History of randomized controlled trials in the treatment of pediatric nephrotic syndrome and precision medicine

Background/Aims: The diagnosis and treatment of Nephrotic syndrome (NS) dates back to Hippocrates. The treatment has undergone a lot of transition from the use of intramuscular injections of cortisone to use of oral prednisolone, and a group of other immunosuppressive medications. Nevertheless, despite intense investigations into the etiologies and targeted treatments, the full potential for precision medicine as it applies to pediatric glomerular diseases remains unfilled. Methods: A literature search was completed of all randomized clinical trials in pediatric nephrotic syndrome. Results: The International study of kidney disease in children (ISKDC) conducted the first international collaborative randomized blinded controlled trial in pediatric nephrology in 1960s and has progressed to more recent trials. Optimal therapy of patients with frequent relapsing steroid sensitive NS and steroid-resistant primary FSGS has remained challenging with treatment failures, complications and impairment in the quality of life of the patients. Conclusions: The discovery of biomarkers associated with NS have led to the innovation of Precision medicine in the management of glomerular disease which is tailored to individual patients. The review has looked at the history of randomized controlled trials on the treatment of NS including steroid sensitive, steroid resistant NS and focal segmental glomerulosclerosis (FSGS) and advanced therapies to provide individualized therapies which are based on biomarkers from NEPTUNE match clinical trials, FONT, DUET and APOL 1 studies to improve treatment outcomes and minimizing side effects of unnecessary immunosuppressants (Precision Medicine).