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1.
BMC Nephrol ; 23(1): 291, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35999520

RESUMO

BACKGROUND: Hyperphosphatemia occurs frequently in end-stage renal disease patients on hemodialysis and is associated with increased mortality. Hyperphosphatemia contributes to vascular calcification in these patients, but there is emerging evidence that it is also associated with endothelial cell dysfunction. METHODS: We conducted a cross-sectional study in hypertensive hemodialysis patients. We obtained pre-hemodialysis measurements of total peripheral resistance index (TPRI, non-invasive cardiac output monitor) and plasma levels of endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA). We ascertained the routine peridialytic blood pressure (BP) measurements from that treatment and the most recent pre-hemodialysis serum phosphate levels. We used generalized linear regression analyses to determine independent associations between serum phosphate with BP, TPRI, ET-1, and ADMA while controlling for demographic variables, parathyroid hormone (PTH), and interdialytic weight gain. RESULTS: There were 54 patients analyzed. Mean pre-HD supine and seated systolic and diastolic BP were 164 (27), 158 (21), 91.5 (17), and 86.1 (16) mmHg. Mean serum phosphate was 5.89 (1.8) mg/dL. There were significant correlations between phosphate with all pre-hemodialysis BP measurements (r = 0.3, p = .04; r = 0.4, p = .002; r = 0.5, p < .0001; and r = 0.5, p = .0003.) The correlations with phosphate and TPRI, ET-1, and ADMA were 0.3 (p = .01), 0.4 (p = .007), and 0.3 (p = .04). In our final linear regression analyses controlling for baseline characteristics, PTH, and interdialytic weight gain, independent associations between phosphate with pre-hemodialysis diastolic BP, TPRI, and ET-1 were retained (ß = 4.33, p = .0002; log transformed ß = 0.05, p = .005; reciprocal transformed ß = -0.03, p = .047). CONCLUSIONS: Serum phosphate concentration is independently associated with higher pre-HD BP, vasoconstriction, and markers of endothelial cell dysfunction. These findings demonstrate an additional negative impact of hyperphosphatemia on cardiovascular health beyond vascular calcification. TRIAL REGISTRATION: The study was part of a registered clinical trial, NCT01862497 (May 24, 2013).


Assuntos
Hiperfosfatemia , Hipertensão , Falência Renal Crônica , Calcificação Vascular , Pressão Sanguínea/fisiologia , Estudos Transversais , Células Endoteliais , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Falência Renal Crônica/complicações , Hormônio Paratireóideo , Fosfatos , Diálise Renal/efeitos adversos , Calcificação Vascular/complicações , Vasoconstrição , Aumento de Peso
2.
J Investig Med ; 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35853670

RESUMO

Natriuretic peptide levels are elevated in persons with chronic kidney disease (CKD) stages 1-3, but it remains unclear whether this is associated with extracellular volume excess or early cardiovascular changes. We hypothesized that patients with CKD stages 1-3 would have evidence of cardiovascular changes, which would associate with brain natriuretic peptide (BNP), amino-terminal-pro-BNP (NT-pro-BNP), and patient-reported symptoms.Outpatients with CKD stages 1-3 and non-CKD controls were enrolled. Cardiovascular parameters included extracellular water (ECW) normalized to body weight measured using whole-body multifrequency bioimpedance spectroscopy, and total peripheral resistance index (TPRI) and cardiac index measured by impedance cardiography. Dyspnea, fatigue, depression, and quality of life were quantified using questionnaires.Among 21 participants (13 with CKD), median (IQR) BNP was 47.0 (28.0-302.5) vs 19.0 (12.3-92.3) pg/mL, p=0.07, and NT-pro-BNP was 245.0 (52.0-976.8) vs 26.0 (14.5-225.8) pg/mL, p=0.08, in the CKD and control groups, respectively. Those with CKD had higher pulse pressure (79 (66-87) vs 64 (49-67) mm Hg, p=0.046) and TPRI (3721 (3283-4278) vs 2933 (2745-3198) dyn×s/cm5/m2, p=0.01) and lower cardiac index (2.28 (2.08-2.78) vs 3.08 (2.43-3.37) L/min/m2, p=0.02). In the overall cohort, natriuretic peptides correlated with pulse pressure (BNP r=0.59; NT-pro-BNP r=0.58), cardiac index (BNP r=-0.76; NT-pro-BNP r=-0.62), and TPRI (BNP r=0.48), p<0.05 for each, but not with ECW/weight. TPRI and blood pressure correlated moderately with symptoms.Elevated natriuretic peptides may coincide with low cardiac index and elevated peripheral resistance in patients with CKD stages 1-3. The role of these biomarkers to detect subclinical cardiovascular changes needs to be further explored.

