Urinalysis is more specific and urinary neutrophil gelatinase-associated lipocalin is more sensitive for early detection of acute kidney injury

Carrie Schinstock, Merfake H. Semret, Steven J. Wagner, Timothy M. Borland, Sandra C. Bryant, Kianoush B. Kashani, Timothy S. Larson, John C Lieske

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Background Neutrophil gelatinase-associated lipocalin (NGAL) protein is a promising biomarker to detect acute kidney injury (AKI). Earlier detection of AKI could facilitate evaluation of novel therapeutic strategies. Methods Random and 24-h urine samples were prospectively obtained from 125 normal volunteers for analytic validation of a urinary enzyme-linked immunosorbent assay for NGAL. For clinical validation of the test, urine from 363 emergency department patients admitted to the hospital was obtained for NGAL enzyme-linked immunosorbent assay and urinalysis and AKI was determined by the use of Acute Kidney Injury Network (AKIN) criteria.ResultsNGAL was stable in urine for 7 days when ambient, 4°C or frozen (-20 or -70°C). The assay was linear between 0.24 and10 000 ng/mL with a limit of quantitation of 0.24 ng/mL. Intra- and inter-assay precision were excellent (coefficient of variation <5%); however, urinary white blood cells were associated with increased NGAL levels. The 95th percentile reference value for NGAL in females is ≤65.0 and ≤23.4 ng/mL in males. Urinary NGAL levels increased with AKI stage but had only fair sensitivity (65%) and specificity (65%) to differentiate no AKI versus Stages 1, 2 or 3 (area under the curve 0.70). Urinalysis with microscopy was very specific (91%) but not very sensitive (22%) with an area under the curve of 0.57. Conclusions NGAL can be reliably measured in clinical urine samples, although pyuria is an important potential confounder. In our cohort, increased urinary NGAL was associated with AKI by the AKIN criteria; however, the sensitivity and specificity were only fair, in part because patients with pre-renal causes are not excluded by AKIN criteria. Conversely, findings on microscopic urinalysis are very specific for AKI.

Original languageEnglish (US)
Pages (from-to)1175-1185
Number of pages11
JournalNephrology Dialysis Transplantation
Volume28
Issue number5
DOIs
StatePublished - May 2013

Fingerprint

Urinalysis
Acute Kidney Injury
Urine
Area Under Curve
Enzyme-Linked Immunosorbent Assay
Lipocalin-2
Pyuria
Sensitivity and Specificity
Hospital Emergency Service
Microscopy
Healthy Volunteers
Reference Values
Leukocytes
Biomarkers
Kidney

Keywords

  • acute kidney injury
  • emergency department
  • neutrophil gelatinase-associated lipocalin
  • reference range
  • urinalysis

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Urinalysis is more specific and urinary neutrophil gelatinase-associated lipocalin is more sensitive for early detection of acute kidney injury. / Schinstock, Carrie; Semret, Merfake H.; Wagner, Steven J.; Borland, Timothy M.; Bryant, Sandra C.; Kashani, Kianoush B.; Larson, Timothy S.; Lieske, John C.

In: Nephrology Dialysis Transplantation, Vol. 28, No. 5, 05.2013, p. 1175-1185.

Research output: Contribution to journalArticle

Schinstock, Carrie ; Semret, Merfake H. ; Wagner, Steven J. ; Borland, Timothy M. ; Bryant, Sandra C. ; Kashani, Kianoush B. ; Larson, Timothy S. ; Lieske, John C. / Urinalysis is more specific and urinary neutrophil gelatinase-associated lipocalin is more sensitive for early detection of acute kidney injury. In: Nephrology Dialysis Transplantation. 2013 ; Vol. 28, No. 5. pp. 1175-1185.
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abstract = "Background Neutrophil gelatinase-associated lipocalin (NGAL) protein is a promising biomarker to detect acute kidney injury (AKI). Earlier detection of AKI could facilitate evaluation of novel therapeutic strategies. Methods Random and 24-h urine samples were prospectively obtained from 125 normal volunteers for analytic validation of a urinary enzyme-linked immunosorbent assay for NGAL. For clinical validation of the test, urine from 363 emergency department patients admitted to the hospital was obtained for NGAL enzyme-linked immunosorbent assay and urinalysis and AKI was determined by the use of Acute Kidney Injury Network (AKIN) criteria.ResultsNGAL was stable in urine for 7 days when ambient, 4°C or frozen (-20 or -70°C). The assay was linear between 0.24 and10 000 ng/mL with a limit of quantitation of 0.24 ng/mL. Intra- and inter-assay precision were excellent (coefficient of variation <5{\%}); however, urinary white blood cells were associated with increased NGAL levels. The 95th percentile reference value for NGAL in females is ≤65.0 and ≤23.4 ng/mL in males. Urinary NGAL levels increased with AKI stage but had only fair sensitivity (65{\%}) and specificity (65{\%}) to differentiate no AKI versus Stages 1, 2 or 3 (area under the curve 0.70). Urinalysis with microscopy was very specific (91{\%}) but not very sensitive (22{\%}) with an area under the curve of 0.57. Conclusions NGAL can be reliably measured in clinical urine samples, although pyuria is an important potential confounder. In our cohort, increased urinary NGAL was associated with AKI by the AKIN criteria; however, the sensitivity and specificity were only fair, in part because patients with pre-renal causes are not excluded by AKIN criteria. Conversely, findings on microscopic urinalysis are very specific for AKI.",
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T1 - Urinalysis is more specific and urinary neutrophil gelatinase-associated lipocalin is more sensitive for early detection of acute kidney injury

