Is tacrolimus for childhood steroid-dependent nephrotic syndrome better than ciclosporin A?

The dosage and 3 months duration of glucocorticoid treatment in steroid-sensitive childhood idiopathic nephrotic syndrome, mainly associated with the histological picture of minimal change glomerulopathy, is based on the evidence of randomized clinical trials with clear-cut end points [1–3]. Duration of up to 7 months of the therapy may even be more effective in achieving sustained remission. A further well-designed and adequately powered randomized controlled trial is, however, required. To avoid steroid toxicity, there is convincing evidence for the use of oral cyclophosphamide in patients with frequent relapses [4]. The evidence, however, is less stable for the treatment of steroid-dependent nephrotic syndrome (SDNS), i.e. recurrence of nephrotic syndrome within 2 weeks of cessation of steroid treatment [5,6]. One of the major concerns with regard to the use of alkylating agents such as cyclophosphamide or chlorambucil in children and adolescents is gonadotoxicity [7]. Therefore, ciclosporin A (CSA) has been advocated when toxic effects of prednisone and cyclophosphamide are expected. CSA results in a remission rate of 85% in children with SDNS, bearing, however, the risk of calcineurin inhibitor-induced nephrotoxicity [8]. Thus, alternative immunosuppressive drugs such as mycophenolate mofetil [9,10], rituximab [11] and sirolimus [12] are currently under investigation. Levamisol has been found to be of benefit in SDNS and has limited toxicity [13]. Data on the use of the calcineurin inhibitor tacrolimus (TAC) are scarce.