Long-term effects of methylprednisolone pulses and mycophenolate mofetil in IgA nephropathy patients at risk of progression

Background: IgA nephropathy (IgAN) is a microcosm of glomerular lesions. Some histologic lesions are irreversible and progress toward obliteration of glomerular capillaries. Others are acute inflammatory processes potentially susceptible to reversal by means of immunosuppressive therapies. Methods: The effects of a combined schedule of steroids and mycophenolate mofetil (MMF) was prospectively examined in a subset of IgAN patients with acute inflammatory histologic changes associated with proteinuria (mean 2,400 mg/day, range 1,130-5,250), hematuria (76 red cells per high-power microscopic field, range 30-100) and renal failure (serum creatinine 1.6 mg/dL, range 1.2-2.9). Patients had diffuse mesangial proliferation with at least 10% florid crescents, mild to moderate degrees of glomerular sclerosis and interstitial changes, and both mesangial and capillary deposition of immunoreactants at immunofluorescence. Treatment consisted of 3 pulses of methylprednisolone (15 mg/kg) followed by oral prednisone (0.8 mg/kg body weight, tapered until discontinuation within 4 months) and MMF 2 g for 6 months. Results: Serum creatinine, proteinuria and microscopic hematuria significantly dropped at 6 months compared with baseline values (p=0.01) and remained lower at the end of follow-up 51 months (range 24-90) later (p<0.01, for proteinuria and hematuria; p=0.08, for serum creatinine). Conclusion: Therapy with steroids and MMF may be considered in a subset of IgAN patients with florid glomerular changes, functional impairment and major urinary abnormalities, to prevent subsequent progression toward renal failure.