title: Up-regulation of urinary markers predict outcome in IgA nephropathy but their predictive value is influenced by treatment with steroids and azathioprine.
abstract: OBJECTIVE
  Steroids and immunosuppressants can delay progression of renal function in IgAN, but their possible effect in local cytokines has not been studied.
  
  
  METHODS
  Histology in 53 IgAN patients (M/F 35/18 age 40.5 years (17 - 65)) was evaluated using the Oxford classification system. IL-1β, -2, -4, -5, -6, -10, -12 and -17, INF-γ and MCP-1 were measured subsequently by multiplex cytokine assay in first morning urine samples taken at the day of renal biopsy. After a 6-month course with RAASinhibitors + fish oils (FO), 35/53 patients, Group A, responded and continued on the same treatment, while in 18/53 who did not respond, Group B, steroids + azathiopine were added.
  
  
  RESULTS
  The presence of endocapillary proliferation had significant correlation with the urinary excretion of pro-inflammatory and pro-fibrotic cytokines (IL-1β, MCP-1, IL-17, INF-γ, IL-6 and IL-10). Serum creatinine at time of diagnosis had significant correlation with proteinuria (p = 0.02), urinary levels of IL-1β (p = 0.03), IL-2 (p = 0.01) and MCP-1 (p = 0.03). GFR was reduced from 65 ± 29 to 57 ± 34 ml/min, p = 0.005 in Group A and remained stable in Group B patients (GFR from 63 ± 24 to 61 ± 30 ml/min, p = NS). Most of the measured cytokines in the urine predicted deterioration of renal function in Group A, but the urinary excretion of IL-6 seemed to predict renal function outcome in both groups of patients.
  
  
  CONCLUSIONS
  Several cytokines are excreted in the urine of patients with IgAN, and their levels predict the outcome of the disease. Steroids + aza may exert their beneficial effect through suppression of the production or activation of most cytokines.
authors.forename: Maria
authors.initials: M
authors.lastname: Stangou
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Papagianni
authors.forename: Christos
authors.initials: C
authors.lastname: Bantis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Moisiadis
authors.forename: Stratis
authors.initials: S
authors.lastname: Kasimatis
authors.forename: Michael
authors.initials: M
authors.lastname: Spartalis
authors.forename: Afroditi
authors.initials: A
authors.lastname: Pantzaki
authors.forename: George
authors.initials: G
authors.lastname: Efstratiadis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Memmos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001379:Azathioprine / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000652:urine*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005355:Fibrosis; D005922:Glomerulonephritis, IGA / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000652:urine; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000652:urine*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy / Q000276:immunology / Q000652:urine; D013256:Steroids / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D013256:Steroids; D003404:Creatinine; D001379:Azathioprine