AU - Schinstock, Carrie

AU - Semret, Merfake H.

AU - Wagner, Steven J.

AU - Borland, Timothy M.

AU - Bryant, Sandra C.

AU - Kashani, Kianoush B.

AU - Larson, Timothy S.

AU - Lieske, John C

PY - 2013/5

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N2 - Background Neutrophil gelatinase-associated lipocalin (NGAL) protein is a promising biomarker to detect acute kidney injury (AKI). Earlier detection of AKI could facilitate evaluation of novel therapeutic strategies. Methods Random and 24-h urine samples were prospectively obtained from 125 normal volunteers for analytic validation of a urinary enzyme-linked immunosorbent assay for NGAL. For clinical validation of the test, urine from 363 emergency department patients admitted to the hospital was obtained for NGAL enzyme-linked immunosorbent assay and urinalysis and AKI was determined by the use of Acute Kidney Injury Network (AKIN) criteria.ResultsNGAL was stable in urine for 7 days when ambient, 4°C or frozen (-20 or -70°C). The assay was linear between 0.24 and10 000 ng/mL with a limit of quantitation of 0.24 ng/mL. Intra- and inter-assay precision were excellent (coefficient of variation <5%); however, urinary white blood cells were associated with increased NGAL levels. The 95th percentile reference value for NGAL in females is ≤65.0 and ≤23.4 ng/mL in males. Urinary NGAL levels increased with AKI stage but had only fair sensitivity (65%) and specificity (65%) to differentiate no AKI versus Stages 1, 2 or 3 (area under the curve 0.70). Urinalysis with microscopy was very specific (91%) but not very sensitive (22%) with an area under the curve of 0.57. Conclusions NGAL can be reliably measured in clinical urine samples, although pyuria is an important potential confounder. In our cohort, increased urinary NGAL was associated with AKI by the AKIN criteria; however, the sensitivity and specificity were only fair, in part because patients with pre-renal causes are not excluded by AKIN criteria. Conversely, findings on microscopic urinalysis are very specific for AKI.

AB - Background Neutrophil gelatinase-associated lipocalin (NGAL) protein is a promising biomarker to detect acute kidney injury (AKI). Earlier detection of AKI could facilitate evaluation of novel therapeutic strategies. Methods Random and 24-h urine samples were prospectively obtained from 125 normal volunteers for analytic validation of a urinary enzyme-linked immunosorbent assay for NGAL. For clinical validation of the test, urine from 363 emergency department patients admitted to the hospital was obtained for NGAL enzyme-linked immunosorbent assay and urinalysis and AKI was determined by the use of Acute Kidney Injury Network (AKIN) criteria.ResultsNGAL was stable in urine for 7 days when ambient, 4°C or frozen (-20 or -70°C). The assay was linear between 0.24 and10 000 ng/mL with a limit of quantitation of 0.24 ng/mL. Intra- and inter-assay precision were excellent (coefficient of variation <5%); however, urinary white blood cells were associated with increased NGAL levels. The 95th percentile reference value for NGAL in females is ≤65.0 and ≤23.4 ng/mL in males. Urinary NGAL levels increased with AKI stage but had only fair sensitivity (65%) and specificity (65%) to differentiate no AKI versus Stages 1, 2 or 3 (area under the curve 0.70). Urinalysis with microscopy was very specific (91%) but not very sensitive (22%) with an area under the curve of 0.57. Conclusions NGAL can be reliably measured in clinical urine samples, although pyuria is an important potential confounder. In our cohort, increased urinary NGAL was associated with AKI by the AKIN criteria; however, the sensitivity and specificity were only fair, in part because patients with pre-renal causes are not excluded by AKIN criteria. Conversely, findings on microscopic urinalysis are very specific for AKI.

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KW - emergency department

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KW - reference range

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