Short- and long-term efficacy of levamisole in children with steroid-sensitive nephrotic syndrome

Elmas, Ahmet Taner; Tabel, Yılmaz; Elmas, Özlem

doi:10.1007/s11255-012-0241-x

Cited by 14 publications

(18 citation statements)

References 30 publications

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“…In three patients remission was maintained long after levamisole was stopped. This observation is in accordance with the results of recent studies suggesting that its steroidsparing effects last for months after its withdrawal [13, 20, 24, 25]. Boyer et al .…”

Section: Discussionsupporting

confidence: 92%

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Levamisole therapy in children with frequently relapsing and steroid-dependent nephrotic syndrome: a single-center experience

Kuźma-Mroczkowska

Skrzypczyk

Pańczyk-Tomaszewska

2016

cejoi

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IntroductionNumerous studies suggest that levamisole, an antihelmintic agent with an immunomodulatory effect, reduces the number of relapses in children with frequently relapsing and steroid-dependent nephrotic syndrome (FRNS/SDNS). The aim of the study was to present a single center’s experience in treatment of FRNS and SDNS with levamisole.Material and methodsAmong 72 children with FRNS/SDNS treated in our department with levamisole in the years 1984-2011 we studied in detail 53 patients (mean age: 6.5 ±3.0 years), in whom the medication was administered for at least 6 months. In these 53 patients we evaluated: the course of the disease before levamisole, the renal biopsy result, medications used, prednisone dose on levamisole initiation, duration of levamisole treatment, time to first relapse and number of relapses on levamisole, and levamisole side effects.ResultsThe duration of nephrotic syndrome was 3.4 ±2.9 years, and the number of relapses before levamisole treatment was 6.0 ±3.4. The dose of prednisone on initiation of levamisole treatment was 1.2 ±0.6 mg/kg/24 h, and the duration of levamisole treatment was 15.0 ±7.3 months. During levamisole treatment proteinuria relapsed in 34/53 (64.2%) children, and the time to first relapse was 8.8 ±8.1 months. During levamisole therapy relapses of the disease decreased significantly (2.7 ±2.0 vs. 1.8 ±2.1 relapses/year, p = 0.02). Time to first relapse correlated with total number of relapses (R = –0.59, p < 0.001) and number of relapses in one year during levamisole treatment (R = –0.60, p < 0.001).ConclusionsLevamisole is effective in reducing the number of relapses in children with frequently relapsing and steroid-dependent nephrotic syndrome. Early relapse of proteinuria on levamisole treatment in children with FRNS/SDNS suggests low efficacy of further treatment.

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Section: Discussionsupporting

confidence: 92%

“…[25], Elmas et al . [24], and Ekambaram et al . [20] found that in some children levamisole has a long-lasting effect even 12 months after withdrawal.…”

Section: Discussionmentioning

confidence: 99%

Levamisole therapy in children with frequently relapsing and steroid-dependent nephrotic syndrome: a single-center experience

Kuźma-Mroczkowska

Skrzypczyk

Pańczyk-Tomaszewska

2016

cejoi

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“…[6][7][8] In 7 cohort studies (2 RCTs and 5 cohort studies), largely from Middle East countries and India, neutropenia was only reported in 8 of a total of 573 included patients in these studies. [14][15][16][17][18][19][20] Most of these studies checked the blood counts on a regular basis (biweekly or monthly), but Dayal et al 8 and Ekambaram et al 15 analyzed blood counts every 3 months. Madani et al, 17 who included the majority of the patients (304/573 patients), did not report the frequency of follow-up visits.…”

Section: Discussionmentioning

confidence: 99%

A randomized clinical trial indicates that levamisole increases the time to relapse in children with steroid-sensitive idiopathic nephrotic syndrome

