NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease.
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=-0.53, P<0.001), interstitial fibrosis (mild vs. severe disease; mean 54 vs. 167 μg uNGAL/g Cr, P<0.01), and tubular atrophy (mild vs. severe disease; mean 54 vs. 164 μg uNGAL/g Cr, P<0.01). Monospecific assays of the NGAL monomer demonstrated a correlation with histology that typifies progressive, severe CKD.
Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA. tln2001@columbia.edu
Thomas L
TL
Nickolas
Catherine S
CS
Forster
Meghan E
ME
Sise
Nicholas
N
Barasch
David
D
Solá-Del Valle
Melanie
M
Viltard
Charles
C
Buchen
Shlomo
S
Kupferman
Maria Luisa
ML
Carnevali
Michael
M
Bennett
Silvia
S
Mattei
Achiropita
A
Bovino
Lucia
L
Argentiero
Andrea
A
Magnano
Prasad
P
Devarajan
Kiyoshi
K
Mori
Hediye
H
Erdjument-Bromage
Paul
P
Tempst
Landino
L
Allegri
Jonathan
J
Barasch
D000209:Acute-Phase Proteins / Q000652:urine*; D000328:Adult; D000368:Aged; D001284:Atrophy; D015415:Biomarkers / Q000652:urine; D001706:Biopsy; D015153:Blotting, Western; D002411:Cation Exchange Resins; D016009:Chi-Square Distribution; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011507:Proteinuria / Q000175:diagnosis / Q000473:pathology / Q000652:urine; D011518:Proto-Oncogene Proteins / Q000652:urine*; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology / Q000652:urine; D012720:Severity of Illness Index; D016482:Urinalysis
D000209:Acute-Phase Proteins; D015415:Biomarkers; D002411:Cation Exchange Resins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins