Long-term effects of levamisole treatment in childhood nephrotic syndrome

Abstract

The effects of levamisole treatment on long-term outcome were evaluated in a retrospective study of frequently-relapsing (FRNS, n=15), steroid-dependent (SDNS, n=13), and steroid-resistant (SRNS, n=6) nephrotic syndrome in 34 children (21 boys, 13 girls, mean age 5.0+/-3.4 years) during a 60-month follow-up period. The definition of frequent relapses was > or = 4 relapses per year. The current relapse was treated with prednisolone 60 mg/m2 per day for 4 weeks, then with 40 mg/m2 every other day for 4 weeks, after which the dose was tapered by 10 mg weekly. From the beginning of the 5th week, levamisole was introduced at a dose of 2 mg/kg per day. The duration of levamisole treatment was 17+/-7 months. Before starting levamisole treatment the mean level of proteinuria was 2.17+/-1.34 g/day and the relapse rate was 4.41/year. By the end of levamisole therapy, proteinuria had fallen to 0.142+/-0.211 g/day and the relapse rate to 0.41/year. No relapse occurred in 23 of the 34 patients during levamisole treatment. In the 24-month follow-up period after the discontinuation of levamisole, 28 children remained in total remission, while 6 had relapses. The cumulative steroid dose before levamisole therapy was 7,564.4+/-3,497.1 mg/year and following the introduction of levamisole 1,472.9+/-1,729.9 mg/year (P<0.0001). We observed reversible neutropenia in 5 patients, but no other side effects were seen. Our findings suggest that in FRNS and SDNS levamisole significantly reduces both the relapse rate and the cumulative steroid dose; therefore, it could be recommended for these patients. In SRNS patients it has also some benefit because proteinuria and the cumulative steroid dose could be reduced significantly.

Short- and long-term efficacy of levamisole as adjunctive therapy in childhood nephrotic syndrome

“…Limited data exist, however, as to the long-term efficacy of levamisole therapy after its cessation. A recent retrospective study [9] evaluated frequently relapsing steroid-dependent NS in 13 children treated with 2 mg/kg per day of levamisole for a mean duration of 17 months. Among the steroid-dependent children, 6/13 relapsed while on levamisole, but only 2/13 after its cessation, suggesting that levamisole may have a long-lived effect.…”

“…Although prior reports focused on levamisole as an effective adjunctive therapy in reducing short-term relapse frequency (RF), limited data exist as to its long-term efficacy. In a recent retrospective study, its steroid-sparing effects were suggested to last for months after its withdrawal [9]. Even more limited data exists as to the effect of levamisole on steroid-induced clinical complications, such as hypertension, or alterations in somatic measures, such as height and weight.…”

Efficacy of Levamisole as a single agent in maintaining remission in steroid dependant nephrotic syndrome

“…One of the main observations is the reduced 19,20 interleukin-2 (IL-2) production .Some studies have suggested that minimal change nephrotic syndrome (MCNS) is a T helper 2-dominated (Th2) disease, having observed higher levels of serum interleukin-13 (IL-13) Several studies suggested LEV as the first choice of non-steroidal immunosuppressive agent to achieve less frequent relapses and longer sustained remission in children with FRNS or SDNS, in addition to the decrease 23,24 of steroid-related side effects . Significant reduction of both relapse rate and cumulative steroid dose by LEV in SDNS and FRNS patients was reported in the studies of 25,10,11 Sumegi, Madani and Al-Saran . In a later study by Boyer et al LEV had the additional benefits of normalized blood pressure in hypertensive patients and improved height velocity, even after cessation of LEV No literature-based firm recommendations can be made on how prednisolone should be withdrawn during LEV therapy in order to minimise the risk of relapse.…”

Efficacy and safety of long-term levamisole therapy in maintaining remission in steroid dependent nephrotic syndrome

“…Therefore, when commencing on LEV, all patients should be warned about this potential side-effect and should be advised to stop the drug and report immediately. Neutropenia and liver toxicity have been reported in NS patients using LEV 17,18 . However, neutropenia, anaemia or liver toxicity were not observed in the present study.…”