Differentially expressed urinary biomarkers in children with idiopathic nephrotic syndrome.
BACKGROUND
We performed a discovery phase of urinary proteomic profile in children with idiopathic nephrotic syndrome and validated selected biomarkers.


METHODS
Urinary proteomic profile was performed using isobaric tags for relative and absolute quantitation labeling, coupled with liquid chromatography-matrix assisted laser desorption and ionization analysis. Validation of biomarkers apolipoprotein A1, alpha 2 macroglobulin, orosomucoid 2, retinol binding protein 4 and leucine-rich alpha 2-glycoprotein 1 was done by enzyme-linked immunosorbent assay.


RESULTS
Apolipoprotein A1 levels of <0.48 µg/mg of creatinine-differentiated steroid-resistant nephrotic syndrome (SRNS) from first episode nephrotic syndrome, area under curve (AUC) [0.99 (CI 0.9-1.0), 100 % sensitivity and 100 % specificity] and a value of <0.24 µg/mg of creatinine could differentiate SRNS from frequently relapsing nephrotic syndrome/steroid dependent nephrotic syndrome [AUC 0.99 (CI 0.9-1.0), 100 % sensitivity and 100 % specificity]. Alpha 2 macroglobulin could differentiate children with SRNS-focal segmental glomerulosclerosis (FSGS) from SRNS-minimal change disease (MCD) at values >3.3 µg/mg of creatinine [AUC 0.84 (CI 0.62-1.0), 90 % sensitivity and 85 % specificity]. Orosomucoid 2 >1.81 µg/mg of creatinine could distinguish SRNS-FSGS from SRNS-MCD [AUC 0.84 (CI 0.62-1.0), sensitivity 90 % and specificity 85.5 %]. RBP 4 value of >1.54 µg/mg of creatinine differentiated SRNS-FSGS from SRNS-MCD [AUC 0.87 (CI 0.68-1.0), sensitivity 90 % and specificity 85.7 %].


CONCLUSIONS
Lower level of apolipoprotein A1 in urine is suggestive of SRNS. Alpha 2 macroglobulin, retinol binding protein 4 and orosomucoid 2 are markers associated with FSGS, with alpha 2 macroglobulin being most predictive.
Division of Pediatric Nephrology, Department of Pediatrics, Postgraduate Institute of Medical Education and Research and Associated Dr Ram Manohar Lohia Hospital, Room No 406, PGIMER Building, Baba Kharak Singh Marg, New Delhi, 110001, India.
C P
CP
Suresh
Division of Pediatric Nephrology, Department of Pediatrics, Postgraduate Institute of Medical Education and Research and Associated Dr Ram Manohar Lohia Hospital, Room No 406, PGIMER Building, Baba Kharak Singh Marg, New Delhi, 110001, India. drabhijeetsaha@yahoo.com.
Abhijeet
A
Saha
Division of Pediatric Nephrology, Department of Pediatrics, Postgraduate Institute of Medical Education and Research and Associated Dr Ram Manohar Lohia Hospital, Room No 406, PGIMER Building, Baba Kharak Singh Marg, New Delhi, 110001, India.
Manpreet
M
Kaur
Division of Pediatric Nephrology, Department of Pediatrics, Postgraduate Institute of Medical Education and Research and Associated Dr Ram Manohar Lohia Hospital, Room No 406, PGIMER Building, Baba Kharak Singh Marg, New Delhi, 110001, India.
Ritesh
R
Kumar
Division of Pediatric Nephrology, Department of Pediatrics, Postgraduate Institute of Medical Education and Research and Associated Dr Ram Manohar Lohia Hospital, Room No 406, PGIMER Building, Baba Kharak Singh Marg, New Delhi, 110001, India.
N K
NK
Dubey
CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.|Academy of Scientific and Innovative Research, Delhi, India.
Trayambak
T
Basak
CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
Vinay Singh
VS
Tanwar
CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
Gaurav
G
Bhardwaj
CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.|Academy of Scientific and Innovative Research, Delhi, India.
Shantanu
S
Sengupta
Department of Pathology, GB Pant Hospital, New Delhi, India.
Vineeta Vijay
VV
Batra
Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
Ashish Datt
AD
Upadhyay
D015415:Biomarkers / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000652:urine
D015415:Biomarkers
Biomarkers; Children; Nephrotic syndrome; Proteomics