Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus.
OBJECTIVE
Renal involvement in systemic lupus erythematosus (SLE) is associated with poor prognosis. Currently available renal biomarkers are relatively insensitive and nonspecific for diagnosing SLE nephritis. Previous research suggests that neutrophil gelatinase-associated lipocalin (NGAL) is a high-quality renal biomarker of acute kidney injury, while its usefulness in SLE is unclear. We undertook this study to determine the relationship between urinary NGAL excretion and SLE disease activity or damage, with a focus on nephritis.


METHODS
A cohort of 35 patients diagnosed as having SLE prior to age 16 years (childhood-onset SLE) was assessed for disease activity (using the Systemic Lupus Erythematosus Disease Activity Index 2000 update) and damage (using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology SLE Damage Index) in a double-blind, cross-sectional study. Information on current markers of renal function and disease was obtained and compared with NGAL levels (ng/mg of urinary creatinine) measured by enzyme-linked immunosorbent assay. Eight children with juvenile idiopathic arthritis (JIA) served as controls.


RESULTS
NGAL levels did not differ with the age, weight, height, sex, or race of the patients. Patients with childhood-onset SLE had significantly higher NGAL levels than did those with JIA (P < 0.0001). NGAL levels were strongly to moderately correlated with renal disease activity and renal damage (Spearman's r >/= 0.47, P < 0.0001 for both comparisons), but not with extrarenal disease activity or extrarenal damage. NGAL levels of >0.6 ng/mg urinary creatinine were 90% sensitive and 100% specific for identifying childhood-onset SLE patients with biopsy-proven nephritis.


CONCLUSIONS
Urinary NGAL is a promising potential biomarker of childhood-onset SLE nephritis. The results of the current study require validation in a larger cohort to more accurately delineate urinary NGAL excretion in relation to the diverse SLE phenotypes.
Brunner
Hermine I
HI
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. hermine.brunner@cchmc.org
Mueller
Michelle
M
Rutherford
Cynthia
C
Passo
Murray H
MH
Witte
David
D
Grom
Alexei
A
Mishra
Jaya
J
Devarajan
Prasad
P
D000209:Acute-Phase Proteins / Q000652:urine*; D000293:Adolescent; D015415:Biomarkers / Q000652:urine; D002648:Child; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins; D008181:Lupus Nephritis / Q000175:diagnosis* / Q000652:urine*; D008297:Male; D011518:Proto-Oncogene Proteins / 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