title: Association of urinary laminin G-like 3 and free K light chains with disease activity and histological injury in IgA nephropathy.
abstract: OBJECTIVE
  IgA nephropathy has variable clinical presentation and progression. Its definitive diagnosis and prognosis require renal biopsy. The identification of new biomarkers allowing noninvasive diagnosis and monitoring of disease activity would be advantageous. This study analyzed the urine proteome of IgA nephropathy patients at an early stage of disease.
  
  
  METHODS
  Urine from 49 IgA nephropathy patients, 42 CKD patients, and 40 healthy individuals was analyzed by surface-enhanced laser desorption/ionization time of flight/mass spectrometry. Differentially excreted proteins were identified by matrix-enhanced laser desorption/ionization time of flight/mass spectrometry, confirmed by immunologic methods, and validated in an independent set of patients (14 IgA nephropathy and 24 CKD). All patients were recruited at the Division of Nephrology of the University of Foggia from January of 2005 to March of 2007.
  
  
  RESULTS
  Two proteins, with 21,598 and 23,458 m/z, were significantly decreased in IgA nephropathy and identified as Perlecan laminin G-like 3 peptide and Ig κ light chains, respectively. Western blot analysis confirmed the lower urinary excretion of laminin G-like 3 in IgA nephropathy patients compared with CKD patients and healthy individuals. Immunonephelometry analysis confirmed the lower urinary excretion of free κ light chains in IgA nephropathy patients compared with CKD patients and healthy individuals. Immunohistochemistry analysis justified the urinary excretion profile of such proteins in IgA nephropathy. Finally, urinary free κ light chains and laminin G-like 3 concentration inversely correlated with severity of clinical and histologic features of our IgA nephropathy cohort.
  
  
  CONCLUSIONS
  Laminin G-like 3 and free κ light chains can contribute to the noninvasive assessment of IgA nephropathy disease activity.
authors.affiliation: Proteomics and Mass Spectrometry Core Facility, Research Center BioAgroMed, University of Foggia, Foggia, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Rocchetti
authors.forename: Massimo
authors.initials: M
authors.lastname: Papale
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: d'Apollo
authors.forename: Ida Valentina
authors.initials: IV
authors.lastname: Suriano
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Palma
authors.forename: Grazia
authors.initials: G
authors.lastname: Vocino
authors.forename: Eustacchio
authors.initials: E
authors.lastname: Montemurno
authors.forename: Leonarda
authors.initials: L
authors.lastname: Varraso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grandaliano
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Paolo
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000652:urine; D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D005922:Glomerulonephritis, IGA / Q000473:pathology* / Q000652:urine*; D019812:Heparan Sulfate Proteoglycans / Q000652:urine*; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000652:urine*; D007150:Immunohistochemistry; D007797:Laminin / Q000652:urine*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry; D010446:Peptide Fragments / Q000652:urine*; D011237:Predictive Value of Tests; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D019812:Heparan Sulfate Proteoglycans; D007145:Immunoglobulin kappa-Chains; D007797:Laminin; D010446:Peptide Fragments; C071927:perlecan