AACC/NKF Guidance Document on Improving Equity in Chronic Kidney Disease Care.

BACKGROUND: Kidney disease (KD) is an important health equity issue with Black, Hispanic, and socioeconomically disadvantaged individuals experiencing a disproportionate disease burden. Prior to 2021, the commonly used estimated glomerular filtration rate (eGFR) equations incorporated coefficients for Black race that conferred higher GFR estimates for Black individuals compared to non-Black individuals of the same sex, age, and blood creatinine concentration. With a recognition that race does not delineate distinct biological categories, a joint task force of the National Kidney Foundation and the American Society of Nephrology recommended the adoption of the CKD-EPI 2021 race-agnostic equations. CONTENT: This document provides guidance on implementation of the CKD-EPI 2021 equations. It describes recommendations for KD biomarker testing, and opportunities for collaboration between clinical laboratories and providers to improve KD detection in high-risk populations. Further, the document provides guidance on the use of cystatin C, and eGFR reporting and interpretation in gender-diverse populations. SUMMARY: Implementation of the CKD-EPI 2021 eGFR equations represents progress toward health equity in the management of KD. Ongoing efforts by multidisciplinary teams, including clinical laboratorians, should focus on improved disease detection in clinically and socially high-risk populations. Routine use of cystatin C is recommended to improve the accuracy of eGFR, particularly in patients whose blood creatinine concentrations are confounded by processes other than glomerular filtration. When managing gender-diverse individuals, eGFR should be calculated and reported with both male and female coefficients. Gender-diverse individuals can benefit from a more holistic management approach, particularly at important clinical decision points.

AACC Guidance Document on the Clinical Use of Procalcitonin.

BACKGROUND: Procalcitonin (PCT), a peptide precursor of the hormone calcitonin, is a biomarker whose serum concentrations are elevated in response to systemic inflammation caused by bacterial infection and sepsis. Clinical adoption of PCT in the United States has only recently gained traction with an increasing number of Food and Drug Administration-approved assays and expanded indications for use. There is interest in the use of PCT as an outcomes predictor as well as an antibiotic stewardship tool. However, PCT has limitations in specificity, and conclusions surrounding its utility have been mixed. Further, there is a lack of consensus regarding appropriate timing of measurements and interpretation of results. There is also a lack of method harmonization for PCT assays, and questions remain regarding whether the same clinical decision points may be used across different methods. CONTENT: This guidance document aims to address key questions related to the use of PCT to manage adult, pediatric, and neonatal patients with suspected sepsis and/or bacterial infections, particularly respiratory infections. The document explores the evidence for PCT utility for antimicrobial therapy decisions and outcomes prediction. Additionally, the document discusses analytical and preanalytical considerations for PCT analysis and confounding factors that may affect the interpretation of PCT results. SUMMARY: While PCT has been studied widely in various clinical settings, there is considerable variability in study designs and study populations. Evidence to support the use of PCT to guide antibiotic cessation is compelling in the critically ill and in some lower respiratory tract infections but is lacking in other clinical scenarios, and evidence is also limited in the pediatric and neonatal populations. Interpretation of PCT results requires guidance from multidisciplinary care teams of clinicians, pharmacists, and clinical laboratorians.

Characterization of Samples with Minor P3 Peak Elevations in a High Pressure Liquid Chromatography System for HbA1c: Contributions of Hemoglobin Variants and Storage Conditions.

BACKGROUND: In the Bio-Rad D-100TM (Bio-Rad, Hercules, CA) HPLC system for hemoglobin A1c (HbA1c) measurement, 7 peaks elute: HbA1a, HbA1b, HbF, LA1c, HbA1c, P3, and HbA0. HbA1c is calculated from the ratio of the HbA1c peak area to the total area, excluding HbF and peaks after HbA0, if present. A P3 peak >10% flags for potential interferences. METHODS: We investigated 26 samples with elevated P3 peaks to determine the presence of hemoglobin variants, the effect of prolonged specimen storage in the P3 peak. The relationship between the P3 peak and the HbA1c concentration were also investigated. RESULTS: No hemoglobin variants were identified when the P3 peak was <14% (n = 14). Hemoglobin variants were detected in 7 of 12 with a P3 peak between 17.0% and 28.2%. Sample storage at room temperature had minimum impact on the P3 peak area (n = 20); the average P3 bias was -0.5 (-8.1% bias) after 3 days and 0.6 (12.2% bias) after 5 days. P3 increased with increasing HbA1c concentrations in samples with P3 < 10%. Most samples with P3 above 10 and up to 14% had marked HbA1c elevations. CONCLUSIONS: Minor elevations of the P3 peak were due only in part to hemoglobin variants, particularly in samples with P3 above 17% (below 28.2%). These elevations caused a decrease in HbA1c, whether hemoglobin variants are detected or not. Prolonged storage at room temperature did not cause P3 peaks to increase above 10%.

