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1.
Clin Chem ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33257944

RESUMO

BACKGROUND: Establishment and improvement of glomerular filtration rate estimating equations requires accurate and precise laboratory measurement procedures (MPs) for filtration markers. The Advanced Research and Diagnostic Laboratory (ARDL) at the University of Minnesota, which has served as the central laboratory for the Chronic Kidney Disease Epidemiology Collaboration since 2009, has implemented several quality assurance measures to monitor the accuracy and stability of filtration marker assays over time. METHODS: To assess longitudinal stability for filtration marker assays, a 40-sample calibration panel was created using pooled serum, divided into multiple frozen aliquots stored at -80 °C. ARDL monitored 4 markers-creatinine, cystatin C, beta-2-microglobulin (B2M) and beta-trace protein-measuring 15 calibration panel aliquots from 2009 to 2019. Initial target values were established using the mean of the first 3 measurements performed in 2009-10, and differences from target were monitored over time. New MPs for cystatin C and B2M were added in 2012, with target values established using the first measurement. RESULTS: The mean percentage difference from mean target values across time was <2% for all original MPs (-0.59% for creatinine; -0.94% for cystatin C; -0.82% for B2M; 1.24% for beta-trace protein). CONCLUSIONS: Close monitoring of filtration marker trends with a calibration panel at ARDL demonstrates remarkable long-term stability of the MPs. Routine use of a calibration panel for both research studies and clinical care is recommended for filtration markers where longitudinal monitoring is important to detect analytical biases, which can mask or confound true clinical trends in patients.

3.
J Clin Lipidol ; 14(4): 531-541, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32651087

RESUMO

BACKGROUND: Fasting free fatty acid (FFA) levels may be associated with cardiovascular disease (CVD) and mortality, but research among generally healthy adults, females, and racially/ethnically diverse populations is lacking. OBJECTIVE: The primary aim of this project was to investigate prospective associations between fasting FFAs and coronary heart disease (CHD) and CVD incidence and CVD-specific and all-cause mortality in a generally healthy age, sex, and racially/ethnically heterogeneous population. METHODS: This study was conducted in the Multi-Ethnic Study of Atherosclerosis cohort using baseline (2000-2002) fasting FFAs and outcome data through 2015 (N = 6678). Cox proportional hazards regression was used to calculate hazard ratios for associations between FFAs and CHD, CVD, CVD-specific mortality, and all-cause mortality. Interactions by age, sex, race/ethnicity, and metabolic syndrome were evaluated by stratification and cross-product terms. A secondary analysis was conducted to evaluate associations between FFAs, and inflammatory and endothelial activation biomarkers were evaluated using linear regression (analytic N range: 964-6662). RESULTS: FFA levels were not associated with CHD or CVD incidence. Higher FFAs were associated with CVD-specific and all-cause mortality, but associations were attenuated in fully adjusted models with a borderline significant association remaining only for all-cause mortality (fully adjusted, per standard deviation increase hazard ratio = 1.07, 95% confidence interval: 1.00-1.14). Associations did not differ by age, sex, race/ethnicity, or metabolic syndrome. CONCLUSIONS: Fasting FFAs were not associated with CHD, CVD, or CVD-specific mortality and were modestly associated with all-cause mortality, regardless of age, sex, race/ethnicity, or metabolic syndrome status.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32620506

