Yuanhang Yang (1), Jonas F. Ludvigsson (1,2,3), Ola Olén (4,5,6), Arvid Sjölander (1), Juan J. Carrero (1,7)

Affiliates

(1) Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (2) Department of Paediatrics, Örebro University Hospital, Örebro, Sweden (3) Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA (4) Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden (5) Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden (6) Sachs' Children and Youth Hospital, Stockholm, Stockholm South General Hospital, Stockholm, Sweden (7) Division of Nephrology, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden

Abstract

Background: Kidney complications are common in patients with longstanding inflammatory bowel disease (IBD). Whether kidney complications, defined as low estimated glomerular filtration rate (eGFR) may predispose to later IBD is unknown.

Methods: We analyzed the association between eGFR and the risk of being subsequently diagnosed with IBD among 1,612,160 adults from Stockholm. The exposure was categories of eGFR, with 90-104 mL/min/1.73m2 as the reference. Cox regression models were used to investigate the association between eGFR, IBD and IBD subtypes. Subgroup analyses included age strata, sex, education, and comorbidities. To explore the possibility of detection bias/reverse causation, we estimated IBD hazard ratios after excluding cases and individuals censored during early years of follow-up.

Results: During a median of 9 years of follow-up, we detected 9,663 cases of IBD (Crohn’s disease: 3,299, ulcerative colitis: 5,072, IBD unclassified: 1,292). Lower eGFR levels were associated with higher IBD risk (adjusted hazard ratio [HR], 1.15; 95% CI 1.01-1.33 for eGFR 30-59, and 1.65 [1.16-2.37] for eGFR <30 mL/min/1.73m2). This association was stronger in magnitude for Crohn’s disease (HR of 1.33 [1.04-1.72] for eGFR 30-59 and 2.25 [1.26-3.99] for eGFR <30 mL/min/1.73m2). Results were consistent across strata of age, comorbidities and attained education, but suggested the association between eGFR and IBD to be stronger in women (P interaction <0.05). Results attenuated, but were robust to exclusion of early IBD cases.

Conclusions: We observed an association between reduced eGFR and the risk of developing IBD, which was stronger in magnitude for Crohn’s disease.