Defining relapse with asymptomatic seven-day nephrotic range proteinuria in steroid sensitive nephrotic syndrome to reduce steroid therapy usage: a prospective interventional study

Incidence of nephrotic syndrome in children varies between 1.2 to 16.9 per lakh, with higher incidence in Asian children. It is characterized by heavy proteinuria, hypoalbuminemia and edema. Majority of the children (85-90%) respond to steroid therapy with complete resolution of proteinuria which is termed as steroid sensitive nephrotic syndrome (SSNS). Though the outcome of SSNS in satisfactory, 50% children have a frequent relapsing or steroid dependent course and 3-10% show late steroid resistance.

Relapse in nephrotic syndrome is defined as three consecutive days of nephrotic range proteinuria. This definition is empirical and not backed by any evidence from previous studies. Frequent relapsing nephrotic syndrome (FRNS) and steroid dependent nephrotic syndrome (SDNS) are at higher risk of steroid toxicity. In order to reduce the steroid toxicity, these children would require alternate immunosuppressive drugs like levamisole, mycophenolate mofetil (MMF), oral cyclophosphamide. These drugs are associated with serious adverse drug reactions like vasculitis, gastrointestinal disturbances, transaminitis, leukopenia etc.

Previous observational studies have reported spontaneous resolution of  proteinuria in 33-50% between 5-10 days of onset of  nephrotic range proteinuria. These studies suggest further waiting against the conventional definition of 3 consecutive days of nephrotic range proteinuria for relapse. Thus, a possible over diagnosis of FRNS/ SDNS and an unnecessary exposure to higher steroid dose and other  immunosuppressive agents can be avoided.

Since the natural history of isolated proteinuria without symptoms in nephrotic syndrome is largely unknown, there is a need for prospective controlled studies for a more accurate definition of relapse in nephrotic syndrome. Hence, this study is being conducted to see if  delaying the diagnosis of relapse till seven-days of asymptomatic nephrotic range proteinuria will reduce the need for steroid usage in SSNS children with 3 days of nephrotic range proteinuria.