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DOI: 10.1159/000525587; PMCID: PMC9936750


INTRODUCTION: Minimal change disease in childhood can follow a frequently relapsing or steroid-dependent course in up to 40% of cases. Second-line immunosuppressive medications that are used to manage these patients are associated with significant adverse effects. There is a need for safer alternative treatments for difficult-to-treat nephrotic syndrome. Therefore, we conducted an open-label feasibility study to assess the safety and efficacy of a gluten-free diet as treatment for pediatric patients with difficult-to-treat nephrotic syndrome. As a second aim, we sought to determine if the plasma zonulin concentration can identify those who are more likely to respond to this intervention.

METHODS: Seventeen patients were placed on a gluten-free diet for 6 months. A positive response was defined as a 50% reduction in the relapse rate compared to the preceding 6 months or the ability to discontinue 1 immunosuppressive drug.

RESULTS: Five (29%) participants had a positive response to the dietary intervention. The gluten-free diet was well tolerated with no clinical or laboratory adverse events. Plasma zonulin concentration was elevated in patients who failed to benefit from the gluten-free diet.

DISCUSSION/CONCLUSION: A gluten-free diet may be a useful adjunctive intervention for patients with difficult-to-treat nephrotic syndrome that can be implemented prior to resorting to second-line immunosuppressive therapy. Development of the plasma zonulin level as a biomarker to predict efficacy would facilitate rational use of a gluten-free diet in the management of nephrotic syndrome.

Journal Title

Glomerular Dis





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Childhood; Difficult-to-treat disease; Glomerular disease; Gluten-free diet; Nephrotic syndrome; Pilot study; Proteinuria; Zonulin


Grant support

This research was supported in part by an NYU CTSA grant (UL1 TR001445) from the National Center for Advancing Translational Sciences, National Institutes of Health. This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Publisher's Link: