Kidney Survival in Children With Steroid-Resistant Nephrotic Syndrome Treated by Rituximab

Kidney outcomes in children with steroid-resistant nephrotic syndrome (SRNS) following rituximab remain unclear.

We conducted an international retrospective cohort study across 23 centers in 17 countries, including children with SRNS who did not respond to calcineurin inhibitors (CNIs) and subsequently, received rituximab. Patients with genetic variants were excluded. The primary outcome was kidney survival.

We analyzed data on 151 children (53% males; median age at onset: 6.8 years; primary vs. secondary SRNS: 54% vs. 46%; focal segmental glomerulosclerosis [FSGS]: 62%). All subjects received CNIs before rituximab (0-3 months: 21%; 3-6 months: 26%; 6-12 months: 26%; > 12 months: 26%). Upon rituximab, 73 subjects (48%) had normal kidney function, 47 (31%) had chronic kidney disease (CKD)2, and 31 (21%) had CKD3. Twenty-eight (19%) developed kidney failure. Overall kidney survival was 82.7%, 75.8%, and 72.3% at 3, 5, and 7 years post-rituximab. Baseline CKD staging before rituximab was associated with kidney survival at 5 years (log-rank P < 0.001); CKD stage 1, 91.7%; CKD stage 2, 70.4%; and CKD stage 3, 35.5%). The predictive factors for inferior kidney survival were CKD2 (adjusted hazard ratio [HR_adj]: 2.7, 95% confidence interval [CI]: 1.5-4.9, P < 0.001), lower baseline serum albumin (log-rank P = 0.01; HR_adj: 0.88, 95% CI: 0.81-0.95; P < 0.001) and FSGS (log-rank P = 0.03; HR_adj: 3.4, 95% CI: 1.1-10.0; P < 0.001). Nonremission at 6 months was associated with inferior kidney survival (61.2% at 5 years), compared with complete remission (CR) or partial remission (PR) (100% at 5 years) (log-rank P = 0.01; HR_adj: 14.1, 95% CI: 2.2-93.5, P = 0.01). Duration of prior calcineurin inhibition and SRNS type were not significant predictors.

Kidney survival of SRNS following add-on rituximab is 70% to 80% over 3 to 7 years. Nonresponse, preexisting CKD, lower albumin, and FSGS predict inferior kidney survivals.