Inflammatory Bowel Disease Is More Common in Patients with IgA Nephropathy and Predicts Progression of ESKD: A Swedish Population-Based Cohort Study

Johanna Rehnberg; Adina Symreng; Jonas F. Ludvigsson; Louise Emilsson

doi:10.1681/ASN.2020060848

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Visual Abstract

Significance Statement

Earlier case reports of patients with IgA nephropathy and inflammatory bowel disease have discussed the pathophysiologic links and described associations between the conditions and response to treatments. In this nationwide cohort study, the authors compared 3963 patients with IgA nephropathy with 19,978 matched controls, finding that patients with IgA nephropathy had increased risk of inflammatory bowel disease both before and after a confirmed IgA nephropathy diagnosis. They also found that among patients with IgA nephropathy, those with inflammatory bowel disease were more likely than those without it to progress to ESKD. Accordingly, the identification of inflammatory bowel disease in patients with IgA nephropathy may improve ESKD risk prediction. Further studies are needed to establish whether inflammatory bowel disease screening and optimized treatment can improve IgA nephropathy prognosis in patients with both conditions.

Abstract

Background Case reports suggest an association between inflammatory bowel disease, a chronic autoimmune condition linked to increased circulating IgA levels, and IgA nephropathy, the most common form of primary GN and a leading cause of ESKD.

Methods In a Swedish population-based cohort study, we compared 3963 biopsy-verified IgA nephropathy patients with 19,978 matched controls between 1974 and 2011, following up participants until 2015. Inflammatory bowel disease data and ESKD status were obtained through national medical registers. We applied Cox regression to estimate hazard ratios (HRs) for future inflammatory bowel disease in IgA nephropathy and conditional logistic regression to assess risk of earlier inflammatory bowel disease in IgA nephropathy. We also explored whether inflammatory bowel disease affects development of ESKD in IgA nephropathy.

Results During a median follow-up of 12.6 years, 196 (4.95%) patients with IgA nephropathy and 330 (1.65%) matched controls developed inflammatory bowel disease (adjusted HR, 3.29; 95% confidence interval [95% CI], 2.73 to 3.96). Inflammatory bowel disease also was more common before a confirmed IgA nephropathy diagnosis. Some 103 (2.53%) IgA nephropathy patients had an earlier inflammatory bowel disease diagnosis compared with 220 (1.09%) controls (odds ratio [OR], 2.37; 95% CI, 1.87 to 3.01). Both logistic regression (OR, 2.60; 95% CI, 2.02 to 3.35) and time-varying Cox regression (HR, 1.84; 95% CI, 1.33 to 2.55) demonstrated that inflammatory bowel disease was associated with increased ESKD risk in patients with IgA nephropathy.

Conclusions Patients with IgA nephropathy have an increased risk of inflammatory bowel disease both before and after their nephropathy diagnosis. In addition, among patients with IgA nephropathy, comorbid inflammatory bowel disease elevates the risk of progression to ESKD.

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