We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary
steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for
ESRD using multivariate Cox regression models. Complete and partial remission of
proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with
calcineurin inhibitor-based protocols. Ten-year
ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of
minimal change glomerulopathy and FSGS, respectively. Five-year
ESRD-free survival rate was 21% for
diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or
diffuse mesangial sclerosis on initial biopsy as well as age,
serum albumin concentration, and CKD stage at onset affected
ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with
steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with
genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.