The Androstenedione Roche Elecsys immunoassay has superior comparability to the LC-MS/MS assay than the Siemens Immulite immunoassay.

Androstenedione (ASD) is a biomarker used in the diagnostic workup of hyperandrogenism, congenital adrenal hyperplasia, premature adrenarche, and polycystic ovary syndrome (PCOS). The Elecsys ASD competitive electrochemiluminescence immunoassay (Roche Diagnostics, Indianapolis, IN) is a new assay recently available in the US. Objective: This study evaluated the analytical and clinical performance of the Elecsys ASD assay. Design & Methods: We evaluated the linearity/analytical measuring range (AMR), precision, and accuracy of the Elecsys ASD assay on the cobas e601 analyzer. ASD was measured in serum/plasma in the Elecsys ASD, Immulite (Siemens Medical Solutions USA, Inc. Malvern, PA), and LC-MS/MS assays. Reference intervals (RI) were evaluated across genders, menopausal status, and in children. Statistical analysis was performed using EP evaluator and R program. Results: The Elecsys ASD assay had a linear response across the AMR. The intra- and inter-assay coefficients of variation at various concentrations were ≤4.5%. The Elecsys ASD assay had a mean difference of -0.04 ng/mL (-1.7%) with the LC-MS/MS assay, whereas the Immulite assay had a mean difference of 1.17 ng/mL (66%) and -1.22 ng/mL (-38%) compared to the LC-MS/MS and Elecsys ASD assays, respectively. The Roche recommended RIs for healthy men (0.280-1.52 ng/mL) and postmenopausal women (0.187-1.07 ng/mL) were successfully verified. The RIs for children were adopted from published data. For pre-menopausal women, a RI of <1.60 ng/mL was established. The ASD concentrations in women with and without PCOS overlapped. Conclusions: The Elecsys ASD assay has superior comparability to the LC-MS/MS assay than the Immulite assay.

COVID-19 Serology Control Panel Using the Dried-Tube Specimen Method.

The dried-tube specimen (DTS) procedure was used to develop the COVID-19 serology control panel (CSCP). The DTS offers the benefit of shipping materials without a cold chain, allowing for greater access without deterioration of material integrity. Samples in the panel were sourced from COVID-19 convalescent persons from March to May 2020. The immunoglobulin subtypes (total Ig, IgM, and IgG) and their respective reactivity to severe acute respiratory syndrome coronavirus 2 nucleocapsid, spike, and receptor-binding domain antigens of the samples were delineated and compared with the WHO International Standard to elucidate the exact binding antibody units of each CSCP sample and ensure the CSCP provides adequate reactivity for different types of serological test platforms. We distribute the CSCP as a kit with five coded tubes to laboratories around the world to be used to compare test kits for external quality assurance, for harmonizing laboratory testing, and for use as training materials for laboratory workers.

Impact of the AACC Global Laboratory Quality Initiative in Partnership with Professional Societies and Universities in Latin America and the Caribbean.

