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Abstract: TH-PO993

A Pilot Study of a Gluten-Free Dairy-Free Dietary Intervention in Children with Steroid-Resistant Nephrotic Syndrome

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Perez saez, Maria jose, Hospital del Mar, Barcelona, Spain
  • Uffing, Audrey, Brigham and Women's Hospital, Brookline, Massachusetts, United States
  • Leon, Juliette, Hôpital Necker-Enfants Malades, PARIS, France
  • Murakami, Naoka, Brigham and Women's Hospital, Brookline, Massachusetts, United States
  • Watanabe, Andreia, School of Medicine - University of Sao Paulo, Sao Paulo, Brazil
  • Borges, Thiago J., Brigham and Women's Hospital, Brookline, Massachusetts, United States
  • Sabbisetti, Venkata, Brigham and Women's Hospital, Brookline, Massachusetts, United States
  • Cureton, Pam, MassGeneral Hospital for Children, Ellicott City, Maryland, United States
  • Kenyon, Victoria, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Keating, Leigh, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Yee, Karen, Brigham and Women's Hospital, Brookline, Massachusetts, United States
  • Satiro, Carla Aline fernandes, Instituto da Criança HCFMUSP, Sao Paolo, Brazil
  • Serena, Gloria, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Hildebrandt, Friedhelm, Boston Children's Hospital , Boston, Massachusetts, United States
  • Riella, Cristian, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Libermann, Towia, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Wang, Minxian, Broad Institute, Cambridge, Massachusetts, United States
  • Pascual, Julio, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
  • Bonventre, Joseph V., Brigham and Women's Hospital, Brookline, Massachusetts, United States
  • Fasano, Alessio, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Riella, Leonardo V., Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
Background

Steroid-resistant nephrotic syndrome (SRNS) in children often fails immunosuppression and progresses to kidney failure. Case reports have suggested potential beneficial effects of dietary changes on SRNS, especially gluten-dairy restrictions. Zonulin is a circulating protein upregulated in gluten sensitivity, which regulates intestinal barrier. We hypothesize that zonulin might also alter permeability of podocyte tight junctions and contribute to SRNS activity.

Methods

Prospective non-randomized pilot study to investigate the effect of a gluten and dairy-free (GF/DF) diet in children with SRNS. The study was organized as a four-week summer camp with prospective collection of blood, urine and stool.

Results

16 patients (mean age 7 years, range 2-21) met the eligibility criteria. Ten patients had FSGS, while six minimal change disease. Whole exome sequencing did not reveal any SRNS-associated variants. Complete remission following implementation of GF/DF diet occurred in two patients (13%, Fig A –marked in blue and red). Furthermore, GF/DF diet showed anti-inflammatory effects on the immune system in all participants, reducing circulating Th17 cells by 78% (Fig B) and decreasing levels of pro-inflammatory cytokines (Fig C). Microbiota analysis revealed a higher fraction of Faecalibacterium prausnitzii upon dietary intervention. Circulating zonulin levels over 106 ng/mL differentiated responders from non-responders (Fig D).

Conclusion

GF/DF may be an effective coadjuvant treatment in a subset of children with SRNS, in particular those with high zonulin levels. Diet intervention can also have anti-inflammatory benefits. A summer camp is a feasible way to implement dietary interventions in children and assess its short-term effect.

Funding

  • Private Foundation Support