Urine/Plasma Neutrophil Gelatinase Associated Lipocalin Ratio Is a Sensitive and Specific Marker of Subclinical Acute Kidney Injury in Mice

PLoS One. 2016 Jan 29;11(1):e0148043. doi: 10.1371/journal.pone.0148043. eCollection 2016.

Abstract

Background: Detection of acute kidney injury (AKI) is still a challenge if conventional markers of kidney function are within reference range. We studied the sensitivity and specificity of NGAL as an AKI marker at different degrees of renal ischemia.

Methods: Male C57BL/6J mice were subjected to 10-, 20- or 30-min unilateral renal ischemia, to control operation or no operation, and AKI was evaluated 1 day later by histology, immunohistochemistry, BUN, creatinine, NGAL (plasma and urine) and renal NGAL mRNA expression.

Results: A short (10-min) ischemia did not alter BUN or kidney histology, but elevated plasma and urinary NGAL level and renal NGAL mRNA expression although to a much smaller extent than longer ischemia. Surprisingly, control operation elevated plasma NGAL and renal NGAL mRNA expression to a similar extent as 10-min ischemia. Further, the ratio of urine to plasma NGAL was the best parameter to differentiate a 10-min ischemic injury from control operation, while it was similar in the non and control-operated groups.

Conclusions: These results suggest that urinary NGAL excretion and especially ratio of urine to plasma NGAL are sensitive and specific markers of subclinical acute kidney injury in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / diagnosis*
  • Acute Kidney Injury / genetics
  • Acute Kidney Injury / urine
  • Acute-Phase Proteins / genetics*
  • Acute-Phase Proteins / urine
  • Animals
  • Asymptomatic Diseases
  • Biomarkers / blood
  • Biomarkers / urine
  • Blood Urea Nitrogen
  • Corynebacterium / genetics
  • Corynebacterium / metabolism
  • Creatinine / blood
  • Gene Expression
  • Interleukin-6 / blood
  • Interleukin-6 / genetics
  • Lipocalin-2
  • Lipocalins / blood
  • Lipocalins / genetics*
  • Lipocalins / urine
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oncogene Proteins / blood
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / urine
  • RNA, Messenger / genetics
  • RNA, Messenger / urine*
  • Reperfusion Injury / blood
  • Reperfusion Injury / diagnosis*
  • Reperfusion Injury / genetics
  • Reperfusion Injury / urine

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • Interleukin-6
  • Lipocalin-2
  • Lipocalins
  • Oncogene Proteins
  • RNA, Messenger
  • Lcn2 protein, mouse
  • Creatinine

Grant support

Support was provided to PH from the Hungarian Research Fund: OTKA ANN-110810, SNN-114619, ETT 07-011/ 2009 and Bolyai Research Scholarship of the Hungarian Academy of Sciences and Merit Award of Semmelweis University (to PH), as well as by the Lendület program of the Hungarian Academy of Sciences (LP2013-66 to AM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.