Up-regulation of urinary markers predict outcome in IgA nephropathy but their predictive value is influenced by treatment with steroids and azathioprine

Clin Nephrol. 2013 Sep;80(3):203-10. doi: 10.5414/CN107836.

Abstract

Objective: Steroids and immunosuppressants can delay progression of renal function in IgAN, but their possible effect in local cytokines has not been studied.

Material and 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.

Conclusion: 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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • Azathioprine / therapeutic use*
  • Biomarkers / blood
  • Biomarkers / urine
  • Biopsy
  • Creatinine / blood
  • Cytokines / urine*
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Fibrosis
  • Glomerulonephritis, IGA / diagnosis
  • Glomerulonephritis, IGA / drug therapy*
  • Glomerulonephritis, IGA / immunology
  • Glomerulonephritis, IGA / urine
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Inflammation Mediators / urine*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Proteinuria / drug therapy
  • Proteinuria / immunology
  • Proteinuria / urine
  • Steroids / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Up-Regulation
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • Immunosuppressive Agents
  • Inflammation Mediators
  • Steroids
  • Creatinine
  • Azathioprine