dysfunction and reduced survival. Troponin T (cTnT) is released from cardiac myocytes under conditions of stress and is predictive of mortality across a range of renal functions. However, the utility of this biomarker was formerly limited by the lower limit of assay detection. The introduction of a high-sensitivity assay has enabled more detailed study of myocyte stress below the previous limit of detection. We studied the association of mediators of CKD-MBD with arterial stiffness and also of these mediators and arterial stiffness with myocardial damage in patients with CKD stages 3-4. METHODS: OPG and FGF-23 were measured in 200 CKD stages 3-4 patients. cTnT was measured using a high-sensitivity assay. Aortic stiffness was assessed using aortic pulse wave velocity (APWV). RESULTS: Mean age was 69 ± 11 years, mean systolic and diastolic blood pressure was 151 ± 22/81 ± 11 mmHg and renal function was 33 ± 11 mL/min/1.73 m(2). OPG, FGF-23, high-sensitivity troponin T (hs-cTnT) and APWV all correlated with renal function. After multivariate analysis, OPG and age remained independently associated with aortic stiffness. OPG and FGF-23 were independently associated with hs-cTnT in addition to other non-traditional risk factors (Model R(2) = 0.596). CONCLUSION: We have shown that changes in bone mediators and phosphate metabolism induced by CKD are independently associated with vascular and cardiomyocyte dysfunction. Our findings suggest that cardiac dysfunction may be specifically associated with such abnormalities in addition to recognized increases in vascular stiffness.
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Doenças Ósseas/sangue , Cardiomiopatias/sangue , Fatores de Crescimento de Fibroblastos/metabolismo , Falência Renal Crônica/sangue , Osteoprotegerina/metabolismo , Troponina T/metabolismo , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Biomarcadores/sangue , Densidade Óssea , Doenças Ósseas/complicações , Doenças Ósseas/diagnóstico , Cardiomiopatias/complicações , Cardiomiopatias/mortalidade , Cardiomiopatias/patologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/patologia , Estudos de Coortes , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/genética , Prognóstico , Análise de Regressão , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Taxa de Sobrevida , Troponina T/genética , Resistência VascularRESUMO
BACKGROUND: Vascular stiffening occurs in normal ageing and is accelerated in chronic kidney disease (CKD). Vascular calcification contributes to this stiffening and to the high incidence of vascular morbidity and mortality in this population. A network of inhibitors work in concert to reduce mineralization risk in extra-osseous tissue. Fetuin-A is an important systemic inhibitor of ectopic calcification. A fraction of the total circulating fetuin-A interacts with mineral ions to form stable colloidal complexes, calciprotein particles (CPP), preventing deposition. We sought to assess whether CPP fetuin-A levels were associated with procalcific factors and aortic stiffness in a cohort of patients with Stages 3 and 4 CKD. METHODS: We measured fetuin-A CPP levels, serum inflammatory markers [C-reactive protein (CRP), interleukin-6, tumour necrosis factor-α], oxidized low-density lipoprotein (oxLDL), bone morphogenetic protein-2 (BMP-2) and -7 (BMP-7) and aortic pulse wave velocity (APWV) in a cohort of 200 CKD patients. Serum measurements were also made in 78 healthy controls. CPP fetuin-A phosphorylation was characterized by phosphate-affinity gel chromatography. RESULTS: Fetuin-A-containing CPPs were only detectable in the serum of CKD patients. Inflammatory markers, oxLDL and BMP-2 levels were all significantly higher in the CKD than control subjects. CPP fetuin-A levels were independently associated with serum phosphate, high-sensitivity C-reactive protein, oxLDL, BMP-2/7 ratio and inversely with estimated glomerular filtration rate (model R(2) = 0.51). After adjusting for confounders, CPP fetuin-A levels were independently associated with APWV. Only phosphorylated fetuin-A was present in serum CPP. CONCLUSION: Increased CPP fetuin-A levels reflect an increasingly procalcific milieu and are associated with increased aortic stiffness in patients with pre-dialysis CKD.
