NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease Journal Article

Authors: Nickolas, T. L.; Forster, C. S.; Sise, M. E.; Barasch, N.; Valle, D. S. D.; Viltard, M.; Buchen, C.; Kupferman, S.; Carnevali, M. L.; Bennett, M.; Mattei, S.; Bovino, A.; Argentiero, L.; Magnano, A.; Devarajan, P.; Mori, K.; Erdjument-Bromage, H.; Tempst, P.; Allegri, L.; Barasch, J.
Article Title: NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease
Abstract: The type and the extent of tissue damage inform the prognosis of chronic kidney disease (CKD), but kidney biopsy is not a routine test. Urinary tests that correlate with specific histological findings might serve as surrogates for the kidney biopsy. We used immunoblots and ARCHITECT-NGAL assays to define the immunoreactivity of urinary neutrophil gelatinase-associated lipocalin (NGAL) in CKD, and we used mass spectroscopy to identify associated proteins. We analyzed kidney biopsies to determine whether specific pathological characteristics associated with the monomeric NGAL species. Advanced CKD urine contained the NGAL monomer as well as novel complexes of NGAL. When these species were separated, we found a significant correlation between the NGAL monomer and glomerular filtration rate (r=-00.53, P<0.001), interstitial fibrosis (mild vs. severe disease; mean 54 vs. 167 g uNGAL/g Cr, P<0.01), and tubular atrophy (mild vs. severe disease; mean 54 vs. 164 g uNGAL/g Cr, P<0.01). Monospecific assays of the NGAL monomer demonstrated a correlation with histology that typifies progressive, severe CKD. © 2012 International Society of Nephrology.
Keywords: adult; human tissue; aged; middle aged; major clinical study; proto-oncogene proteins; mass spectrometry; biological markers; atrophy; pathology; biopsy; fibrosis; blotting, western; disease severity; severity of illness index; kidney; chronic kidney disease; disease progression; biomarker; atherosclerosis; predictive value of tests; immunoblotting; chi-square distribution; glomerular filtration rate; glomerulus filtration rate; renal insufficiency, chronic; enzyme-linked immunosorbent assay; urinalysis; protein urine level; kidney biopsy; proteinuria; monomer; neutrophil gelatinase associated lipocalin; chromatography, gel; gel filtration; chromatography, ion exchange; kidney fibrosis; glomerulosclerosis; cation exchange; kidney tubule atrophy; kidney tubule damage; acute-phase proteins; cation exchange resins; lipocalins
Journal Title: Kidney International
Volume: 82
Issue: 6
ISSN: 0085-2538
Publisher: Elsevier Inc.  
Date Published: 2012-06-01
Start Page: 718
End Page: 722
Language: English
DOI: 10.1038/ki.2012.195
PROVIDER: scopus
PUBMED: 22695331
PMCID: PMC3519389
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 1 October 2012" - "CODEN: KDYIA" - "Source: Scopus"
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  1. Paul J Tempst
    321 Tempst