Neutrophil gelatinase-associated lipocalin as a biomarker for lupus nephritis.
BACKGROUND
One of the challenges of treating patients with lupus nephritis (LN) is to accurately assess disease activity and predict its outcome. Since renal-biopsy cannot be performed routinely, new surrogate biomarkers are needed.


METHODS
We evaluated neutrophil gelatinase-associated lipocalin (NGAL), to predict renal outcome in LN. Serum and urinary NGAL levels, measured by the enzyme-linked immunosorbent assay, and the fractional excretion (FE) of NGAL relative to the FE of proteins (FE NGAL/FE protein ratio) were determined in a cross-sectional (n = 199) and longitudinal (n = 45) cohort of systemic lupus erythematosus (SLE) patients. Global and renal disease activity was assessed by the SLE disease activity indices, SLEDAI and rSLEDAI, respectively. Correlations between traditional biomarkers were established. Sensitivity, specificity and predictive values of NGAL for renal flare, response to therapy and progression to chronic kidney disease were calculated.


RESULTS
The FE NGAL/FE protein ratio exhibited the best sensitivity and specificity to discriminate patients with active LN from those with non-renal flare and inactive SLE. In the prospective study, this biomarker was found to be the best candidate to predict proteinuric flares with an 87% sensitivity and 62% specificity for ratios >14.56 and complete response with a 61% sensitivity and 78% specificity for ratios >26.54 in the presence of a simultaneous worsening or improving rSLEDAIs, respectively. In both conditions, the FE NGAL/FE protein ratio outperformed the anti-dsDNA antibody titres and C3 predictive value. Progression to chronic kidney disease was best predicted by estimated glomerular filtration rate levels, but persistently high levels of serum NGAL (>444.4 ng/mL, P = 0.0001 by Kaplan-Meier) predicted a faster progression.


CONCLUSIONS
The FE NGAL/FE protein ratio is a reliable marker of disease activity in patients with SLE and could be used as an indicator of response to therapy, although further studies are required to confirm these results.
Department of Medicine, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall d́Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain Department of Statistical, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall d́Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
María Teresa
MT
Torres-Salido
Department of Medicine, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall d́Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain Department of Statistical, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall d́Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Josefina
J
Cortés-Hernández
Department of Medicine, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall d́Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain Department of Statistical, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall d́Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Xavier
X
Vidal
Department of Medicine, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall d́Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain Department of Statistical, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall d́Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Anna
A
Pedrosa
Department of Medicine, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall d́Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain Department of Statistical, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall d́Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Miquel
M
Vilardell-Tarrés
Department of Medicine, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall d́Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain Department of Statistical, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall d́Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Josep
J
Ordi-Ros
D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood* / Q000652:urine; D008181:Lupus Nephritis / Q000097:blood*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000097:blood* / Q000652:urine; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins
lupus nephritis; neutrophil gelatinase-associated lipocalin; urinary biomarkers