Gruppen

Bouts

Weide

et al. 2018

Kidney International

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Levamisole has been considered the least toxic and least expensive steroid-sparing drug for preventing relapses of steroid-sensitive idiopathic nephrotic syndrome (SSINS). However, evidence for this is limited as previous randomized clinical trials were found to have methodological limitations. Therefore, we conducted an international multicenter, placebo-controlled, double-blind, randomized clinical trial to reassess its usefulness in prevention of relapses in children with SSINS. The efficacy and safety of one year of levamisole treatment in children with SSINS and frequent relapses were evaluated. The primary analysis cohort consisted of 99 patients from 6 countries. Between 100 days and 12 months after the start of study medication, the time to relapse (primary endpoint) was significantly increased in the levamisole compared to the placebo group (hazard ratio 0.22 [95% confidence interval 0.11-0.43]). Significantly, after 12 months of treatment, six percent of placebo patients versus 26 percent of levamisole patients were still in remission. During this period, the most frequent serious adverse event (four of 50 patients) possibly related to levamisole was asymptomatic moderate neutropenia, which was reversible spontaneously or after treatment discontinuation. Thus, in children with SSINS and frequent relapses, levamisole prolonged the time to relapse and also prevented recurrence during one year of treatment compared to prednisone alone. However, regular blood controls are necessary for safety issues.

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“…Second-line agents are of variable effectiveness, have major potential toxicities and are not supported by robust clinical trial evidence [2]. One agent that has been shown to be effective in randomized controlled clinical trials (RCTs) in children with SSNS is levamisole [3][4][5][6][7] but there are no reports on the use of this agent in adults with nephrotic syndrome [1]. One agent that has been shown to be effective in randomized controlled clinical trials (RCTs) in children with SSNS is levamisole [3][4][5][6][7] but there are no reports on the use of this agent in adults with nephrotic syndrome [1].…”

Section: Introductionmentioning

confidence: 99%

Levamisole in steroid-sensitive nephrotic syndrome: usefulness in adult patients and laboratory insights into mechanisms of action via direct action on the kidney podocyte

et al. 2015

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Minimal change nephropathy (MCN) is the third most common cause of primary nephrotic syndrome in adults. Most patients with MCN respond to corticosteroid therapy, but relapse is common. In children, steroid-dependent patients are often given alternative agents to spare the use of steroids and to avoid the cumulative steroid toxicity. In this respect, levamisole has shown promise due to its ability to effectively maintain remission in children with steroid-sensitive or steroid-dependent nephrotic syndrome. Despite clinical effectiveness, there is a complete lack of molecular evidence to explain its mode of action and there are no published reports on the use of this compound in adult patients. We studied the effectiveness of levamisole in a small cohort of adult patients and also tested the hypothesis that levamisole's mode of action is attributable to its direct effects on podocytes. In the clinic, we demonstrate that in our adult patients, cohort levamisole is generally well tolerated and clinically useful. Using conditionally immortalized human podocytes, we show that levamisole is able to induce expression of glucocorticoid receptor (GR) and to activate GR signalling. Furthermore, levamisole is able to protect against podocyte injury in a puromycin aminonucleoside (PAN)-treated cell model. In this model the effects of levamisole are blocked by the GR antagonist mifepristone (RU486), suggesting that GR signalling is a critical target of levamisole's action. These results indicate that levamisole is effective in nephrotic syndrome in adults, as well as in children, and point to molecular mechanisms for this drug's actions in podocyte diseases.

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Short- and long-term efficacy of levamisole in children with steroid-sensitive nephrotic syndrome

Abstract: Thus, our study showed that levamisole is a safe and effective steroid-sparing agent, with long-lasting effect even 12 months after withdrawal.

Cited by 14 publications

References 30 publications

Levamisole therapy in children with frequently relapsing and steroid-dependent nephrotic syndrome: a single-center experience

Levamisole therapy in children with frequently relapsing and steroid-dependent nephrotic syndrome: a single-center experience

A randomized clinical trial indicates that levamisole increases the time to relapse in children with steroid-sensitive idiopathic nephrotic syndrome

Levamisole in steroid-sensitive nephrotic syndrome: usefulness in adult patients and laboratory insights into mechanisms of action via direct action on the kidney podocyte

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