3.
Hypertension ; 79(9): 2071-2080, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35766041

RESUMO

BACKGROUND: The SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated reductions in major cardiovascular disease events and mortality with an intensive systolic blood pressure (SBP) goal intervention. However, a detailed description of the blood pressure intervention, antihypertensive medication usage, blood pressure levels, and rates and predictors of blood pressure control has not been reported previously. METHODS: Hypertensive participants (n=9361) 50 years and older with elevated cardiovascular disease risk were randomized 1:1 to SBP goal <120 mm Hg or SBP goal <140 mm Hg. Guideline-recommended antihypertensive medications and dosing were provided at no cost. Intensive group participants were started on at least 2 medications, and medications were adjusted monthly until SBP goal was achieved, if feasible. Standard group participants were treated to achieve SBP 135 to 139 mm Hg. RESULTS: Baseline blood pressure (median±interquartile range) was 138±19/78±16 mm Hg. For intensive group participants, percent at goal rose from 8.9% at baseline to 52.4% at 6 months and average antihypertensive medications rose from 2.2 to 2.7; SBP was <120 mm Hg in 61.6% and <130 mm Hg in 80.0% at their final visit. For the standard group participants, percent at goal rose from 53.0% at baseline to 68.6% at 6 months, while antihypertensive medications fell from 1.9 to 1.8. From 6 to 36 months, median SBP was stable at 119±14 mm Hg for intensive and 136±15 mm Hg for standard participants, with stable numbers of medications. Few predictors of SBP control were found in multiple regression models. CONCLUSIONS: These results may inform and help replicate the benefits of SPRINT in clinical practice. REGISTRATION: URL: http://www. CLINICALTRIALS: gov; Unique identifier: NCT01206062.


Assuntos
Doenças Cardiovasculares , Hipertensão , Anti-Hipertensivos/farmacologia , Pressão Sanguínea , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Fatores de Risco , Resultado do Tratamento
4.
Planta ; 255(2): 35, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35015132

RESUMO

MAIN CONCLUSION: SorghumBase provides a community portal that integrates genetic, genomic, and breeding resources for sorghum germplasm improvement. Public research and development in agriculture rely on proper data and resource sharing within stakeholder communities. For plant breeders, agronomists, molecular biologists, geneticists, and bioinformaticians, centralizing desirable data into a user-friendly hub for crop systems is essential for successful collaborations and breakthroughs in germplasm development. Here, we present the SorghumBase web portal ( https://www.sorghumbase.org ), a resource for the sorghum research community. SorghumBase hosts a wide range of sorghum genomic information in a modular framework, built with open-source software, to provide a sustainable platform. This initial release of SorghumBase includes: (1) five sorghum reference genome assemblies in a pan-genome browser; (2) genetic variant information for natural diversity panels and ethyl methanesulfonate (EMS)-induced mutant populations; (3) search interface and integrated views of various data types; (4) links supporting interconnectivity with other repositories including genebank, QTL, and gene expression databases; and (5) a content management system to support access to community news and training materials. SorghumBase offers sorghum investigators improved data collation and access that will facilitate the growth of a robust research community to support genomics-assisted breeding.


Assuntos
Sorghum , Bases de Dados Genéticas , Grão Comestível , Genoma de Planta/genética , Genômica , Internet , Melhoramento Vegetal , Sorghum/genética
5.
Methods Mol Biol ; 2443: 197-209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35037207

RESUMO

SciApps is an open-source, web-based platform for processing, storing, visualizing, and distributing genomic data and analysis results. Built upon the Tapis (formerly Agave) platform, SciApps brings users TB-scale of data storage via CyVerse Data Store and over one million CPUs via the Extreme Science and Engineering Discovery Environment (XSEDE) resources at Texas Advanced Computing Center (TACC). SciApps provides users ways to chain individual jobs into automated and reproducible workflows in a distributed cloud and provides a management system for data, associated metadata, individual analysis jobs, and multi-step workflows. This chapter provides examples of how to (1) submitting, managing, constructing workflows, (2) using public workflows for Bulked Segregant Analysis (BSA), (3) constructing a Data Analysis Center (DAC), and Data Coordination Center (DCC) for the plant ENCODE project.


