Prescribing Inflammatory Bowel Disease Medications in Chronic Kidney Disease: A Practical Guide

ABSTRACT

Background

The prevalence of chronic kidney disease (CKD) in patients with inflammatory bowel disease (IBD) is increasing. The pharmacokinetic profiles of IBD medications in patients with advanced‐stage CKD are not well studied.

Aim

To provide evidence‐based guidance on the use of medical therapies in patients with IBD and CKD.

Methods

We conducted a narrative review of literature up to 31 March 2025 on studies of therapies currently used for the treatment of IBD in the setting of CKD, with a focus on advanced kidney disease and use in renal replacement therapy.

Results

Mesalazine can cause acute interstitial nephritis. Calcineurin inhibitors have been associated with nephrotoxicity. Methotrexate is contraindicated in advanced renal disease, including while on renal replacement therapy, due to higher risks of toxicity and myelosuppression. Dose adjustment of thiopurines should be considered in advanced renal disease due to metabolite accumulation. Monoclonal antibodies, including anti‐tumour necrosis factor therapy, anti‐integrin therapy and anti‐interleukin 12/23 therapies, appear to be safe in renal insufficiency, including haemodialysis. There is limited data available for small molecule therapies; drug metabolism profiles suggest they are safe in CKD, although, for Janus kinase (JAK) inhibitors, including tofacitinib and upadacitinib, dose reduction should be considered in advanced renal disease.

Conclusion

Most therapies used in IBD, particularly biologic therapies, appear safe and effective when used in patients with CKD, including those on renal replacement therapy. Caution should be considered when using conventional therapies and JAK inhibitors.

Most therapies used in inflammatory bowel disease appear safe and effective when used in chronic kidney disease including on renal replacement therapy, particularly biologic therapies. Some caution should be considered when using conventional therapies and JAK inhibitors.

1. Introduction

Chronic kidney disease (CKD) is a major cause of morbidity and mortality worldwide, rising from the 19th ranked leading cause of death to the 11th in the span of 30 years [1, 2]. The prevalence of CKD in patients with IBD is increasingly recognised, with studies suggesting that 4%–23% of IBD patients may develop kidney involvement during their disease course [3, 4]. Registry data suggest that the incidence of end stage kidney disease (ESKD) or CKD stage V in patients with IBD is 0.42 per 1000 person‐years [5]. This reflects that IBD clinicians need to be cognisant of the impact that IBD medications have on renal metabolism and excretion. This is particularly pertinent to IBD patients with concurrent ESKD, including those on renal replacement therapies such as haemodialysis and peritoneal dialysis.

The presence of CKD in patients with IBD adds complexity to decision making for patient management, particularly in patients with ESKD, as this can impact on diagnostic procedures and medication safety. This is made more difficult by the rapidly growing arsenal of therapeutic agents available for induction and maintenance of remission, which now encompasses a range of drug classes from traditional corticosteroid and 5‐aminosalicylic acid formulations to immunomodulators, biologic therapies and small molecules [6]. The pharmacokinetics and drug distribution of some of these drugs are altered in patients with renal impairment, which may consequently impact choice, dose and combinations of IBD therapy. However, the evidence base for the safety and efficacy of these therapies in IBD patients with co‐existing CKD remains less well studied, particularly for newer agents and often limited to case reports or case series. Patients with comorbidities, including CKD, are customarily excluded from initial registration and safety clinical trials, so there is a reliance on real world data to aid in evidence‐based decision making with significant nuance to the approach in managing a patient with ESKD requiring haemodialysis or peritoneal dialysis; and there is often a need for collaboration between the gastroenterologist and nephrologist when making these decisions.

A greater understanding of therapies and their safety in CKD can potentially be extrapolated from other immune‐mediated inflammatory diseases (IMID), including rheumatological and dermatological conditions such as rheumatoid arthritis, spondyloarthropathies and plaque psoriasis as there is crossover for many therapeutic agents. These populations are generally older and have a higher prevalence of CKD [7, 8, 9, 10]. However, it is noted that drug dosing may be different, and generally lower, compared to IBD indications [11]. Nevertheless, additional safety data from these cohorts, especially in the setting of an ageing IBD population, can pave a potential roadmap for assessing drug safety in IBD‐CKD cohorts. There remains a substantial need for focused research aimed at this unique patient demographic to guide safe and effective treatment paradigms.

A lack of high‐quality data to guide clinicians in the prescription of IBD therapies in patients with advanced CKD, particularly in the context of the growing number and complexity of IBD therapeutics, emphasises the need to provide clinicians with practical guidance across this domain. This review seeks to address this knowledge gap by providing clinicians with an overview of renal metabolism in the context of IBD therapies, real‐world data pertaining to the use of advanced IBD therapies in patients with ESKD, and practical guidance regarding the prescription of IBD therapeutics in patients with advanced‐stage CKD.

2. Methods

2.1. Search Strategy

The literature search was primarily performed using MEDLINE and EMBASE covering articles published from inception up to 31 March 2025, with no restrictions on study design. The following keywords and MeSH terms were used in various combinations: (‘inflammatory bowel disease’ OR ‘IBD’ OR ‘Crohn's disease’ OR ‘ulcerative colitis’) AND (‘chronic kidney disease’ OR ‘CKD’ OR ‘renal insufficiency’) AND (‘therapy’ OR ‘treatment’ OR ‘biologics’ OR ‘immunosuppressants’ OR specific drug names such as ‘azathioprine’, ‘infliximab’, ‘vedolizumab’). Only articles in English were included. Reference lists of relevant articles and review papers were manually screened to identify additional studies of interest. Furthermore, expert opinion and clinical experience were incorporated to provide context and identify gaps in the literature where formal data were limited. The Renal Drug Database [12] was utilised for additional information on drug metabolism profiles. No limitations were placed on trial designs, so case reports were also included. Strong evidence was ascribed to prescribing recommendations supported by manufacturer product information or tertiary renal prescribing guidelines. Recommendations based on case reports or expert opinion were categorised as weak evidence. This approach aimed to ensure a broad yet clinically relevant synthesis of available evidence to guide the narrative review.

3. Causes of Renal Dysfunction in IBD

A systematic review of 54 studies found an odds ratio (OR) of 1.59 of CKD in the IBD population (95% CI 1.31–1.93). CD patients had almost double the risk of kidney disease compared to UC patients (CD OR 3.10, 95% CI 2.11–4.56; and UC OR 1.76, 95% CI 1.26–2.45). Proposed causal links include the immune effects of IBD, metabolic manifestations, anatomical derangements and medication‐related side effects [13]. A retrospective study of more than 80,000 persons found that IBD was associated with the development of CKD; this was more pronounced in younger patients with an almost seven‐fold increase in the rate of CKD at age 16 compared to 77 (age 16 HR 7.88 [95% CI, 2.56–24.19]; and age 77 HR 1.13 [95% CI 1.01–1.25]) [14]. Nevertheless, the current absolute risk for CKD in IBD patients in most cohort studies is low, at less than 5% [15, 16]. Details on the classification of renal dysfunction and drug handling in the setting of renal disease can be found in the Supporting Information: S1 and S2 (Figure 1, Tables 1 and 2).

