Kidney survival in children with steroid-resistant nephrotic syndrome treated by rituximab

Abstract Background Kidney outcomes in children with steroid-resistant nephrotic syndrome (SRNS) following rituximab remains unclear. Method We conducted an international retrospective cohort study across 23 centres in 17 countries, including children with SRNS who did not respond to calcineurin inhibitors and, subsequently, received rituximab. Patients with genetic variants were excluded. Primary outcome was kidney survival. Results We analysed 151 children (53% boy; age at onset, 6.8 years; primary vs secondary SRNS, 54% vs 46%; focal segmental glomerulosclerosis, FSGS, 62%). All subjects received calcineurin inhibitors before rituximab (0-3 months, 21%; 3-6 months, 26%; 6-12 months; 26%; >12 months, 26%). Upon rituximab, 73 (48%) subjects had normal kidney function, 47 (31%) CKD2, and 31 (21%) 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 prior to rituximab was associated with kidney survival at 5 years (log-rank p<0.001); CKD stage 1, 91.7%; CKD stage 2, 70.4%; CKD stage 3, 35.5%). The predictive factors for inferior kidney survival were CKD2 (HRadj 2.7, 95%CI 1.5-4.9, p<0.001), lower baseline serum albumin (log-rank p=0.01; HRadj 0.88, 95%CI 0.81-0.95; p<0.001) and FSGS (log-rank p=0.03; HRadj 3.4, 95%CI 1.1-10.0; p<0.001). Non-remission at 6-months was associated with inferior kidney survival (61.2% at 5 years), compared to CR/PR (100% at 5 years) (log-rank p=0.01; HRadj 14.1, 95%CI 2.2-93.5, p=0.01). Duration of prior calcineurin inhibition and SRNS type were not significant predictors. Conclusion Kidney survival of SRNS following add-on rituximab is 70-80% over 3-7 years. Non-response, pre-existing CKD, lower albumin and FSGS predict inferior kidney survivals.