Increased urinary neutrophil gelatinase associated lipocalin levels in a rat model of upper urinary tract infection.
OBJECTIVE
Recurrent upper urinary tract infection is a common complication of vesicoureteral reflux that often leads to irreversible renal scarring. In our previous study of a rat model of renal bacterial infection we performed global gene expression profiling of the kidney during the onset of renal scarring. We have further investigated the product of an up-regulated gene product, NGAL, in this animal model to evaluate its potential usefulness as a biomarker of renal scarring.


METHODS
Renal NGAL mRNA and protein levels were examined by real-time polymerase chain reaction, Western blot and immunohistochemistry. Urinary NGAL levels were monitored by direct enzyme-linked immunosorbent assay.


RESULTS
Rat renal NGAL mRNA and protein levels were found to be increased soon after bacterial injection. They then decreased rapidly but subsequently persisted at high levels until the 6-week time point after injection. On histological analysis we found that NGAL protein was overproduced in macrophages and renal tubular cells 2 weeks after injection. However, renal tubular cells continued to produce NGAL 6 weeks after injection, whereas this expression was lost in infiltrating cells. Rat urinary NGAL levels were also markedly increased at the early stages of infection and they persisted at high levels throughout the latter stages of the experiment.


CONCLUSIONS
Urinary NGAL may be a potential noninvasive diagnostic biomarker of renal scarring.
Ichino
Manabu
M
Department of Urology, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan. michino@fujita-hu.ac.jp
Kuroyanagi
Yoko
Y
Kusaka
Mamoru
M
Mori
Terumi
T
Ishikawa
Kiyohito
K
Shiroki
Ryoichi
R
Kurahashi
Hiroki
H
Hoshinaga
Kiyotaka
K
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D015153:Blotting, Western; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism / Q000652:urine*; D009393:Nephritis / Q000235:genetics / Q000473:pathology* / Q000652:urine; D011336:Probability; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015854:Up-Regulation; D016482:Urinalysis; D014552:Urinary Tract Infections / Q000235:genetics / Q000473:pathology / Q000652:urine
D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins