"Steroids and Azathioprine Versus Steroids Alone in IgAN"

• evolution of proteinuria over time [ Time Frame: every months for the first six months and then every six months ] [ Designated as safety issue: No ]
• safety [ Time Frame: every months for the first six months and then every six months ] [ Designated as safety issue: Yes ]

In a previous trial the investigators found that the effect of steroids in IgA nephropathy diminish over time. The difference in renal survival is striking up till the third year, but then remains constant. A six-month course of steroid therapy may be not enough to ensure a stable remission. The investigators hypothesized that a more aggressive treatment may obtain long-term better results. The investigators conducted a randomised controlled trial to assess the utility of low-dose azathioprine added to steroids in adult IgAN patients.

In 1999, we published a multicenter, randomized, controlled trial, which compared a 6-month steroid course with supportive therapy in 86 patients with IgAN. After 5 years of follow-up, the risk of a 50% increase in plasma creatinine from baseline was significantly lower in the treated patients; proteinuria also decreased. However, the effect of steroids seemed to diminish over time. The difference in renal survival was particularly striking up till the third year, but then remained constant. We hypothesised that a six-month course of steroid therapy is not enough to ensure a stable remission, and a more aggressive treatment may be required to obtain long-term better results. At this regard, some studies of combined treatment with corticosteroids and azathioprine found that treatment was effective in preserving renal function and in reducing proteinuria. However, these studies did not clarify whether azathioprine added further benefit to steroids in the long term. We conducted a randomised controlled trial to assess the utility of low-dose azathioprine added to steroids in adult IgAN patients.

• Drug: steroids plus azathioprine
  methylprednisolone 1 g i.v. for three consecutive days at the beginning of months 1, 3 and 5, followed by oral prednisone 0.5 mg/kg every other day plus azathioprine 1.5 mg/kg/day for six months
  Other Names:

  • solumedrol
  • deltacortene
  • azatioprina
• Drug: steroids
  methylprednisolone 1 g i.v. for three consecutive days at the beginning of months 1, 3 and 5, followed by oral prednisone 0.5 mg/kg every other day for six months
  Other Names:

  • solumedrol
  • deltacortene

• Experimental: 1
  Six month steroid course plus azathioprine
  Intervention: Drug: steroids plus azathioprine
• Active Comparator: 2
  six month steroid course
  Intervention: Drug: steroids

Inclusion Criteria:

• biopsy proven IgA nephropathy
• creatinine ≤ 2.0 mg/dl for at least three months
• proteinuria ≥ 1.0 g/day for at least three months

Exclusion Criteria:

• treatment with steroids or cytotoxic drugs during the previous three years
• contraindications to steroids or azathioprine
• Henoch-Schöenlein purpura
• diabetes mellitus
• severe hypertension (diastolic blood pressure > 120 mmHg)
• lupus erythematosus systemicus
• malignancies
• active peptic-ulcer disease
• pregnancy
• viral hepatitis or other infections