Dataset Information

Reference intervals for urinary renal injury biomarkers KIM-1 and NGAL in healthy children.

ABSTRACT: The aim of this study was to establish reference intervals in healthy children for two novel urinary biomarkers of acute kidney injury, kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL).Urinary biomarkers were determined in samples from children in the UK (n = 120) and the USA (n = 171) using both Meso Scale Discovery (MSD) and Luminex-based analytical approaches.95% reference intervals for each biomarker in each cohort are presented and stratified by sex or ethnicity where necessary, and age-related variability is explored using quantile regression. We identified consistently higher NGAL concentrations in females than males (p < 0.0001), and lower KIM-1 concentrations in African-Americans than Caucasians (p = 0.02). KIM-1 demonstrated diurnal variation, with higher concentrations in the morning (p < 0.001).This is the first report of reference intervals for KIM-1 and NGAL using two analytical methods in a healthy pediatric population in both UK and US-based populations.

SUBMITTER: McWilliam SJ

PROVIDER: S-EPMC4076175 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Reference intervals for urinary renal injury biomarkers KIM-1 and NGAL in healthy children.

McWilliam Stephen J SJ Antoine Daniel J DJ Sabbisetti Venkata V Pearce Robin E RE Jorgensen Andrea L AL Lin Yvonne Y Leeder J Steven JS Bonventre Joseph V JV Smyth Rosalind L RL Pirmohamed Munir M

Biomarkers in medicine 20140101 10

<h4>Aim</h4>The aim of this study was to establish reference intervals in healthy children for two novel urinary biomarkers of acute kidney injury, kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL).<h4>Materials & methods</h4>Urinary biomarkers were determined in samples from children in the UK (n = 120) and the USA (n = 171) using both Meso Scale Discovery (MSD) and Luminex-based analytical approaches.<h4>Results</h4>95% reference intervals for each biomarke ...[more]

PMID: 24661102

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Project description:Chronic Kidney Disease of uncertain etiology (CKDu) is an emerging epidemic among farming communities in rural Sri Lanka. Victims do not exhibit common causative factors, however, histopathological studies revealed that CKDu is a tubulointerstitial disease. Urine albumin or albumin-creatinine ratio is still being used as a traditional diagnostic tool to identify CKDu, but accuracy and prevalence data generated are questionable. Urinary biomarkers have been used in similar nephropathy and are widely recognised for their sensitivity, specificity and accuracy in determining CKDu and early renal injury. However, these biomarkers have never been used in diagnosing CKDu in Sri Lanka. Male farmers (n = 1734) were recruited from 4 regions in Sri Lanka i.e. Matara and Nuwara Eliya (farming locations with no CKDu prevalence) and two CKDu emerging locations from Hambantota District in Southern Sri Lanka; Angunakolapelessa (EL1) and Bandagiriya (EL2). Albuminuria (ACR ≥ 30mg/g); serum creatinine based estimation of glomerular filtration rate (eGFR); creatinine normalized urinary kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were measured. Fourteen new CKDu cases (18%) from EL1 and nine CKDu cases (9%) from EL2 were recognized for the first time from EL1, EL2 locations, which were previously considered as non-endemic of the disease and associated with persistent albuminuria (ACR ≥ 30mg/g Cr). No CKDu cases were identified in non-endemic study locations in Matara (CM) and Nuwara Eliya (CN). Analysis of urinary biomarkers showed urinary KIM-1 and NGAL were significantly higher in new CKDu cases in EL1 and EL2. However, we also reported significantly higher KIM-1 and NGAL in apparently healthy farmers in EL 1 and EL 2 with comparison to both control groups. These observations may indicate possible early renal damage in absence of persistent albuminuria and potential capabilities of urinary KIM-1 and NGAL in early detection of renal injury among farming communities in Southern Sri Lanka.

Project description:ObjectivesAs a screening index of diabetic kidney disease (DKD), urinary albumin/creatine ratio (UACR) is commonly used. However, approximately 23.3%-56.6% of DKD patients with estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2 are normoalbuminuric. Thus, urinary biomarkers of nonalbuminuric renal insufficiency in type 2 diabetes mellitus (T2DM) patients are urgently needed.MethodsThis cross-sectional study enrolled 209 T2DM patients with normoalbuminuria whose diabetes duration was more than 5 years. The patients were classified into two groups, NO-CKD (eGFR ≥ 60 ml/min per 1.73 m2, n = 165) and NA-DKD (eGFR < 60 ml/min per 1.73 m2, n = 44). Levels of urinary neutrophil gelatinase-associated lipocalin (NGAL), retinol-binding protein (RBP), plasminogen activator inhibitor-1 (PAI-1), vascular cell adhesion molecule-1 (VCAM-1), and E-cadherin were detected, and their correlations with eGFR, plasma TNF-α, IL-6, endothelin-1 (ET-1), and 8-hydroxydeoxyguanosine (8-OHdG) were assessed.ResultsAmong patients with renal insufficiency, 26.0% was normoalbuminuric. Compared to the NO-CKD group, the NA-DKD group was older with lower hemoglobin (HB) levels and higher systolic blood pressure (SBP), plasma TNF-α, IL-6, and 8-OHdG levels. Logistic regression analysis suggested that age, TNF-α, and 8-OHdG were independent risk factors for nonalbuminuric renal insufficiency. Compared to the NO-CKD group, the NA-DKD group exhibited significant increases in urinary NGAL and RBP levels but not PAI-1, VCAM-1, and E-cadherin. Urinary NGAL and RBP both correlated negatively with eGFR and positively with plasma IL-6 and 8-OHdG. Multiple linear regression indicated NGAL (β = -0.287, p = 0.008) and RBP (β = -44.545, p < 0.001) were independently correlated with eGFR.ConclusionAge, plasma TNF-α, and 8-OHdG are independent risk factors for renal insufficiency in T2DM patients with normoalbuminuria. Urinary NGAL and RBP can serve as noninvasive biomarkers of normoalbuminuric renal insufficiency in T2DM.

Dataset Information

Reference intervals for urinary renal injury biomarkers KIM-1 and NGAL in healthy children.

Publications

Reference intervals for urinary renal injury biomarkers KIM-1 and NGAL in healthy children.

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