RESUMO

BACKGROUND: Lipoprotein (a) [Lp(a)] is a risk factor for coronary heart disease and calcific aortic valve disease. We determined the relationships of Lp(a) with prevalence and progression of coronary artery calcification (CAC), mitral annular calcification (MAC), and thoracic aortic calcification (TAC) in a multi-ethnic cohort of middle to older-aged adults. METHODS: This analysis included 6705 Multi-Ethnic Study of Atherosclerosis participants. Lp(a) was measured with a turbidimetric immunoassay. CAC, MAC, and TAC were assessed by cardiac computed tomography both at baseline and once during follow-up. RESULTS: In adjusted relative risk regression cross-sectional analysis, a Lp(a) level ≥50 mg/dL was associated with a 22% higher prevalence of MAC (relative risk (RR) = 1.22, 95% confidence interval (CI) 1.00, 1.49). No significant associations were observed for prevalent CAC or TAC. In adjusted prospective analyses, participants with Lp(a) ≥50 mg/dL were at significantly higher risk for rapid CAC progression (median follow-up = 8.9 years), defined as ≥100 units/year, compared to those with lower Lp(a) levels (RR = 1.67, 95% CI = 1.23, 2.27). The association between higher Lp(a) levels and incident CHD was no longer significant after adjusting for CAC progression. No significant associations were observed for MAC or TAC progression (median follow-up = 2.6 years). CONCLUSIONS: Higher Lp(a) levels are associated with more rapid CAC progression. Additional study is needed to better understand how this relationship can further improve the ability of Lp(a) to enhance cardiovascular disease risk prediction.

5.
N Engl J Med ; 382(26): 2493-2503, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32579810

RESUMO

BACKGROUND: Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease. METHODS: In a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m2 of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed. RESULTS: A total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m2 in the allopurinol group and 67.3 ml per minute per 1.73 m2 in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m2 (95% confidence interval [CI], -1.9 to 1.9; P = 0.99). The mean decrease in the iohexol-based GFR was -3.0 ml per minute per 1.73 m2 per year with allopurinol and -2.5 ml per minute per 1.73 m2 per year with placebo (between-group difference, -0.6 ml per minute per 1.73 m2 per year; 95% CI, -1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups. CONCLUSIONS: We found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; PERL ClinicalTrials.gov number, NCT02017171.).


Assuntos
Alopurinol/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Inibidores Enzimáticos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Ácido Úrico/sangue , Xantina Oxidase/antagonistas & inibidores , Adulto , Idoso , Alopurinol/efeitos adversos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina , Falha de Tratamento
7.
Clin Nutr ; 39(10): 3031-3041, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32008872

RESUMO

BACKGROUND & AIMS: Omega-6 polyunsaturated fatty acids (PUFAs) have been shown to relate to insulin resistance and type 2 diabetes (T2D), but influence of race/ethnicity has not been investigated. The aim of this study was to determine whether omega-6 PUFAs, and estimated desaturase enzyme activity, are associated with fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and incident T2D, and whether associations differ by race/ethnicity. METHODS: This study was conducted in the Multi-Ethnic Study of Atherosclerosis (MESA) (N = 6282). Associations between baseline plasma phospholipid fatty acids (LA, Linoleic Acid; GLA, γ-linoleic acid; DGLA, Dihomo-γ-linolenic acid; AA, arachidonic acid; D5D, delta-5 desaturase; D6D, delta-6 desaturase), fasting glucose, insulin, and HOMA-IR [(fasting insulin - fasting glucose)/22.5] were evaluated using linear regression. Associations between omega-6 PUFAs (N = 5508 after excluding diabetics at baseline) and T2D incidence were assessed using Cox proportional hazards regression. Analyses were replicated/stratified by race/ethnicity (White, Black, Chinese, Hispanic) and tests for interaction were assessed by inclusion of a cross-product term in models. RESULTS: In fully adjusted models, insulin and HOMA-IR were positively associated with LA (insulin: 0.213 per SD, p = 0.01; HOMA-IR: 0.252 per SD, p < 0.001), GLA (insulin: 0.010 per SD, p < 0.001; HOMA-IR: 0.006 per SD, p < 0.001), DGLA (insulin: 0.279 per SD, p < 0.001; HOMA-IR: 0.175 per SD, p < 0.001) and D6D activity (insulin: 0.001 per SD, p < 0.001; HOMA-IR: 0.006 per SD, p < 0.001), and inversely associated with AA (insulin -0.272 per SD, p < 0.001; HOMA-IR: -0.125 per SD, p = 0.03) and D5D activity (insulin: -0.530 per SD, p < 0.001; HOMA-IR: -0.322 per SD, p < 0.001), while weak or no associations were observed with fasting glucose, and associations appeared to differ by race/ethnicity. After accounting for HOMA-IR at baseline, LA was inversely (HR: 0.87, p = 0.003) and DGLA (HR: 1.17, p < 0.001) and AA (HR: 1.15, p = 0.001) were positively associated with T2D in the overall population, but associations were attenuated or no longer present when stratified by race/ethnicity (P-interaction >0.05). CONCLUSIONS: Results confirm previous reports that omega-6 PUFAs are associated with hyperinsulinemia. Findings suggest omega-6 PUFAs are more likely markers of hyperinsulinemia rather than a protective/risk factor for T2D and indicate racial/ethnic differences in associations, but further research is needed to confirm findings.