FIGURE 1.

Renal excretion at the nephron. Renal excretion in the nephron begins with filtration, whereby a capillary bed known as the glomerulus is in contact with the Bowman's capsule of the nephron. Filtration of drugs occurs via fenestrations within Bowman's capsule, whereby small molecules can travel freely into Bowman's space. Drugs that are sufficiently small can also be filtered to variable degrees based on whether they are positively charged (filters more) or negatively charged (filters less, given the negative charge of Bowman's capsule). Larger molecules, such as monoclonal antibodies and protein‐bound drugs, are unable to be filtered and do not enter the glomerulus. Within the tubules of the nephron, exchange of a drug can occur via tubular secretion (facilitating excretion) and tubular reabsorption (reduced renal excretion); renal impairment is unlikely to impact clinically meaningful secretion or reabsorption in the IBD medicines discussed in this review.

TABLE 1.

Classification of chronic kidney disease based on GFR and albuminuria categories [KDIGO].

	Estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2)
GFR
Stage I	> 90 a
Stage II	60–89
Stage IIIa	45–59
Stage IIIb	30–44
Stage IV	15–29
Stage V	< 15 b

	mg/g creatinine
Albuminuria
A1—Normal	< 30
A2—Moderately increased	30–300
A3—Severely increased	> 300

^a Structural abnormality or proteinuria.

^b End stage kidney disease.

TABLE 2.

Real‐world use of biologic and small molecule therapies in patients with end stage renal disease (ESRD).

(A) Inflammatory bowel disease (IBD)
	Author (year) country	Study type (number of patients)	Age in years/gender	IBD subtype	CKD stage	Dose	IBD outcome	Adverse drug reactions (ADR)	Follow‐up	Previous therapies
Upadacitinib	Hilley et al. (2023) [17] Australia	Case study	75/F	UC	CKD V (eGFR 11)—not on dialysis	45 mg daily for 3 days, then 30 mg daily for 8 weeks (induction), 15 mg daily (maintenance)	Steroid‐free clinical and biochemical remission	Nil ADR or infections, stable eGFR	4 months	UST, VDZ
Vedolizumab	Albertini Petroni et al. (2023) [18] Italy	Case study	75/M	UC	CKD V—haemodialysis	300 mg VDZ 24 h before haemodialysis at Weeks 0, 2, 6; then 8‐weekly for 2 doses, then 9‐weekly due to rapid clinical improvement	Endoscopic healing of right colon, mild disease in left colon	Nil ADR stable/increased VDZ levels pre‐ and post‐dialysis	12 months	Oral and enema 5‐ASA
Ustekinumab	Spathakis et al. (2023) Greece	Case study	47/F	CD	CKD V—haemodialysis	260 mg IV induction, 90 mg SC 2‐monthly administered within 24 h of dialysis	Clinical remission	Nil ADR, stable creatinine Improved urea levels leading to decreased dialysis frequency	2 years	ADA, IFX (pre‐dialysis initiation)
Infliximab	Kume et al. (2011) Japan	Case study	33/M	CD	CKD V—haemodialysis	5 mg/kg at weeks 0, 2, 6; then maintenance	Clinical remission Improvement in CDAI < 150	Nil ADR at 5 years Stable IFX serum levels pre‐ and post‐dialysis	5 years
Infliximab	Chiba et al. (2014) Japan	Case study	76/M	CD	CKD V—haemodialysis	5 mg/kg at weeks 0, 2, 6; then maintenance	Rapid improvement in CDAI after two infusions Reduced radiological wall thickness	Nil ADR at 4 months	4 months

(B) Non‐IBD immune‐mediated inflammatory diseases (IMID)
	Author (year) country	Study type (number of patients)	Age in years/gender	Disease	CKD Stage	Dose	IMID outcome	Adverse drug reactions (ADR)	Follow‐up	Previous therapies
Anti‐TNF 62.5% ETC 16.7% IFX 16.7% ADA 4.1% GOM	Coskun et al. (2022) Turkey	Case series (24 patients)	Mean age 54.7/M	AS	eGFR < 60, of which 11 CKD V (haemodialysis)	ETC dose reduced 25 mg SC weekly in 4/9 dialysis patients Standard dosing for rest	Treatment effective in 91.7% patients (n = 22)	No statistical change in creatinine or eGFR at 12 months; increased creatinine last visit Mortality rate 29.2% (n = 7) Serious infections 25% (n = 6), minor infections 25%	46.5 (8–108) months
Infliximab	Singh et al. (2002) USA	Case study	60/F	RA	CKD V—haemodialysis	5 mg/kg at Weeks 0, 2, 6; then 3 mg/kg 8‐weekly	Clinical remission with improvement in ESR	Nil ADR	2 years	AZA 150 mg/daily—good initial response, stopped due to anaemia MTX 2.5‐5 mg/week—stopped due to nil response and ADR concerns
Infliximab	Hammoudeh (2006) Qatar	Case study	45/F	RA	CKD V—haemodialysis	3 mg/kg at Weeks 0, 2, 6; then 8‐weekly	Disease response	Transient itching at first two infusions Nil ADR	8 months
Infliximab	Saougou et al. (2010) Greece	Case study	52/M	PsA	CKD V—haemodialysis	5 mg/kg at Weeks 0, 2, 6; then 8‐weekly	Improved PASI	Nil ADR	6 months
Infliximab	Marocchi et al. (2010) Italy	Case study	46/M	AS	CKD V—haemodialysis commenced at Week 37 of IFX	5 mg/kg at Weeks 0, 2, 6; then 8‐weekly Dose reduced to 2.8 mg/kg (200 mg) 9‐weekly	Clinical remission	Nil ADR	24 months	SZS—ineffective
Infliximab	Yee et al. (2001) USA	Case study	72/F	Sarcoidosis	CKD V—haemodialysis	5 mg/kg at Weeks 0, 2, 6	Improved enteropathic and myopathic symptoms	Discontinued due to hypercoagulable state associated with anticardiolipin ab	6 weeks
Infliximab	Ortiz Santamaria et al. (2003) Spain	Case series (2 patients)	Mean age 59.3	AA	CKD—haemodialysis	3 mg/kg	N/A	Both discontinued—1 developed transient pancytopaenia, 1 due to unknown safety at the time in CKD	N/A
Ustekinumab	De Unamuno Bustos et al. (2013) Spain	Case study	65/M	Psoriasis vulgaris	CKD V—haemodialysis	45 mg SC 4‐weekly for two doses (pre‐dialysis initiation), then 12‐weekly	Improved PASI	Nil renal function changes Nil ADR	17 months	Etanercept—previously
Ustekinumab	Umezawa et al. (2015) Japan	Case series	68/M 64/M 57/M	Psoriasis	CKD V—haemodialysis	45 mg SC at Weeks 0, 4; then 12‐weekly	Improved PASI	Nil ADR	52 weeks
Ustekinumab	Nimmannitya et al. (2015) Japan	Case study	57/M	Psoriasis vulgaris	CKD V—haemodialysis	45 mg SC at Weeks 0, 4; then 12‐weekly; escalated to 90 mg for partial response	Improved PASI	Nil ADR Stable renal function	3 years
Adalimumab	Kobak (2012) Turkey	Case study	65/M	AS	CKD V—peritoneal dialysis	40 mg SC 2‐weekly	Clinical improvement	Nil ADR	12 weeks	MTX—severe pancytopaenia
Adalimumab	Kusakari et al. (2015) Japan	Case study	46/M	Psoriasis vulgaris	CKD V—haemodialysis	40 mg SC 2‐weekly	Improved PASI	Nil ADR	1 year	Infliximab—previously, stopped at week 56 due to pulmonary oedema with each infusion Ustekinumab—ineffective
Adalimumab	Shimojima et al. (2012) Japan	Case study	57/M	PsA	CKD V—haemodialysis	80 mg SC, then 40 mg 2‐weekly	Improved PASI and polyarthritis	Nil ADR	12 weeks	SZS—ineffective
Adalimumab	Seishima et al. (2022) Japan	Case study	69/M	PG	CKD V—haemodialysis	160 mg and 80 mg, biweekly, then 40 mg weekly	Complete epithelisation after 12 weeks, then discontinued with no recurrence	Nil ADR	6 months
Etanercept*	Cassano et al. (2008) Italy	Case study	69/M	Psoriasis vulgaris	CKD V—haemodialysis	50 mg SC weekly	Improved PASI	Nil ADR	24 weeks	Cyclosporine—initially effective with no adverse events, did not respond to repeat induction
Etanercept	Sugioka (2008) Japan	Case study	64/F	RA	CKD V—haemodialysis	25 mg SC twice‐weekly	Clinical response at 2–8 weeks Discontinued at 12 weeks due to cataract surgery, with remission at 18 weeks off treatment	Nil ADR	18 weeks
Certolizumab	Nishimura et al. (2015) Japan	Case study	63/F	RA	CKD V—haemodialysis	400 mg at Weeks 2, 4; then 200 mg 2‐weekly	Clinical improvement	Nil ADR	12 weeks	ETN—previous, ineffective

