CLINICAL OUTCOMES AND TREATMENT RESPONSE IN JAPANESE PATIENTS WITH IGA NEPHROPATHY WITH AND WITHOUT INFLAMMATORY BOWEL DISEASE: A SINGLE-CENTER STUDY

Inflammatory bowel disease (IBD) can cause renal involvement via immune mechanisms along the gut–kidney axis, with IgA nephropathy (IgAN) being the most frequent manifestation. In Japan, tonsillectomy is often combined with corticosteroids for IgAN based on mucosal immune hypotheses; however, its benefit in IBD-associated IgAN is unclear. To clarify the clinical and pathological differences, treatment responses, and renal outcomes, we compared patients with IgAN with and without IBD in a single-center Japanese cohort.

We retrospectively reviewed 127 patients diagnosed with IgAN by biopsy at our hospital between 2013 and 2021. After excluding 11 patients aged ≤18 years and those lost to follow-up, 116 patients (non-IBD-associated IgAN, 101 cases; IBD-associated IgAN, 15 cases) were analyzed. Primary endpoints evaluated were changes in proteinuria over two years after treatment, estimated glomerular filtration rate (eGFR) slope, proteinuria remission rate based on the Oxford classification, and cumulative proteinuria remission rate. Statistical analyses included t-tests or Mann-Whitney U tests for continuous variables, chi-square tests or Fisher's exact tests for categorical variables, multiple linear regression analysis for determinants of eGFR slope, and Cox proportional hazards models for the cumulative proteinuria remission rate. 

No significant differences in baseline renal function or proteinuria between patients with IgAN without IBD and those with IBD-associated IgAN were observed (eGFR 74.2 ± 27.5 vs 80.0 ± 21.4 mL/min/1.73 m², p=0.44; proteinuria 0.76 [0.46–1.70] vs 0.72 [0.50–1.08] g/gCr, p=0.62). The IBD group had a higher proportion of males (93%, p<0.001) and higher serum IgA levels (587 [435–632] mg/dL, p<0.001). Treatment frequencies were comparable for RAS inhibitors (96.0% vs. 86.7%, p=0.17), corticosteroids (74.3% vs. 80.0%, p=0.76), and tonsillectomies (80.2% vs. 60.0%, p=0.10). No differences were observed in the Oxford MEST-C scores. Among patients with IBD-associated IgAN, Crohn’s disease and ulcerative colitis accounted for 73.3% and 26.7%, respectively. At the time of renal diagnosis, 86.7% of the patients had inactive IBD. At 2 years, the reduction rate in proteinuria was similar (−77.6% [−87.1 to −57.8] vs −85.2% [−95 to −50], p=0.36), and no difference was observed in the eGFR slope (−2.54 [−5.25 to 1.36] vs −1.03 [−6.52 to −0.54] mL/min/1.73 m²/year, p=0.93). In multivariate analysis, the eGFR slope was independently associated with: baseline eGFR (β=−0.49, p<0.001), baseline proteinuria (β=−0.20, p=0.049), tonsillectomy (β=0.32, p=0.02), segmental sclerosis (S lesions; β=−0.21, p=0.048), but was not associated with IBD status (β=0.13, p=0.23). Urinary protein remission rates based on the Oxford classification did not differ between MEST-C classifications. Cox regression analysis revealed no association between IBD and cumulative urinary protein remission rates (Hazard ratio, 1.14; 95% confidence interval, 0.53–2.45; p=0.7).

In this Japanese cohort, patients with IBD-associated IgAN showed clinical features, treatment responses, and renal outcomes comparable to those without IBD. These findings suggest that the coexistence of IBD does not adversely affect renal prognosis if intestinal inflammation is adequately controlled and evidence-based IgAN therapy is administered.