Urine biomarkers for monitoring juvenile lupus nephritis: a prospective longitudinal study.
BACKGROUND
In juvenile-onset systemic lupus erythematosus (JSLE), renal involvement (lupus nephritis) is frequently seen and can result in long-term morbidity. This prospective longitudinal study aimed to identify the utility of standard and/or novel biomarkers for monitoring and predicting lupus nephritis in a real world setting.


METHODS
Using an unselected JSLE cohort, urine samples were collected during routine clinical review. Protein concentrations of urinary monocyte chemo-attractant protein 1 (uMCP1) and neutrophil gelatinase-associated lipocalin (uNGAL) were analysed along with standard disease activity markers, and were compared with current and subsequent disease activity.


RESULTS
JSLE patients (n = 64; median age 14.1 years) were seen at 3 (interquartile range: 2-5) clinical reviews over 364 (182-532) days. Multivariate analysis demonstrated uMCP1 and serum C3 as independent variables (p < 0.001) for active renal disease at the time of the current review. uMCP1 was an excellent predictor of improved renal disease over time (AUC: 0.81; p = 0.013). uNGAL was a good predictor of worsened renal disease activity (AUC 0.76; p = 0.04) over time.


CONCLUSIONS
Biomarkers (uMCP1, serum C3) can indicate current renal involvement in JSLE, whilst uMCP1 and uNGAL are able to predict subsequent renal disease activity changes. Moving towards biomarker-led monitoring may improve the renal outcome for our patients.
Department of Women's and Children's Health, University of Liverpool, Liverpool, UK, lw1@liv.ac.uk.
Louise
L
Watson
Kjell
K
Tullus
Clarissa
C
Pilkington
Christine
C
Chesters
Stephen D
SD
Marks
Paul
P
Newland
Caroline A
CA
Jones
Michael W
MW
Beresford
D000209:Acute-Phase Proteins / Q000652:urine*; D000293:Adolescent; D017668:Age of Onset; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000652:urine*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003176:Complement C3 / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D016014:Linear Models; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008137:Longitudinal Studies; D008181:Lupus Nephritis / Q000097:blood / Q000175:diagnosis* / Q000628:therapy / Q000652:urine; D008297:Male; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine*; D013997:Time Factors; D006113:United Kingdom; D016482:Urinalysis
D000209:Acute-Phase Proteins; D015415:Biomarkers; C038245:C3 protein, human; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D003176:Complement C3; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins