The Gut-Renal Connection in IgA Nephropathy

Semin Nephrol. 2018 Sep;38(5):504-512. doi: 10.1016/j.semnephrol.2018.05.020.

Abstract

The connection between a dysregulated gut-associated lymphoid tissue and IgA nephropathy (IgAN) was supposed decades ago after the observation of increased association of IgAN with celiac disease. Pivotal studies have shown a role for alimentary antigens, particularly gliadin in developing IgAN in BALB/c mice, and a reduction in IgA antigliadin antibodies and proteinuria was reported after gluten free-diet in patients with IgAN. Recently a genome-wide association study showed that most loci associated with IgAN also are associated with immune-mediated inflammatory bowel diseases, maintenance of the intestinal barrier, and response to gut pathogens. Transgenic mice that overexpress the B-cell activating factor develop hyper-IgA with IgAN modulated by alimentary components and intestinal microbiota. Mice expressing human IgA1 and a soluble form of the IgA receptor (sCD89) develop IgAN, which is regulated by dietary gluten. Recent observations have confirmed gut-associated lymphoid tissue hyper-reactivity in IgAN patients with IgA against alimentary components. Interesting results were provided by the NEFIGAN randomized controlled trial, which adopted an enteric controlled-release formulation of the corticosteroid budesonide targeted to Peyer's patches. After 9 months of treatment, a reduction in proteinuria was observed with stabilized renal function and limited adverse events. The gut-renal connection is an area of promising new treatment approaches for patients with IgAN.

Keywords: IgA nephropathy; diet; gluten-free diet; gut-kidney axis; intestinal immunity; microbiota.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies / immunology
  • Budesonide / therapeutic use
  • Celiac Disease / epidemiology
  • Celiac Disease / immunology*
  • Comorbidity
  • Gastrointestinal Microbiome / immunology
  • Gliadin / immunology
  • Glomerulonephritis, IGA / drug therapy
  • Glomerulonephritis, IGA / epidemiology
  • Glomerulonephritis, IGA / immunology*
  • Glomerulonephritis, IGA / metabolism
  • Glucocorticoids / therapeutic use
  • Glutens / immunology
  • Humans
  • Immunoglobulin A / immunology*
  • Inflammatory Bowel Diseases / epidemiology
  • Inflammatory Bowel Diseases / immunology*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Intestines / immunology
  • Lymphoid Tissue / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Peyer's Patches / immunology*
  • Proteinuria / immunology
  • Receptors, Fc / immunology

Substances

  • Antibodies
  • Glucocorticoids
  • IgA receptor
  • Immunoglobulin A
  • Receptors, Fc
  • Budesonide
  • Glutens
  • Gliadin