Gluten-Free Diet in Childhood Difficult-to-Treat Nephrotic Syndrome: A Pilot Feasibility Study

Overview

Journal Glomerular Dis

Specialty Nephrology

Date 2023 Feb 23

PMID 36817288

Authors

Tarak Srivastava

Katherine M Dell

Kevin V Lemley

Debbie S Gipson

Frederick J Kaskel

Kevin Edward Meyers

Christian Faul

Ayelet Goldhaber

LauraJane Pehrson

Howard Trachtman

Affiliations

Soon will be listed here.

Abstract

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.

References

Levine J, Hauptman L, Moy L, Trachtman H . Effect of a gluten-free diet on albuminuria in children with newly diagnosed celiac disease. Glomerular Dis. 2021; 1(1):3-9. PMC: 8336695. DOI: 10.1159/000514635. View

Laurent J, Rostoker G, Robeva R, Bruneau C, LAGRUE G . Is adult idiopathic nephrotic syndrome food allergy? Value of oligoantigenic diets. Nephron. 1987; 47(1):7-11. DOI: 10.1159/000184448. View

Faul C, Asanuma K, Yanagida-Asanuma E, Kim K, Mundel P . Actin up: regulation of podocyte structure and function by components of the actin cytoskeleton. Trends Cell Biol. 2007; 17(9):428-37. DOI: 10.1016/j.tcb.2007.06.006. View

Metz D, Kausman J . Childhood nephrotic syndrome in the 21st century: What's new?. J Paediatr Child Health. 2014; 51(5):497-504. DOI: 10.1111/jpc.12734. View

Fasano A . Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011; 91(1):151-75. DOI: 10.1152/physrev.00003.2008. View

Gipson D, Massengill S, Yao L, Nagaraj S, Smoyer W, Mahan J . Management of childhood onset nephrotic syndrome. Pediatrics. 2009; 124(2):747-57. DOI: 10.1542/peds.2008-1559. View

Madhusudhan T, Wang H, Straub B, Grone E, Zhou Q, Shahzad K . Cytoprotective signaling by activated protein C requires protease-activated receptor-3 in podocytes. Blood. 2011; 119(3):874-83. PMC: 3398751. DOI: 10.1182/blood-2011-07-365973. View

Lemley K, Faul C, Schramm K, Meyers K, Kaskel F, Dell K . The Effect of a Gluten-Free Diet in Children With Difficult-to-Manage Nephrotic Syndrome. Pediatrics. 2016; 138(1). PMC: 4983765. DOI: 10.1542/peds.2015-4528. View

Di Nardo G, Villa M, Conti L, Ranucci G, Pacchiarotti C, Principessa L . Nutritional Deficiencies in Children with Celiac Disease Resulting from a Gluten-Free Diet: A Systematic Review. Nutrients. 2019; 11(7). PMC: 6683263. DOI: 10.3390/nu11071588. View

10.

SANDBERG D, Bernstein C, McIntosh R, Carr R, Strauss J . Severe steroid-responsive nephrosis associated with hypersensitivity. Lancet. 1977; 1(8008):388-91. DOI: 10.1016/s0140-6736(77)92603-4. View

11.

Uy N, Graf L, Lemley K, Kaskel F . Effects of gluten-free, dairy-free diet on childhood nephrotic syndrome and gut microbiota. Pediatr Res. 2014; 77(1-2):252-5. PMC: 4827614. DOI: 10.1038/pr.2014.159. View

12.

Noone D, Iijima K, Parekh R . Idiopathic nephrotic syndrome in children. Lancet. 2018; 392(10141):61-74. DOI: 10.1016/S0140-6736(18)30536-1. View

13.

Guandalini S, Assiri A . Celiac disease: a review. JAMA Pediatr. 2014; 168(3):272-8. DOI: 10.1001/jamapediatrics.2013.3858. View

14.

LAGRUE G, Laurent J, Rostoker G . Food allergy and idiopathic nephrotic syndrome. Kidney Int Suppl. 1989; 27:S147-51. View

15.

Angeletti A, Drovandi S, Sanguineri F, Santaniello M, Ferrando G, Forno R . COVID-19 in Children with Nephrotic Syndrome on Anti-CD20 Chronic Immunosuppression. Clin J Am Soc Nephrol. 2020; 15(10):1494-1495. PMC: 7536764. DOI: 10.2215/CJN.06400420. View

16.

Oh J, Reiser J, Mundel P . Dynamic (re)organization of the podocyte actin cytoskeleton in the nephrotic syndrome. Pediatr Nephrol. 2003; 19(2):130-7. DOI: 10.1007/s00467-003-1367-y. View

17.

Trachtman H, Gipson D, Lemley K, Troost J, Faul C, Morrison D . Plasma Zonulin Levels in Childhood Nephrotic Syndrome. Front Pediatr. 2019; 7:197. PMC: 6532587. DOI: 10.3389/fped.2019.00197. View

18.

Somlo S, Mundel P . Getting a foothold in nephrotic syndrome. Nat Genet. 2000; 24(4):333-5. DOI: 10.1038/74139. View

19.

Perez-Saez M, Uffing A, Leon J, Murakami N, Watanabe A, Borges T . Immunological Impact of a Gluten-Free Dairy-Free Diet in Children With Kidney Disease: A Feasibility Study. Front Immunol. 2021; 12:624821. PMC: 8208082. DOI: 10.3389/fimmu.2021.624821. View

20.

Troost J, Trachtman H, Nachman P, Kretzler M, Spino C, Komers R . An Outcomes-Based Definition of Proteinuria Remission in Focal Segmental Glomerulosclerosis. Clin J Am Soc Nephrol. 2017; 13(3):414-421. PMC: 5967666. DOI: 10.2215/CJN.04780517. View