Pediatr Nephrol (2005) 20:1420–1425 DOI 10.1007/s00467-005-1943-4 ORIGINAL ARTICLE Ahmed Farouk Donia · Hesham Mohamed Ammar · Amgad El-Baz El-Agroudy · Fatma El-Husseini Moustafa · Mohamed Abdel-Kader Sobh Long-term results of two unconventional agents in steroid-dependent nephrotic children Received: 5 January 2004 / Revised: 14 January 2005 / Accepted: 14 January 2005 / Published online: 27 July 2005  IPNA 2005 Abstract Children with steroid-dependent minimal change nephrotic syndrome are prone to serious steroid side effects. Alternative therapies, such as oral cyclo- phosphamide, may also have serious side effects. We conducted this novel prospective study to compare the long-term efficacies of levamisole and I.V. pulse cyclo- phosphamide as therapies with potentially fewer side ef- fects. This study included 40 children with idiopathic steroid-dependent minimal change nephrotic syndrome (age 3–15 years; 31 boys and 9 girls). The patients were randomized into two equal groups. One group received levamisole 2.5 mg/kg on alternate days (levamisole group) while the other group received I.V. cyclophos- phamide 500 mg/m 2 /month for six months (cyclophos- phamide group). Prednisolone was gradually withdrawn. After stopping treatment, the number of patients that maintained remission was five (25%) in each group at six months, four (20%) versus two (10%) at one year and three (15%) versus one (5%) at two years in the levami- sole and cyclophosphamide groups respectively, and one (5%) in each group at three and four years. The overall side effects were mild and both drugs were well tolerated. In view of the results, we recommend trial of levamisole before adopting other therapies with more serious side effects in such patients. Keywords Levamisole · Pulse cyclophosphamide · Steroid-dependent · Minimal change Introduction Minimal change nephrotic syndrome (MCNS) accounts for 80% of idiopathic nephrotic syndrome in children. Although 93% of patients will be steroid-responsive, only 38% of the primary responders will be non-relapsers, while the remaining will display a relapsing course and commonly acquire steroid dependency. Steroid-dependent patients are prone to serious steroid side effects, such as growth retardation, peptic ulceration, cataracts, osteopo- rosis, aseptic necrosis of the femoral head, acne, moon facies and psychiatric disturbances. Thus, the physician may attempt adjunctive therapy in such patients [1, 2]. Oral cyclophosphamide is usually recommended in this situation. However, long-term side effects like gonadal toxicity become an important issue [3]. I.V. cyclophos- phamide pulse administration may lead to a reduction in total dose compared to daily oral treatment. Therapy with I.V. cyclophosphamide pulses is therefore an emerging therapeutic option in an attempt to maintain remission with less frequent side effects [4]. On the other hand, the long-term immunosuppression in such patients and the cumulative risk of further alkylating therapy are worrying in a condition that ultimately has an excellent prognosis. Thus, alternative therapy with the immunostimulant agent levamisole would be another attractive option, especially in MCNS, which is a condition characterized by altered cellular immunity [5]. Only one study has retrospectively compared levami- sole with oral cyclophosphamide in frequently relapsing steroid-dependent nephrotic syndrome, and it concluded that levamisole may be considered an alternative for oral cyclophosphamide as a second-line agent after corticos- teroids in such patients [6]. However, to our knowledge, no studies have compared the efficacy and safety of le- vamisole with that of I.V. cyclophosphamide pulse ther- apy as two therapeutic options with potentially fewer side effects in steroid-dependent MCNS children. Therefore, we conducted this prospective random study to accom- plish this goal. A. F. Donia · H. M. Ammar · A. E.-B. El-Agroudy · F. E.-H. Moustafa · M. A.-K. Sobh ( ) ) Nephrology Department, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt e-mail: afdonia@hotmail.com Tel.: +20-5022-62222 Fax: +20-5022-63717