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Aorta/fisiopatologia , Calcinose/sangue , Nefropatias/sangue , Nefropatias/fisiopatologia , Rigidez Vascular/fisiologia , alfa-2-Glicoproteína-HS/metabolismo , Idoso , Idoso de 80 Anos ou mais , Aorta/metabolismo , Biomarcadores/sangue , Proteína Morfogenética Óssea 2/sangue , Proteína Morfogenética Óssea 7/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Doença Crônica , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Interleucina-6/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Fosforilação , Fator de Necrose Tumoral alfa/sangueRESUMO
Background: Evidence of longitudinal serum potassium (sK+) concentrations in hyperkalemic hemodialysis patients is sparse. Objective: These post hoc analyses of the placebo arm of the phase 3b DIALIZE study (NCT03303521) explored the course of hyperkalemia in hemodialysis patients receiving placebo. Methods: In DIALIZE, 196 patients receiving hemodialysis three times weekly were randomized to placebo or sodium zirconium cyclosilicate 5 g starting dose once daily on nondialysis days for 8 weeks. In these post hoc analyses of placebo patients overall (n = 86) and by predialysis sK+ subgroups at randomization <5.5 mmol/L, 5.5 to <6.0 mmol/L, 6.0 to <6.5 mmol/L, and ≥6.5 mmol/L, we assessed mean predialysis sK+ concentration by visit and the proportions of patients with mean predialysis sK+ ranges of 4.0-5.0 and 4.0-5.5 mmol/L by visit. Results: In placebo patients, the mean predialysis sK+ concentration at randomization was 5.9 mmol/L, and 5.8 mmol/L at the end of the study (day 57). For placebo patients overall and across all predialysis sK+ subgroups, the mean predialysis sK+ concentration remained ≥5.0 mmol/L for all visits over 8 weeks. Overall, 7-21% and 27-62% of placebo patients had predialysis sK+ ranges of 4.0-5.0 and 4.0-5.5 mmol/L, respectively, at any visit. The proportions of placebo patients with either predialysis sK+ range were greatest for those who were least hyperkalemic (<5.5 mmol/L) and generally decreased with increasing predialysis sK+ concentration. Conclusions: Patients receiving placebo and hemodialysis maintained high predialysis sK+ concentrations over 8 weeks following a hyperkalemic event. Most placebo patients remained hyperkalemic and may be at continued risk of adverse events.
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BACKGROUND AND OBJECTIVES: Patients receiving in-center hemodialysis treatment face unique challenges during the coronavirus disease 2019 (COVID-19) pandemic, specifically the need to attend for treatment that prevents self-isolation. Dialysis unit attributes and isolation strategies that might reduce dialysis center COVID-19 infection rates have not been previously examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We explored the role of variables, including community disease burden, dialysis unit attributes (size and layout), and infection control strategies, on rates of COVID-19 among patients receiving in-center hemodialysis in London, United Kingdom, between March 2, 2020 and May 31, 2020. The two outcomes were defined as (1) a positive test for infection or admission with suspected COVID-19 and (2) admission to the hospital with suspected infection. Associations were examined using a discrete time multilevel time-to-event analysis. RESULTS: Data on 5755 patients dialyzing in 51 units were analyzed; 990 (17%) tested positive and 465 (8%) were admitted with suspected COVID-19 between March 2 and May 31, 2020. Outcomes were associated with age, diabetes, local community COVID-19 rates, and dialysis unit size. A greater number of available side rooms and the introduction of mask policies for asymptomatic patients were inversely associated with outcomes. No association was seen with sex, ethnicity, or deprivation indices, nor with any of the different isolation strategies. CONCLUSIONS: Rates of COVID-19 in the in-center hemodialysis population relate to individual factors, underlying community transmission, unit size, and layout.
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COVID-19/etiologia , Diálise Renal , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Feminino , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
BACKGROUND: Vascular calcification is highly prevalent in chronic kidney disease (CKD) patients. This calcification leads to arterial stiffening. Fetuin-A is an endogenous inhibitor of vascular calcification and has been associated with arterial stiffness and mortality in dialysis patients. We tested the relationship between fetuin-A and change in arterial stiffness in CKD stages 3 and 4. METHODS: We measured fetuin-A concentrations in 92 patients with CKD stages 3 and 4 and studied the association with clinical, biochemical and vascular parameters including arterial stiffness measured by carotid-femoral pulse wave velocity (PWV) at 0 and 12 months. RESULTS: Fetuin-A was significantly lower in the non-diabetic group (n = 73) compared to the diabetic group (n = 19, P = 0.018). There was a significant interaction between diabetic status and fetuin-A concentration. Univariate analysis of the non-diabetic group showed association between change in aortic stiffness over 1 year with fetuin-A (r = -0.481, P < 0.0001) and systolic blood pressure (r = 0.389, P = 0.001) and baseline PWV (r = 0.240, P = 0.041). In multivariate analysis, fetuin-A, systolic blood pressure and baseline PWV independently predicted change in carotid-femoral PWV at 1 year (beta = -0.355, P = or< 0.001; beta = 0.426, P < 0.001; and beta = -0.383, P < 0.001, respectively; model R(2) = 0.455). CONCLUSIONS: In patients with non-diabetic CKD stages 3 and 4, fetuin-A is an independent risk factor for progressive arterial stiffness.
