Urinary low-molecular-weight protein excretion in pediatric idiopathic nephrotic syndrome.
BACKGROUND
Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most common causes of idiopathic nephrotic syndrome (INS). We have evaluated the reliability of urinary neutrophil-gelatinase-associated lipocalin (uNGAL), urinary alpha1-microglobulin (uα1M) and urinary N-acetyl-beta-D-glucosaminidase (uβNAG) as markers for differentiating MCD from FSGS. We have also evaluated whether these proteins are associated to INS relapses or to glomerular filtration rate (GFR).


METHODS
The patient cohort comprised 35 children with MCD and nine with FSGS; 19 healthy age-matched children were included in the study as controls. Of the 35 patients, 28 were in remission (21 MCD, 7 FSGS) and 16 were in relapse (14 MCD, 2 FSGS). The prognostic accuracies of these proteins were assessed by receiver operating characteristic (ROC) curve analyses.


RESULTS
The level of uNGAL, indexed or not to urinary creatinine (uCreat), was significantly different between children with INS and healthy children (p = 0.02), between healthy children and those with FSGS (p = 0.007) and between children with MCD and those with FSGS (p = 0.01). It was not significantly correlated to proteinuria or GFR levels. The ROC curve analysis showed that a cut-off value of 17 ng/mg for the uNGAL/uCreat ratio could be used to distinguish MCD from FSGS with a sensitivity of 0.77 and specificity of 0.78. uβNAG was not significantly different in patients with MCD and those with FSGS (p = 0.86). Only uα1M, indexed or not to uCreat, was significantly (p < 0.001) higher for patients in relapse compared to those in remission.


CONCLUSIONS
Our results indicate that in our patient cohort uNGAL was a reliable biomarker for differentiating MCD from FSGS independently of proteinuria or GFR levels.
Division of Pediatric Nephrology, Department of Pediatrics, Lausanne University Hospital, Rue Bugnon 46, 1011, Lausanne, Switzerland, hassib.chehade@chuv.ch.
Hassib
H
Chehade
Paloma
P
Parvex
Antoine
A
Poncet
Dominique
D
Werner
Dolores
D
Mosig
Francois
F
Cachat
Eric
E
Girardin
D000118:Acetylglucosaminidase / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine*; D000293:Adolescent; D000367:Age Factors; D000510:Alpha-Globulins / Q000652:urine; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D003430:Cross-Sectional Studies; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008970:Molecular Weight; D009402:Nephrosis, Lipoid / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D009404:Nephrotic Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011507:Proteinuria / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000652:urine*; D012372:ROC Curve; D012008:Recurrence
D000209:Acute-Phase Proteins; D000510:Alpha-Globulins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; C016001:alpha-1-microglobulin; D003404:Creatinine; D000118:Acetylglucosaminidase