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Differentially expressed urinary biomarkers in children with idiopathic nephrotic syndrome

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Abstract

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.

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Acknowledgments

This paper was presented at the 16th Congress of the International Pediatric Nephrology Association in Shanghai 2013 in the Symposium 06 ‘Omics’ in Pediatric Nephrology.

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Authors and Affiliations

  1. 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. Suresh, Abhijeet Saha, Manpreet Kaur, Ritesh Kumar & N. K. Dubey

  2. CSIR-Institute of Genomics and Integrative Biology, New Delhi, India

    Trayambak Basak, Vinay Singh Tanwar, Gaurav Bhardwaj & Shantanu Sengupta

  3. Academy of Scientific and Innovative Research, Delhi, India

    Trayambak Basak & Shantanu Sengupta

  4. Department of Pathology, GB Pant Hospital, New Delhi, India

    Vineeta Vijay Batra

  5. Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India

    Ashish Datt Upadhyay

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  1. C. P. Suresh
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Correspondence to Abhijeet Saha.

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Suresh, C.P., Saha, A., Kaur, M. et al. Differentially expressed urinary biomarkers in children with idiopathic nephrotic syndrome. Clin Exp Nephrol 20, 273–283 (2016). https://doi.org/10.1007/s10157-015-1162-7

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  • DOI: https://doi.org/10.1007/s10157-015-1162-7

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