In children with celiac disease, the protein zonulin increased gut permeability after exposure to gliadin. In children with nephrotic syndrome, plasma zonulin levels are increased. The zonulin effect in electrolytes is mediated by protease activated receptor-2. Elevations in zonulin induced by gluten may affect glomerular permeability and mediate proteinuria in children with nephrotic syndrome.
Researchers conducted a multicenter, open-label trial to assess the efficacy of a gluten-free diet in children with steroid-responsive, difficult-to-manage nephrotic syndrome. The treatment period was 6 months. The researchers defined positive response as ≥50% reduction in relapse rate versus the prior 6 months or discontinuation of one or more immunosuppression medications. Relevant data included age, sex, race/ethnicity, serum creatinine, proteinuria, histopathology if available, and treatment.
The study enrolled 14 children (eight females, six males). Mean age was 7.8 years, mean baseline serum creatinine was 0.46 mg/dL, and mean urine protein:creatinine ratio was 0.45 mg. Eleven of the cohort were white, one was black and other racial groups, and two were Hispanic/Latino. In ten of the children, the underlying disease was minimal change disease; in four cases it was focal segmental glomerulosclerosis.
Four participants had a positive response at the end of the treatment period (two had reduced relapse rate and two had reduced medication burden). Five had no benefit (two withdrew prior to 6 months), three are in the 6-month treatment period, and one child was lost to follow-up. One adolescent had no change in relapse rate, but responded more rapidly to corticosteroids while on the gluten-free diet.
In nonresponders (n=4), mean baseline plasma zonulin concentration was 19.4 pg/mL compared with 13.4 pg/mL in gluten-free diet responders (n=2; P=0.01).
“Up to a third of patients with difficult-to-manage nephrotic syndrome have a favorable response to implementation of a gluten-free diet. An elevated plasma zonulin level may predict a poor response to the maneuver. A trial of this dietary intervention may be warranted in children with frequently relapsing or steroid dependent nephrotic syndrome to minimize the need for immunosuppressive agents,” the researchers said.
Source: Trachtman H, Meyers K, Faul C, et al. Efficacy of a gluten-free diet (GFD) in children with difficult-to-manage nephrotic syndrome (NS). Abstract of a poster presented at the American Society of Nephrology Kidney Week 2019, November 9, 2019 (Abstract SA-PO675), Washington, DC.