Immunoglobulin A nephropathy in association with inflammatory bowel diseases: results from a national study and systematic literature review

Abstract

Background Little is known about clinical characteristics and kidney outcome in patients with biopsy-proven immunoglobulin A nephropathy (IgAN) in a context of inflammatory bowel disease (IBD). Methods We conducted a retrospective multicenter study with centralized histological review, to analyze the presentation, therapeutic management and outcome of 24 patients suffering from IBD associated IgAN relative to a cohort of 134 patients with primary IgAN without IBD. Results Crohn’s disease and ulcerative colitis accounted for 75% and 25% of IBD-associated IgAN cases, respectively. IBD was diagnosed before IgAN in 23 cases (a mean of 9 years previously) and was considered active at IgAN onset in 23.6% of patients. Hypertension was present in 41.7% of patients. Urinary protein-to-creatinine ratio exceeded 100 mg/mmol in 70.8% of patients (mean: 254 mg/mmol). Estimated glomerular filtration rate (eGFR) exceeded 60 ml/min/1.73m2 in 13/24 patients and only one patient required dialysis. In the Oxford MEST-C classification of renal biopsies, 57% were M1, 48% E1, 76% S1, 57% T1+T2 and 38% C1+C2. Steroids were administered in 50% of cases. After a mean follow-up of 7.2 years, four patients (16.7%) had a poor kidney outcome: end-stage renal disease (n = 3) or a > 50% decrease in eGFR from initial values (n = 1). A similar evolution was observed in patients with primitive IgAN. Conclusions This first case series suggests that IBD-associated IgAN have frequent inflammatory lesions at onset and variable long-term outcome.

Differentiation of T Helper 17 Cells May Mediate the Abnormal Humoral Immunity in IgA Nephropathy and Inflammatory Bowel Disease Based on Shared Genetic Effects

“…IgAN has distinct geographical and ethnic differences, it is more common in Asian populations than in Caucasians ( 3 ). Recently, IgAN has attracted attention as a major renal manifestation of inflammatory bowel disease (IBD), which is characterized by chronic inflammation of the gastrointestinal tract and mainly contains Crohn’s disease (CD) and ulcerative colitis (UC) ( 4 ).…”

Causal association between inflammatory bowel disease and IgA nephropathy: A bidirectional two-sample Mendelian randomization study

“…Although the exact mechanisms linking IBD and IgAN are not fully understood, the gut–kidney axis hypothesis might potentially support the pathophysiological relationship. It was assumed that dysregulation of the interplay among intestinal immunity, microbiota, and diet could lead to the production of Gd-IgA1, which plays an important role in IgAN ( Joher et al, 2022 ). Together with mucus and antimicrobial peptides, IgA forms the first line of defense against environmental and microbial antigenic exposures occurring in the intestinal mucosa ( He et al, 2020 ).…”

Associaion of Gout with Crohn’s disease, and Inflammatory Bowel Disease with IgA Nephropathy: A Mendelian Randomization

“…One example is BAFF overexpression in both IBD and IgAN patients. Moreover, some IBD patients have higher levels of miR-133b expression, which inhibits Treg differentiation in IgAN [24]. IgAN loci are genetically linked to IBD risk genes (HLA-DQ and HORMAD2), mucosal integrity, and immune response genes (DEFA and VAV3).…”