Backgrounds: Cyclophosphamide or high dose steroids have been used as limited induction therapy in progressive IgA nephropathy (IgAN) to reduce the loss of renal function and proteinuria. We evaluated the effect of cyclophosphamide pulses (CyP) and mycophenolic acid (MPA) as sequential therapy on renal function in patients with progressive IgAN. Methods: Twenty patients with progressive IgAN and advanced renal failure (median MDRD 2 GFR 22 ml/min per 1.73 m2) and further disease activity (Δ MDRD 2 GFR -0.8 ml/min per month) after cyclophosphamide (CyP; n = 18) or steroid pulse therapy (n = 2) were treated with mycophenolate mofetil 1g for a median of 27 months. Results: The monthly loss of renal function was significantly reduced in linear regression analysis from -2.4 ml/min before CyP to -0.12 ml/min with CyP/MPA (p = 0.0009). Estimated renal survival time was significantly prolonged by a median of 65 months (p = 0.0014). Proteinuria decreased significantly from 1.7 g/l to 0.4 g/l during MPA treatment (p = 0.015). In Cox regression analysis, only proteinuria >1.0 g/l was an independent risk factor for doubling of creatinine during CyP/MPA treatment (p = 0.03). Conclusion: A sequential therapy with CyP/MPA may arrests or slow down the loss of renal function and reduces proteinuria even in patients who passed the so called "point of no return" with progressive IgAN.