ORIGINAL ARTICLE Long-term follow-up after cyclophosphamide and cyclosporine-A therapy in steroid-dependent and -resistant nephrotic syndrome Viktória Sümegi & Ibolya Haszon & Csaba Bereczki & Ferenc Papp & Sándor Túri Received: 1 July 2007 / Revised: 29 December 2007 / Accepted: 2 January 2008 / Published online: 7 March 2008 # IPNA 2008 Abstract A retrospective study was made on 37 children with idiopathic nephrotic syndrome (INS). At the beginning, all patients were steroid sensitive but received more than one steroid course (median 4). Following several relapses, they became steroid dependent or steroid resistant. Group 1 con- sisted of 22 children [3 focal segmental glomerulosclerosis (FSGS), 19 minimal-change NS (MCNS)] who received cyclophosphamide (CP) orally for 2.5±0.5 months. Group 2 consisted of 15 children (7 FSGS, 8 MCNS) who received cyclosporine-A (CSA) for 28±15 months. The level of proteinuria decreased significantly and remained low during the follow-up. The relapse-free period was significantly longer in the CP group (CP 30±21.5; CSA 26.2±18 months, p <0.001). The relapse rate decreased significantly in both groups and remained in this lower level during the follow-up (from 3.4±2.8 to 0.1±0.2/year in group 1, and from 3.7±3.1 to 0.6± 0.8/year in group 2). At the end of the 5-year follow- up, 20/22 patients (90.9%) and 10/15 patients (66.6%) were in remission in groups 1 and 2 respectively, with or without treatment (p <0.05). In the long term, both CP and CSA is effective second-line therapy following steroid monotherapy in INS patients, but the relapse rate was lower and the relapse free period was significantly longer in the CP-treated group. Keywords Cyclosporine-A . Cyclophosphamide . Immunosuppressive therapy . Steroid resistant . Steroid dependent Introduction Childhood idiopathic nephrotic syndrome (INS) is often characterized by a relapsing course. Relapses result in the administration of further courses of high-dose cortico- steroids, placing the child at the risk of side effects, including obesity, Cushing syndrome, hypertension, bone disease, growth retardation, striae, cataracts, and behavioral disturbances [1]. In the past two decades, alkylating agents such as cyclophosphamide (CP) and chlorambucil (Chl), the immunomodulatory drug levamisole, and calcineurin inhibitors such as cyclosporine A (CSA) have been used as the main steroid-sparing agents. Because of the relatively low prevalence of the disease, it is difficult to establish the precise stage at which a steroid-sparing agent should be introduced or which one should be prescribed to control the disease and minimize steroid toxicity [2]. In idiopathic steroid-dependent NS (SDNS) and frequently relapsing NS (FRNS), cytotoxic therapy is indicated after steroid using, and there is no significant difference between CP and Chl results. CSA can be used in teenage boys to avoid CP gonad toxicity or in children with steroid toxicity and in steroid-resistant NS (SRNS). In FRNS cases, levamisole can be used to reduce relapse rate [3]. CP has been used in nephrology since the 1960s, whereas CSA and levamisole were added to the armamen- tarium of therapies in 1987, and a consensus guideline for the treatment of NS was published by the British Association of Paediatric Nephrology in 1994 [4]. The alkylating agent CP is widely used in SDNS and FRNS in children, either orally (2–3 mg/kg per day for 8– 12 weeks) or in intravenous form (500–750 mg/m 2 per month for 6 months) [5]. CP has been shown to prevent progressive scarring within the kidney, preserve renal function, induce remission, and reduce the risk of end-stage Pediatr Nephrol (2008) 23:1085–1092 DOI 10.1007/s00467-008-0771-8 V. Sümegi (*) : I. Haszon : C. Bereczki : F. Papp : S. Túri Department of Paediatrics, University of Szeged, Faculty of Medicine, Korányi fasor 14-15, 6720 Szeged, Hungary e-mail: sumegi@pedia.szote.u-szeged.hu