Long-term treatment with cyclosporin A (CyA) of children with frequently relapsing steroid-sensitive nephrotic syndrome (SSNS) carries the risk of nephrotoxicity. We have analyzed renal function in 23 children with SSNS during CyA therapy. Repeated measurements of glomerular filtration rate (single-shot 51Cr-EDTA clearance) showed a decline from 131 +/- 21 ml/min per 1.73 m2 to 116 +/- 27 ml/min per 1.73 m2 at last follow-up. Similarly, effective renal plasma flow (simultaneous 123 I-hippurate clearance) was correlated with duration of CyA treatment, and showed a decline from 980 +/- 318 ml/min per 1.73 m2 to 724 +/- 242 ml/min per 1.73 m2. In a pilot study we investigated the effect of mycophenolate mofetil (MMF) in 7 children with a median age of 12.7 years [6 with minimal change nephrotic syndrome (MCNS), 1 with focal segmental glomerulosclerosis (FSGS)] with signs of nephrotoxicity because of long-term CyA therapy. Only 1 patient with SSNS showed a relapse during MMF therapy. In the patient with FSGS, MMF was started in addition to CyA, resulting in complete remission for a follow-up of 28 months. This preliminary study demonstrates that children with MCNS treated with CyA may be successfully converted to MMF without major side effects. In all cases, including FSGS, MMF had a beneficial effect on renal function. These data should be confirmed by a prospective randomized clinical trial.