Nephrotic syndrome is one of the most common chronic glomerular disorders in childhood and is characterised by heavy proteinuria, hypoalbuminaemia, oedema, and hyperlipidaemia. Although the majority of children achieve initial remission with corticosteroid therapy, a substantial proportion develop complicated disease phenotypes such as FRNS, SDNS, or SRNS, which are associated with increased morbidity and long-term complications.[¹–³]

Prolonged corticosteroid exposure in these children leads to significant adverse effects, including growth suppression, obesity, hypertension, behavioural disturbances, and increased infection risk.⁴,⁵ Steroid-sparing agents have therefore become essential to maintain remission while reducing steroid-related toxicity. In SRNS, immunosuppressive agents are often required due to poor steroid responsiveness.[⁶]

Levamisole continues to be widely used in FRNS and SDNS owing to its immunomodulatory effects, favourable safety profile, oral administration, and affordability, especially in low- and middle-income countries.[¹⁰–¹²] Despite guideline recommendations, variability in real-world treatment practices persists, and patient-centred outcomes such as quality of life are often under-reported.¹³–¹⁶ This study aimed to address these gaps.

METHODS

This prospective observational study was conducted at two tertiary-care centres after institutional ethics approval. Children aged 2–12 years with FRNS, SDNS, or SRNS initiated on a steroid-sparing agent for the first time were enrolled after informed consent. Baseline demographic, clinical, and laboratory data were recorded.

Patients were followed monthly for six months, with a subset followed up to twelve months. Outcomes included remission status, relapse frequency, steroid discontinuation, adverse events, renal function, and quality of life assessed using PedsQL Family Impact and ESRD modules. Data were analysed using descriptive statistics, with p < 0.05 considered statistically significant.

RESULTS

Of the 104 enrolled children, 56 had FRNS, 44 had SDNS, and 4 had SRNS. Baseline demographic and clinical characteristics are summarised in Table 1. Levamisole was the predominant first-line steroid-sparing agent, while cyclophosphamide and mycophenolate mofetil were used selectively, mainly in SRNS or after levamisole failure (Figure 1).

At six months, levamisole achieved high rates of complete remission with low relapse frequency. Sustained remission remained predominant at twelve months, although relapse and treatment failure increased modestly, necessitating escalation in some cases (Figure 2). Steroid discontinuation increased substantially over time. Quality-of-life scores improved significantly at both six and twelve months (Table 2). Adverse events were mostly mild and reversible, with no new safety signals identified.

Table 1. Demographic and Baseline Characteristics of Study Participants (N = 104)

Table 2. Quality of Life Scores with Levamisole Therapy at Baseline, Six Months, and Twelve Months

Figure 1. Distribution of Steroid-Sparing Agents Used in the Study Population

Figure 2. Comparison of Clinical Outcomes with Levamisole Therapy at Six-Month and Twelve-Month Follow-Up

DISCUSSION

This multicentric observational study provides robust real-world evidence supporting the continued role of levamisole as an effective and safe first-line steroid-sparing agent in children with FRNS and SDNS. The remission rates and steroid-sparing benefits observed are consistent with previous observational studies and randomised trials.[¹⁰–¹²,¹⁷–¹⁹]

Comparative studies have demonstrated that levamisole is not inferior to mycophenolate mofetil for relapse prevention, supporting its use before escalation to more intensive immunosuppression.¹¹,¹⁸–²¹ Current KDIGO and IPNA recommendations continue to endorse levamisole in relapse-prone steroid-sensitive nephrotic syndrome.[¹,²,²⁰]

Importantly, this study highlights significant improvement in health-related quality of life, reflecting reduced disease burden and improved psychosocial well-being of children and caregivers. These findings align with contemporary evidence indicating persistent quality-of-life impairment in nephrotic syndrome, particularly in SRNS.[¹⁴,¹⁶,²¹]

CONCLUSION

Levamisole remains an effective, safe, and feasible first-line steroid-sparing agent in children with FRNS and SDNS. Its use is associated with sustained remission, significant steroid reduction, and meaningful improvement in quality of life. Outcomes in SRNS remain less favourable, underscoring the need for further research in this subgroup.

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