Levamisole: adjunctive therapy in steroid dependent minimal change nephrotic children

Abstract

In children with minimal change nephrotic syndrome (MCNS), the steroid dependent group constitutes an especially difficult case for management. Patients in this group are prone to serious steroid side effects. Additionally, alkylating agents commonly fail to maintain remission and expose patients to more side effects. Therapy with the immunostimulant drug levamisole may therefore be another option in the attempt to maintain remission with minimal side effects. We prospectively treated 20 of our steroid dependent primary MCNS patients with levamisole. All patients were children, with an age range of 3-15 years; 16 were boys and 4 were girls. Remission was firstly induced by steroids, then levamisole was added in a dose of 2.5 mg/kg body weight on alternate days for 6 months. During this period we attempted to withdraw steroids completely and maintain patients on levamisole alone. We followed up our patients for the occurrence of relapse and side effects during this period and for a further 6 months after stopping levamisole. In 11 out of 20 children (55%), we successfully stopped steroids for more than 2 weeks. At the end of the 6-month treatment period (i.e. after 4 months of steroid discontinuation), ten patients (50%) were maintaining remission on levamisole alone. At the end of the 12-month study period (i.e. after 6 months of levamisole discontinuation), five patients (25%) were still in remission without any treatment for the previous 6 months. No significant side effects were reported during levamisole therapy. None of the patients developed neutropenia, but the leukocyte count showed a significant reduction in those who responded to levamisole treatment. We concluded that levamisole therapy for 6 months is a safe and perhaps effective therapy in a subset of children with steroid dependent MCNS to enable an otherwise infeasible withdrawal of steroids. This may be worth a trial before other types of more hazardous adjunctive therapies are considered.

Long-term effects of levamisole treatment in childhood nephrotic syndrome

“…duction in the relapse rate in SDNS patients. In a prospective trial, Donia et al [38] treated 20 SDNS patients with levamisole for 6 months and followed them for a further 6 months. At the end of the 6-month treatment period, 10 patients were maintaining remission on levamisole alone.…”

“…The immunomodulatory agent levamisole has been used as an adjunctive therapy in such patients [31,32,33,34,35,36,37,38] as a good alternative to major immunosuppressives [39]. This treatment leads to decreases in the number of relapses and the amount of prednisolone required.…”

Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy

“…Nevertheless, some patients remain steroid dependent despite this therapy. For these patients various therapeutic strategies have been suggested, including other immunosuppressive agents such as tacrolimus [3] or mycophenolate mofetil [4,5], or the immunostimulatory drug levamisole [6]. However, these strategies often fail to maintain complete remission of nephrotic syndrome [7].…”

Can lactoferrin modulate the immunostimulant activity of levamisole in rats immunosuppressed by cyclophosphamide?

“…It is having an immunostimulating effect in immunosuppressed condition [5] but it has been found that it is also having a useful effect in autoimmune diseases like nephrotic syndrome and rheumatoid arthritis. It helps to make steroid free period of up to 6 months to 1 year in nephrotic syndrome [6,7]. Lactoferrin (Lac) is an 80 kDa multifunctional glycoprotein belonging to the transferrin family.…”