Assuntos
Genômica , Software , Biologia Computacional , Genoma de Planta , Genômica/métodos , Armazenamento e Recuperação da Informação , Fluxo de Trabalho
6.
Hemodial Int ; 26(1): 124-133, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34396668

RESUMO

INTRODUCTION: Extracellular volume (ECV) predicts mortality in hemodialysis patients, but it is difficult to assess clinically. Peridialytic blood pressure (BP) measurements can help ECV assessment. Orthostatic BP is routinely measured clinically, but its association with ECV is unknown. METHODS: In a cohort of hypertensive hemodialysis patients, we measured posthemodialysis ECV/weight with bioimpedance spectroscopy and analyzed its association with post-HD orthostatic BP measurements obtained during routine care. Using linear and logistic regression, the primary outcomes were orthostatic BP change and orthostatic hypotension (OH) defined by systolic BP decrease of at least 20 mmHg or diastolic decrease of at least 10 mmHg. Model 1 controlled for sex, age, and diabetes. Model 2 additionally controlled for ultrafiltration rate and antihypertensive medications. We conducted sensitivity analysis using OH definition of systolic BP decrease of at least 30 mmHg. FINDINGS: Among 57 participants, mean orthostatic systolic BP change was -7.30 (20) mmHg and mean ECV/weight was 0.24 (0.04) L/kg. Post-HD ECV/weight was not associated with orthostatic systolic BP change (ß = 8.2, p = 0.6). There were 16 participants with and 41 participants without OH. The ECV/weight did not differ between these groups (0.22 [0.04] vs. 0.24 [0.05] L/Kg, p = 0.09) and did not predict OH in logistic regression (OR 11, 4.04; 95% CI 0.2-671, 0.03-0.530 in the two models.) In a sensitivity analysis, ECV/weight was lower in the OH group (0.22 [0.03] vs. 0.25 [0.04] L/kg, p = 0.005), but this was accompanied by differences in sex and diabetes. Using logistic regression, there was no independent association between ECV/weight with OH. DISCUSSION: Orthostatic systolic BP change after HD completion is not a reliable indicator of posthemodialysis ECV. When considering other factors associated with orthostatic BP, ECV/weight is not independently associated with OH. Although transient postdialytic differences in intravascular volume may be associated with OH, posthemodialysis OH does not necessarily indicate ECV depletion.


Assuntos
Diabetes Mellitus , Hipertensão , Hipotensão Ortostática , Pressão Sanguínea/fisiologia , Humanos , Hipertensão/tratamento farmacológico , Diálise Renal
7.
Clin Kidney J ; 14(5): 1450-1457, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34221373

RESUMO

BACKGROUND: Hypertension and extracellular volume (ECV) overload are interrelated mortality risk factors in hemodialysis (HD) patients, but confounding related to changes in ECV and vasoconstriction during and between treatments obfuscate their relationship. We sought to clarify independent contributions of post-HD ECV and intradialytic changes in vasoconstriction on ambulatory blood pressure (BP) in patients with and without recurrent intradialytic hypertension (IH). METHODS: In this prospective observational study, we obtained measurements of pre- and post-HD ECV with bioimpedance spectroscopy (BIS), pre- and post-HD total peripheral resistance index and 44-h ambulatory BP. Linear regression determined associations between post-HD ECV/weight and intradialytic change in total peripheral resistance index (TPRI) with interdialytic BP and slope. RESULTS: In fully-adjusted models for participants with complete data, post-HD ECV/weight associated with mean ambulatory BP (ß = 133, P = 0.01; n = 52) and ambulatory BP slope (ß = -4.28, P = 0.03; n = 42). ECV/weight was associated with mean ambulatory BP in those with recurrent IH (ß = 314, P = 0.0005; n = 16) and with ambulatory BP slope in those without recurrent IH (ß = -4.56, P = 0.04; n = 28). Interdialytic weight gain percentage and intradialytic TPRI change were not associated with ambulatory BP or slope in any analyses. CONCLUSION: Ambulatory BP in HD patients is more strongly associated with post-HD ECV assessed with BIS than with intradialytic TPRI changes or interdialytic ECV increases. These findings highlight the essential role of recognizing and managing chronic ECV overload to improve ambulatory BP in HD patients, particularly so for those with IH.

