Indian Pediatr 2014;51:
Efficacy of Levamisole in Children with
Frequently Relapsing and Steroid-dependent Nephrotic Syndrome
Sudha Ekambaram, Vijayakumar Mahalingam, Prahlad Nageswaran, Amish Udani,
Sangeetha Geminiganesan and Shweta Priyadarshini
From the Department of Pediatric Nephrology, Mehta Children’s
Hospital, Chennai, India.
Correspondence to: Dr M Vijayakumar, Consultant Pediatric
Nephrologist, Mehta Children’s Hospitals, No.2(e) Mc Nichols Road, 3rd
Lane, Chetpet, Chennai 600 031, Tamilnadu, India.
Received: August 05, 2013;
Initial Review: August 28, 2013;
Accepted: March 06, 2014.
Objectives: To assess the efficacy of levamisole in frequently
relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome.
Study Design: Retrospective analysis of hospital
Setting: Pediatric nephrology department of a
tertiary referral pediatric hospital.
Participants: 62 children with frequently
relapsing nephrotic syndrome and 35 children with steroid-dependent
Methods: Case records of children who were
diagnosed as steroid-dependant or frequently-relapsing nephrotic
syndrome from June 2004 to June 2011, were reviewed. Levamisole was
given daily (2 mg/kg/d) along with tapering doses of alternate day
steroids after remission on daily steroids.
Results: Levamisole was effective in 77.3%
children with a better (80.6%) efficacy in frequently relapsing
nephrotic syndrome. A total of 34 children completed 1 year follow-up
post levamisole therapy. The cumulative mean (SD) steroid dose 1-year
before therapy was 4109(1154) mg/m2 and 1-year post therapy was 661 (11)
mg/m2 (P<0.001). The relapses were also less during the period of post-levamisole
Conclusion: Levamisole is an effective
alternative therapy in frequently relapsing and steroid-dependent
Keywords: Treatment, Steroids, Outcome, Relapse,
he most commonly used drugs in the treatment of
nephrotic syndrome (NS) are steroids. Children exposed to steroids for a
prolonged period may experience adverse effects such as growth failure,
infections, hypertension and osteoporosis. In order to reduce steroid
toxicity, alternative drugs such as cyclophosphamide, cyclosporine and
levamisole are used [1,2]. Levamisole is an immunomodulator that has
been used for more than two decades, and is often used as the first
option in the treatment of steroid-dependent or frequently relapsing NS
in children. Its major advantages are steroid-sparing property and less
toxicity in comparison to the other immunosuppresants . This study
was conducted to evaluate the efficacy of levamisole in
steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing
nephrotic syndrome (FRNS) in children. The specific objectives were: (a)
to determine the efficacy of daily levamisole in SDNS and FRNS children;
(b) to compare the efficacy of levamisole between SDNS and FRNS
children; and (c) to evaluate the response of levamisole in
SDNS/FRNS children post-cyclophosphamide therapy.
The records of children, who attended the Pediatric
Nephrology clinic at a tertiary pediatric referral hospital, in Southern
India between June 2004 and June 2011 were analyzed retrospectively.
Children aged 1-18 years receiving levamisole for at least six months
for treatment of SDNS or FRNS were included. Infantile NS, congenital NS
and NS secondary to systemic illnesses were excluded. SDNS was defined
when there were two consecutive relapses while on alternate day steroids
or within 14 days of their discontinuation. FRNS was defined by two or
more relapses in six months or more than three relapses in any twelve
months. Relapses were treated according to Indian Pediatric Nephrology
Group guidelines . Levamisole was started in SDNS/FRNS children daily
at a dose of 2 mg/kg/day at the end of two weeks of daily steroids on
inducing remission. Prednisolone was given at a dose of 1.5 mg/kg every
other day for 4 weeks and then gradually tapered to a maintenance dose
of 0.5 mg/kg every other day at 6 months and 0.25 mg/kg every other day
at end of 1 year.
All children were monitored every three months for
response and side effects; urinalysis, total and differential blood cell
counts, and liver enzymes were done. At the end of one year, serum
albumin, serum cholesterol and urine albumin were checked, and if under
remission, prednisolone was discontinued. Levamisole was stopped at the
end of two years and these children were followed up for at least one
year following cessation of therapy.
Levamisole was considered effective, if the children
were able to maintain remission when steroids were tapered and stopped.
It was considered ineffective if child developed two or more relapses
while on every other day steroids or when steroids could not be
withdrawn. Levamisole was stopped when it was considered ineffective.