Abbreviations: 5‐ASA, 5‐aminosalicylate; ADA, adalimumab; CD, Crohn's disease; CDAI, Crohn's disease activity index; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; IBD, inflammatory bowel disease; IFX, infliximab; IV, intravenous; SC, subcutaneous; UC, ulcerative colitis; UST, ustekinumab; VDZ, vedolizumab.

4. Use of Medical Therapies for IBD in the Setting of Renal Dysfunction

The therapeutic landscape for IBD has evolved significantly over time, expanding from non‐targeted immunosuppressive agents including steroids to more specific advanced therapies with greater precision against anti‐inflammatory pathways.

This section will present IBD therapies, including corticosteroids, aminosalicylates, immunomodulators including thiopurines and methotrexate, calcineurin inhibitors, biologics including monoclonal antibodies targeting tumour necrosis factor (TNF), integrin receptors and interleukins, and small molecules such as JAK inhibitors and S1P receptor modulators, according to their mechanism of action, and examine drug specific aspects of renal metabolism and adverse events, whilst also illuminating practical prescribing considerations for each therapeutic class.

4.1. Corticosteroids

Key Practice Points

• Apply the lowest effective dose and shortest duration of corticosteroid therapy whenever possible (weak evidence)

• Dose adjustment is not required in advanced kidney disease (eGFR < 30 mL/min/1.73 m²) including dialysis (strong evidence)

• Consider budesonide rather than prednisolone in patients with advanced kidney disease (weak evidence)

Corticosteroids, including prednisolone and budesonide, are indicated for induction therapy and management of flares in IBD through their potent anti‐inflammatory and immunosuppressive effects.

4.1.1. Renal Metabolism and Clearance

Prednisolone is extensively metabolised by the liver, with less than 1% excreted unchanged in urine, indicating minimal direct renal clearance. Moreover, the inactive metabolites of prednisolone are primarily excreted via the kidneys in a concentration‐dependent manner [19]. In contrast, budesonide has up to 90% first‐pass metabolism in the liver, resulting in less than 10% reaching systemic circulation and minimal renal involvement [20]. This implies that renal dysfunction poses minimal effects on the therapeutic activity and accumulation of the active corticosteroid metabolites.

4.1.2. Renal Adverse Events

The mineralocorticoid effect of corticosteroids has been shown to impact fluid retention, hypertension and electrolyte disturbances such as hypokalaemia and hypernatraemia. Chronic use can lead to exacerbation of renal dysfunction, primarily through the development of steroid‐induced diabetes or hyperglycaemia and hypertension, factors that independently contribute to renal deterioration.

Corticosteroids are one of the mainstay treatments for intrinsic renal disease including acute interstitial nephritis, IgA nephropathy and other proteinuric kidney disorders as well as prevention of rejection in kidney transplantation [21, 22]. In non‐IBD populations with CKD, studies have shown corticosteroids to be associated with an increased risk of adverse events in a dose‐dependent manner [23]. A registry review found a 40% increase in the risk of adverse events with corticosteroid exposure (95% CI 1.3–1.6) [23].

4.1.3. Dosing and Prescribing Considerations

Dose adjustments of corticosteroid agents are not required in renal dysfunction as per manufacturer and tertiary renal prescribing guidelines [24]. Care should be taken to utilise corticosteroids at the lowest effective dose for the shortest duration possible to achieve adequate inflammatory control, with strong consideration for transition to a steroid‐sparing agent [25]. Due to its limited systemic bioavailability and primary liver metabolism, budesonide should be considered as the preferred corticosteroid in patients with CKD as it poses a lower risk of systemic accumulation and adverse effects. In patients with pre‐existing or risk factors for diabetes or hypertension, greater vigilance of blood sugar and blood pressure monitoring should be undertaken, especially at high doses or with dose alterations.

4.1.4. Use in Dialysis

Prednisolone undergoes extensive protein binding to transcortin and albumin, with the unbound drug exerting its intracellular therapeutic effect. In haemodialysis, the level of free drug is less than 10% lower than in control populations [26], hence dose adjustments are rarely required. Nevertheless, in patients with ESKD, prednisolone is likely to potentiate the concerns of hyperglycaemia, hypertension and added infection risk in an already immunocompromised and vulnerable host. Fluid retention can disturb the already precarious fluid balance in patients on dialysis, necessitating careful monitoring.

Clinical data for budesonide is scarce; systemic effects, while less prominent, must still be considered.

4.2. Aminosalicylates

Key Practice Points

• Monitor renal function at baseline, 3 months then 12 months, annually ongoing (strong evidence)

• Sulfasalazine: dose reduce and use with caution if eGFR < 10 mL/min/1.73 m² (strong evidence)

• Mesalazine: eGFR < 50 mL/min/1.73 m²: use with caution; beware mesalazine‐induced renal toxicity (strong evidence)

5‐aminosalicylic acid (5‐ASA) compounds, including mesalazine (mesalamine) and sulfasalazine, are a well‐established treatment for induction and maintenance therapy for IBD, particularly in the management of mild to moderate UC [27]. In UC, topical 5‐ASA is a first‐line treatment. A combination of oral 5‐ASA combined with a suppository formulation to target rectal disease, or an enema formulation for left colon involvement, is superior to oral or rectal monotherapy alone [28].

