Kidney-Safe IBD Treatment: A Guide for Prescribers Treating CKD

A review article gave an overview of renal metabolism and evidence-based practice guidelines for each class of medications used to treat inflammatory bowel disease (IBD) in patients with chronic kidney disease (CKD), including end-stage kidney disease (ESKD).

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Overall, the reviewers wrote, most IBD therapies “appear safe and effective when used in chronic kidney disease, including on renal replacement therapy, particularly biologic therapies.” However, they advised caution when using conventional therapies and small molecules such as Janus kinase (JAK) inhibitors.

According to the authors, optimizing treatment effectiveness while minimizing harm to the kidneys requires a tailored approach. The proportion of patients with IBD with coexisting CKD is increasing.

Therefore, clinicians treating patients with IBD need to be aware of any impact of IBD medications on renal metabolism. The presence of CKD in the context of IBD “adds complexity to decision making” for clinicians treating these patients, especially because of the wide range of drug classes available to treat IBD.

Corticosteroids

The reviewers recommended using the lowest effective dose and shortest duration of corticosteroid therapy, notwithstanding strong evidence suggesting that dose adjustment is not required in advanced kidney disease, including dialysis. Although the level of evidence was weak, they also recommended budesonide instead of prednisolone in patients with advanced kidney disease, since it carries a lower risk of systemic accumulation and adverse effects. Blood glucose and blood pressure should be monitored in patients with additional risk factors for diabetes or hypertension, they added.

Aminosalicylates

In patients with IBD and CKD receiving 5‐aminosalicylic acid (5‐ASA) compounds, such as mesalazine (mesalamine) and sulfasalazine, the authors recommend monitoring renal function at baseline, at 3 months, and then every 12 months. Clinicians should remind patients of the importance of adequate fluid intake to avoid dehydration, they added.

The authors provided guidance on dose reduction based on Estimated Glomerular Filtration Rate (eGFR). In patients with impaired renal function or those on dialysis, aminosalicylates should be used with caution because of the risk of acute interstitial nephritis, “a well‐described complication of aminosalicylate therapy.”

Immunomodulators

The authors recommended dose adjustment of thiopurines should be considered in patients with advanced renal disease because of the potential for metabolite accumulation and provided guidance on dose adjustment based on eGFR. The reviewers said that since azathioprine has been more thoroughly studied in populations with CKD, it is preferred over mercaptopurine and thioguanine. They added that allopurinol is a “safe and effective adjunct to thiopurine therapy,” but it may require dose reduction and monitoring.

Methotrexate should be avoided in ESKD, the authors said, because renal insufficiency is a risk factor for toxicity and myelosuppression with methotrexate therapy. They noted that even low doses of methotrexate have been found to worsen renal function. In earlier stages of CKD, dose adjustment may be necessary. The authors provided suggested dose reductions based on creatinine clearance.

Biologics

Monoclonal antibodies, such as those targeting tumor necrosis factor (TNF)-α, integrins, and interleukins 12 and 23, “appear to be safe” in patients with renal insufficiency, including those on dialysis, the authors wrote. Generally, since biologics have a high molecular weight and are predominantly metabolized via cellular pathways and proteolytic degradation, not renal excretion, dose adjustment based on renal function is not necessary.

However, they noted that anti‐TNF–related renal disease “is a rare but described phenomenon,” though largely observed in immune-mediated inflammatory diseases other than IBD. They cited a systematic review reporting a prevalence rate of biologic‐induced autoimmune renal disease of less than 0.5%. In these rare cases, “timely cessation is imperative as long‐term renal failure is possible.” They also noted the volume of saline in biologic infusions may require care in patients on fluid restriction.

Calcineurin Inhibitors

Calcineurin inhibitors can be nephrotoxic, the reviewers cautioned, due to a reduction in renal blood flow and glomerular filtration rate. Acute kidney injury and CKD are the most common renal side effects associated with calcineurin inhibitors. For patients with renal dysfunction, trough levels should be monitored closely. Also, clinicians should be aware of possible systemic absorption of rectal preparations. However, they said, tacrolimus is safe in patients undergoing dialysis.

JAK Inhibitors

Although there is “limited data” for small molecule therapies, including JAK inhibitors, dose reduction should be considered in advanced renal disease. The authors provided guidelines for dose adjustment of upadacitinib, tofacitinib, and filgotinib based on eGFR.

Sphingosine‐1 Phosphate (S1P) Receptor Modulators

The reviewers said there is strong evidence that no dose adjustment of S1P receptor modulators is required in CKD, including ESKD. However, “cautious use and robust clinical judgement are recommended given the lack of studies in real‐world settings.” They added that there are no published data on S1P inhibitors in patients requiring dialysis.

The authors concluded based on their review of the literature, that selecting appropriate IBD therapy in patients with CKD requires a tailored approach, with “diligent surveillance of renal function to optimise treatment efficacy and minimise renal compromise.”

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. Aliment Pharmacol Ther. 2025;62(4):400-418. doi:10.1111/apt.70262