The Gut-Renal Connection in IgA Nephropathy

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.