Demographic data for urinary Acute Kidney Injury (AKI) marker [IGFBP7]·[TIMP2] reference range determinations.

This data in brief describes characteristics of chronic stable comorbid patients who were included in reference range studies of [IGFBP7]·[TIMP-2] "Reference Intervals of Urinary Acute Kidney Injury (AKI) Markers [IGFBP7]·[TIMP2] in Apparently Healthy Subjects and Chronic Comorbid Subjects without AKI" [1]. In order to determine the specificity of [IGFBP7]·[TIMP-2] for identifying patients at risk of developing AKI we studied a cohort with nine broad classification of disease who did not have AKI. Details regarding the population that was targeted for inclusion in the study are also described. Finally, we present data on the inclusion criteria for the healthy subjects used in this investigation to determine the reference range

Reference intervals comparison of calculation methods and evaluation of procedures for merging reference measurements fromTwo US medical centers

Objectives: To analyze consistency of reference limits and widths of reference intervals (RIs) calculated by six procedures and evaluate a protocol for merging intrainstitutional reference data. Methods: The differences between reference limits were compared with "optimal" bias goals. Also, widths of the RIs were compared. RIs were calculated using Mayo-SAS quantile, EP Evaluator, and four International Federation of Clinical Chemistry and Laboratory Medicine methods: parametric and nonparametric (NP) with and without latent abnormal values exclusion (LAVE). Regression parameters from cotested samples were evaluated for harmonizing intrainstitutional reference data. Results: Mayo-SAS quintile, LAVE(-) NP, and EP Evaluator generated similar RIs, but these RIs often were wider than RIs from parametric procedures. LAVE procedures generated narrower RIs for nutritional and inflammatory markers. Transformation with regression parameters did not ensure homogeneity of merged data. Conclusions: Parametric methods are recommended when inappropriate values cannot be excluded. The nonparametric procedures may generate wider RIs. Data sets larger than 200 are recommended for robust estimates. Caution should be exercised when merging intrainstitutional data

A global multicenter study on reference values: 2. Exploration of sources of variation across the countries.

This global multicenter study on reference values (RVs) allowed us to explore biological sources of variation (SVs) of RVs across the world.As described in the first part of this paper, RVs of 50 major analytes from 13,396 healthy individuals living in 12 countries were obtained. Analyzed in this study were 23 clinical chemistry analytes and 8 analytes measured by immunoturbidimetry. Multiple regression analysis was performed for each gender, country by country, analyte by analyte, by setting four major SVs (age, BMI, and levels of drinking and smoking) as a fixed set of explanatory variables. For analytes with skewed distributions, log-transformation was applied. The association of each source of variation with RVs was expressed as partial correlation coefficient (rp).Obvious gender and age-related changes in the RVs were observed in many analytes, almost consistently between countries. Compilation of age-related change profiles of RVs after adjusting for between-country differences revealed peculiar patterns specific to each analyte. Judged fromrp, BMI related changes were observed in many nutritional and inflammatory markers in almost all countries. However, the slope of linear BMI vs. RV relationship differed greatly among countries for some analytes. Alcohol and smoking-related changes were observed less conspicuously in a limited number of analytes.Features of sex, age, alcohol, and smoking-related changes in RVs of major analytes were almost comparable worldwide. The finding of differences in BMI-related changes among countries in some analytes is quite relevant to understanding ethnic differences in susceptibility to nutritionally related diseases

Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication.

RationaleWe recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest.ObjectivesWe now validate a clinical test for urinary [TIMP-2]·[IGFBP7] at a high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse population of critically ill patients.MethodsWe conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary [TIMP-2]·[IGFBP7] to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were masked to the results of the test.Measurements and main resultsUrinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. The primary endpoint was reached in 17% of patients. For a single urinary [TIMP-2]·[IGFBP7] test, sensitivity at the prespecified high-sensitivity cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval [CI], 85-98%) with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill patients with urinary [TIMP-2]·[IGFBP7] greater than 0.3 had seven times the risk for AKI (95% CI, 4-22) compared with critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary [TIMP-2]·[IGFBP7] remained statistically significant and a strong predictor of AKI (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs. area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus [TIMP-2]·[IGFBP7]).ConclusionsUrinary [TIMP-2]·[IGFBP7] greater than 0.3 (ng/ml)(2)/1,000 identifies patients at risk for imminent AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 01573962)

