Mendelian steroid resistant nephrotic syndrome in childhood: is it as common as reported?

Primary steroid resistant nephrotic syndrome (SRNS) is thought to have either genetic or immune-mediated aetiology. Knowing which children to screen for genetic causes can be difficult. Several studies have described the prevalence of genetic causes of primary SRNS to be between 30 and 40%, but these may reflect a selection bias for genetic testing in children with congenital, infantile, syndromic or familial NS and thus may overestimate the true prevalence in a routine clinical setting.

Retrospective electronic patient record analysis was undertaken of all children with non-syndromic SRNS and presentation beyond the first year of life, followed at our centre between 2005 and 2020.

Of the 49 children who met the inclusion criteria, 5 (10%) had causative variants identified, predominantly in NPHS2. None responded to immunosuppression. Of the 44 (90%) who had no genetic cause identified, 33 (75%) had complete or partial remission after commencing second-line immunosuppression and 67% of these had eGFR > 90 ml/min/1.73 m² at last clinical follow-up. Of the children who did not respond to immunosuppression, 64% progressed to kidney failure.

In our cohort of children with non-syndromic primary SRNS and presentation beyond the first year of life, we report a prevalence of detectable causative genetic variants of 10%. Those with identified genetic cause were significantly (p = 0.003) less likely to respond to immunosuppression and more likely (p = 0.026) to progress to chronic kidney disease. Understanding the genetics along with response to immunosuppression informs management in this cohort of patients and variant interpretation. A higher resolution version of the Graphical abstract is available as Supplementary information.