Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide

Nephrol Dial Transplant. 2003 Jul;18(7):1321-9. doi: 10.1093/ndt/gfg081.


Background: IgA nephropathy is an immune-complex glomerulopathy that can result in capillary or extra-capillary proliferation. Previous attempts to correlate specific histological findings including cellular crescents or endocapillary proliferation, with clinical outcomes, have produced conflicting results.

Methods: We conducted a prospective open-labelled trial of 12 patients with crescentic, proliferative IgA nephropathy and clinically progressive disease and treated them with pulse steroids and intravenous cyclophosphamide. Therapy included pulse solumedrol at 15 mg/kg/day for 3 days, followed by monthly intravenous cyclophosphamide at 0.5 g/m(2) body surface area for 6 months. Clinically significant proteinuria (>1.0 g/24 h) was present in all patients, while nephrotic-range proteinuria (>3.0 g/24 h) was observed in eight of 12 patients. All patients were hypertensive (BP >140/90 mmHg).

Results: After 6 months of treatment, the mean serum creatinine was reduced from a maximum of 2.65+/-0.39 to 1.51+/-0.10 mg/dl (P<0.03), while proteinuria was reduced from 4.04 to 1.35 g/24 h (P<0.01). The mean slope of 1/serum creatinine increased from -0.0398+/-0.02 to 0.0076+/-0.01 after 6 months of therapy, but this trend did not reach statistical significance (P<0.08). A repeat kidney biopsy was performed in all treated patients. Endocapillary proliferation, cellular crescents and karyorrhexis were eliminated in all 12 patients after 6 months of therapy, while interstitial fibrosis and tubule dropout remained unchanged. To determine the long-term efficacy of the treatment, treated patients were compared to 12 historical controls matched for severity of IgA on initial biopsy. After 36 months, the rate of end-stage renal disease in the treated group was lower (1/12) than in the historical controls (5/12).

Conclusions: We conclude that steroids and intravenous cyclophosphamide reduce proliferative lesions, reduce proteinuria and stabilize renal function in patients with crescentic IgA nephropathy.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / therapeutic use*
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Glomerulonephritis, IGA / complications
  • Glomerulonephritis, IGA / drug therapy*
  • Glomerulonephritis, IGA / pathology*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / therapeutic use*
  • Injections, Intravenous
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / pathology*
  • Kidney Failure, Chronic / prevention & control*
  • Male
  • Methylprednisolone Hemisuccinate / administration & dosage*
  • Methylprednisolone Hemisuccinate / therapeutic use*
  • Middle Aged
  • Outcome Assessment, Health Care
  • Prospective Studies
  • Pulse Therapy, Drug
  • Time Factors


  • Anti-Inflammatory Agents
  • Immunosuppressive Agents
  • Methylprednisolone Hemisuccinate
  • Cyclophosphamide