Urine proteomic profiling of pediatric nephrotic syndrome.
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 beta2-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.
Khurana
Mona
M
Department of Pediatrics, Division of Nephrology, Children's Hospital Boston, Boston, MA, USA.
Traum
Avram Z
AZ
Aivado
Manuel
M
Wells
Meghan P
MP
Guerrero
Manuel
M
Grall
Franck
F
Libermann
Towia A
TA
Schachter
Asher D
AD
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D006801:Humans; D009404:Nephrotic Syndrome / Q000378:metabolism*; D011507:Proteinuria / Q000378:metabolism*; D020543:Proteome
D020543:Proteome