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Aorta/fisiopatologia , Proteínas Sanguíneas/metabolismo , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Idoso , Aorta/patologia , Pressão Sanguínea , Proteína C-Reativa/metabolismo , Calcinose/patologia , Calcinose/fisiopatologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fluxo Pulsátil , Insuficiência Renal Crônica/classificação , Insuficiência Renal Crônica/patologia , Fatores de Risco , Fatores de Tempo , Resistência Vascular , alfa-2-Glicoproteína-HSRESUMO
Background: Patients on dialysis with frequent comorbidities, advanced age, and frailty, who visit treatment facilities frequently, are perhaps more prone to SARS-CoV-2 infection and related death-the risk factors and dynamics of which are unknown. The aim of this study was to investigate the hospital outcomes in patients on dialysis infected with SARS-CoV-2. Methods: Data on 224 patients on hemodialysis between February 29, 2020 and May 15, 2020 with confirmed SARS-CoV-2 were analyzed for outcomes and potential risk factors for death, using a competing risk-regression model assessed by subdistribution hazards ratio (SHR). Results: Crude data analyses suggest an overall case-fatality ratio of 23% (95% CI, 17% to 28%) overall, but that varies across age groups from 11% (95% CI, 0.9% to 9.2%) in patients ≤50 years old and 32% (95% CI, 17% to 48%) in patients >80 years; with 60% of deaths occurring in the first 15 days and 80% within 21 days, indicating a rapid deterioration toward death after admission. Almost 90% of surviving patients were discharged within 28 days. Death was more likely than hospital discharge in patients who were more frail (WHO performance status, 3-4; SHR, 2.16 [95% CI, 1.25 to 3.74]; P=0.006), had ischemic heart disease (SHR, 2.28 [95% CI, 1.32 to 3.94]; P=0.003), cerebrovascular disease (SHR, 2.11 [95% CI, 1.20 to 3.72]; P=0.01), smoking history (SHR, 2.69 [95% CI, 1.33 to 5.45]; P=0.006), patients who were hospitalized (SHR, 10.26 [95% CI, 3.10 to 33.94]; P<0.001), and patients with high CRP (SHR, 1.35 [95% CI, 1.10 to 1.67]) and a high neutrophil:lymphocyte ratio (SHR, 1.03 [95% CI, 1.01 to 1.04], P<0.001). Our data did not support differences in the risk of death associated with sex, ethnicity, dialysis vintage, or other comorbidities. However, comparison with the entire dialysis population attending these hospitals, in which 13% were affected, revealed that patients who were non-White (62% versus 52% in all patients, P=0.001) and those with diabetes (54% versus 22%, P<0.001) were disproportionately affected. Conclusions: This report discusses the outcomes of a large cohort of patients on dialysis. We found SARS-CoV-2 infection affected more patients with diabetes and those who were non-White, with a high case-fatality ratio, which increased significantly with age, frailty, smoking, increasing CRP, and neutrophil:lymphocyte ratio at presentation.
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COVID-19 , COVID-19/epidemiologia , Estudos de Coortes , Humanos , Londres/epidemiologia , Pessoa de Meia-Idade , Diálise Renal , SARS-CoV-2RESUMO
Artifact in one form or another needs to be contended with in all EEG and EP studies. Various methods have been employed to avoid, eliminate, or minimize artifact. This article has described the methods that have been available for some time and newer methods and their advantages. It is the authors' hope that through the use of these methods the accuracy of all EP and ERP measurements will be improved and promote the validity and general acceptance of EP and ERP recordings. Genuine and valuable data are contained in EPs and ERPs. The challenge is to extract relatively small voltage signals often occurring within a higher voltage background of artifact. The computing power required to perform the artifact removal/reduction procedures now is available with basic laptop and desktop computers, as are the software programs that provide the artifact removal/reduction capabilities. It may be of interest for a prudent researcher to integrate the currently available artifact rejection methods before subjecting the ERP and EP data for further analysis and subsequent publication.