Genetics of childhood steroid-sensitive nephrotic syndrome.

The pathogenesis of childhood-onset nephrotic syndrome (NS), disparity in incidence of NS among races, and variable responses to therapies in children with NS have defied explanation to date. In the last 20 years over 50 genetic causes of steroid-resistant nephrotic syndrome (SRNS) have been identified, and at least two disease loci for two pathologic variants of SRNS (focal segmental glomerulosclerosis and membranous nephropathy) have been defined. However, the genetic causes and risk loci for steroid-sensitive nephrotic syndrome (SSNS) remain elusive, partly because SSNS is relatively rare and also because cases of SSNS vary widely in phenotypic expression over time. A recent study of a well-defined modest cohort of children with SSNS identified variants in HLA-DQA1 as a risk factor for SSNS. Here we review what is currently known about the genetics of SSNS and also discuss how recent careful phenotypic and genomic studies reinforce the role of adaptive immunity in the molecular mechanisms of SSNS.

Ofatumumab for the treatment of childhood nephrotic syndrome.

BACKGROUND: Ofatumumab is a humanized anti-CD20 monoclonal antibody that has recently garnered interest as a potential therapeutic agent for nephrotic syndrome. We report our center's experience in administering ofatumumab to five pediatric patients with idiopathic nephrotic syndrome. METHODS: Between March 2015 and November 2016, five patients were treated with ofatumumab. One patient had post-transplant recurrent focal segmental glomerulosclerosis (FSGS) which had been resistant to plasmapheresis and numerous immunosuppressive agents. Four patients had nephrotic syndrome in their native kidneys, one with initial steroid-resistant disease and the others with subsequent development of steroid resistance. Two of the patients were treated with a desensitization protocol after experiencing hypersensitivity reactions to ofatumumab. RESULTS: One patient did not complete ofatumumab treatment due to infusion reactions. Of the four remaining patients, three achieved complete remission after treatment, and one achieved partial remission. One of the patients achieving complete remission represents the first reported case of successful treatment of post-transplant recurrent FSGS using ofatumumab. Two patients who received ofatumumab with our desensitization protocol were able to complete their treatments after initially experiencing hypersensitivity reactions. CONCLUSIONS: Ofatumumab may be an effective treatment for refractory childhood nephrotic syndrome and post-transplant recurrent FSGS. A desensitization protocol may be helpful to address hypersensitivity reactions.