4.2.1. Renal Metabolism and Clearance

Renal clearance accounts for 37% of sulfasalazine elimination, with metabolites primarily excreted in urine as free metabolites or glucuronide conjugates [29]. Approximately 20% of extended‐release oral mesalazine is absorbed, after which less than 8% is eliminated unchanged in the urine and 13% is eliminated as its metabolite acetyl‐5‐aminosalicylic acid [30]. Elimination rates are similar in rectal preparations. Based on testing of total plasma levels and urinary and faecal excretion, Sandborn et al. found that all oral mesalazine formulations and pro‐drugs conferred a comparable systemic exposure [31].

4.2.2. Renal Adverse Events

Mesalazine‐induced acute interstitial nephritis (AIN), an idiosyncratic adverse reaction, is a well‐described complication of aminosalicylate therapy [32]. A Japanese adverse drug event report database found mesalazine compounds were the 7th most frequent cause of drug‐induced AIN [33]. As expected from previous pharmacokinetic trials, there are no discernible differences in safety or efficacy across the different formulations of 5‐ASA, as described in a Cochrane review of 2925 patients across 17 studies [34]. Moss et al. conducted a systematic review of 41 case reports. They found that the diagnosis of AIN occurred at a median duration of 2.3 years after mesalazine commencement [35]. Dosing and duration of treatment had no bearing on the degree of creatinine change. There was no association between age and the time or onset, its severity or recovery. ESKD developed in 14.6% of patients despite treatment [35]. A retrospective review of 151 cases by Heap et al. found a genetic link with a three‐fold increase in the risk of developing drug‐induced AIN in patients with HLA‐DRB1*01:02 allele carriage. Furthermore, a cumulative risk was demonstrated as 5‐ASA dose and length of treatment were inversely proportional to the likelihood of renal function recovery. Sulfasalazine‐induced crystalluria occurs when sulfasalazine metabolites, especially sulfapyridine, become concentrated in the urine. Risk factors include renal dysfunction and dehydration. Subsequent nephrolithiasis causes obstructive uropathy and acute kidney injury [36, 37].

Conversely, large scale epidemiological studies across 37,984 patients in Britain found a low overall incidence of renal toxicity [38] and a meta‐analysis of more than 100,000 patients found no direct association between mesalazine and an increased risk of kidney disease (adjusted OR 1.14, 95% CI 0.73–1.9) [13]. Instead, it has been postulated that increased rates of renal disease in mesalazine‐exposed patients may be attributable to IBD itself or a physiological decline in renal function related to ageing [38, 39].

4.2.3. Dosing and Prescribing Considerations

In patients with impaired renal function, there is a risk of drug accumulation and increased toxicity. 5‐ASA dependent renal disease is unpredictable, with no clear evidence to suggest an altered or added risk in CKD. The British Society of Gastroenterology recommends renal function monitoring in all patients on 5‐ASA agents, with eGFR at baseline, 2–3 months after commencement, then annually [27]. In patients with CKD, greater caution may be prudent in the context of increased vulnerability to additional renal injury. Manufacturer data cautions against the use of mesalazine in patients with eGFR < 20 mL/min/1.73 m² and recommends the lowest dose possible with close monitoring for eGFR < 50 mL/min/1.73 m². Overall risks and consideration of alternate therapies must be weighed against 5‐ASA therapy's utility as an effective cornerstone treatment in IBD, especially with milder phenotypes, and relative safety profile as a more topical therapy.

When prescribing sulfasalazine, recommendations include adequate fluid intake to avoid dehydration, especially in the context of increased gastrointestinal losses in active inflammatory disease. Consultation with a nephrologist should be advised in the setting of existing fluid restrictions in CKD.

4.2.4. Use in Dialysis

Data in ESKD patients on dialysis is scarce; however, pharmacokinetic studies on salazosulfapyridine suggest safe dosing up to 1000 mg and no requirement for dose adjustment in ESKD [40, 41]. Guidelines suggest cautious use in patients on dialysis; sulfasalazine has minimal dialysability due to protein binding [42] although its metabolites and the 5‐ASA component may be dialysed or partially dialysed [43, 44].

4.3. Immunomodulators

4.3.1. Thiopurines

Key Practice Points

• Dose adjustment: eGFR 10–50 mL/min/1.73 m²: decrease by 25%; eGFR < 10 mL/min/1.73 m²: decrease by 50% (strong evidence)

• Consider azathioprine if eGFR < 30 mL/min/1.73 m² (weak evidence)

Thiopurines, including azathioprine, mercaptopurine and thioguanine, are commonly used as first‐line therapy or as an immunomodulator to reduce the risk of immunogenicity in IBD [45].

4.3.1.1. Renal Metabolism and Clearance

Thiopurines are rapidly oxidised or methylated then eliminated from blood, with less than 2% of azathioprine dose excreted unchanged in urine and trace quantities of thioguanine found in urine after a single radiolabelled dose [46, 47]. Elimination of azathioprine metabolites is reduced in renal impairment, but its biologic activity is not affected due to this very rapid metabolic inactivation.

4.3.1.2. Renal Adverse Events

Nephrotoxicity is rare; azathioprine has been used in the past to treat lupus nephritis and prevent rejection post‐renal transplant [48, 49].

4.3.1.3. Dosing and Prescribing Considerations

Due to its use in renal indications, azathioprine has been better studied in CKD populations and is the preferred agent compared to mercaptopurine and thioguanine. Target dosing in IBD is weight based, with a standard approach to aim for 2–2.5 mg/kg for azathioprine and 1.15 mg/kg for mercaptopurine. Dose reduction of thiopurines is not necessary in mild or moderate renal failure. It is recommended by renal prescribing guidelines to dose reduce by 25% in patients with eGFR between 10 and 50 mL/min/1.73 min², and 50% in eGFR < 10 mL/min/1.73 m² [50]. Although bone marrow and liver toxicity are rare on established thiopurine treatments, 3‐ to 6‐monthly blood tests for early detection of these complications are recommended for all patients. Significant alterations in kidney function or weight should trigger more frequent investigations and TDM.

Allopurinol is a safe and effective adjunct to thiopurine therapy to reduce the effect of shunting and optimise the balance between therapeutic and toxic metabolites [51, 52]. It inhibits xanthine oxidase, an enzyme involved in the catabolism of mercaptopurine, leading to increased levels of TGNs and a heightened risk of myelosuppression. Thus, the addition of allopurinol corrects hypermethylation and is used therapeutically in combination with dose‐reduced azathioprine or mercaptopurine to achieve a therapeutic response with lower risk of hepatoxicity [53]. Of note, allopurinol is a commonly used uric acid‐lowering therapy in the prevention of gout, a condition present in 25% of patients with CKD [54]. Caution should be taken in assessing drug interactions if commencing allopurinol for gout‐related indications to ensure appropriate dose reduction (25% of recommended dose) and monitoring.

