title: Proteomic profiling identifies haptoglobin as a potential serum biomarker for steroid-resistant nephrotic syndrome.
abstract: BACKGROUND
  Long-term outcomes for patients with adult idiopathic nephrotic syndrome correlate closely with steroid responsiveness. The aim of this prospective study was to evaluate the difference in serum proteomes between steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) patients and identify potential biomarkers for the prediction of SRNS.
  
  
  METHODS
  We performed a gel-based proteomic study of serum obtained from SRNS and SSNS patients and healthy controls at the time of presentation (n = 6 for each group). Proteins from the serum samples were separated using 2-D electrophoresis, digested in-gel and subjected to MALDI-TOF-MS/MS analysis. Further validation was performed utilizing Western blot and ELISA. The sensitivities and specificities of the candidate proteins for predicting SRNS were determined using receiver operating characteristic curves.
  
  
  RESULTS
  Thirteen differentially expressed proteins were identified as haptoglobin (Hp) with different isoelectric points and molecular weights. Western blot and ELISA analysis of samples from 146 subjects (healthy controls = 52, SSNS = 54, SRNS = 40) showed a markedly increased level of Hp in the serum, but not urine, of SRNS compared to SSNS patients. The optimal serum cutoff level of Hp was set at ≥1,279 µg/ml using the receiver operating characteristic curve. The sensitivity and specificity for predicting SRNS were 85.0 and 96.3%, respectively.
  
  
  CONCLUSIONS
  This study provides a novel overview of the difference in serum proteomes of SSNS and SRNS patients. Serum Hp may be a useful predictive biomarker for steroid therapy efficacy in the treatment of idiopathic nephrotic syndrome.
authors: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, and Key Laboratory of Nephrology, Ministry of Health, Guangzhou, PR China.
authors: Qiong
authors: Q
authors: Wen
authors: Lan-Ting
authors: LT
authors: Huang
authors: Ning
authors: N
authors: Luo
authors: Yong-Tao
authors: YT
authors: Wang
authors: Xiao-Yan
authors: XY
authors: Li
authors: Hai-Ping
authors: HP
authors: Mao
authors: Li
authors: L
authors: Zhang
authors: Xiu-Qing
authors: XQ
authors: Dong
authors: Xue-Qing
authors: XQ
authors: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006242:Haptoglobins / Q000378:metabolism* / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000097:blood / Q000151:congenital* / Q000175:diagnosis; D011237:Predictive Value of Tests; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods*; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult
chemical_list: D015415:Biomarkers; C485359:HP protein, human; D006242:Haptoglobins; D002784:Cholesterol; D003404:Creatinine