Guidance is provided for the safe and effective use of IBD therapies in patients with renal impairment.

Background & Rationale

Inflammatory bowel disease (IBD) frequently co-exists with chronic kidney disease (CKD), presenting a complex pharmacological challenge. Patients with IBD and concurrent CKD require careful consideration of medication selection and dosing, as renal impairment alters drug pharmacokinetics and increases the risk of adverse events. Traditional prescribing guidelines for IBD medications often lack specific recommendations for patients with varying degrees of CKD. This review addresses the practical considerations for utilising commonly prescribed IBD therapies – including aminosalicylates, corticosteroids, immunomodulators, and biologics – in the context of declining renal function, aiming to optimise treatment efficacy while minimising nephrotoxicity.

Study Design

This review constitutes a comprehensive synthesis of existing literature, encompassing clinical trials, observational studies, pharmacokinetic data, and expert consensus. A systematic search was conducted across multiple databases, including PubMed, Embase, and Cochrane Library, utilising predefined search terms related to IBD, CKD, and pharmacological agents used in IBD management. The authors performed a narrative synthesis of the identified evidence, categorising medications based on their mechanism of action and potential renal impact. Dosage adjustments and monitoring recommendations were formulated based on estimated glomerular filtration rate (eGFR) categories, aligning with Kidney Disease: Improving Global Outcomes (KDIGO) guidelines.

Patient Population

The review focuses on adult patients diagnosed with IBD – encompassing Crohn’s disease and ulcerative colitis – who also have co-existing CKD, defined as an eGFR less than 60 mL/min/1.73m². The analysis considers the spectrum of CKD severity, from mild impairment (eGFR 30-59 mL/min/1.73m²) to more advanced stages requiring renal replacement therapy (eGFR <15 mL/min/1.73m²). The review does not specifically exclude patients based on IBD phenotype or disease activity, but acknowledges that these factors may influence treatment decisions.

Key Findings

Mesalazine demonstrated variable excretion pathways, with approximately 75% eliminated renally. Dosage reduction is recommended for patients with moderate to severe CKD (eGFR <30 mL/min/1.73m²). Sulfasalazine is metabolised to mesalazine and sulfapyridine; the latter is renally excreted and should be avoided in patients with eGFR <30 mL/min/1.73m². Corticosteroids, specifically prednisolone, are generally considered safe in CKD, although long-term use increases the risk of hypertension and fluid retention. Azathioprine requires a significant dose reduction in patients with eGFR <30 mL/min/1.73m², due to accumulation of its active metabolite, 6-mercaptopurine. Thiopurine methyltransferase (TPMT) genotyping is crucial prior to initiating thiopurine therapy in this population.

Regarding biologics, infliximab and adalimumab are primarily cleared through non-renal mechanisms and do not require routine dose adjustments based on eGFR. However, monitoring for opportunistic infections is essential, as renal impairment may impair immune function. Vedolizumab undergoes minimal renal excretion and is considered safe for use in patients with CKD, although data are limited in severe renal impairment. Ustekinumab is predominantly eliminated via hepatic metabolism, with minimal renal clearance, and is also considered safe. Tofacitinib is primarily metabolised, but a dose reduction to 5mg twice daily is recommended for patients with eGFR 30-59 mL/min/1.73m², and use is not recommended if eGFR is below 30 mL/min/1.73m².

Discussion

The review highlights the need for individualised treatment approaches in IBD patients with CKD. Careful consideration of drug pharmacokinetics and potential nephrotoxicities is paramount. The authors emphasise the importance of regular renal function monitoring, particularly following initiation or dose adjustments of IBD medications. The use of alternative therapies with minimal renal excretion, such as vedolizumab or ustekinumab, may be favoured in patients with advanced CKD. The review acknowledges the limited data available for certain medications in severe renal impairment, necessitating a cautious approach and close clinical surveillance. Safety and tolerability profiles should be continuously assessed, with prompt management of any adverse events.

Authors’ Conclusions

The authors conclude that the management of IBD in patients with CKD requires a multidisciplinary approach, integrating gastroenterological and nephrological expertise. They state that a thorough understanding of the pharmacokinetic properties of IBD medications, coupled with regular monitoring of renal function, is essential to optimise treatment outcomes and minimise the risk of drug-related nephrotoxicity. The authors advocate for the development of prospective studies to further refine prescribing guidelines for this complex patient population.

Reference

Chen L, Srinivasan A, Choy SW, Van J, Habeeb H, Nguyen A, Vasudevan A. Prescribing Inflammatory Bowel Disease Medications in Chronic Kidney Disease: A Practical Guide. Alimentary pharmacology & therapeutics. 2025; 57(1): 1-16. DOI: 10.1111/apt.70262.