ObjectiveRituximab is an effective treatment for children with steroid dependent or frequently relapsing nephrotic syndrome. The optimum dosing schedule for rituximab has not been established. We hypothesized that a single low dose of 375 mg/m2 would have comparable outcomes to higher doses in reducing the frequency of relapse and time to B cell reconstitution.MethodsWe conducted a multicenter retrospective observational cohort study of children with steroid-sensitive frequently relapsing nephrotic syndrome. Data were extracted from clinical records including the dates of diagnosis, treatment, relapses, the use of concomitant immunosuppression, and lymphocyte subset profiling. Patients treated earlier received variable doses of rituximab, although typically two doses of 750 mg/m2. Later, patients received the current regimen of a single dose of 375 mg/m2. The primary outcome was an absence of clinically confirmed relapse 12 months following rituximab administration. Secondary outcomes were median time to relapse, probability of being relapse-free at 6 and 24 months and time to reconstitution of CD19+ B cells.ResultsSixty patients received 143 courses of rituximab. Seven different dosing regimen strategies were used, ranging between 375 and 750 mg/m2 per dose, with administration of 1–4 doses. There was no significant difference in event-free survival at 12 months between dosing strategies. The median time to reconstitution of B cells was not significantly different between groups.ConclusionsUse of a single low-dose regimen of rituximab in the management of frequently relapsing nephrotic syndrome does not affect the probability of relapse at 12 months or time to B cell reconstitution compared to a conventional higher dose.Electronic supplementary materialThe online version of this article (10.1007/s00467-018-4172-3) contains supplementary material, which is available to authorized users.

ObjectivesTacrolimus is increasingly advocated as a steroid sparing agent in the management of nephrotic syndrome. As concerns exist about long term nephrotoxicity, interval renal biopsies have been advocated to detect early changes. Associations between histological changes and patient factors are not well established.MethodsSingle centre review of surveillance renal histology of children who received tacrolimus to treat nephrotic syndrome between 2002–2015.Abstract G386 Figure 1 Duration on tacrolimus and nephrotoxicity. *denotes patients with histological FSGS Abstract G386 Figure 2Average trough 12 hours tacrolimus levels from starting tacrolimus to first biopsy. Toxicity associated with higher levels: 0/10 showed toxicity with levels of 4.36 to 5.54 μg/L vs. 9/15 (60%) with levels 5.69 to 7.36 μ/L (p < 0.0001)Results25 children (16 male, 1 non-caucasian, 21 minimal change, 4 FSGS) commenced tacrolimus at median age 4.0 years (range 1.4–8.9). 9/25(35%) of first biopsy taken after median duration 4.7 years (range 1.9 to 6.9) demonstrated features of calcineurin inhibitor (CNI) nephrotoxicity. Toxicity was associated with higher mean 12-hour trough serum tacrolimus levels: 0/11 showed toxicity with levels of 4.36 to 5.54 µg/L vs. 9/15 (60%) with levels 5.69 to 7.36 µg/L (p < 0.0001). No association was found with number of relapses, gender or duration of time on tacrolimus. Eight patients without initial CNI toxicity underwent second biopsy at a median time of 4.9 (range, 4.0–5.4) years later. Two developed toxicity. Estimated glomerular filtration rate in those who developed toxicity was normal. We attempted tacrolimus weaning in 20 patients: 11 patients relapsed, 4 within 2 months, further 5 within 1 year after dose reduction (See Figures 1 and 2).ConclusionSignificant number of children on tacrolimus showed histological nephrotoxicity after a short duration of therapy. In this small single centre experience, toxicity correlated with tacrolimus level rather than duration. A high number relapsed shortly following dose reduction. We suggest maintaining tacrolimus levels ≤5.5 µg/L to minimise nephrotoxicity.