Within-subject and between-subject biological variation of first morning void urine amino acids in 12 healthy subjects

2020 ◽  
Vol 58 (11) ◽  
pp. 1901-1909
Author(s):  
Hamit Hakan Alp ◽  
Halil İbrahim Akbay ◽  
Erdem Çokluk ◽  
Zubeyir Huyut ◽  
Sıddık Keskin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Analysis ◽  
Healthy Subjects ◽  
Total Error ◽  
Reference Intervals ◽  
Biological Variation ◽  
Reference Change Value ◽  
Index Of Individuality ◽  
Variance Homogeneity

AbstractBackgroundUrine amino acid analysis is used for the assessment of various diseases. The aim of this study was to estimate the valid biological variation (BV) components (within- and between-subjects) required for the safe clinical application of free urine amino acids.MethodsFirst morning void urine samples were taken from 12 healthy subjects (five females, seven males) once a week for 10 consecutive weeks, and amino acid analysis was performed using an Agilent 6470 triple quadrupole tandem mass spectrometer instrument. The obtained data were subjected to normality, outlier and variance homogeneity analyses prior to coefficient of variation (CV) analysis. Within- and between-subject BV values (CVI and CVG) of 39 amino acids were determined for all subjects. In addition, the index of individuality (II), reference change value (RCV), imprecision, bias and total error were estimated using BV data obtained from our study.ResultsThe CVI values ranged from 8.9 (histidine) to 36.8% (trans-4-hydroxyprolin), while the CVG values ranged from 25.0 (1-methyl-L-histidine) to 63.3% (phenylalanine). The II value of most amino acids was less than 0.6 and ranged between 0.21 and 0.88. The imprecision, bias and total error ranged between 4.45 and 16.6, between 7.69 and 16.6, and between 18.4 and 43.2, respectively.ConclusionsThis study, designed according to a rigorous protocol, has the feature of being the first to give information about BV data of urine amino acids. We believe that the reference intervals have a limitation in the evaluation of consecutive results from an individual, so the use of RCV would be more appropriate.

scholarly journals Biological Variation of Vitamins in Blood of Healthy Individuals

2005 ◽  
Vol 51 (11) ◽  
pp. 2145-2150 ◽  
Author(s):  
Dinesh K Talwar ◽  
Mohammed K Azharuddin ◽  
Cathy Williamson ◽  
Yee Ping Teoh ◽  
Donald C McMillan ◽  
...  
Keyword(s):  
Whole Blood ◽  
Total Error ◽  
Reference Intervals ◽  
Biological Variation ◽  
Reference Change Value ◽  
Objective Quality ◽  
Variation Data ◽  
Quality Specifications ◽  
Index Of Individuality ◽  
Apparently Healthy

Abstract Background: Components of biological variation can be used to define objective quality specifications (imprecision, bias, and total error), to assess the usefulness of reference values [index of individuality (II)], and to evaluate significance of changes in serial results from an individual [reference change value (RCV)]. However, biological variation data on vitamins in blood are limited. The aims of the present study were to determine the intra- and interindividual biological variation of vitamins A, E, B1, B2, B6, C, and K and carotenoids in plasma, whole blood, or erythrocytes from apparently healthy persons and to define quality specifications for vitamin measurements based on their biology. Methods: Fasting plasma, whole blood, and erythrocytes were collected from 14 healthy volunteers at regular weekly intervals over 22 weeks. Vitamins were measured by HPLC. From the data generated, the intra- (CVI) and interindividual (CVG) biological CVs were estimated for each vitamin. Derived quality specifications, II, and RCV were calculated from CVI and CVG. Results: CVI was 4.8%–38% and CVG was 10%–65% for the vitamins measured. The CVIs for vitamins A, E, B1, and B2 were lower (4.8%–7.6%) than for the other vitamins in blood. For all vitamins, CVG was higher than CVI, with II <1.0 (range, 0.36–0.95). The RCVs for vitamins were high (15.8%–108%). Apart from vitamins A, B1, and erythrocyte B2, the imprecision of our methods for measurement of vitamins in blood was within the desirable goal. Conclusions: For most vitamin measurements in plasma, whole blood, or erythrocytes, the desirable imprecision goals based on biological variation are obtainable by current methodologies. Population reference intervals for vitamins are of limited value in demonstrating deficiency or excess.

