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 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.

scholarly journals Immunoradiometric Assay for Intact Human Osteocalcin(1–49) without Cross-Reactivity to Breakdown Products

1999 ◽  
Vol 45 (4) ◽  
pp. 526-531 ◽  
Author(s):  
John W Colford ◽  
Bruce A Lueddecke ◽  
Michael Salvati ◽  
Dave Hanna ◽  
Dawn Sailer ◽  
...  
Keyword(s):  
Renal Failure ◽  
Solid Phase ◽  
Reference Interval ◽  
Serum Marker ◽  
Cross Reactivity ◽  
Plasma Samples ◽  
Serum Samples ◽  
Calcium Chelation ◽  
Heparin Plasma ◽  
Edta Plasma

Abstract Background: Osteocalcin (Oc), a serum marker of bone turnover, circulates in several forms. We developed an assay for intact human Oc and investigated its clinical features. Methods: We generated goat antibodies and N- and C-terminal Oc. The former was used on solid phase (polystyrene beads), and the latter was used as the tracer in an IRMA. Results: The assay was linear with no cross-reactivity to Oc(1–43), total imprecision (CV) of &lt;10%, and recovery of 100% ± 10%. Assay values for intact Oc in EDTA plasma samples were unchanged at 18–25 °C for 6 h. Values for intact Oc in serum, EDTA plasma, and heparin plasma samples did not change after storage on ice for 8 h. Serum samples from patients with various conditions were stored at −70 or −135 °C for up to 5 years and yielded z-scores comparable to an Oc(1-43) IRMA for all conditions except for renal failure. In renal failure, the Oc(1–43) assay values were increased, whereas the intact assay values were in the reference interval. Conclusion: Decreases in Oc assay values are inhibited by calcium chelation, and slowed by reduced temperatures. The described assay for intact Oc allows improved specificity for bone compared with an assay for Oc(1–43).

Pediatric reference interval verification for endocrine and fertility hormone assays on the Abbott Alinity system

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mary Kathryn Bohn ◽  
Siobhan Wilson ◽  
Alexandra Hall ◽  
Khosrow Adeli
Keyword(s):  
Clinical Decision Making ◽  
De Novo ◽  
Reference Interval ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Healthy Children ◽  
Confidence Limits ◽  
Test Results ◽  
Serum Samples ◽  
Abbott Architect

Abstract Objectives The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has developed an extensive database of reference intervals (RIs) for several biomarkers on various analytical systems. In this study, pediatric RIs were verified for key immunoassays on the Abbott Alinity system based on the analysis of healthy children samples and comparison to comprehensive RIs previously established for Abbott ARCHITECT assays. Methods Analytical performance of Alinity immunoassays was first assessed. Subsequently, 100 serum samples from healthy children recruited with informed consent were analyzed for 16 Alinity immunoassays. The percentage of test results falling within published CALIPER ARCHITECT reference and confidence limits was determined. If ≥ 90% of test results fell within the confidence limits, they were considered verified based on CLSI guidelines. If <90% of test results fell within the confidence limits, additional samples were analyzed and new Alinity RIs were established. Results Of the 16 immunoassays assessed, 13 met the criteria for verification with test results from ≥ 90% of healthy serum samples falling within the published ARCHITECT confidence limits. New CALIPER RIs were established for free thyroxine and prolactin on the Alinity system. Estradiol required special considerations in early life. Conclusions Our data demonstrate excellent concordance between ARCHITECT and Alinity immunoassays, as well as the robustness of previously established CALIPER RIs for most immunoassays, eliminating the need for de novo RI studies for most parameters. Availability of pediatric RIs for immunoassays on the Alinity system will assist clinical laboratories using this new platform and contribute to improved clinical decision-making.

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.

Pediatric reference intervals for 1,25-dihydroxyvitamin D using the DiaSorin LIAISON XL assay in the healthy CALIPER cohort

2018 ◽  
Vol 56 (6) ◽  
pp. 964-972 ◽  
Author(s):  
Victoria Higgins ◽  
Dorothy Truong ◽  
Nicole M.A. White-Al Habeeb ◽  
Angela W.S. Fung ◽  
Barry Hoffman ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Critical Role ◽  
Reference Interval ◽  
Reference Intervals ◽  
Biologically Active ◽  
Specific Reference ◽  
Healthy Children ◽  
Serum Samples ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D

Abstract Background: 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active vitamin D metabolite, plays a critical role in calcium and phosphate homeostasis. 1,25(OH)2D is measured to assess calcium and phosphate metabolism, particularly during periods of profound growth and development. Despite its importance, no reliable pediatric reference interval exists, with those available developed using adult populations or out-dated methodologies. Using the fully automated chemiluminescence immunoassay by DiaSorin, we established 1,25(OH)2D pediatric reference intervals using healthy children and adolescents from the CALIPER cohort. Methods: Serum samples from healthy subjects (0 to <19 years) were analyzed for 1,25(OH)2D using the DiaSorin LIAISON XL assay and age-specific reference intervals were established. The Mann-Whitney U-test was used to determine seasonal differences. Pooled neonatal and infantile samples were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine if elevated concentrations during the first year of life may be attributed to cross-reacting moieties. Results: Three reference interval age partitions were required with highest levels in subjects 0 to <1 year (77–471 pmol/L), which declined and narrowed after 1 year (113–363 pmol/L) and plateaued at 3 years (108–246 pmol/L). 1,25(OH)2D concentration was not significantly affected by seasonal variation or sex. Elevated 1,25(OH)2D concentrations in neonatal and infantile samples may be the result of an interfering substance. The absence of 3-epi-1,25-dihydroxyvitamin D in the pooled samples makes it unlikely to be the interfering moiety. Conclusions: Pediatric reference intervals for 1,25(OH)2D were established to improve test result interpretation in children and adolescents. 1,25(OH)2D is elevated in a proportion of neonates and infants, which may be the result of a cross-reacting moiety.

