Elevated plasma zonulin levels, which are supportive of a diagnosis of CD (celiac disease) in children with gastrointestinal symptoms, may indicate patients with difficult-to-manage NS who will benefit from initiation of a GFD (gluten free diet). This pilot study will determine whether high plasma zonulin levels can be used as a screening tool to identify patients with NS (nephrotic syndrome) who are likely to demonstrate a beneficial response to a GFD. It will provide important information about the feasibility of testing the efficacy of a GFD for this condition and assist in the design and sample size calculation for a definitive trial to test the beneficial effect of this dietary intervention. Although NS is a rare condition in childhood, it is a chronic disease that can lead to short- and long-term disability especially in those with difficult-to-manage disease. There is an urgent need to develop safe and effective new therapies in this subgroup. This project may indicate the utility of a common dietary modification, a GFD, to treat these patients. The growing medical use of and greater access to gluten-free food items underscore the feasibility and timeliness of this approach.

Inclusion Criteria:

• Steroid sensitive NS: complete remission of proteinuria in response to administration of a standard course of corticosteroids
• Difficult-to-manage NS: disease that cannot be controlled without incurring intolerable side effects from currently available immunosuppressive agents, namely corticosteroids, calcineurin inhibitors, mycophenolate mofetil, or rituximab. Patients with biopsy-proven MCD or FSGS will be eligible as long as they have steroid sensitive disease. However, a renal biopsy will not be required for enrollment into the trial.

Exclusion Criteria:

• Any patient diagnosed with nephrotic syndrome that is not considered steroid sensitive or frequently relapsing
• Pre-existing celiac disease or gastro-intestinal disorder that precludes use of a GFD

Children age 9 months to 18 years of age with steroid sensitive Nephrotic Syndrome