8.
J Am Heart Assoc ; 9(3): e013934, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32013703

RESUMO

Background While elevated homocysteine has been associated with calcification in several studies, its importance as a cardiovascular risk factor remains unclear. This study examines the relationship between homocysteine and vascular and valve calcification in the MESA (Multi-ethnic Study of Atherosclerosis) cohort. Methods and Results MESA participants with baseline homocysteine measurements and cardiac computed tomography scans were included (N=6789). Baseline and follow-up assessment of vascular (coronary artery [CAC], descending thoracic aorta [DTAC]) and valve (aortic valve [AVC], mitral annular [MAC]) calcification was performed. Prevalence ratio/relative risk regression was used to assess the relationship of homocysteine with prevalent and incident calcification, and multivariable logistic regression was used to assess associations between homocysteine and calcification progression. Elevated homocysteine was associated with greater relative risk of prevalent and incident CAC and incident DTAC. We also identified a strong association between elevated homocysteine and CAC and DTAC progression. Elevated homocysteine was found to confer a >2-fold increased risk of severe CAC progression (defined as ΔCAC ≥100/year) and an ≈1.5-fold increased risk for severe DTAC progression (defined as ΔDTAC ≥100/year). Conclusions To our knowledge, this is the first study demonstrating an association between elevated homocysteine and both incidence and progression of coronary and extra-coronary vascular calcification. Our findings suggest a potential role for elevated homocysteine as a risk factor for severe vascular calcification progression. Future studies are warranted to further assess the utility of homocysteine as a biomarker for vascular calcification incidence and progression. Clinical Trial Registration https://www.clinicaltrials.gov/. Unique identifier: NCT00005487.

9.
Perit Dial Int ; 40(1): 84-92, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32063147

RESUMO

BACKGROUND: International Society for Peritoneal Dialysis guidelines recommend to routinely monitor the total measured clearance (mCl) of small solutes such as creatinine; however, collection of 24-h urine and peritoneal dialysis (PD) fluid is burdensome to patients and prone to errors. We hypothesized that equations could be developed to estimate mCl (estimated clearance (eCl)) using endogenous filtration markers. METHODS: In the Guangzhou PD Study (n = 980), we developed eCl equations using linear regression in two-third and validated them in the remaining one-third. Reference tests were mCl for urea nitrogen (UN) (mClUN, ml/min) and average mCl for UN and creatinine (mClUN-cr, ml/min/1.73 m2). Index tests were various eCl equations using UN, creatinine, low-molecular-weight proteins (LMWPs) (beta-trace protein (BTP), beta-2 microglobulin (B2M), and cystatin C), demographic variables, and body size. After reexpression of the equations in the combined data set, we analyzed accuracy (eCl within ± 2.0 units of mCl) and the predictive value of eCl to detect a weekly total standard Kt/V (weekly mClUN indexed for total body water) > 1.7 using receiver operating characteristic curve. RESULTS: Mean age of the cohort was 50 ± 15 years, 53% were male; mClUN was 6.9 ± 1.8 and mClUN-cr was 7.5 ± 2.8. Creatinine but not UN contributed to eCl for both mCl. LMWP did not improve accuracy for mClUN (range 88-89%). BTP and B2M improved the accuracy for mClUN-cr (82% vs. 80%); however, differences were small. The area under the curve for predicting a weekly Kt/V > 1.7 was similar for all equations (range 0.79-0.80). CONCLUSIONS: Total small solute clearance can be estimated moderately well in continuous ambulatory PD patients using serum creatinine and demographic variables without urine and dialysate collection.