scholarly journals Biological variation and reference change value data for serum copper, zinc and selenium in Turkish adult population

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ceylan Bal ◽  
Serpil Erdogan ◽  
Gamze Gök ◽  
Cemil Nural ◽  
Betül Özbek ◽  
...  
Keyword(s):  
Adult Population ◽  
Reference Intervals ◽  
Serum Copper ◽  
Biological Variation ◽  
Serum Samples ◽  
Reference Change Value ◽  
Index Of Individuality ◽  
Copper Zinc ◽  
Clinically Significant ◽  
Analytical Variation

Abstract Objectives Calculation of biological variation (BV) components is very important in evaluating whether a test result is clinically significant. The aim of this study is to analyze BV components for copper, zinc and selenium in a cohort of healthy Turkish participants. Methods A total of 10 serum samples were collected from each of the 15 healthy individuals (nine female, six male), once a week, during 10 weeks. Copper, zinc and selenium levels were analyzed by atomic absorption spectrometer. BV parameters were calculated with the approach suggested by Fraser. Results Analytical variation (CVA), within-subject BV (CVI), between-subject BV (CVG) values were 8.4, 7.1 and 4.3 for copper; 4.2, 9.1 and 13.7 for zinc; 7.6, 2.5 and 6.9 for selenium, respectively. Reference change values (RCV) were 30.46, 27.56 and 22.16% for copper, zinc and selenium, respectively. The index of individuality (II) values were 1.65, 0.66 and 0.36 for copper, zinc and selenium, respectively. Conclusions According to the results of this study, traditional reference intervals can be used for copper but we do not recommend using it for zinc and selenium. We think that it would be more accurate to use RCV value for zinc and selenium in terms of following significant changes in recurrent results of a patient.

Annual biological variation and personalized reference intervals of clinical chemistry and hematology analytes

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shuo Wang ◽  
Min Zhao ◽  
Zihan Su ◽  
Runqing Mu
Keyword(s):  
Clinical Chemistry ◽  
Population Based ◽  
Reference Intervals ◽  
Biological Variation ◽  
Annual Data ◽  
Healthy Individuals ◽  
Reference Change Value ◽  
Index Of Individuality ◽  
Personalized Diagnosis

Abstract Objectives A large number of people undergo annual health checkup but accurate laboratory criterion for evaluating their health status is limited. The present study determined annual biological variation (BV) and derived parameters of common laboratory analytes in order to accurately evaluate the test results of the annual healthcare population. Methods A total of 43 healthy individuals who had regular healthcare once a year for six consecutive years, were enrolled using physical, electrocardiogram, ultrasonography and laboratory. The annual BV data and derived parameters, such as reference change value (RCV) and index of individuality (II) were calculated and compared with weekly data. We used annual BV and homeostatic set point to calculate personalized reference intervals (RIper) which were compared with population-based reference intervals (RIpop). Results We have established the annual within-subject BV (CVI), RCV, II, RIper of 24 commonly used clinical chemistry and hematology analytes for healthy individuals. Among the 18 comparable measurands, CVI estimates of annual data for 11 measurands were significantly higher than the weekly data. Approximately 50% measurands of II were <0.6, the utility of their RIpop were limited. The distribution range of RIper for most measurands only copied small part of RIpop with reference range index for 8 measurands <0.5. Conclusions Compared with weekly BV, for annual healthcare individuals, annual BV and related parameters can provide more accurate evaluation of laboratory results. RIper based on long-term BV data is very valuable for “personalized” diagnosis on annual health assessments.

scholarly journals Year-Long Validation Study and Reference Values for Urinary Amino Acids Using a Reversed-Phase HPLC Method

2001 ◽  
Vol 47 (3) ◽  
pp. 575-583 ◽  
Author(s):  
Rafael Venta
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Reference Values ◽  
Amino Acid Analysis ◽  
Reference Intervals ◽  
Reversed Phase ◽  
Hplc Method ◽  
Rp Hplc ◽  
Age Related