9.
Hypertension ; 77(3): 948-959, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33423525

RESUMO

Visit-to-visit blood pressure variability (BPV) is associated with cardiovascular events in the general population. Data are scarce in chronic kidney disease. We hypothesized that BPV would be associated with cardiovascular outcomes, death, and end-stage kidney disease (ESKD) and that diuretics would modify these associations in patients with chronic kidney disease. We studied US Veterans with nondialysis chronic kidney disease stages 1-5 and hypertension on nondiuretic antihypertensive monotherapy. At the time of second antihypertensive agent prescription, we propensity-matched for exposure to a loop or thiazide diuretic versus any other antihypertensive. BPV was defined as the coefficient of variation of systolic blood pressure over 6 months after second agent prescription. Cox proportional hazards regression measured associations of BPV with a primary cardiovascular event composite (fatal or nonfatal myocardial infarction or ischemic stroke; heart failure hospitalization). Secondary outcomes included all-cause death, each primary outcome component, end-stage kidney disease, and cardiovascular death. There were 31 394 participants in each group. BPV was associated with composite cardiovascular events, hazard ratio (95% CI) at second, third, fourth, and fifth versus first quintile: 1.79 (1.53-2.11), 2.32 (1.99-2.71), 2.60 (2.24-3.02), and 3.12 (2.68-3.62). Diuretics attenuated associations between the fourth and fifth BPV quintiles with composite events (Pinteraction=0.03 and 0.04, respectively). BPV was associated with all secondary outcomes except end-stage kidney disease, with no diuretic interactions. BPV was associated with cardiovascular events and death but not end-stage kidney disease in patients with chronic kidney disease, with attenuated associations with cardiovascular events in the diuretic-treated group at high BPV quintiles. Future studies should investigate whether other antihypertensive classes modify these risks.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Diuréticos/uso terapêutico , Hipertensão/tratamento farmacológico , Insuficiência Renal Crônica/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Estudos de Coortes , Feminino , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/prevenção & controle , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia
10.
Kidney360 ; 2(10): 1553-1559, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-35372968

RESUMO

Background: Various causes of hypokalemia (HK) from renal potassium wasting, including distal renal tubular acidosis (RTA), have been described in lupus nephritis (LN). We report a phenomenon of otherwise unexplained HK among a population with LN. Methods: From our population of 403 patients with LN, we identified a cohort of 20 patients with idiopathic HK, defined by serum potassium <3.5 mmol/L without any apparent explanation. This cohort is compared with 90 LN controls (CON) and ten patients with LN with distal RTA from the same population. Results: The patients with HK had lower median serum potassium compared with CON and RTA subjects (3.26 versus 4.00 versus 3.75 mmol/L, respectively; P<0.001). The median serum bicarbonate was normal in HK and CON, but low in RTA (26.0 versus 25.0 versus 19.4 mmol/L; P<0.001). The median urine pH was abnormally high only in the RTA group (6.00 versus 6.25 versus 6.67; P=0.012). The median serum magnesium was modestly lower in HK compared with the CON and RTA groups (1.73 versus 2.00 versus 1.85 mg/dl; P=0.002). Although both HK and RTA showed a higher rate of seropositivity than CON for anti-Ro/SSA (79% and 80% versus 37%, respectively; P<0.001), only HK revealed a higher rate of seropositivity than CON for anti-RNP (84% versus 42%; P=0.003) and only RTA showed a higher rate of seropositivity than CON for anti-La/SSB (40% versus 12%; P=0.05). Conclusions: A syndrome of idiopathic HK was revealed in 20 out of 403 (5%) of patients within our LN population, and proved to be distinct from the RTA that occurs in LN. Furthermore, it was associated with a distinct pattern of autoantibodies. We speculate that idiopathic HK is the result of a novel target of autoimmunity in LN, affecting renal tubular potassium transport.