10.
J Clin Lipidol ; 14(1): 109-121.e5, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882375

RESUMO

BACKGROUND: Discordant levels of apolipoprotein B (apo B) relative to low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) may be associated with subclinical atherosclerotic cardiovascular disease (ASCVD). OBJECTIVE: The present study investigated whether discordance between apo B and LDL-C or non-HDL-C levels was associated with subclinical ASCVD measured by coronary artery calcium (CAC). METHODS: This study was conducted in a subpopulation of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, aged 45 to 84 years, free of ASCVD, and not taking lipid-lowering medications at the baseline (2000-2002) (prevalence analytic N = 4623; incidence analytic N = 2216; progression analytic N = 3947). Apo B discordance relative to LDL-C and non-HDL-C was defined using residuals and percentile rankings (>5/10/15 percentile). Associations with prevalent and incident CAC (CAC > 0 vs CAC = 0) were assessed using prevalence ratio/relative risk regression and CAC progression (absolute increase/year) using multinomial logistic regression. RESULTS: Higher apo B levels were associated with CAC prevalence, incidence, and progression. Apo B discordance relative to LDL-C or non-HDL-C was inconsistently associated with CAC prevalence and progression. Discordantly high apo B relative to LDL-C and non-HDL-C was associated with CAC progression. Associations for apo B discordance with non-HDL-C remained after further adjustment for metabolic syndrome components. CONCLUSION: Apo B was associated with CAC among adults aged ≥45 years not taking statins, but provided only modest additional predictive value of apo B for CAC prevalence, incidence, or progression beyond LDL-C or non-HDL-C. Apo B discordance may still be important for ASCVD risk assessment and further research is needed to confirm findings.

11.
Am J Kidney Dis ; 76(1): 54-62, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31879216

RESUMO

RATIONALE & OBJECTIVE: Glomerular filtration rate (GFR) estimation based on creatinine or cystatin C level is currently the standard method for assessing GFR in epidemiologic research and clinical trials despite several important and well-known limitations. Plasma iohexol clearance has been proposed as an inexpensive method for measuring GFR that could replace estimated GFR in many research projects. However, lack of standardization for iohexol assays and the use of different protocols such as single- and multiple-sample methods could potentially hamper comparisons across studies. We compared iohexol assays and GFR measurement protocols in 3 population-based European cohorts. STUDY DESIGN: Cross-sectional investigation. SETTING & PARTICIPANTS: Participants in the Age, Gene/Environment Susceptibility-Kidney Study (AGES-Kidney; n=805), the Berlin Initiative Study (BIS, n=570), and the Renal Iohexol Clearance Survey Follow-up Study (RENIS-FU; n=1,324). TESTS COMPARED: High-performance liquid chromatography analyses of iohexol. Plasma iohexol clearance calculated using single- versus multiple-sample protocols. OUTCOMES: Measures of agreement between methods. RESULTS: Frozen samples from the 3 studies were obtained and iohexol concentrations were remeasured in the laboratory at the University Hospital of North Norway. Lin's concordance correlation coefficient ρ was>0.96 and Cb (accuracy) was>0.99 for remeasured versus original serum iohexol concentrations in all 3 cohorts, and Passing-Bablok regression did not find differences between measurements, except for a slope of 1.025 (95% CI, 1.006-1.046) for the log-transformed AGES-Kidney measurements. The multiple-sample iohexol clearance measurements in AGES-Kidney and BIS were compared with single-sample GFRs derived from the same iohexol measurements. Mean bias for multiple-sample relative to single-sample GFRs in AGES-Kidney and BIS were-0.25 and-0.15mL/min, and 99% and 97% of absolute differences were within 10% of the multiple-sample result, respectively. LIMITATIONS: Lack of comparison with an independent gold-standard method. CONCLUSIONS: Agreement between the iohexol assays and clearance protocols in the 3 investigated cohorts was substantial. Our findings indicate that plasma iohexol clearance measurements can be compared across these studies.


