POS-458 PERSPECTIVES OF CALCINEURIN INHIBITORS TREATMENT IN HEREDITARY STEROID-RESISTANT NEPHROTIC SYNDROME

Abstract

Therapy of steroid-resistant nephrotic syndrome (SRNS) remains an actual problem of pediatric nephrology despite the expansion of therapeutic options. It is considered that calcineurin inhibitors (CNIs) have limited efficacy for the majority of patients with SRNS especially in cases with confirmed genetic causes. We observed 136 children (66 - 48,5% males) from 58 regions of the Russian Federation with SRNS and/or hereditary NS who received CNI during 1 month - 7 years. The average age of our patients accounted for 11 y. 7 m. (SD 60,753 m.) The average age of manifestation was 4 y. 7 m. (SD 51,29 m.) Family history was positive in 13,2% (18 patients). Steroids were previously applied in 128 children (94,1%) with no remission achieved. Genetic testing by next-generation sequencing was performed in all patients. We detected pathogenic variants of genes associated with nephrotic syndrome and its phenotypic copies in 71 patients (52,2%).CNI inefficiency was observed in 82 children (60,3%): 44,6% in non-genetic and 74,6% of SRNS associated with pathogenic variants of podocyte genes. In idiopathic NS partial and complete remission had been achieved in an approximately equal percentage of cases - 29,2% (19) and 26,2% (17) children. In monogenic SRNS complete and partial remission was observed in 11,3% (8) and 14,1% (10) children respectively. Due to the small number of patients with different pathogenic variants, it is difficult to make any accurate conclusions. Three of ten WT1-associated SRNS had achieved partial remission.Twenty children - 14,7% (18 - genetic SRNS, 2 - non-genetic SRNS) - progressed to the end-stage renal disease during the observation period (2010-2020), 17 of them were transplanted (12,5%), recurrence of NS to the graft occurred in 5 patients (29,4%): with pathogenic variants in NPHS2, WT1, ARHGAP24, MYH9, and 1 child without any revealed genetic cause of SRNS.View Large Image Figure ViewerDownload Hi-res image Download (PPT) CNI treatment can be effective in children with SRNS in 39,8% of cases. Only 26,7% of genetic NS achieved complete or partial remission so CNI prescription can be effective but should not be used routinely. Moreover, the expectation for remission in genetic SRNS is meaningless after 3 months of treatment.