Assuntos
Acidose Tubular Renal , Hipopotassemia , Nefrite Lúpica , Acidose Tubular Renal/complicações , Bicarbonatos , Humanos , Hipopotassemia/etiologia , Nefrite Lúpica/complicações , Potássio
11.
Front Plant Sci ; 11: 289, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32296450

RESUMO

MaizeCODE is a project aimed at identifying and analyzing functional elements in the maize genome. In its initial phase, MaizeCODE assayed up to five tissues from four maize strains (B73, NC350, W22, TIL11) by RNA-Seq, Chip-Seq, RAMPAGE, and small RNA sequencing. To facilitate reproducible science and provide both human and machine access to the MaizeCODE data, we enhanced SciApps, a cloud-based portal, for analysis and distribution of both raw data and analysis results. Based on the SciApps workflow platform, we generated new components to support the complete cycle of MaizeCODE data management. These include publicly accessible scientific workflows for the reproducible and shareable analysis of various functional data, a RESTful API for batch processing and distribution of data and metadata, a searchable data page that lists each MaizeCODE experiment as a reproducible workflow, and integrated JBrowse genome browser tracks linked with workflows and metadata. The SciApps portal is a flexible platform that allows the integration of new analysis tools, workflows, and genomic data from multiple projects. Through metadata and a ready-to-compute cloud-based platform, the portal experience improves access to the MaizeCODE data and facilitates its analysis.

14.
Bioinformatics ; 34(22): 3917-3920, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-29897418

RESUMO

Motivation: The rapid accumulation of both sequence and phenotype data generated by high-throughput methods has increased the need to store and analyze data on distributed storage and computing systems. Efficient data management across these heterogeneous systems requires a workflow management system to simplify the task of analysis through automation and make large-scale bioinformatics analyses accessible and reproducible. Results: We developed SciApps, a web-based platform for reproducible bioinformatics workflows. The platform is designed to automate the execution of modular Agave apps and support execution of workflows on local clusters or in a cloud. Two workflows, one for association and one for annotation, are provided as exemplar scientific use cases. Availability and implementation: https://www.sciapps.org. Supplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Biologia Computacional , Fluxo de Trabalho , Computação em Nuvem , Software
15.
Nephron ; 139(2): 120-130, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29439257

RESUMO

BACKGROUND/AIMS: Extracellular volume (ECV) overload is a mortality risk factor in hemodialysis patients, but no standard approach exists to objectively assess this clinically. We aimed to quantify relationships between slopes of repeated intradialytic blood pressure (BP) measurements and ECV. METHODS: In a cross-sectional study of 71 hemodialysis patients, we calculated BP slopes from all intradialytic measurements using Gaussian regression. We measured extracellular and total body water (TBW) with bioimpedance spectroscopy. We analyzed unconditional and conditional associations between BP slope and volume metrics with mixed linear models and sensitivity analyses using non-linear intradialytic BP trajectory. RESULTS: Mean systolic intradialytic BP slope (IBPS) was -0.06 (0.1) mm Hg/min. Post-dialysis extracellular water (ECW)/weight was the volume metric mostly strongly associated with slope (r = 0.34, p = 0.007 for unconditional analysis; ß = 1.45, p = 0.001 for conditional analysis). Among subjects with post-dialysis systolic BP ≥130 mm Hg, the association strengthened (r = 0.40, p = 0.006; ß = 1.42, p = 0.003). ECV was more strongly associated with the BP slope than with pre-dialysis, post-dialysis, or delta systolic BP (r = -0.07, 0.19, 0.28; p = 0.6, 0.1, 0.03). In nonlinear models, BP trajectory also had the strongest association with post-dialysis ECW/body weight (p < 0.001). CONCLUSIONS: In hypertensive hemodialysis patients, measurements of ECV excess are more strongly associated with IBPSs than with pre-dialysis, post-dialysis, or change in systolic BP. Among varying volume metrics, post-dialysis ECW/weight has the strongest association with these slopes. Determining IBPS is a novel method to optimize clinical assessment of ECV in hemodialysis patients.