Assuntos
Envelhecimento/sangue , Meios de Contraste/metabolismo , Taxa de Filtração Glomerular/fisiologia , Iohexol/metabolismo , Taxa de Depuração Metabólica/fisiologia , Vigilância da População , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Interação Gene-Ambiente , Alemanha/epidemiologia , Humanos , Islândia/epidemiologia , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia
12.
Clin Biochem ; 71: 74-76, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31287996

RESUMO

OBJECTIVE: During the last decade, guidelines published by the American College of Obstetricians and Gynecologists (ACOG) and Society for Maternal Fetal Medicine (SMFM) have emphasized an increasingly limited role for fetal lung maturity (FLM) testing. As a reference laboratory for FLM testing, we were therefore interested in determining the impact of changing guidelines on our test volumes. METHODS: We retrospectively reviewed FLM test volume data from 2006 to 2016 for the following FLM assays: lecithin/sphingomyelin ratio, phosphatidylglycerol, disaturated lecithin, and lamellar body count. RESULTS: We found that there was a precipitous decline in test volumes from 2006 to 2016; our analysis led us to discontinue providing reference laboratory FLM testing in 2016 given the very low volumes. CONCLUSIONS: The 2019 ACOG guidelines now state that FLM testing no longer has clinical utility. Therefore, clinical laboratory directors should meet with obstetrics providers to discuss discontinuation of FLM testing at their institutions.


Assuntos
Guias como Assunto , Pulmão/embriologia , Maturidade dos Órgãos Fetais , Humanos , Estudos Retrospectivos
13.
Diabetes Care ; 42(8): 1454-1463, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31186299

RESUMO

OBJECTIVE: Higher serum uric acid (SUA) is associated with diabetic kidney disease (DKD). Preventing Early Renal Loss in Diabetes (PERL) evaluates whether lowering SUA with allopurinol slows glomerular filtration rate (GFR) loss in people with type 1 diabetes (T1D) and mild to moderate DKD. We present the PERL rationale, design, and baseline characteristics. RESEARCH DESIGN AND METHODS: This double-blind, placebo-controlled, multicenter trial randomized 530 participants with T1D, estimated GFR (eGFR) of 40-99.9 mL/min/1.73 m2, SUA ≥4.5 m/dL, and micro- to macroalbuminuric DKD or normoalbuminuria with declining kidney function (NDKF) (defined as historical eGFR decline ≥3 mL/min/1.73 m2/year) to allopurinol or placebo. The primary outcome is baseline-adjusted iohexol GFR (iGFR) after 3 years of treatment plus a 2-month washout period. RESULTS: Participants are 66% male and 84% white. At baseline, median age was 52 years and diabetes duration was 35 years, 93% of participants had hypertension, and 90% were treated with renin-angiotensin system inhibitors (median blood pressure 127/71 mmHg). Median HbA1c was 8%, SUA 5.9 mg/dL, iGFR 68 mL/min/1.73 m2, and historical eGFR slope -3.5 mL/min/1.73 m2/year. Compared with participants with albuminuria (n = 419), those with NDKF (n = 94) were significantly older (56 vs. 52 years), had lower HbA1c (7.7 vs. 8.1%) and SUA (5.4 vs. 6.0 mg/dL), and had higher eGFR (82 vs. 74 mL/min/1.73 m2) and historical eGFR loss (-4.7 vs. -2.5 mL/min/1.73 m2/year). These differences persisted when comparing groups with similar rates of historical eGFR loss. CONCLUSIONS: PERL will determine the effect of allopurinol on mild to moderate DKD in T1D, with or without albuminuria. Participants with normoalbuminuria and rapid GFR loss manifested many DKD risk factors of those with albuminuria, but with less severity.


Assuntos
Alopurinol/uso terapêutico , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/tratamento farmacológico , Taxa de Filtração Glomerular/efeitos dos fármacos , Ácido Úrico/sangue , Idoso , Albuminúria/tratamento farmacológico , Albuminúria/etiologia , Albuminúria/fisiopatologia , Pressão Sanguínea , Diabetes Mellitus Tipo 1/sangue , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina/efeitos dos fármacos , Fatores de Risco
14.
Clin Biochem ; 66: 95-99, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30790543

RESUMO

OBJECTIVE: The LeadCare Ultra® (LCU) was compared to inductively coupled plasma mass spectrometry ICP-MS for use as a screening test for elevated blood lead levels (BLLs) in capillary samples from children. METHODS: During the validation, method comparisons between LCU and ICP-MS were analyzed to determine the bias above, near, and below the BLL cut-off of 5 µg/dL. Additionally, capillary samples that screened positive by LCU (above the 5 µg/dL cut-off) were compared to venous samples analyzed by ICP-MS for confirmatory testing. RESULTS: LCU had a positive bias (1.7 µg/dL) below the cut-off of BLL <5 µg/dL, no bias near the cut-off from BLL 5-10 µg/dL, and a negative bias (-0.8 µg/dL) for BLL >10 µg/dL compared to ICP-MS. Of the 59 capillary samples that screened positive by LCU between May of 2017 to April of 2018, 19 were confirmed positive by ICP-MS, 30 were confirmed negative by ICP-MS, and 10 did not have a confirmed result. CONCLUSION: The LCU assay is an acceptable screen for capillary samples with the BLL cut-off of 5 µg/dL.


Assuntos
Análise Química do Sangue/métodos , Chumbo/sangue , Técnicas Eletroquímicas , Reações Falso-Positivas , Humanos , Espectrometria de Massas/métodos
15.
Arterioscler Thromb Vasc Biol ; 39(3): 523-529, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30727753

RESUMO

Objective- Lp(a) [lipoprotein(a)] is a well-described risk factor for atherosclerosis, but Lp(a)-associated risk may vary by race/ethnicity. We aimed to determine whether race/ethnicity modifies Lp(a)-related risk of carotid atherosclerotic plaque outcomes among black, white, Chinese, and Hispanic individuals. Approach and Results- Carotid plaque presence and score were assessed by ultrasonography at baseline (n=5155) and following a median 9.4 year period (n=3380) in MESA (Multi-Ethnic Study of Atherosclerosis) participants. Lp(a) concentrations were measured by immunoassay and examined as a continuous and categorical variable using clinically-based cutoffs, 30 and 50 mg/dL. Lp(a) was related to greater risk of prevalent carotid plaque at baseline in whites alone (all P<0.001): per log unit (relative risk, 1.05); Lp(a)≥30 mg/dL (relative risk, 1.16); and Lp(a)≥50 mg/dL (relative risk, 1.20). Lp(a) levels over 50 mg/dL were associated with a higher plaque score at baseline in whites (all P<0.001) and Hispanics ( P=0.04). In prospective analyses, whites with Lp(a) ≥50 mg/dL were found to have greater risk of plaque progression (relative risk, 1.12; P=0.03) and higher plaque scores (all P<0.001) over the 9.4-year follow-up. Race-based differences between whites and black participants were significant for cross-sectional associations and for carotid plaque score following the 9.4 year study period. Conclusions- Race was found to be a modifying variable in Lp(a)-related risk of carotid plaque, and Lp(a) levels may have greater influence on plaque burden in whites than in black individuals. Borderline results in Hispanics suggest that elevated Lp(a) may increase the risk of carotid plaque, but follow-up studies are needed.


Assuntos
Doenças das Artérias Carótidas/etnologia , Grupos de Populações Continentais , Lipoproteína(a)/sangue , Placa Aterosclerótica/etnologia , Grupo com Ancestrais do Continente Africano , Idoso , Idoso de 80 Anos ou mais , Antropometria , Americanos Asiáticos , Doenças das Artérias Carótidas/sangue , Comorbidade , Estudos Transversais , Diabetes Mellitus/etnologia , Grupo com Ancestrais do Continente Europeu , Feminino , Seguimentos , Hispano-Americanos , Humanos , Hipertensão/etnologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Prevalência , Risco , Fumar/etnologia , Fatores Socioeconômicos
16.
Lab Med ; 49(3): 280-283, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29608741

RESUMO

Hyperkalemia in specimens from patients with chronic lymphocytic leukemia (CLL) may be due to tumor lysis syndrome (TLS) or specimen processing. This report describes a 55-year-old Caucasian woman with CLL who presented to an outside hospital with hyperkalemia and was transferred to a second hospital. Initial evaluation on the core laboratory chemistry analyzer (the VITROS 5600) and the ABL90 FLEX blood gas analyzer showed markedly elevated levels of potassium (K+). TLS was subsequently diagnosed, and dialysis was initiated. However, follow-up K+ measurements in whole blood (WB) yielded low levels that were unexpected after a single dialysis treatment. We then discovered that the initially elevated K+ level was from centrifuged plasma specimens and concluded that it indicated pseudohyperkalemia, likely from centrifugation. This case demonstrates that medical teams need be alert to potentially false K+ results in patients with elevated white blood cell counts. WB specimens are preferable, and steps to minimize trauma to the specimen and immediate analysis using blood gas instruments are recommended.


Assuntos
Hiperpotassemia , Leucemia Linfocítica Crônica de Células B , Potássio/sangue , Centrifugação , Feminino , Humanos , Hiperpotassemia/sangue , Hiperpotassemia/fisiopatologia , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/fisiopatologia , Contagem de Leucócitos , Pessoa de Meia-Idade , Síndrome de Lise Tumoral
17.
Clin Biochem ; 55: 86-88, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29588177

RESUMO

OBJECTIVE: This case report investigates an unusual hCG result in a woman who is not pregnant. PATIENT AND METHODS: A 43-year-old woman was admitted for recurrence of thrombotic thrombocytopenic purpura (TTP) and therapeutic plasma exchange (TPE) was initiated. Prior to transitioning the patient from TPE to immunosuppressive therapy, a serum qualitative hCG test was performed and was positive. Several etiologies for elevated hCG were considered and investigated, including heterophile antibody interference, endogenous hCG from pituitary or malignancy, and exogenous hCG. RESULTS: Retrospective measurement of hCG levels in remnant samples, including a sample obtained prior to TPE initiation, demonstrated that the hCG elevation occurred with plasma administration for TPE. Further investigation with the American Red Cross confirmed that a plasma donor was unknowingly pregnant and in the latter half of the first trimester at the time of donation, when hCG levels peak. CONCLUSION: In plasma recipients with unexplained hCG elevation, passive transfer of hCG from plasma should be considered in the differential diagnosis. Retrospective measurement of hCG in remnant samples obtained prior to plasma exchange can assist in confirming the source.


Assuntos
Gonadotropina Coriônica/sangue , Púrpura Trombocitopênica Trombótica/sangue , Adulto , Feminino , Humanos , Imunossupressão , Troca Plasmática , Púrpura Trombocitopênica Trombótica/terapia
18.
Adv Chronic Kidney Dis ; 25(1): 76-83, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29499891

RESUMO

Accurate determination of glomerular filtration rate (GFR) is crucial for the diagnosis of kidney disease. Estimated GFR (eGFR) calculated by serum creatinine and/or cystatin C is a mainstay in clinical practice and epidemiologic research but lacks precision and accuracy until GFR <60 mL/min/1.73 m2. Furthermore, eGFR may not precisely and accurately represent changes in GFR longitudinally. The lack of precision and accuracy is of concern in populations at high risk for kidney disease, as the dissociation between changes in eGFR and GFR may lead to missed diagnoses of early kidney disease. Therefore, improved methods to quantify GFR are needed. Whereas direct measures of GFR have been too cumbersome for screening and ambulatory care, a practical method of measuring GFR by iohexol clearance using dried capillary blood spots exists. In this review, we examine the current literature and data addressing GFR measurements by dried capillary blood spots and its potential application in high-risk groups.