The Global Lab Quality Initiative (GLQI), formerly known as the Emerging Countries program, was funded through a generous endowment from the Wallace H. Coulter Foundation. The aims of GLQI are to develop and implement innovative programs to promote education and training in laboratory medicine for low- or lower middle-income countries worldwide. From its inception in 2010, the GLQI was focused solely on the Latin America and Caribbean (LAC) region under the purview of AACC's Latin American Working Group (LAWG), the members of which have strong ties to the region thereby facilitating the partnerships with national societies. The LAWG has provided in-person workshops in the LAC countries, at the AACC Annual Scientific Meeting, and on-demand webinars. The LAWG aims to implement the GLQI aims in the LAC region. In-person workshops are based on best-practice recommendations and sources such as Clinical Laboratory Standard Institute guidelines and supplemented with professional experiences of the LAWG's lecturers and local experts of the countries visited. In 2015, the GLQI expanded to other regions of the world. Here we report the experience of the LAWG workshops, results of participant surveys, in-person visits to laboratories post-workshop, and the lessons learned throughout the years across different geographic areas. We are hopeful this report provides insights into the challenges and successes of the LAWG in LAC to help support the expansion of the GLQI.

Evaluation of the Clinical Performance of 7 Serological Assays for SARS-CoV-2 for Use in Clinical Laboratories.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays have emerged as a response to the global pandemic, warranting studies evaluating their clinical performance. This study investigated 7 commercially available SARS-CoV-2 serological assays in samples from noninfected individuals and hospitalized patients. METHODS: SARS-CoV-2 qualitative serological assays by Abbott (IgG), Beckman (IgG), DiaSorin (IgG), EUROIMMUN (IgG and IgA), Roche and Bio-Rad (Total) were evaluated using specimens collected pre-December 2019 (n = 393), from nucleic acid amplification testing (NAAT) negative patients (n = 40), and from 53 patients with COVID-19 by NAAT collected 3-21 days post-onset of symptoms (POS) (N = 83). Negative agreement (NA), positive agreement (PA), and positive and negative predictive values (PPV and NPV) at prevalences of 5% and 10% were calculated. RESULTS: The overall %NA; 95% CI in the negative samples were: Roche 99.8%; 99.3-100.2, Beckman 99.8%; 98.7-100.0, Abbott and Bio-Rad 99.3%; 98.0-99.9, DiaSorin 98.4; 97.2-99.6, EUROIMMUN IgG 97.5%; 95.5-98.7, and EUROIMMUN IgA 79.7%; 75.9-83.5), accounting for positive/equivocal results as false positives. The %PA; 95% CI in samples collected 14+ days POS (n = 24) were: Bio-Rad 83.3%; 68.4-98.2, Abbott and Roche 79.2%; 62.9-95.4, EUROIMMUN IgA 70.8%; 52.6-89.0, Beckman 58.3%; 38.6-78.1, DiaSorin 54.2; 34.2-74.1, and EUROIMMUN IgG 50.0%; 30.0-70.0, accounting for negative/equivocal results as false negatives. NPVs ranged from 97.4%-98.9% and 94.7%-97.7% for prevalences 5% and 10%, respectively. PPVs ranged from 15.5%-94.8% and 27.9%-97.4% for prevalences 5% and 10%, respectively. CONCLUSION: The Roche and Beckman assays resulted in fewer false positives, followed by the Bio-Rad and Abbott assays. While the Bio-Rad assay demonstrated higher antibody detection in COVID-19-positive patients, PA claims cannot be established with a high level of confidence in our sample population.

New Cutoffs for the Biochemical Diagnosis of Adrenal Insufficiency after ACTH Stimulation using Specific Cortisol Assays.

CONTEXT: The normal cortisol response 30 or 60 minutes after cosyntropin (ACTH[1-24]) is considered to be ≥18 µg/dL (500 nmol/L). This threshold is based on older serum cortisol assays. Specific monoclonal antibody immunoassays or LC-MS/MS may have lower thresholds for a normal response. OBJECTIVE: To calculate serum cortisol cutoff values for adrenocorticotropic hormone (ACTH) stimulation testing with newer specific cortisol assays. METHODS: Retrospective analysis of ACTH stimulation tests performed in ambulatory and hospitalized patients suspected of adrenal insufficiency (AI). Serum samples were assayed for cortisol in parallel using Elecsys I and Elecsys II immunoassays, and when volume was available, by Access immunoassay and LC-MS/MS. RESULTS: A total of 110 patients were evaluated. Using 18 µg/dL as the cortisol cutoff after ACTH stimulation, 14.5%, 29%, 22.4%, and 32% of patients had a biochemical diagnosis of AI using the Elecsys I, Elecsys II, Access, and LC-MS/MS assays, respectively. Deming regressions of serum cortisol were used to calculate new cortisol cutoffs based on the Elecsys I cutoff of 18 µg/dL. For 30-minute values, new cutoffs were 14.6 µg/dL for Elecsys II, 14.8 µg/dL for Access, and 14.5 µg/dL for LC-MS/MS. Baseline cortisol <2 µg/dL was predictive of subnormal stimulated cortisol values. CONCLUSION: To reduce false positive ACTH stimulation testing, we recommend a new serum cortisol cutoff of 14 to 15 µg/dL depending on the assay used (instead of the historical value of 18 µg/dL with older polyclonal antibody assays). Clinicians should be aware of the new cutoffs for the assays available to them when evaluating patients for AI.

