Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activity.
OBJECTIVE
To determine whether neutrophil gelatinase-associated lipocalin (NGAL) can predict worsening of global and renal disease activity in childhood-onset systemic lupus erythematosus (SLE).


METHODS
One hundred eleven patients with childhood-onset SLE were enrolled in a longitudinal, prospective study with quarterly study visits and had at least 3 study visits. At each visit, global disease activity was measured using 3 external standards: the numerically converted British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index 2000 update score, and the physician's assessment of global disease activity. Renal and extrarenal disease activity were measured by the respective domain scores. The disease course over time was categorized at the most recent visit (persistently active, persistently inactive, improved, or worsening). Plasma and urinary NGAL levels were measured by enzyme-linked immunosorbent assay, and urinary NGAL levels were standardized to the urinary creatinine concentration. The longitudinal changes in NGAL levels were compared with the changes in SLE disease activity using mixed-effect models.


RESULTS
Significant increases in standardized urinary NGAL levels of up to 104% were detected up to 3 months before worsening of lupus nephritis (as measured by all 3 external standards). Plasma NGAL levels increased significantly by as much as 26% up to 3 months before worsening of global SLE disease activity as measured by all 3 external standards. Plasma NGAL levels increased significantly by 26% as early as 3 months prior to worsening of lupus nephritis as measured by the BILAG renal score.


CONCLUSIONS
Serial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhood-onset SLE disease activity.
Hinze
Claas H
CH
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Suzuki
Michiko
M
Klein-Gitelman
Marisa
M
Passo
Murray H
MH
Olson
Judyann
J
Singer
Nora G
NG
Haines
Kathleen A
KA
Onel
Karen
K
O'Neil
Kathleen
K
Silverman
Earl D
ED
Tucker
Lori
L
Ying
Jun
J
Devarajan
Prasad
P
Brunner
Hermine I
HI
D000209:Acute-Phase Proteins / Q000652:urine*; D000293:Adolescent; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002648:Child; D003404:Creatinine / Q000652:urine; D018450:Disease Progression; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood* / Q000652:urine*; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism*; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000097:blood* / Q000652:urine*; D012720:Severity of Illness Index
D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D003404:Creatinine