Assuntos
Pressão Sanguínea/fisiologia , Falência Renal Crônica/terapia , Diálise Renal , Adulto , Determinação da Pressão Arterial , Água Corporal , Peso Corporal , Estudos Transversais , Impedância Elétrica , Feminino , Humanos , Hipertensão/etiologia , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Desequilíbrio Hidroeletrolítico
16.
Semin Dial ; 30(6): 545-552, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28666072

RESUMO

Hypertension is a comorbidity that is present in the majority of end-stage renal disease patients on maintenance hemodialysis. This population is particularly unique because of the dynamic nature of blood pressure (BP) during dialysis. Modest BP decreases are expected in most hemodialysis patients, but intradialytic hypotension and intradialytic hypertension are two special situations that deviate from this as either an exaggerated or paradoxical response to the dialysis procedure. Both of these phenomena are particularly important because they are associated with increased mortality risk compared to patients with modest decreases in BP during dialysis. While the detailed pathophysiology is complex, intradialytic hypotension occurs more often in patients prescribed fast ultrafiltration rates, and reducing this rate is recommended in patients that regularly exhibit this pattern. Patients with intradialytic hypertension have a poorly explained increase in vascular resistance during dialysis, but the consistent associations with extracellular volume overload point toward more aggressive fluid management as the initial management choices for these patients. This up to date review provides the most recent evidence supporting these recommendations as well as the most up to date epidemiologic and mechanistic research studies that have added to this area of dialysis management.


Assuntos
Hipertensão/etiologia , Hipotensão/etiologia , Falência Renal Crônica/complicações , Diálise Renal/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Volume Sanguíneo/fisiologia , Doença Crônica , Feminino , Humanos , Hipertensão/tratamento farmacológico , Falência Renal Crônica/terapia , Masculino
17.
J Investig Med High Impact Case Rep ; 5(1): 2324709617700648, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28491878

RESUMO

Moxifloxacin is commonly prescribed in the inpatient and outpatient management of community-acquired pneumonia and other common infections. We report a case of a 76-year-old man who developed severe neutropenia after several days of treatment for community-acquired pneumonia. The patient had a history of alcohol abuse; however, there were no other offending medications prescribed, and a thorough laboratory workup for other possible causes of neutropenia was negative. The patient's neutrophils and white blood count responded quickly to cessation of fluoroquinolones. This case highlights the importance of identifying patients that might be at high risk for neutropenia that may need closer monitoring on this commonly prescribed medication.

18.
JAMA ; 317(19): 1958-1966, 2017 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-28510680

RESUMO

IMPORTANCE: Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced functional capacity and mortality. However, the efficacy of inexpensive readily available oral iron supplementation in heart failure is unknown. OBJECTIVE: To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency. DESIGN, SETTING, AND PARTICIPANTS: Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF (<40%) and iron deficiency, defined as a serum ferritin level of 15 to 100 ng/mL or a serum ferritin level of 101 to 299 ng/mL with transferrin saturation of less than 20%. Participants were enrolled between September 2014 and November 2015 at 23 US sites. INTERVENTIONS: Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was a change in peak oxygen uptake (V̇o2) from baseline to 16 weeks. Secondary end points were change in 6-minute walk distance, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and health status as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life). RESULTS: Among 225 randomized participants (median age, 63 years; 36% women) 203 completed the study. The median baseline peak V̇o2 was 1196 mL/min (interquartile range [IQR], 887-1448 mL/min) in the oral iron group and 1167 mL/min (IQR, 887-1449 mL/min) in the placebo group. The primary end point, change in peak V̇o2 at 16 weeks, did not significantly differ between the oral iron and placebo groups (+23 mL/min vs -2 mL/min; difference, 21 mL/min [95% CI, -34 to +76 mL/min]; P = .46). Similarly, at 16 weeks, there were no significant differences between treatment groups in changes in 6-minute walk distance (-13 m; 95% CI, -32 to 6 m), NT-proBNP levels (159; 95% CI, -280 to 599 pg/mL), or KCCQ score (1; 95% CI, -2.4 to 4.4), all P > .05. CONCLUSIONS AND RELEVANCE: Among participants with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks. These results do not support use of oral iron supplementation in patients with HFrEF. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02188784.