Abstract Background: Reversed-phase HPLC (RP-HPLC) has become an alternative to ion-exchange chromatography for amino acid analysis in biological fluids. However, validation studies for its urine application are limited, and the corresponding reference values have not been reported extensively. We studied the long-term performance of a commercial HPLC method for urine amino acid analysis and established specific age-related reference values for urine amino acid excretion. Methods: Method performance was continuously assessed by recovery and precision studies with urine samples and controls, respectively. Healthy individuals were prospectively analyzed throughout a 5-year period. Excretion of individual amino acids, expressed as mmol/mol of creatinine, was included in six age-related groups for random urine samples (0–1 month, 1–12 months, 1–3 years, 3–8 years, 8–16 years, and &gt;16 years) and in two groups for 24-h urine collections (8–16 years and &gt;16 years). Results: Over a 1-year period, CVs for retention times were &lt;0.5% and 3.3% for within- and between-run imprecision, respectively. For amino acid concentrations, within-run CVs were 2.9–17% and between-run CVs were 7.1–46% for the same period. Amino acid recoveries were 78–122%. Reference intervals for 35 amino acids were calculated and compared with the concentrations observed in patients diagnosed with specific pathologies. A few statistically significant differences were found between the reference intervals derived using random and 24-h urine collections. Conclusions: Long-term reliability of the RP-HPLC method for urine amino acid analysis has been demonstrated. Representative age-related reference intervals for the RP-HPLC method in both random urine and 24-h urine collections have been established, and their feasibility for diagnosis of aminoaciduria has been shown. These intervals could serve as a guide for laboratories changing to HPLC methods.

scholarly journals A Practical Approach to the Investigation of Amino Acid Disorders

1988 ◽  
Vol 25 (2) ◽  
pp. 129-141 ◽  
Author(s):  
M A Edwards ◽  
S Grant ◽  
A Green
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Analysis ◽  
Practical Approach ◽  
The Common ◽  
Common Problems

We have, in this paper, highlighted some of the common problems in amino acid analysis in our experience and listed the possible causes for increases in specific amino acids in urine—together with guidance on appropriate follow-up investigations.

Reference intervals and biological variation for kallikrein 6: influence of age and renal failure

2012 ◽  
Vol 50 (5) ◽  
Author(s):  
Eduardo Martínez-Morillo ◽  
Anastasia Diamandis ◽  
Eleftherios P. Diamandis
Keyword(s):  
Renal Failure ◽  
Significant Positive Correlation ◽  
Reference Interval ◽  
Serum Marker ◽  
Reference Intervals ◽  
Biological Variation ◽  
Serum Samples ◽  
Positive Correlation ◽  
Reference Change Value ◽  
Kallikrein 6

AbstractKallikrein 6 (KLK6) is a serine protease involved in numerous cellular processes, up-regulated in many cancers and associated with some neurodegenerative disorders. The aim of this study was to establish a reference interval and estimate the biological variation of KLK6 in serum samples of adults. Furthermore, levels of this protein in patients with renal failure were also studied.Serum samples from healthy volunteers (n=136) were collected. Between 15 and 18 additional samples from four of these subjects were obtained over a period of 2 months. Samples from individuals (n=1043) who visited the University Health Network for a routine check-up were collected to study the association between KLK6 with age and gender. Samples from patients with renal failure (n=106) were also obtained and KLK6 and creatinine concentrations were analyzed by ELISA and an automated enzymatic method, respectively.The reference interval was established to be 1.04–3.93 ng/mL. The index of individuality was 0.43 and the reference change value was 35%. Only two serum samples would be required to estimate the homeostatic setting point of an individual. There is a weak but highly significant positive correlation between KLK6 and age (p<0.0001). Furthermore, there is a significant positive correlation between serum concentrations of KLK6 and creatinine (p<0.0001), in patients with renal failure.The established reference interval for KLK6 and the estimation of its biological variation will further aid in the clinical use of this protein as a serum marker of malignancy and other diseases.

scholarly journals Within-subject and between-subject biological variation estimates of 21 hematological parameters in 30 healthy subjects

