Urinary proteome of steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome of childhood.
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 (approximately 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.
Woroniecki
Robert P
RP
Section of Pediatric Nephrology, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10467, USA. rworonie@aecom.yu.edu
Orlova
Tatyana N
TN
Mendelev
Natasha
N
Shatat
Ibrahim F
IF
Hailpern
Susan M
SM
Kaskel
Frederick J
FJ
Goligorsky
Michael S
MS
O'Riordan
Edmond
E
D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D004351:Drug Resistance; D005260:Female; D006801:Humans; D009404:Nephrotic Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000652:urine*; D020543:Proteome / Q000032:analysis*; D013256:Steroids / Q000627:therapeutic use*
D015415:Biomarkers; D020543:Proteome; D013256:Steroids