Steroid Resistant Nephrotic Syndrome

Nephrotic syndrome is among the most common forms of kidney disease seen in children. Steroid resistant nephrotic syndrome (SRNS), which accounts for up to 20% of all cases of childhood NS, is the most common glomerular cause of end stage kidney disease (ESKD) in children. The pathogenesis of FSGS has not been completely delineated; however, there is growing evidence to suggest that it is a primary defect of the podocyte. Up to 30% of cases are caused by monogenic hereditary podocyte disorders. A role for circulating factors has also been implicated in disease pathogenesis. Histopathological changes vary; focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are the most common findings. The treatment of SRNS is challenging, as only about 30-60% of all cases will respond completely or partially to currently available therapies, yet response to therapy is the most important determinant of future progression to end-stage kidney disease (ESKD). The poorest long-term prognosis is associated with genetic disease forms (80% ESKD 15 years after disease onset), followed by patients without a genetic cause who show resistance to intensified immunosuppressive therapeutic attempts (multidrug resistant nephrotic syndrome, 60% 15-year ESKD risk), whereas patients achieving full disease remission upon intensified immunosuppression rarely develop ESKD (<10% at 15 years). The risk of SRNS recurrence in kidney transplant is estimated at 30%, with a lower risk (0-5%) in patients with monogenic SRNS and close to 80% in patients with secondary steroid resistance and progression to ESKD. Further studies of familial and non-familial forms of SRNS are needed in order to elucidate disease mechanisms, develop a robust pathogenesis based classification, develop personalized approach to therapy, and identify specific non-toxic therapeutic targets.