Hind Malaeb , Sarah Zilka , Angela Jarden , Ursula Klause , Joe M. El-Khoury , Nicholaos Tsaniklides , Jessica M. Colón-Franco
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The test sensitivity, specificity, and linearity were evaluated. The test reproducibility was studied in three laboratories using seven pediatric urine samples. The stability of urine NGAL was assessed in sixteen native urine pediatric samples after storage at room temperature, refrigerated, and frozen.</div></div><div><h3>Results</h3><div>The limits of blank (LoB), detection (LoD), and quantitation (LoQ) were determined as 9, 14, and 18 ng/mL, respectively. Linearity was confirmed across the range of 50–3000 ng/mL. Precision studies following CLSI EP5-03 guidelines showed coefficients of variation (CVs) for repeatability, between-run, between-day, and total precision at ≤5.0 %, ≤3.1 %, ≤1.7 %, and ≤4.9 %, respectively. Reproducibility across three laboratories was ≤6.6 %. Specificity tests showed no significant interference from high specific gravity, 15 endogenous substances, 3 contrast agents, pH variations (3.3–10.3), or 33 pharmaceutical compounds, except very high concentrations of cefepime and ceftriaxone. Cross-reactivity was not observed from 10 potential cross-reactive biomarkers. NGAL stability in urine was tested with samples from 16 patients, demonstrating stability for 2 days at ambient temperature, 4 days refrigerated, 13 months frozen (−70 °C or below), and 3 freeze/thaw cycles.</div></div><div><h3>Conclusions</h3><div>The ProNephroAKI™ assay shows excellent precision, reproducibility, sensitivity, specificity, and stability, meeting the required analytical performance for clinical use in diagnosing and managing AKI in critically ill pediatric patients.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"578 ","pages":"Article 120511"},"PeriodicalIF":2.9000,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multicenter evaluation of the ProNephro AKI™ assay performance and stability in pediatric patients\",\"authors\":\"Hind Malaeb , Sarah Zilka , Angela Jarden , Ursula Klause , Joe M. El-Khoury , Nicholaos Tsaniklides , Jessica M. Colón-Franco\",\"doi\":\"10.1016/j.cca.2025.120511\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><div>Acute Kidney Injury (AKI), defined by increased serum creatinine or decreased urine volume, is highly prevalent in critically ill pediatric patients. Reliance on these for AKI diagnosis is unreliable due to inaccuracy and delayed response. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a promising biomarker for early AKI detection. This study investigated the analytical performance of a new automated urine NGAL test in pediatric patients.</div></div><div><h3>Materials and methods</h3><div>The ProNephroAKI™ particle-enhanced turbidimetric immunoassay was run on the Roche cobas® c501 analyzer to measure urine NGAL in pediatric patients. The test sensitivity, specificity, and linearity were evaluated. The test reproducibility was studied in three laboratories using seven pediatric urine samples. The stability of urine NGAL was assessed in sixteen native urine pediatric samples after storage at room temperature, refrigerated, and frozen.</div></div><div><h3>Results</h3><div>The limits of blank (LoB), detection (LoD), and quantitation (LoQ) were determined as 9, 14, and 18 ng/mL, respectively. Linearity was confirmed across the range of 50–3000 ng/mL. Precision studies following CLSI EP5-03 guidelines showed coefficients of variation (CVs) for repeatability, between-run, between-day, and total precision at ≤5.0 %, ≤3.1 %, ≤1.7 %, and ≤4.9 %, respectively. Reproducibility across three laboratories was ≤6.6 %. Specificity tests showed no significant interference from high specific gravity, 15 endogenous substances, 3 contrast agents, pH variations (3.3–10.3), or 33 pharmaceutical compounds, except very high concentrations of cefepime and ceftriaxone. Cross-reactivity was not observed from 10 potential cross-reactive biomarkers. NGAL stability in urine was tested with samples from 16 patients, demonstrating stability for 2 days at ambient temperature, 4 days refrigerated, 13 months frozen (−70 °C or below), and 3 freeze/thaw cycles.</div></div><div><h3>Conclusions</h3><div>The ProNephroAKI™ assay shows excellent precision, reproducibility, sensitivity, specificity, and stability, meeting the required analytical performance for clinical use in diagnosing and managing AKI in critically ill pediatric patients.</div></div>\",\"PeriodicalId\":10205,\"journal\":{\"name\":\"Clinica Chimica Acta\",\"volume\":\"578 \",\"pages\":\"Article 120511\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-07-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinica Chimica Acta\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0009898125003900\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinica Chimica Acta","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0009898125003900","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
Multicenter evaluation of the ProNephro AKI™ assay performance and stability in pediatric patients
Introduction
Acute Kidney Injury (AKI), defined by increased serum creatinine or decreased urine volume, is highly prevalent in critically ill pediatric patients. Reliance on these for AKI diagnosis is unreliable due to inaccuracy and delayed response. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a promising biomarker for early AKI detection. This study investigated the analytical performance of a new automated urine NGAL test in pediatric patients.
Materials and methods
The ProNephroAKI™ particle-enhanced turbidimetric immunoassay was run on the Roche cobas® c501 analyzer to measure urine NGAL in pediatric patients. The test sensitivity, specificity, and linearity were evaluated. The test reproducibility was studied in three laboratories using seven pediatric urine samples. The stability of urine NGAL was assessed in sixteen native urine pediatric samples after storage at room temperature, refrigerated, and frozen.
Results
The limits of blank (LoB), detection (LoD), and quantitation (LoQ) were determined as 9, 14, and 18 ng/mL, respectively. Linearity was confirmed across the range of 50–3000 ng/mL. Precision studies following CLSI EP5-03 guidelines showed coefficients of variation (CVs) for repeatability, between-run, between-day, and total precision at ≤5.0 %, ≤3.1 %, ≤1.7 %, and ≤4.9 %, respectively. Reproducibility across three laboratories was ≤6.6 %. Specificity tests showed no significant interference from high specific gravity, 15 endogenous substances, 3 contrast agents, pH variations (3.3–10.3), or 33 pharmaceutical compounds, except very high concentrations of cefepime and ceftriaxone. Cross-reactivity was not observed from 10 potential cross-reactive biomarkers. NGAL stability in urine was tested with samples from 16 patients, demonstrating stability for 2 days at ambient temperature, 4 days refrigerated, 13 months frozen (−70 °C or below), and 3 freeze/thaw cycles.
Conclusions
The ProNephroAKI™ assay shows excellent precision, reproducibility, sensitivity, specificity, and stability, meeting the required analytical performance for clinical use in diagnosing and managing AKI in critically ill pediatric patients.
期刊介绍:
The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)
Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells.
The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.