scholarly journals Personalized Reference Intervals in Laboratory Medicine: A New Model Based on Within-Subject Biological Variation

2020 ◽  
Author(s):  
Abdurrahman Coşkun ◽  
Sverre Sandberg ◽  
Ibrahim Unsal ◽  
Coskun Cavusoglu ◽  
Mustafa Serteser ◽  
...  
Keyword(s):  
Steady State ◽  
Personalized Medicine ◽  
Clinical Chemistry ◽  
Reference Interval ◽  
Reference Intervals ◽  
Biological Variation ◽  
Test Results ◽  
Steady State Condition ◽  
Laboratory Test Results ◽  
Measurement Results

Abstract Background The concept of personalized medicine has received widespread attention in the last decade. However, personalized medicine depends on correct diagnosis and monitoring of patients, for which personalized reference intervals for laboratory tests may be beneficial. In this study, we propose a simple model to generate personalized reference intervals based on historical, previously analyzed results, and data on analytical and within-subject biological variation. Methods A model using estimates of analytical and within-subject biological variation and previous test results was developed. We modeled the effect of adding an increasing number of measurement results on the estimation of the personal reference interval. We then used laboratory test results from 784 adult patients (&gt;18 years) considered to be in a steady-state condition to calculate personalized reference intervals for 27 commonly requested clinical chemistry and hematology measurands. Results Increasing the number of measurements had little impact on the total variation around the true homeostatic set point and using ≥3 previous measurement results delivered robust personalized reference intervals. The personalized reference intervals of the study participants were different from one another and, as expected, located within the common reference interval. However, in general they made up only a small proportion of the population-based reference interval. Conclusions Our study shows that, if using results from patients in steady state, only a few previous test results and reliable estimates of within-subject biological variation are required to calculate personalized reference intervals. This may be highly valuable for diagnosing patients as well as for follow-up and treatment.

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 &lt;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.

Analytical quality specifications for common reference intervals

2004 ◽  
Vol 42 (7) ◽  
Author(s):  
Carmen Ricós ◽  
Maria Vicenta Doménech ◽  
Carmen Perich
Keyword(s):  
Real Life ◽  
Reference Interval ◽  
Population Based ◽  
Reference Intervals ◽  
Healthy Population ◽  
Analytical Quality ◽  
Related Factors ◽  
Cross Sectional ◽  
Reference Change Value ◽  
Quality Specifications

AbstractInterpretation oflaboratory test results requires comparison to some type of reference value or reference interval. These comparisons can be cross-sectional (population-based reference interval and cut-off values) or longitudinal (reference change value). Quality specifications for cross-sectional comparison have been established by determining the influence of analytical bias and imprecision on the percentage ofthe healthy population falling outside the reference limits, when sharing population-based reference intervals in a Gaussian distribution ofresults. Quality specifications for longitudinal comparisons are equally important and are often overlooked, since less work has been done in this area. Some criteria suggest that a difference between consecutive results designates a true change in a patient health status when the difference is higher than the within-subject biological variation plus the within-laboratory analytical variation. In this chapter we discuss the clinical considerations and laboratory-related factors that must be considered when quality specifications are applied to sharing reference comparisons. Real life experience shows that different analytical methods can produce comparable results when common quality goals are established, and quality can be achieved through a willingness to work together. Within the existing organization, the current specifications for analytical quality and a dedication to quality health care makes it possible to achieve transferability between laboratories within a geographic area.

Evaluation of biological variations in glucose and glycated hemoglobin levels in healthy individuals

2017 ◽  
Vol 43 (5) ◽  
pp. 495-501
Author(s):  
Cihan Coskun ◽  
Berrin Bercik Inal ◽  
Humeyra Ozturk Emre ◽  
Sehide Baz ◽  
Alper Gumus ◽  
...  
Keyword(s):  
International Organizations ◽  
Glycated Hemoglobin ◽  
Reference Interval ◽  
Reference Intervals ◽  
Study Group ◽  
Test Results ◽  
Healthy Individuals ◽  
Reference Change Value ◽  
Performance Specifications ◽  
Index Of Individuality

Abstract Objective: In this study, we firstly aimed to determine components of biological variations (BVCs) in levels of glucose and glycated hemoglobin (HbA1c) in detail based on guidance from relevant organizations and experts. We also investigated whether reference intervals for both analytes were useful for evaluations, particularly consecutive test results. Methods: The study group consisted of 36 healthy volunteers. Samples were collected from each individual 4 times every 2 weeks for 45 days. All samples were assayed in duplicate within a single run. Finally, we estimated BVCs and the analytical performance specifications of both analytes. Results: Our results were fairly compatible with current biological variations (BVs) in both analytes reported in a database. It was calculated as within biological variation (CVI)=4.2% and between-subject variation (CVG)=5.3% for glucose while calculating as CVI=1.7% and CVG=4.5% for HbA1c. According to these results, the index of individuality (II) of glucose was higher than 0.6 while HbA1c’s II was lower than this value. Conclusion: We thought that guidelines from relevant international organizations should be followed to standardize the study design and to appropriately calculate BVCs for any analyte in BV studies. Finally, reference change value should be used to evaluate meaningful differences in HbA1c levels instead of reference interval.

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.

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