Pediatric Nephrology

, Volume 21, Issue 9, pp 1257–1265 | Cite as

Urine proteomic profiling of pediatric nephrotic syndrome

  • Mona Khurana
  • Avram Z. Traum
  • Manuel Aivado
  • Meghan P. Wells
  • Manuel Guerrero
  • Franck Grall
  • Towia A. Libermann
  • Asher D. Schachter
Original Article

Abstract

The prognosis of pediatric nephrotic syndrome (NS) correlates with the responsiveness to glucocorticoid therapy. Steroid-resistant NS (SRNS) patients progress to end-stage renal disease, while steroid-sensitive NS (SSNS) and steroid-dependent (SDNS) patients do not. We have performed proteomic profiling of urine samples from a cross section of pediatric and adolescent subjects with SSNS, SRNS, and orthostatic proteinuria (OP) to identify urinary biomarkers of steroid resistance. We performed surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS) on urine from 19 subjects with SSNS/SDNS in remission, 14 with SSNS/SDNS in relapse, 5 with SRNS in relapse, and 6 with OP. Genetic algorithm search of principal component space revealed a group of five peaks distinguishing SRNS subjects, with mass/charge (m/z) values of 3,917.07, 4,155.53, 6,329.68, 7,036.96, and 11,117.4. Our analyses identified the peak at m/z 11,117.4 with an accuracy of 95% for classifying SRNS. Multidimensional protein fractionation and mass spectrometric analysis of SRNS urine samples combined with immunodepletion identified the 11,117.4 protein as β2-microglobulin (B2M). Using an unbiased protein profiling approach, we have validated previously reported findings of B2M as a biomarker associated with SRNS. Prospective studies are warranted to establish additional biomarkers that would be predictive of SRNS.

Keywords

Focal segmental glomerulosclerosis Nephrotic syndrome Steroid resistance Urine proteomics β2-Microglobulin 

Abbreviations

B2M

β2-Microglobulin

FSGS

Focal segmental glomerulosclerosis

GA

Genetic algorithm

HPRP

High-performance reverse phase

MALDI

Matrix-assisted laser desorption/ionization

MS

Mass spectrometry

m/z

Mass/charge

NS

Nephrotic syndrome

OP

Orthostatic proteinuria

PCA

Principal component analysis

SD

Steroid dependent

SDNS

Steroid-dependent nephrotic syndrome

SELDI

Surface-enhanced laser desorption/ionization

SR

Steroid resistant

SRNS

Steroid-resistant nephrotic syndrome

SS

Steroid sensitive

SSNS

Steroid-sensitive nephrotic syndrome

TOF

Time of flight

Notes

Acknowledgements

This work was supported in part by NIH Training Grant T32 DK 007726 (MK and AZT), and by NIH grant K23 RR 16080 (ADS). Parts of this work were presented (abstract TH-PO160) at the American Society of Nephrology Renal Week 2005, Philadelphia, PA.

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Copyright information

© IPNA 2006

Authors and Affiliations

  • Mona Khurana
    • 1
    • 5
  • Avram Z. Traum
    • 1
    • 5
  • Manuel Aivado
    • 2
    • 3
    • 5
  • Meghan P. Wells
    • 2
    • 3
  • Manuel Guerrero
    • 2
    • 3
  • Franck Grall
    • 2
    • 3
    • 5
  • Towia A. Libermann
    • 2
    • 3
    • 5
  • Asher D. Schachter
    • 1
    • 4
    • 5
  1. 1.Department of PediatricsDivision of Nephrology, Children’s Hospital BostonBostonUSA
  2. 2.Beth Israel Deaconess Medical CenterBostonUSA
  3. 3.Dana Farber/Harvard Cancer Center Proteomics CoreBostonUSA
  4. 4.Children’s Hospital Informatics Program at Harvard-MIT Division of Health Sciences and TechnologyBostonUSA
  5. 5.Harvard Medical SchoolBostonUSA

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