Assuntos
Tolerância ao Exercício , Ferritinas/sangue , Insuficiência Cardíaca/fisiopatologia , Compostos de Ferro/administração & dosagem , Deficiências de Ferro , Consumo de Oxigênio , Volume Sistólico/fisiologia , Administração Oral , Idoso , Método Duplo-Cego , Feminino , Nível de Saúde , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/metabolismo , Humanos , Compostos de Ferro/efeitos adversos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Qualidade de Vida , Fatores de Tempo , Transferrina/metabolismo , Resultado do Tratamento , Teste de Caminhada
19.
Curr Opin Nephrol Hypertens ; 26(4): 303-310, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28399019

RESUMO

PURPOSE OF REVIEW: Intradialytic hypertension occurs regularly in 10--15% of hemodialysis patients. A large observational study recently showed that intradialytic hypertension of any magnitude increased mortality risk comparable to the most severe degrees of intradialytic hypotension. The present review review discusses the most recent evidence underlying the pathophysiology of intradialytic hypertension and implications for its management. RECENT FINDINGS: Patients with intradialytic hypertension typically have small interdialytic weight gains, but bioimpedance spectroscopy shows these patients have significant chronic extracellular volume excess. Intradialytic hypertension patients have lower albumin and predialysis urea nitrogen levels, which may contribute to small reductions in osmolarity that prevents blood pressure decreases. Intradialytic vascular resistance surges remain implicated as the driving force for blood pressure increases, but mediators other than endothelin-1 may be responsible. Beyond dry weight reduction, the only controlled intervention shown to interrupt the blood pressure increase is lowering dialysate sodium. SUMMARY: Patients with recurrent intradialytic hypertension should be identified as high-risk patients. Dry weight should be re-evaluated, even if patients do not clinically appear volume overloaded. Antihypertensive drugs should be prescribed because of the persistently elevated ambulatory blood pressure. Dialysate sodium reduction should be considered, although the long term effects of this intervention are uncertain.


Assuntos
Hipertensão/fisiopatologia , Diálise Renal/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/fisiopatologia
20.
Kidney Blood Press Res ; 41(6): 802-814, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27832647

RESUMO

BACKGROUND/AIMS: Intradialytic hypertension (IH) occurs frequently in some hemodialysis patients and increases mortality risk. We simultaneously compared pre-dialysis, post-dialysis and changes in extracellular volume and hemodynamics in recurrent IH patients and controls. METHODS: We performed a case-control study among prevalent hemodialysis patients with recurrent IH and hypertensive hemodialysis controls. We used bioimpedance spectroscopy and impedance cardiography to compare pre-dialysis, post-dialysis, and intradialytic change in total body water (TBW) and extracellular water (ECW), as well as cardiac index (CI) and total peripheral resistance index (TPRI). RESULTS: The ECW/TBW was 0.453 (0.05) pre-dialysis and 0.427 (0.04) post-dialysis in controls vs. 0.478 (0.03) and 0.461 (0.03) in IH patients (p=0.01 post-dialysis). The ECW/TBW change was -0.027 (0.03) in controls and -0.013 (0.02) in IH patients (p=0.1). In controls, pre- and post-dialysis TPRI were 3254 (994) and 2469 (529) dynes/sec/cm2/m2 vs. 2983 (747) and 3408 (980) dynes/sec/cm2/m2 in IH patients (p=0.002 post-dialysis). There were between-group differences in TPRI change (0=0.0001), but not CI (p=0.09). CONCLUSIONS: Recurrent intradialytic hypertension is associated with higher post-dialysis extracellular volume and TPRI. Intradialytic TPRI surges account for the vasoconstrictive state post-dialysis, but intradialytic fluid shifts may contribute to post-hemodialysis volume expansion.


Assuntos
Líquido Extracelular/fisiologia , Hipertensão/fisiopatologia , Diálise Renal/efeitos adversos , Vasoconstrição , Adulto , Água Corporal/metabolismo , Estudos de Casos e Controles , Impedância Elétrica , Feminino , Deslocamentos de Líquidos Corporais/fisiologia , Humanos , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Recidiva
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