Children in post-immunosuppressive therapy (cyclophosphamide),
presenting with SDNS/FRNS were included and their response to levamisole
was analyzed. Statistical analyses were done using Repeated measures
ANOVA, F-test, and Chi-Squared test. P <0.05 was taken as
A total of 97 children (53 boys) completed 6 months
of levamisole therapy; 62 (64%) of these were FRNS. None of the children
had renal failure, hypertension or gross hematuria. The baseline
characteristics at the start of levamisole therapy are shown in
TABLE I Baseline Characteristics of The Study Population
Male gender, n (%)
Age at diagnosis, y
Age at beginning of therapy, y
SDNS – Steroid-dependent nephrotic syndrome; FRNS –
Frequently relapsing nephrotic syndrome; * Values in mean (SD).
The duration of levamisole therapy ranged from 6 to
24 months with a mean (SD) duration of 18.7 (6.4) months. Levamisole was
effective in 77.3% children, was stopped in 15 (15.5%) children as it
was ineffective, and 7 (7.2%) children were lost to follow-up. Frequent
relapsers showed a better efficacy to levamisole in comparison to
steroid-dependent NS (80.6% vs. 71.4%; P=0.001).
Prednisolone was tapered to 0.5 mg/kg/day at the end
of 6 months with a mean (SD) duration of 5 (1.1) months. Sixty-five
children completed one year of therapy and prednisolone was stopped with
a mean (SD) duration of 11.84 (1.3) months. Mean (SD) serum albumin at
the start of therapy was 2.32 (0.5) g/dL and at completion of therapy
was 4.12 (0.3) g/dL.
At the end of 24 months, 40 children completed
therapy and these children were kept under surveillance for at least a
year. A total of 34 children were followed-up for 1 year post-therapy
and the cumulative steroid dose and relapse rates are shown in
Table II. The steroid dose and relapse rates were significantly
less after levamisole therapy. Relapse free period was observed in 25
(73.5%) children during therapy and in 22 (64.7%) children during the
one year period of post-levamisole therapy.
TABLE II Cumulative Steroids and Relapse Rates in Children With FRNS/SDNS
Dose of steroids
No. of relapses
1 y before levamisole
1 y after levamisole
Before the administration of levamisole, 7 SDNS
children had received cyclophosphamide. Renal biopsy was performed in
all these children. Four children had minimal change disease and 3 had
diffuse mesangial proliferation by histopathology. Levamisole therapy
was effective in 5 children.
In this retrospective study of 97 children with SDNS
or FRNS, levamisole was found to be effective in majority (77.3%), with
a better efficacy in children with FRNS as compared to those with SDNS.
In our study, levamisole was administered in daily
dosing schedule based on personal experience; most guidelines suggest
alternate day therapy in nephrotic syndrome. Fu, et al. , in a
comparative study between daily and alternate day levamisole usage in
children with FRNS and SDNS, reported that daily levamisole usage can be
considered when response to alternate day usage is unsatisfactory. We
did not have any comparison group as this study was a retrospective
Madani, et al.  evaluated the efficacy of
levamisole among 304 children and demonstrated that it was effective in
children with both SDNS and FRNS. In their study, the relapse rates
reduced by about one-half after levamisole therapy. Alsaran, et al.
 documented response in 90.6% children with FRNS/SDNS. Sumegi, et
al.  followed 34 children for a duration of 5–36 months and
documented a reduction in relapse rate after levamisole therapy. Our
results are in concordance with the above studies. In children with
effective therapy, we were able to taper and stop steroids in majority
of patients. Bagga, et al.  also showed that levamisole was
effective in children with SDNS. In a meta-analysis of randomized
controlled trials , Durkan, et al. showed that prolonged
course of levamisole reduces the incidence of relapses.
Various studies have reported side effects while on
alternate day levamisole schedule, though these were not
life-threatening and were reversible on discontinuing levamisole
[6,7,9,11]. We did not observe any side effects, even in those who
completed 2 years of daily levamisole therapy.
To conclude, daily levamisole along with initial low
dose steroid therapy can be effective in children with FRNS/SDNS with a
better efficacy in children with FRNS. It significantly reduces the
cumulative dose of steroid intake and relapse rates. Levamisole can be
used as an effective steroid-sparing agent in children with
frequently-relapsing and steroid dependent nephrotic syndrome.
What Is Already Known?
• Levamisole is commonly used as a steroid
sparing agent in children with steroid dependent or frequently
relapsing nephrotic syndrome.
What This Study Adds?
• Daily levamisole along with initial low
dose steroid therapy can be effective in FRNS/SDNS children with
a better efficacy in children with FRNS.
• Cumulative dosage of steroids reduces with levamisole
therapy in FRNS/SDNS.
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