Urinary proteome of steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome of childhood

Robert P. Woroniecki, Tatyana N. Orlova, Natasha Mendelev, Ibrahim F. Shatat, Susan M. Hailpern, Frederick J. Kaskel, Michael S. Goligorsky, Edmond O'Riordan

Research output: Contribution to journalArticle

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Abstract

The response to steroid therapy is used to characterize the idiopathic nephrotic syndrome (INS) of childhood as either steroid-sensitive (SSNS) or steroid-resistant (SRNS), a classification with a better prognostic capability than renal biopsy. The majority (∼80%) of INS is due to minimal change disease but the percentage of focal and segmental glomerulosclerosis is increasing. We applied a new technological platform to examine the urine proteome to determine if different urinary protein excretion profiles could differentiate patients with SSNS from those with SRNS. Twenty-five patients with INS and 17 control patients were studied. Mid-stream urines were analyzed using surface enhanced laser desorption and ionization mass spectrometry (SELDI-MS). Data were analyzed using multiple bioinformatic techniques. Patient classification was performed using Biomarker Pattern Software™ and a generalized form of Adaboost and predictive models were generated using a supervised algorithm with cross-validation. Urinary proteomic data distinguished INS patients from control patients, irrespective of steroid response, with a sensitivity of 92.3%, specificity of 93.7%, positive predictive value of 96% and a negative predictive value of 88.2%. Classification of patients as SSNS or SRNS was 100%. A protein of mass 4,144 daltons was identified as the single most important classifier in distinguishing SSNS from SRNS. SELDI-MS combined with bioinformatics can identify different proteomic patterns in INS. Characterization of the proteins of interest identified by this proteomic approach with prospective clinical validation may yield a valuable clinical tool for the non-invasive prediction of treatment response and prognosis.

Original languageEnglish (US)
Pages (from-to)258-267
Number of pages10
JournalAmerican Journal of Nephrology
Volume26
Issue number3
DOIs
StatePublished - Jul 2006

Fingerprint

Proteome
Steroids
Proteomics
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Computational Biology
Urine
Lipoid Nephrosis
Focal Segmental Glomerulosclerosis
Proteins
Nephrotic syndrome, idiopathic, steroid-resistant
Software
Biomarkers
Congenital Nephrosis
Kidney
Biopsy
Sensitivity and Specificity
Therapeutics

Keywords

  • Childhood nephrosis
  • Nephrotic syndrome
  • Proteome
  • SELDI
  • Steroid sensitivity
  • Urinary biomarkers

ASJC Scopus subject areas

  • Nephrology

Cite this

Woroniecki, R. P., Orlova, T. N., Mendelev, N., Shatat, I. F., Hailpern, S. M., Kaskel, F. J., ... O'Riordan, E. (2006). Urinary proteome of steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome of childhood. American Journal of Nephrology, 26(3), 258-267. https://doi.org/10.1159/000093814

Urinary proteome of steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome of childhood. / Woroniecki, Robert P.; Orlova, Tatyana N.; Mendelev, Natasha; Shatat, Ibrahim F.; Hailpern, Susan M.; Kaskel, Frederick J.; Goligorsky, Michael S.; O'Riordan, Edmond.

In: American Journal of Nephrology, Vol. 26, No. 3, 07.2006, p. 258-267.

Research output: Contribution to journalArticle

Woroniecki, RP, Orlova, TN, Mendelev, N, Shatat, IF, Hailpern, SM, Kaskel, FJ, Goligorsky, MS & O'Riordan, E 2006, 'Urinary proteome of steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome of childhood', American Journal of Nephrology, vol. 26, no. 3, pp. 258-267. https://doi.org/10.1159/000093814
Woroniecki, Robert P. ; Orlova, Tatyana N. ; Mendelev, Natasha ; Shatat, Ibrahim F. ; Hailpern, Susan M. ; Kaskel, Frederick J. ; Goligorsky, Michael S. ; O'Riordan, Edmond. / Urinary proteome of steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome of childhood. In: American Journal of Nephrology. 2006 ; Vol. 26, No. 3. pp. 258-267.
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