2018 ◽  
Vol 56 (8) ◽  
pp. 1309-1318 ◽  
Author(s):  
Abdurrahman Coşkun ◽  
Anna Carobene ◽  
Meltem Kilercik ◽  
Mustafa Serteser ◽  
Sverre Sandberg ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Complete Blood Count ◽  
Hematological Parameters ◽  
Hemoglobin Concentration ◽  
Biological Variation ◽  
Mean Corpuscular Hemoglobin ◽  
Mean Values ◽  
Performance Specifications ◽  
The Mean ◽  
Variance Homogeneity

Abstract Background: The complete blood count (CBC) is used to evaluate health status in the contexts of various clinical situations such as anemia, infection, inflammation, trauma, malignancies, etc. To ensure safe clinical application of the CBC, reliable biological variation (BV) data are required. The study aim was to define the BVs of CBC parameters employing a strict protocol. Methods: Blood samples, drawn from 30 healthy subjects (17 females, 13 males) once weekly for 10 weeks, were analyzed using a Sysmex XN 3000 instrument. The data were assessed for normality, trends, outliers and variance homogeneity prior to coefficient of variation (CV)-analysis of variance (ANOVA). Sex-stratified within-subject (CVI) and between-subjects (CVG) BV estimates were determined for 21 CBC parameters. Results: For leukocyte parameters, with the exception of lymphocytes and basophils, significant differences were found between female/male CVI estimates. The mean values of all erythrocyte-, reticulocyte- and platelet parameters differed significantly between the sexes, except for mean corpuscular hemoglobin concentration, mean corpuscular volume and platelet numbers. Most CVI and CVG estimates appear to be lower than those previously published. Conclusions: Our study, based on a rigorous protocol, provides updated and more stringent BV estimates for CBC parameters. Sex stratification of data is necessary when exploring the significance of changes in consecutive results and when setting analytical performance specifications.

Biological variation of intact fibroblast growth factor 23 measured on a fully automated chemiluminescent platform

2019 ◽  
Vol 56 (3) ◽  
pp. 381-386 ◽  
Author(s):  
Antonín Jabor ◽  
Zdenek Kubíček ◽  
Jitka Komrsková ◽  
Tereza Vacková ◽  
Jiří Vymětalík ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Biological Variation ◽  
Fibroblast Growth ◽  
Vitamin D Metabolism ◽  
Automated Assay ◽  
Reference Change Value ◽  
Index Of Individuality ◽  
Non Gaussian

Background Fibroblast growth factor 23 (FGF23), a potent regulator of phosphate and vitamin D metabolism, is a new biomarker of kidney, bone and cardiovascular disorders. The aim of this study was to assess the biological variation of intact fibroblast growth factor 23 (iFGF23). Methods The within-subject (CVI) and between-subject (CVG) biological variations were assessed in 14 healthy volunteers in a six-week protocol (seven samples). Imprecision (CVA) was assessed by duplicate measurements and the EP15-A2 protocol. Intact FGF23 was measured using a fully automated chemiluminescent assay (Liaison XL, DiaSorin S.p.A., Saluggia, Italy). Two methods with different sensitivities to non-Gaussian distribution were used to estimate the CVI, SD ANOVA and CV ANOVA methods. We calculated the index of individuality (II) and reference change values. Results Depending on the statistical method used, the CVI and CVA were 14.2 and 3.7% (SD ANOVA) or 12.5 and 3.9% (CV ANOVA), respectively. The corresponding reference change values were 40.5 and 36.4%, respectively. The CVG was 13.4% (SD ANOVA was the only option), and the total imprecision (EP15-A2) was less than 7%. Conclusions The measurement of iFGF23 demonstrated a CVA less than 4% during the experimental estimation of biological variation. The total imprecision was less than 7% in the EP15-A2 experiment. The CVI values of iFGF23 in healthy persons were 14.2 (SD ANOVA) and 12.5% (CV ANOVA), respectively. The CVG was 13.4%, and the resulting index of individuality was 1.06. The reference change value was less than 41%. The availability of this automated assay for iFGF23 with well-characterized biological variation data delivers opportunities for improved availability and application of this assay clinically.

Sign in / Sign up

Export Citation Format

Share Document