Best practices in mitigating the risk of biotin interference with laboratory testing.

Dietary biotin intake does not typically result in blood biotin concentrations that exceed interference thresholds for in vitro diagnostic tests. However, recent trends of high-dose biotin supplements and clinical trials of very high biotin doses for patients with multiple sclerosis have increased concerns about biotin interference with immunoassays. Estimates of the prevalence of high biotin intake vary, and patients may be unaware that they are taking biotin. Since 2016, 92 cases of suspected biotin interference have been reported to the US Food and Drug Administration. Immunoassays at greatest risk from biotin interference include thyroid and reproductive hormones, cardiac, and immunosuppressive drug tests. Several case studies have highlighted the challenge of biotin interference with thyroid hormone assays and the potential misdiagnosis of Graves' disease. Biotin interference should be suspected when immunoassay test results are inconsistent with clinical information; a clinically relevant biotin interference happens when the blood biotin concentration is high and the assay is sensitive to biotin. We propose a best practice workflow for laboratory scientists to evaluate discrepant immunoassay results, comprising: (1) serial dilution; (2) retesting after biotin clearance and/or repeat testing on an alternate platform; and (3) confirmation of the presence of biotin using depletion protocols or direct measurement of biotin concentrations. Efforts to increase awareness and avoid patient misdiagnosis should focus on improving guidance from manufacturers and educating patients, healthcare professionals, and laboratory staff. Best practice guidance for laboratory staff and healthcare professionals would also provide much-needed information on the prevention, detection, and management of biotin interference.

Intraoperative ex vivo parathyroid aspiration: A point-of-care test to confirm parathyroid tissue.

BACKGROUND: Ex vivo aspiration of a parathyroid gland with intraoperative parathyroid hormone determination is a method for intraoperative confirmation of parathyroid tissue. The aim of this study was to describe the use and applicability of this technique at a single, high-volume institution. METHODS: This is a retrospective review of patients who underwent parathyroidectomy and ex vivo aspiration of suspected, abnormal parathyroid tissue for intraoperative parathyroid hormone level (pg/mL). Sensitivity and specificity were calculated for aspirate intraoperative parathyroid hormone levels which were compared with the baseline serum aspirate intraoperative parathyroid hormone obtained prior to parathyroid excision in each patient. RESULTS: Of 921 tissue aspirates, 847 (92%) were confirmed as parathyroid on histopathology, with a mean ± standard deviation aspirate intraoperative parathyroid hormone of 3,838 ± 1,615 pg/mL. The 847 aspirates included 833 (98%) with aspirate intraoperative parathyroid hormone levels greater than the serum aspirate intraoperative parathyroid hormone and 14 (2%) with aspirate intraoperative parathyroid hormone levels less than the serum aspirate intraoperative parathyroid hormone; 74 (8%) aspirates were not parathyroid tissue, with a mean aspirate intraoperative parathyroid hormone level of 25 ± 12.7 pg/mL. An aspirate intraoperative parathyroid hormone ≥1.5 times the serum aspirate intraoperative parathyroid hormone represented the optimal threshold for confirmation of parathyroid tissue. CONCLUSION: Intraoperative ex vivo aspiration of presumed parathyroid gland is a sensitive and specific point-of-care method to confirm the presence of parathyroid tissue. An aspirate intraoperative parathyroid hormone ≥1.5 times greater than the baseline serum aspirate intraoperative parathyroid hormone minimizes the likelihood of misidentifying parathyroid tissue.