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Inflammatory Bowel Disease Is More Common in Patients with IgA Nephropathy and Predicts Progression of ESKD: A Swedish Population-Based Cohort Study
Örebro University, School of Medical Sciences. Department of Nephrology and Centre for Clinical Research, County Council of Värmland, Central Hospital Karlstad, Karlstad, Sweden.
Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Örebro University Hospital. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York, USA; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom.ORCID iD: 0000-0003-1024-5602
Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Årjäng Health Care Center and Centre for Clinical Research, County Council of Värmland, Värmland, Sweden; Department of General Practice, Institute of Health and Society, University of Oslo, Oslo, Norway.ORCID iD: 0000-0001-9137-2800
2021 (English)In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 32, no 2, p. 411-423Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
American Society of Nephrology , 2021. Vol. 32, no 2, p. 411-423
Keywords [en]
ESKD, IgA nephropathy, clinical epidemiology, end stage kidney disease
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-87367DOI: 10.1681/ASN.2020060848ISI: 000616498800015PubMedID: 33177116Scopus ID: 2-s2.0-85100345214OAI: oai:DiVA.org:oru-87367DiVA, id: diva2:1500797
Note

Funding Agency:

County Council of Värmland (Region Värmland), Sweden  

Available from: 2020-11-13 Created: 2020-11-13 Last updated: 2025-09-19Bibliographically approved
In thesis
1. IgA Nephropathy: Comorbidities and Prognosis - Registry-based Studies
Open this publication in new window or tab >>IgA Nephropathy: Comorbidities and Prognosis - Registry-based Studies
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis investigates the associations between IgA nephropathy (IgAN), a common form of primary glomerulonephritis, and several health outcomes including inflammatory bowel disease (IBD), cancer, infections, and the reliability of biopsy data from the Swedish Renal Registry (SRR).

In a population-based cohort study of 3,963 IgAN patients and 19,978 controls, IgAN was linked to a significantly higher risk of both future and preceding IBD diagnoses. IBD also increased the risk of developing end-stage renal disease (ESRD) in IgAN patients, underscoring the importance of monitoring gastrointestinal comorbidities in this population.

Another cohort study of 3,882 IgAN patients examined the association between IgAN and cancer. An elevated cancer risk was identified, but only in patients who progressed to ESRD, suggesting that the increased cancer incidence is related to advanced kidney disease rather than IgAN itself.

A third study explored the frequency of infections in IgAN patients, revealing a higher incidence of infections and increased antimicrobial use compared to both the general population and sibling controls. The study highlighted a marked risk of sepsis, emphasizing the need for proactive infection prevention in IgAN management.

Finally, validation of biopsy data from the SRR demonstrated a high positive predictive value (95%) for IgAN diagnosis. This reinforces the reliability of the SRR as a valuable tool for future research on IgAN.

Together, these findings contribute to a deeper understanding of IgAN’s broader clinical implications, and the potential risks associated with its progression.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2025. p. 88
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 330
Keywords
IgA Nephropathy, Epidemiology, Comorbidities
National Category
General Medicine
Identifiers
urn:nbn:se:oru:diva-120648 (URN)9789175296760 (ISBN)9789175296777 (ISBN)
Public defence
2025-10-17, Örebro universitet, Campus USÖ, Tidefeltsalen, Södra Grev Rosengatan 32, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2025-04-16 Created: 2025-04-16 Last updated: 2025-09-19Bibliographically approved

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Ludvigsson, Jonas F.Emilsson, Louise

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