ORIGINAL ARTICLE Levamisole and ANCA positivity in childhood nephrotic syndrome Leah Krischock 1,2 & Pasan Pannila 2 & Sean E. Kennedy 1,2 Received: 4 November 2020 /Revised: 3 December 2020 /Accepted: 31 December 2020 # Crown 2021 Abstract Background This study aimed to determine the prevalence of ANCA positivity in children managed with levamisole as a steroid- sparing agent for nephrotic syndrome (NS). Methods Medical records of children with steroid-sensitive NS managed with levamisole therapy at Sydney Children’s Hospital between 1/1/2000 and 31/12/2018 were retrospectively reviewed. Main outcome measure was side effects of levamisole therapy including ANCA positivity. Results Seventy-one children, median age 3 years and 1 month (IQR 29–68 months) at first presentation, were subsequently managed with levamisole. 60.6% were male and 65% Caucasian. 47.9% had frequently relapsing (FR)NS and 52.1% steroid- dependent (SD)NS. Overall, there was a median reduction in relapses from 3 (IQR 1–5) to 0.4 relapses (IQR 0–1) per year after levamisole was commenced. Levamisole was successful in preventing relapse in 19 (29%) patients and was used for median 24 (22 to 25) months. Levamisole was discontinued due to relapse in 25 patients (38%) after median 12 (5–28) months. Side effects occurred in 28 patients (42.4%); the most common side effect was ANCA positivity in 12 patients. In eleven of these patients, levamisole was discontinued; in one patient, low-level titres were documented and spontaneously resolved without cessation of levamisole. Two patients developed ANCA-associated vasculitis. Conclusion ANCA positivity is a common side effect of levamisole and was seen in 18.2% of our patients. Monitoring is required to determine side effects including ANCA positivity and treatment modified accordingly. Keywords Nephrotic syndrome . ANCA-associated vasculitis . Levamisole . Paediatrics . Drug effect Background Levamisole, an anti-helminth agent with immunomodulatory effects, has been used in the management of nephrotic syn- drome (NS) since the 1980s [1]. Interest in levamisole as a steroid-sparing agent has increased with the results of a double-blinded placebo-controlled randomised trial of levam- isole demonstrating a significant reduction in relapse frequen- cy in patients with both steroid-sensitive frequently relapsing (FR) and steroid-dependent (SD)NS [2]. Levamisole use varies geographically, with higher rates in India compared to the US where it was withdrawn from the market in 1999 due to its side effect profile [3]. It can be difficult to access in some regions such as Europe, where its production was limited in 2004 due to lack of clear indication for use in humans [4]. In Australia, patient-specific approval from the Therapeutic Goods Administration is required to prescribe levamisole [5]. Side effects of levamisole include gastro-intestinal distur- bances, leukopaenia, neutropaenia, rash, fever, abdominal pain and elevated liver enzymes [1]. ANCA-associated vas- culitis (AAV) is a possible side effect of levamisole but has more commonly been reported in cocaine users where cocaine is mixed with levamisole [1, 3]. Barbano et al. reported dis- seminated autoimmune disease in a 5-year-old boy with SDNS who had received levamisole for 2 years [6]. The child developed hepatosplenomegaly, haemolytic anaemia, and leu- kopenia with high titres of p-ANCA antibodies without a cu- taneous vasculitis. All signs and symptoms of autoimmune disease resolved within 1 month of stopping levamisole ther- apy, although whether ANCA positivity resolved was not re- ported. More recently, Aoun et al. report persistent * Leah Krischock Leah.Krischock@health.nsw.gov.au 1 Department of Nephrology, Sydney Children’s Hospital, Randwick, NSW, Australia 2 School of Women’s and Children’s Health, UNSW Medicine, University of New South Wales, Sydney, NSW, Australia https://doi.org/10.1007/s00467-020-04915-7 / Published online: 23 January 2021 Pediatric Nephrology (2021) 36:1795–1802