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-related complications are considered relatively common extraintestinal manifestations of inflammatory bowel disease (IBD), but absolute risks are not well characterized. We aimed at providing a comprehensive characterization of the burden of kidney-related complications in people with incident IBD by analyzing issued clinical diagnoses and trajectories of estimated glomerular filtration rate (eGFR) in the population of Stockholm, Sweden.

Methods: We included 1,682,795 participants aged 11 or older, free from IBD or chronic kidney disease (CKD) diagnosis and who had a measurement of eGFR during 2006-2018. We analyzed the association between developing IBD (time-varying exposure) and the risk of receiving a CKD diagnosis, acute kidney injury (AKI), nephrolithiasis, or secondary amyloidosis, and experiencing the composite of declining their eGFR>30% from baseline or kidney failure (collectively termed as CKD progression). Absolute risks were calculated at 5- and 10-year of follow-up, and relative risks were calculated with Cox regression. We compared kidney-related risks overall and for Crohn’s disease (CD) and ulcerative colitis (UC) separately.

Results: After median 9-years, 10,117 participants newly developed IBD. Their mean age was 45 years. Compared with non-IBD periods, developing IBD associated with higher relative risks: the HR (95% CI) for the risk of receiving a CKD diagnosis was 1.24 (1.10-1.40), 1.11 (1.00-1.24) for the risk of CKD progression, and 1.25 (1.14-1.36) for the composite outcome of these two events. Within 10 years from IBD diagnosis, 6.4% (5.8-7.0%) of participants received a diagnosis of CKD, but 11.4% (10.4-12.4%) had a clinically relevant reduction in eGFR. The risks of AKI (HR 1.97 [1.70-2.29]; 10-y absolute risk 3.6%), nephrolithiasis (HR 1.69 [1.48-1.93]; 10-y risk 5.6%) and secondary amyloidosis (HR 2.77 [1.44-5.35]; 10-y risk 0.2%) were also higher in persons developing IBD compared to non-IBD periods. In general, CD patients exhibited higher absolute and relative kidney risks than UC patients.

Conclusions: One in ten persons with IBD develop chronic kidney disease within 10 years from diagnosis, with many of these events not being identified through diagnostic codes. This, together with higher risks of AKI and nephrolithiasis emphasizes the need for monitoring of kidney function and established protocols for referral to nephrological/urological care.