Biomarkers in reproductive health

There is no doubt that reproductive health matters: fertility and infertility clearly affect us as a society. Multidisciplinary teams are a key feature of assessing reproductive health and this special issue reflects that with contributions from both clinicians and laboratorians. The field of fertility is also among the best for using laboratory tests to guide diagnosis and treatment selection. Indeed, measurements of glycoproteins, hormones, and steroids are part of multiple decision algorithms for the diagnosis of hypogonadism, amenorrhea, hirsutism, and infertility. From brain to gonads, from hormones to cells, from immunoassays to mass spectrometry, the area of reproductive health is extremely broad and a fantastic source for multiple innovations. New biomarkers and development of assays with enhanced performance offer more perspectives for a better understanding of pathophysiological processes, identification of new therapeutic targets, and personalized care. [...

Erratum to 'Editorial: Biomarkers in reproductive health' [Clinical Biochemistry 62 (2018) 1].

The publisher regrets the authors' first and surnames were transposed in this Editorial. The author names appear correctly (first name, followed by surname) above

The significance of reporting to the thousandths place: Figuring out the laboratory limitations

Objectives: A request to report laboratory values to a specific number of decimal places represents a delicate balance between clinical interpretation of a true analytical change versus laboratory understanding of analytical imprecision and significant figures. Prostate specific antigen (PSA) was used as an example to determine if an immunoassay routinely reported to the hundredths decimal place based on significant figure assessment in our laboratory was capable of providing analytically meaningful results when reported to the thousandths places when requested by clinicians. Design and methods: Results of imprecision studies of a representative PSA assay (Roche MODULAR E170) employing two methods of statistical analysis are reported. Sample pools were generated with target values of 0.01 and 0.20 μg/L PSA as determined by the E170. Intra-assay imprecision studies were conducted and the resultant data were analyzed using two independent statistical methods to evaluate reporting limits. Results: These statistical methods indicated reporting results to the thousandths place at the two assessed concentrations was an appropriate reflection of the measurement imprecision for the representative assay. This approach used two independent statistical tests to determine the ability of an analytical system to support a desired reporting level. Importantly, data were generated during a routine intra-assay imprecision study, thus this approach does not require extra data collection by the laboratory. Conclusions: Independent statistical analysis must be used to determine appropriate significant figure limitations for clinically relevant analytes. Establishing these limits is the responsibility of the laboratory and should be determined prior to providing clinical results. Keywords: Significant figures, Imprecision, Prostate cancer, Prostate specific antigen, PS

A Risk Assessment of the Jaffe vs Enzymatic Method for Creatinine Measurement in an Outpatient Population.

BackgroundThe Jaffe and enzymatic methods are the two most common methods for measuring serum creatinine. The Jaffe method is less expensive than the enzymatic method but is also more susceptible to interferences. Interferences can lead to misdiagnosis but interferences may vary by patient population. The overall risk associated with the Jaffe method depends on the probability of misclassification and the consequences of misclassification. This study assessed the risk associated with the Jaffe method in an outpatient population. We analyzed the discordance rate in the estimated glomerular filtration rate based on serum creatinine measurements obtained by the Jaffe and enzymatic method.MethodsMethod comparison and risk analysis. Five hundred twenty-nine eGFRs obtained by the Jaffe and enzymatic method were compared at four clinical decision limits. We determined the probability of discordance and the consequence of misclassification at each decision limit to evaluate the overall risk.ResultsWe obtained 529 paired observations. Of these, 29 (5.5%) were discordant with respect to one of the decision limits (i.e. 15, 30, 45 or 60 ml/min/1.73m2). The magnitude of the differences (Jaffe result minus enzymatic result) were significant relative to analytical variation in 21 of the 29 (72%) of the discordant results. The magnitude of the differences were not significant relative to biological variation. The risk associated with misclassification was greatest at the 60 ml/min/1.73m2 decision limit because the probability of misclassification and the potential for adverse outcomes were greatest at that decision limit.ConclusionThe Jaffe method is subject to bias due to interfering substances (loss of analytical specificity). The risk of misclassification is greatest at the 60 ml/min/1.73m2 decision limit; however, the risk of misclassification due to bias is much less than the risk of misclassification due to biological variation. The Jaffe method may pose low risk in selected populations if eGFR results near the 60 ml/min/1.73m2 decision limit are interpreted with caution