Assuntos
Biomarcadores/sangue , Teste em Amostras de Sangue Seco , Taxa de Filtração Glomerular , Nefropatias/diagnóstico , Humanos , Nefropatias/sangue , Nefropatias/complicações , Nefropatias/fisiopatologia
19.
Clin Biochem ; 53: 139-142, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29402415

RESUMO

INTRODUCTION: Delta checks are a long-standing practice for identifying errors in the laboratory. However, with the decrease in errors due to laboratory automation, their utility is unclear. The objective of this retrospective analysis was to determine whether establishment of a creatinine delta check would be an effective means for capturing true laboratory error. METHODS: All patients with a minimum of two creatinine results during March of 2015 were selected for review (n = 23,410 creatinine results). The lowest % change for a previously confirmed creatinine error in our laboratory was approximately 60%; therefore only results that changed by at least ±60% (n = 254) were reviewed. The etiology of creatinine value change was categorized as laboratory error, pathologic change, or non-pathologic change, based upon chart review. RESULTS: 1.2% (3/254) of reviewed delta checks were determined to reflect 2 instances of true laboratory error that went unrecognized by laboratory staff. 91.3% (232/254) of the delta checks were determined to reflect a pathologic or dialysis-related change in creatinine levels. The remaining 7.5% of delta checks (19/234) were deemed to be non-pathologic changes in creatinine. DISCUSSION: This study identified two instances of laboratory error reflected by 3 delta checks (1.2%); the vast majority (91.3%) of creatinine results that changed by ±60% were pathologic or dialysis-related. Thus, establishment of a ±60% delta check for creatinine would overwhelmingly flag true biological change and would not be an efficient means for identifying rare laboratory errors. Clinical laboratories should perform similar retrospective analyses prior to enacting delta checks to determine whether they will effectively capture laboratory error.


Assuntos
Técnicas de Laboratório Clínico/normas , Creatinina/análise , Creatinina/metabolismo , Erros de Diagnóstico/prevenção & controle , Técnicas de Laboratório Clínico/métodos , Feminino , Humanos , Masculino , Estudos Retrospectivos
20.
JAMA ; 318(12): 1150-1160, 2017 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-28973622

RESUMO

Importance: Biotinylated antibodies and analogues, with their strong binding to streptavidin, are used in many clinical laboratory tests. Excess biotin in blood due to supplemental biotin ingestion may affect biotin-streptavidin binding, leading to potential clinical misinterpretation. However, the degree of interference remains undefined in healthy adults. Objective: To assess performance of specific biotinylated immunoassays after 7 days of ingesting 10 mg/d of biotin, a dose common in over-the-counter supplements for healthy adults. Design, Setting, and Participants: Nonrandomized crossover trial involving 6 healthy adults who were treated at an academic medical center research laboratory. Exposure: Administration of 10 mg/d of biotin supplementation for 7 days. Main Outcomes and Measures: Analyte concentrations were compared with baseline (day 0) measures on the seventh day of biotin treatment and 7 days after treatment had stopped (day 14). The 11 analytes included 9 hormones (ie, thyroid-stimulating hormone, total thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine, parathyroid hormone, prolactin, N-terminal pro-brain natriuretic peptide, 25-hydroxyvitamin D) and 2 nonhormones (prostate-specific antigen and ferritin). A total of 37 immunoassays for the 11 analytes were evaluated on 4 diagnostic systems, including 23 assays that incorporated biotin and streptavidin components and 14 assays that did not include biotin and streptavidin components and served as negative controls. Results: Among the 2 women and 4 men (mean age, 38 years [range, 31-45 years]) who took 10 mg/d of biotin for 7 days, biotin ingestion-associated interference was found in 9 of the 23 (39%) biotinylated assays compared with none of the 14 nonbiotinylated assays (P = .007). Results from 5 of 8 biotinylated (63%) competitive immunoassays tested falsely high and results from 4 out of 15 (27%) biotinylated sandwich immunoassays tested falsely low. Conclusions and Relevance: In this preliminary study of 6 healthy adult participants and 11 hormone and nonhormone analytes measured by 37 immunoassays, ingesting 10 mg/d of biotin for 1 week was associated with potentially clinically important assay interference in some but not all biotinylated assays studied. These findings should be considered for patients taking biotin supplements before ordering blood tests or when interpreting results. Trial Registration: clinicaltrials.gov Identifier: NCT03034707.


Assuntos
Biotina/farmacologia , Erros de Diagnóstico , Interações Medicamentosas , Imunoensaio , Adulto , Artefatos , Estudos Cross-Over , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Prolactina/sangue , Antígeno Prostático Específico/sangue , Testes de Função Tireóidea , Hormônios Tireóideos/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue
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