Rituximab treatment for difficult-to-treat nephrotic syndrome in children: a multicenter, retrospective study

Abstract

Background/aim: This study aimed to evaluate the efficacy of rituximab in children with difficult-to-treat nephrotic syndrome, considering the type of disease (steroid-sensitive or –resistant) and the dosing regimen.

Materials and methods: This multicenter retrospective study enrolled children with difficult-to-treat nephrotic syndrome on rituximab treatment from 13 centers. The patients were classified based on low (single dose of 375 mg/m2) or high (2-4 doses of 375 mg/m2) initial dose of rituximab and the steroid response. Clinical outcomes were compared.

Results: Data from 42 children [20 steroid-sensitive (frequent relapsing / steroid-dependent) and 22 steroid-resistant nephrotic syndrome, aged 1.9–17.3 years] were analyzed. Eleven patients with steroid-sensitive nephrotic syndrome (55%) had a relapse following initial rituximab therapy, with the mean time to first relapse of 8.4 ± 5.2 months. Complete remission was achieved in 41% and 36% of steroid-resistant patients, with the median remission time of 3.65 months. At Year 2, eight patients in steroid-sensitive group (40%) and four in steroid-resistant group (18%) were drug-free. Total cumulative doses of rituximab were higher in steroid-resistant group (p = 001). Relapse rates and time to first relapse in steroid-sensitive group or remission rates in steroid-resistant group did not differ between the low and high initial dose groups.

Conclusion: The current study reveals that rituximab therapy may provide a lower relapse rate and prolonged relapse-free survival in the steroid-sensitive group, increased remission rates in the steroid-resistant group, and a significant number of drug-free patients in both groups. The optimal regimen for initial treatment and maintenance needs to be determined.

Keywords: Frequently relapsing nephrotic syndrome; immunosuppressive agents; remission; steroid-dependent nephrotic syndrome; steroid- resistant nephrotic syndrome.

Figure 1

Study flow chart. Of 49 screened patients, 42 fulfilled the selection criteria and consent to study participation. Exclusion criteria were the presence of genetic mutations, hypocomplementemia, and/or immune deposits in kidney biopsy specimens. The NPHS2 gene encodes podocin that is vital for the normal glomerular filtration barrier in kidneys. NPHS2 mutation causes steroid-resistant nephrotic syndrome. ARHGAP24mutation influences podocyte cell shape and membrane structure, can causing focal segmental glomerulosclerosis. SSNS: steroid-sensitive nephrotic syndrome (including SDNS steroid-dependent nephrotic syndrome and FRNS frequently relapsing nephrotic syndrome). SRNS: steroid-resistant nephrotic syndrome.

Figure 2

Relaps-free survival in the SSNS group (a), and adjusted for the initial dose regimens (b). SSNS: steroid-sensitive nephrotic syndrome (including SDNS: steroid-dependent nephrotic syndrome and FRNS: frequently relapsing nephrotic syndrome).