4.3.1.4. Use in Dialysis

Azathioprine and mercaptopurine have moderate protein binding (30%) and can be partially removed by dialysis. Schusziarra et al. demonstrated approximately 45% of a radioactively labelled dose of AZA was eliminated during an 8‐h haemodialysis session, thereby reducing its half‐life to 2.5 h (compared to 4.5 h in individuals with normal renal function) [55]. Night‐time or post‐dialysis dosing is recommended with careful TDM in response to significant changes in dialysis prescription [24].

4.3.2. Methotrexate

Key Practice Points

• Dose adjustment: CrCl 30–60 mL/min: decrease by 50%; CrCl < 30 mL/min: contraindicated (strong evidence)

• Avoid in ESKD (strong evidence)

Methotrexate is a folate antagonist that has been effectively employed as an immunosuppressant in the treatment of IBD, particularly CD [56], and is a cornerstone treatment for other IMID, especially rheumatoid arthritis [57].

4.3.2.1. Renal Metabolism and Clearance

Methotrexate is primarily excreted unchanged by the kidneys, with 80% eliminated through glomerular filtration and active tubular secretion, and to a lesser extent via biliary excretion (10%–30%) [58, 59]. The elimination half‐life of methotrexate increases and total clearance decreases linearly according to renal function [60].

4.3.2.2. Renal Adverse Events

There are no large‐scale studies regarding the use of methotrexate in patients with concurrent CD and CKD. A randomised control trial comparing low‐dose methotrexate to placebo in RA patients with metabolic syndrome (54% stage II CKD, 18% stage III CKD) reported fewer renal‐related adverse events (HR 0.77; 95% CI 0.61–0.96), including severe adverse events (HR 0.49; 95% CI 0.09–2.70) and a less dramatic decline in eGFR over time [61]. Nevertheless, renal insufficiency is a known risk factor for toxicity, especially myelotoxicity [62, 63, 64], with implications for serious complications including sepsis and death. An observational cohort study of 120 patients with RA and CKD (97% stage IIIa CKD, 22% stage IIIb CKD, 1% stage IV CKD) reported methotrexate toxicity in nearly 30% of patients (leukopaenia most common, 10%), with baseline eGFR being a significant factor for toxicity in multivariate analysis (HR 0.938, 95% CI 0.89–0.99) [64].

In the absence of folic acid supplementation, the risk of haematological toxicity was more pronounced in CKD populations compared to those with normal renal function (OR 3.72; 95% CI 2.87–4.81). However, this risk significantly decreased with folic acid supplementation, highlighting the necessity to ensure regular folic acid supplementation in this population [65].

4.3.2.3. Dosing and Prescribing Considerations

Impaired renal function can lead to drug accumulation and an increased risk of adverse effects, such as myelosuppression, mucositis and hepatotoxicity [66]. High dose methotrexate, defined as doses > 50 mg/m², is directly nephrotoxic due to precipitation and injury to renal tubules, but is largely limited to chemotherapy, with doses in IBD rarely exceeding 15–25 mg weekly [67].

Renal prescribing guidelines recommend a dose reduction to 50% of standard dose for patients with eGFR 30–60 mL/min/1.73 m², and use should be avoided in patients with severe kidney disease with eGFR < 30 mL/min/1.73 m² [68]. All patients should be prescribed folic acid supplementation.

4.3.2.4. Use in Dialysis

Methotrexate can have irreversible or fatal complications in patients with ESKD, with even low doses of methotrexate (2–4 mg per week) documented to worsen renal function, cause profound myelosuppression, and increase mortality in patients on haemodialysis [62], with studies showing detectable drug at 3 weeks after doses of 2.5 mg [69].

Hence, even at reduced doses, methotrexate is not recommended in patients with ESKD given that standard dialysis regimes have low rates of methotrexate clearance due to the drug's low protein binding affinity and an inability to remove polyglutamated methotrexate sequestered in cells [70, 71]. However, in the event of methotrexate‐related toxicity, high‐flux dialysis is a viable salvage treatment [72, 73].

4.4. Biologic Therapies

Biologic therapies remain an advanced IBD therapeutic that is typically reserved for patients who fail to demonstrate adequate response to, or manifest adverse effects related to, immunomodulator therapies. As a class, biologic agents have a high molecular weight and are predominantly metabolised through cellular pathways and proteolytic degradation, rather than via renal excretion. Consequently, the pharmacokinetic profile of biologics is not generally affected by renal function, obviating the need for routine dose adjustment in IBD patients with co‐existing CKD. The most frequently prescribed classes of biologics in IBD are anti‐TNFa, anti‐IL23/12, anti‐IL23 and anti‐integrin.

Key Practice Points

• No dose adjustment required in CKD (weak evidence)

• No pharmacokinetic basis to adjust timing of administration in dialysis (weak evidence)

4.4.1. ANTI‐TNF‐a

Anti‐TNF biologic therapies, such as infliximab, adalimumab, etanercept, certolizumab and golimumab, have significantly advanced the management of IBD since its introduction by targeting tumour necrosis factor‐alpha (TNF‐α), a pivotal pro‐inflammatory cytokine.

4.4.1.1. Renal Adverse Events

Anti‐TNF‐related renal disease is a rare but described phenomenon, largely in non‐IBD IMID. A systematic review by Piga et al. reported a low prevalence of biologic‐induced autoimmune renal disease (less than 0.5%) with an incidence rate of 0.9 cases per 1000 patient years [74]. These include IgA nephropathy [75], nephrotic syndrome [76], glomerulonephritis [77] and membranous nephropathy [78]. Anti‐TNF is more commonly implicated compared to other biologics, and timely cessation is imperative as long‐term renal failure is possible [74].

Sumida et al. conducted a retrospective cohort study on 10,689 patients with IBD newly initiated on anti‐TNF through the United States Department of Veterans Affairs healthcare data. Anti‐TNF use was associated with a 30% decline in eGFR compared to a matched cohort of anti‐TNF non‐users (adjusted HR 1.34, 95% CI 1.18–1.52) [79]. It is difficult to draw causal relationships from this observational study, and it is unclear if changes in muscle mass and thereby creatinine or postulated effects of anti‐TNF induced lupus may play an effect in this predominantly older male population (mean age 67.4, 93.5% male). A prospective study of 211 consecutive patients with ankylosing spondylitis commencing anti‐TNF (median age 42) showed a non‐clinically significant decline in eGFR over 2 years of treatment (delta −2.4, SD 15.6) despite high rates of concurrent NSAID use in this population (79.6%) [80].

Conversely, studies in RA have shown anti‐TNF to improve kidney function in patients with existing CKD stage III or IV compared to controls [81]. In patients with existing CKD, retrospective analysis of patients with RA or ankylosing spondylitis and CKD treated with anti‐TNF by Hueber (n = 11), Sumida (n = 65) and Coskun (n = 24) et al. each reported effective treatment, with no reduction in renal function beyond expected natural progression [82, 83, 84].

4.4.1.2. Dosing and Prescribing Considerations

The pharmacokinetic properties of anti‐TNF agents are generally not significantly altered in patients with CKD [85]. This property is particularly advantageous as it allows for standard dosing regimens in patients with renal insufficiency, including those on dialysis, without adjustments.

Compared to other biologics, anti‐TNF agents have higher rates of immunogenicity and potential for anti‐drug antibody formation; this can reduce their efficacy and increase the risk of infusion reactions [86]. As such, co‐therapy with an immunomodulator such as thiopurine or methotrexate is common. The potential requirement for an additional immunosuppressive therapy has additive implications in infection risk, especially in a high‐risk population such as patients with CKD and higher baseline risk of anti‐TNF compared to other biologic agents [87].

4.4.1.3. Use in Dialysis

The safe use of infliximab in patients with CD on dialysis has been well‐documented in case reports [88, 89, 90]. In line with its known pharmacokinetic behaviour, Kume et al. described unchanged serum levels of infliximab before and after haemodialysis [89]. Interestingly, Kusakari et al. described a case of pulmonary oedema that occurred in a patient with psoriasis vulgaris on haemodialysis following infliximab infusion, who later responded to adalimumab treatment without complication [91]. Standard infusions are delivered in 250 mL of normal saline with a maximum recommended concentration of 4 mg/mL [92], highlighting the need for care in managing fluid balance in patients with CKD on a fluid restriction, especially for high weight and high dose patients. In other IMID, etanercept [85, 93] and adalimumab [94, 95] have also been safely used in cases of both haemodialysis and peritoneal dialysis.

4.4.2. Anti‐Interleukins

Interleukin‐12/23 biologics, including ustekinumab, and interleukin‐23 (IL‐23) biologics, such as guselkumab, risankizumab and mirikizumab, have gained prominence as effective treatments of IBD.

4.4.2.1. Renal Adverse Events

Multiple clinical trials, including long‐term safety data up to 5 years and real‐world analyses, have reported rates of adverse events associated with ustekinumab akin to placebo [96, 97, 98]. Renal impairment‐related symptoms are rarely reported [99]. There were no renal events noted in the phase 3b head‐to‐head trials comparing risankizumab and ustekinumab [100]. The favourable infection risk profile is a positive consideration considering the heightened susceptibility to infections in patients with CKD.

Case reports exist describing IL‐23 therapy causing renal injury, including acute interstitial nephritis [101], focal segmental glomerulosclerosis [102] and crescentic IgA glomerulonephritis [103]. Renal function resolved to baseline following IL‐23 discontinuation and steroid treatment in all three cases. Conversely, a recent case report by Larson et al. describes a case of risankizumab effectively treating concurrent CD and IBD‐associated IgA nephropathy with improvement in proteinuria and haematuria together with endoscopic remission [104].

4.4.2.2. Dosing and Prescribing Considerations

Renal impairment does not substantially alter its pharmacokinetics, allowing for standard dosing regimens in patients with CKD.

4.4.2.3. Use in Dialysis

The use of ustekinumab in ESKD requiring haemodialysis is described in three case reports across the spectrum of IBD and psoriasis. Spathakis et al. described the safe and clinically efficacious use of ustekinumab to induce and maintain remission in a patient with treatment refractory CD on haemodialysis [105]. Data from dialysis patients with psoriasis vulgaris support the efficacy and safety of IL‐23 administration in patients with ESKD requiring haemodialysis [106, 107].

4.4.3. Anti‐Integrins

Vedolizumab represents the only anti‐integrin therapy routinely used in patients with IBD [108].

4.4.3.1. Metabolism and Renal Clearance

Renal impairment does not significantly alter the pharmacokinetics of vedolizumab, allowing for standard dosing regimens without the need for significant adjustments. Vedolizumab pharmacokinetics are characterised by a two‐compartment model with parallel linear and nonlinear elimination. Only extreme albumin and body weight values were identified as potential clinically important predictors of drug clearance [109].

4.4.3.2. Renal Adverse Events

Accumulated safety data from six clinical studies of vedolizumab (two phase 2 and four phase 3 studies) in patients with IBD reported no significant adverse renal events, although two cases of renal cancer were reported [110, 111, 112]. Long‐term safety data over 8 years from the phase 3 study [113] and a systematic review of real world safety data [114] do not mention renal complications. Biologic‐induced renal disorders are rare, with a systematic review by Forss et al. finding nine cases of AIN in IBD patients treated with vedolizumab (CD n = 3, UC n = 9), with 6/9 cases deemed ‘possible’ or ‘probable’ causality. Five patients sustained permanent kidney injury [115].

4.4.3.3. Dosing and Prescribing Considerations

Renal impairment does not substantially alter its pharmacokinetics, allowing for standard dosing regimens in patients with CKD. Vedolizumab's selectivity is particularly advantageous for IBD patients with multiple comorbidities including CKD, as it minimises the risk of systemic infections and other complications associated with broad immunosuppression.

4.4.3.4. Use in Dialysis

The use of vedolizumab in patients requiring haemodialysis is likely safe in the context of its pharmacokinetics, although data supporting this is limited. Albertini Petroni et al. described a case of refractory UC with ESKD requiring haemodialysis achieving clinical remission with vedolizumab without harm [18]. Drug monitoring before and 1 h following haemodialysis demonstrated a slight increase in the vedolizumab concentration, postulated to be due to the reduction in total circulatory volume and electrolyte changes caused by haemodialysis [18].

4.5. Small Molecules

4.5.1. Calcineurin Inhibitors

Key Practice Points

• Can be nephrotoxic due to reduction in renal blood flow and glomerular filtration rate (strong evidence)

• Monitor trough levels closely in patients with renal dysfunction (strong evidence)

• Be aware of systemic absorption of rectal preparations (weak evidence)

Calcineurin inhibitors (CNI), consisting of cyclosporine and tacrolimus, serve as effective immunosuppressive agents in the induction of remission of severe ulcerative colitis [116]. Rectal formulations of tacrolimus, including suppository, ointment and enema, provide localised treatment for distal disease or refractory proctitis with reduced systemic absorption [117].

4.5.1.1. Metabolism and Renal Clearance

Cyclosporine and tacrolimus are extensively metabolised in the liver via the cytochrome P450 3A enzyme system. The metabolites are primarily excreted through the biliary route, with minimal renal clearance. However, nephrotoxicity is a significant concern as calcineurin inhibitors have been shown to induce vasoconstriction in the afferent arterioles in the kidneys.

4.5.1.2. Renal Adverse Events

Nephrotoxic effects are a known precaution in the use of CNIs. The most common renal side effects include acute kidney injury (AKI) and CKD, which result from the drug‐induced reduction in renal blood flow and glomerular filtration rate [118].

A systematic review found topical tacrolimus to be safe, with a reduced incidence of tremors and creatinine change and no clear association between drug levels and side effects. Suppository form resulted in lower systemic levels compared to the other rectal formulations [119].

