Urinary neutrophil gelatinase-associated lipocalin as a novel biomarker for disease activity in lupus nephritis.
OBJECTIVE
Clinical and laboratory markers in current use have limited specificity and sensitivity for predicting the development of renal disease in lupus patients. In this longitudinal study, we investigated whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts active nephritis and renal flares in lupus patients with and without a history of biopsy-proven lupus nephritis.


METHODS
Renal disease activity and flare status was determined by SLEDAI and BILAG scores. Random effects models were used to determine whether uNGAL was a significant predictor for renal disease activity in SLE patients, and for renal flares in patients with established nephritis. To assess the predictive performance of uNGAL, receiver operating characteristic (ROC) curves were constructed using the previous visit's uNGAL level. These curves were then compared with curves constructed with currently used biomarkers. Cut-offs determined by ROC curves were tested in an independent validation cohort.


RESULTS
uNGAL was found to be a significant predictor of renal disease activity in all SLE patients, and a significant predictor for flare in patients with a history of biopsy-proven nephritis, in multivariate models adjusting for age, race, sex and anti-double-stranded (ds)DNA antibody titres. As a predictor of renal flare in patients with biopsy-proven nephritis, uNGAL outperformed anti-dsDNA antibody titres. These results were confirmed in an independent validation cohort.


CONCLUSIONS
uNGAL predicts renal flare in patients with a history of biopsy-proven nephritis with high sensitivity and specificity. Furthermore, uNGAL is a more sensitive and specific forecaster of renal flare in patients with a history of lupus nephritis than anti-dsDNA antibody titres.
Rubinstein
Tamar
T
Department of Medicine, Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Pitashny
Milena
M
Levine
Benjamin
B
Schwartz
Noa
N
Schwartzman
Julie
J
Weinstein
Elena
E
Pego-Reigosa
Jose M
JM
Lu
Tim Y-T
TY
Isenberg
David
D
Rahman
Anisur
A
Putterman
Chaim
C
D000209:Acute-Phase Proteins / Q000652:urine*; D000328:Adult; D015415:Biomarkers / Q000378:metabolism / Q000652:urine*; D018450:Disease Progression; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008181:Lupus Nephritis / Q000378:metabolism / Q000503:physiopathology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011518:Proto-Oncogene Proteins / Q000652:urine*; D012044:Regression Analysis; D012720:Severity of Illness Index
D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins