Sequential therapy with cyclophosphamide and mycophenolic acid in patients with progressive immunoglobulin A nephropathy: a long-term follow-up

In progressive immunoglobulin (Ig)A nephropathy (IgAN), cyclophosphamide pulse therapy (CyP), high-dose intravenous immunoglobulins (IVIg) and mycophenolic acid (MPA) have been used to stop progressive loss of renal function, but disease progression may occur after the end of the initial treatment. Here, we report the long-term follow-up of patients with progressive IgAN with MPA as maintenance therapy after CyP (CyP-MPA). In a median observation time of 62 years, we analysed the slopes of the loss of renal function of 47 patients with biopsy-proven IgAN and treated with CyP. Thirty-one patients with further progression were treated with MPA maintenance for a median time of 52 years. Follow-up was compared with symptomatic therapy and IVIg as historically matched control groups. Median loss of renal function was reduced significantly from 09 ml/min to 01 ml/min per month with CyP (P<005), and with MPA in patients with a relapse from -04 ml/min to -01 ml/min per month (P<005) until the end of the study. Proteinuria decreased significantly from 16 g/l to 10 g/l after CyP, and during MPA treatment to 06 g/l (P=0001 Friedman test). Median renal survival time was in patients with CyP 105 years (range=32-178), with CyP-MPA 107 years (range=83-131), with IVIg 47 years (range=26-66), and in untreated patients 12 years (range=08-16; log-rank test P<001). In patients with progressive IgAN, our long-term follow-up observation indicates that sequential CyP-MPA therapy maintains renal survival significantly.