4.5.1.3. Dosing and Prescribing Considerations

Careful monitoring of renal function and drug levels is necessary when prescribing CNIs. Although topical formulations have fewer systemic effects compared to oral and intravenous preparations, significant active absorption can contribute to systemic levels and therefore nephrotoxicity [120].

In all patients prescribed a CNI, baseline levels of renal function, electrolytes, fasting cholesterol and blood pressure should be taken. Additional caution should be exercised in patients with uncorrected hypomagnesaemia and hypocholesterolaemia (total cholesterol < 3 mmol/L) due to concerns regarding increased risk of neurological toxicity secondary to alterations in the blood– brain barrier [121, 122]. The serum trough levels of CNIs should be assessed once steady‐state concentrations have been achieved, which generally corresponds to 3–5 half‐lives (72 h) and checked alternately daily in acute severe colitis where intravenous cyclosporine is being used, and up to 1–2 weekly on oral therapy. Nephrotoxic side effects are dose‐dependent, with the risk of toxicity increasing at levels over 300 μg/L for cyclosporin [123] and 15 ng/mL for tacrolimus [124]. Thus, care should be taken to dose towards the lower end of the therapeutic window.

While the rates of systemic absorption in rectal preparations are low, with three‐quarters having detectable or low (< 5 ng/mL) trough levels in a randomised control trial, a retrospective review by Jaeger et al. found elevated trough levels and one case of mild reversible renal impairment [120]. This highlights the importance of routine monitoring of trough levels and renal function for rectal tacrolimus administration.

4.5.1.4. Use in Dialysis

Tacrolimus is safe to use in patients undergoing dialysis as it undergoes minimal renal excretion and is not dialysed. Tacrolimus is continued in renal transplant patients with graft failure needing dialysis if planned for re‐transplantation to prevent sensitisation [125, 126]. Collaboration with a nephrologist is advisable when managing such patients to provide expertise in handling the compounded complexity of renal impairment with CNI therapy as more rigorous monitoring and conservative dosing may be required given its side effect profile.

4.6. JAK‐Inhibitors

Key Practice Points

• Upadacitinib dose adjustment: eGFR < 30 mL/min/1.73 m²: use induction/maintenance 30/15 mg; eGFR < 15 mL/min/1.73 m²: caution advised (strong evidence)

• Tofacitinib dose adjustment: eGFR < 50 mL/min/1.73 m²: decrease by 50% (strong evidence)

• Filgotinib dose adjustment: eGFR 15–60 mL/min/1.73 m²: decrease by 50% (100 mg once daily); eGFR < 15 mL/min/1.73 m²: not recommended (strong evidence)

Janus kinase (JAK) inhibitors, such as tofacitinib, upadacitinib and filgotinib, have emerged as potent rapid‐onset therapeutic agents for moderate to severe UC and CD. These small molecules inhibit the JAK–STAT signalling pathway, which is critical in the pathogenesis of IBD due to its role in mediating cytokine signalling involved in immune cell activation and inflammatory responses.

4.6.1. Tofacitinib

Tofacitinib primarily undergoes hepatic metabolism via cytochrome P450 enzymes (CYP3A4 and CYP2C19), with approximately 30% of the drug excreted unchanged in the urine [127]. Consequently, renal impairment can lead to increased plasma concentrations of tofacitinib, necessitating dose adjustments. A non‐randomised parallel‐group Phase I study by Krishnaswami et al. compared the pharmacokinetics of tofacitinib in patients with impaired renal function to healthy controls. The half‐life (t _1/2) increased with increasing severity of renal dysfunction but was similar in participants with normal, mild and moderate renal impairment (t _1/2 = 2.4, 2.8, 2.9, respectively) with a more pronounced increase with severe renal impairment (t _1/2 = 3.8) [128].

4.6.1.1. Use in Renal Failure

A dose reduction of 50% is recommended by manufacturer product information in patients with eGFR < 50 mL/min/1.73 m². There is no literature to date on the use of tofacitinib in ESKD or patients on dialysis. From a separate cohort of patients undergoing haemodialysis in the same Phase I study, Krishnaswami et al. found tofacitinib was rapidly eliminated even without dialysis, due to a high level of non‐renal clearance. They estimated 3 h of high‐flux haemodialysis would contribute to less than 10% of the overall clearance. Thrombocytopaenia was reported in a single patient, which resolved prior to second dosing [128]. As such, renal prescribing guidelines recommend the same 50% reduction in patients with ESKD due to minimal removal by dialysis [24].

4.6.2. Upadacitinib

Upadacitinib is primarily metabolised by CYP3A4, with a minor contribution from CYP2D6. A portion is excreted unchanged in urine (24%) and faeces (38%) [129]. A single‐dose open‐label study showed renal impairment had a limited effect on upadacitinib pharmacokinetics, with similar maximum observed plasma concentrations in participants with renal impairment compared to healthy controls [130].

4.6.2.1. Use in Renal Failure

Dose adjustment of upadacitinib is not required in the setting of renal impairment as per manufacturer product information; however, a conservative dosing approach may be warranted in the context of its dose‐dependent side effect profile and paucity of data. To date, there is no literature on the use of upadacitinib in dialysis.

Hilley et al. described the safe use of standard dose upadacitinib as salvage therapy in a biologic‐experienced patient with acute severe ulcerative colitis with concurrent ESKD not requiring dialysis. Serum creatinine and eGFR remained stable on induction and maintenance doses; however, a rapid dose de‐escalation (3 days of 45 mg daily, followed by 8 weeks of 30 mg daily, then maintenance of 15 mg daily) was employed due to rapid clinical improvement on induction and concerns regarding herpes zoster risk [17].

4.6.2.2. Renal Adverse Events

Landmark trials for the efficacy and safety of JAK inhibitors in IBD for tofacitinib and upadacitinib [131] do not mention significant renal adverse events. Long‐term safety up to 7 years in the OCTAVE trial for tofacitinib for UC [132] and similarly pooled data across other immune‐mediated conditions do not highlight any renal risks [133, 134, 135].

4.6.2.3. Prescribing Considerations

The lowest effective dose of JAK‐inhibitors should be used. Concerns regarding adverse events, in particular herpes zoster infections, venous thromboembolism, malignancy and cardiovascular complications, are thought to be dose related, highlighting the need to use the appropriate and least harm‐causing dose of JAK inhibitors [136]. Other risk mitigation strategies include cardiovascular screening and vaccination against herpes zoster infection [137, 138]. Vigilant monitoring is imperative in patients with CKD, especially as this population has pre‐existing elevated baseline risk for these complications.

4.6.3. Filgotinib

Filgotinib and its metabolites are predominantly renally excreted (85%), with a small percentage excreted in faeces (15%). Phase I studies indicate proportional changes to AUC (area under the curve) depending on the degree of renal impairment, with minimal change in mild renal impairment, a 2‐fold increase in moderate renal impairment and a three‐fold increase in severe renal impairment. Filgotinib has not been studied in patients with eGFR < 15 mL/min/1.73 m² [139].

4.6.3.1. Use in Renal Failure

A dose reduction of 50% is recommended by manufacturer product information in patients with eGFR < 60 mL/min/1.73 m². There is no literature to date on the use of filgotinib in ESKD or patients on dialysis.

4.6.4. Sphingosine‐1 Phosphate Receptor Modulators

Key Practice Points

• No dose adjustment required in CKD (strong evidence)

Sphingosine‐1‐phosphate (S1P) receptor modulators, such as ozanimod and etrasimod, are the newest class of advanced therapies used in the management of IBD. S1P receptors are expressed on the surface of a variety of inflammatory cells, which play a part in immune activation.

4.6.4.1. Metabolism and Renal Clearance

These drugs are predominantly hepatically metabolised via the cytochrome P450 enzyme system, particularly CYP3A4. S1P receptor modulators undergo extensive first‐pass metabolism and are subsequently excreted into the faeces through the biliary system and minimally unchanged in urine [140]. Peak concentrations and area under the curve (AUC) were comparable between subjects with advanced kidney disease (eGFR < 30 mL/min/1.73 m²) and controls in registration trials for etrasimod [141]. Exposure AUC of ozanimod and its metabolites was 23%–27% higher or lower in patients with ESKD compared to normal renal function following a single dose [142]. As renal clearance of its metabolites is relatively low, renal function does not significantly impact drug elimination.

4.6.4.2. Renal Adverse Events

To date, few renal complications have been reported in the literature. Long‐term safety of ozanimod in the TOUCHSTONE open‐label extension study with more than 4 years of follow up does not report any renal or urinary disorders in the ozanimod population [143]. Similar safety signals for renal disease have come out of the equivalent etrasimod studies up to 52 weeks [144].

4.6.4.3. Dosing and Prescribing Considerations

As a class, S1P receptor modulators do not require dose adjustments in patients with renal impairment [142], including ESKD as per manufacturer guidelines. Cautious use and robust clinical judgement are recommended given the lack of studies in real‐world settings and post‐marketing surveillance to provide deeper insights into the safe use of S1P inhibitors in these vulnerable populations.

4.6.4.4. Use in Dialysis

To date, there is no published data on the use of S1P inhibitors in patients requiring haemodialysis, suggesting that caution should be used in these populations.

5. Implications for Clinical Practice

Selecting appropriate therapeutics for managing IBD in patients with CKD necessitates a tailored approach, emphasising diligent surveillance of renal function to optimise treatment efficacy and minimise renal compromise. Dose adjustments of IBD therapeutics are not required for patients with stage I or II CKD. Depending on specific drug metabolism and renal excretion, dose adjustments may be required at more advanced‐stage CKD (Table 3). Guidelines from major gastroenterological and nephrological organisations advocate for regular monitoring of renal function in this patient cohort; however, specific monitoring intervals are clinician dependent.

TABLE 3.

Recommendations for prescribing IBD therapeutics in CKD.

		Stage I	Stage II	Stage III	Stage IV	Stage V a
Corticosteroids	Prednisolone
	Budesonide
Aminosalicylates	Aminosalicylates
	Sulfasalazine
Immunomodulators	Thiopurine					Azathioprine preferred
	Methotrexate
Biologics	Anti‐TNFa
	Anti‐IL‐12/23, IL‐23
	Anti‐Integrin
Small molecules	Calcineurin Inhibitors
	Tofacitinib
	Upadacitinib
	Filgotinib
	S1P

^a Including dialysis .

Surveillance protocols should include baseline assessment of kidney function prior to the initiation of any IBD therapy, especially those with potential nephrotoxic effects. The frequency of subsequent monitoring should correlate with the CKD stage—patients with more advanced stages of CKD require more frequent evaluations [1]. This typically involves measurements of serum creatinine, calculation of eGFR and monitoring for albuminuria, which can serve as an early indicator of deteriorating renal function.

Collaborative management involving both gastroenterologists and nephrologists is recommended, particularly when navigating complex cases that require the integration of IBD treatment with ongoing CKD management. Gastroenterologists should be cognisant that eGFR is less accurate at the extremes of body weight or in low muscle mass, and monitoring creatinine change is preferential in acute kidney injury.

Significant knowledge gaps remain with limited real‐world data on practical aspects of management in IBD patients with CKD. Product information for mesalazine recommends caution with co‐administration of mesalazine with azathioprine due to increased risk of renal adverse events [30]. However, real‐world associations remain scarce. To date, there is no literature on the use of co‐therapies, including combined immunomodulator with biologic and dual biologic therapy, or escalated dosing in this vulnerable population, nor in similar populations with IMID.

Therapeutic drug monitoring has become standard of care in dose optimising thiopurines within the therapeutic window [145]. Its use has also gained prominence in achieving therapeutic targets for anti‐TNFa, particularly infliximab and adalimumab [146], ustekinumab [147] and vedolizumab [148]. Achieving higher trough levels of biologics through dose escalation has been shown to be efficacious in treating inflammation without increasing the risk of serious infections [149]. Given the pharmacokinetic profile of biologic agents, it is reasonable to extrapolate that dose escalation is safe and that target levels do not need to differ in patients with CKD compared to patients with normal renal function.

6. Conclusion

The prevalence of both inflammatory bowel disease (IBD) and chronic kidney disease (CKD) continues to rise, so knowledge on how best to approach patients with both comorbidities is becoming increasingly important. IBD itself is a risk factor for renal dysfunction, whether it be related to shared disease inflammatory pathways or secondary to drug side effects. The management of IBD in the presence of CKD presents significant challenges due to the complex interplay between disease processes, the impact of renal impairment on drug metabolism, and a higher threshold for accepting drug‐related complications and side effects. While traditional and newer IBD therapies offer effective disease control, their use in CKD patients must be approached with caution, requiring adjustments based on renal function and careful monitoring.

Current data pertaining to the use of IBD therapeutics in patients with CKD, especially in ESKD requiring dialysis, is scarce with a predisposition towards case reports and observational studies. Further larger scale real‐world population‐based studies on this vulnerable and increasingly prevalent cohort of patients are required to assist clinicians and inform clinical practice.

Author Contributions

Lynna Chen: conceptualization, methodology, writing – original draft, resources. Ashish Srinivasan: conceptualization, methodology, supervision, writing – review and editing, resources. Suet‐Wan Choy: writing – review and editing, resources. Jeffrey Van: writing – review and editing, methodology, resources. Habeeb Habeeb: writing – review and editing. Andrew Nguyen: writing – review and editing. Abhinav Vasudevan: conceptualization, writing – review and editing, supervision, resources.

Disclosure

A.S. has served as a speaker for Sandoz and Arrowtex Pharmaceuticals, and received advisory fees from Abbvie, Amgen, Arrotex Pharmaceuticals, Pfizer and Takeda Pharmaceuticals. A.V. has served as a speaker for Pfizer and Abbvie and received advisory fees from Abbvie and Ferring. The remaining authors have no disclosures.

Supporting information

Data S1.

Data Availability Statement

The authors have nothing to report.