Experience of 5‐aminosalicylate nephrotoxicity in the United Kingdom

Muller, A F; Stevens, Paul E.; McIntyre, A. S.; Ellison, Howard; Logan, Richard F.

doi:10.1111/j.1365-2036.2005.02462.x

Cited by 64 publications

(41 citation statements)

References 22 publications

(67 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…More recently, data from the UK General Practice Research Database were used to estimate the incidence of renal disease in patients with IBD in a nested case-control analysis 17 : among the 19,025 5-ASA users with IBD, 130 patients developed renal disease (incidence rate of 0.17 cases per 100 patients per year), while the incidence among patients with IBD but without 5-ASA use was 0.25 and among patients without IBD was 0.08. Also in 2004, in a large European registry containing more than 1500 patients with IBD, reported during a follow-up of 1 year that the incidence of renal failure was not increased in patients using 5-ASA 16 (decreased creatinine clearance was observed in 34 patients, among them 13 with chronic renal impairment; comparing patients with and without renal impairment, no difference 24 : the authors estimated that the incidence of clinical nephrotoxicity in patients taking 5-ASA therapy was Ϸ1 in 4000 patients/year only. Studies with 5-ASA treatment in which serum creatinine or creatinine clearance was measured regularly are summarized in Table 2, 9,[13][14][15]18, where it is shown that nephrotoxicity was exceptional, being reported in few studies.…”

Section: Epidemiological Studies Evaluating Nephrotoxicity In Ibd Patmentioning

confidence: 90%

“…Therefore, more studies are necessary to determine whether serum creatinine gives sufficient warning of nephrotoxicity or whether more elaborate tests of renal function are required. 24 Finally, it should be emphasized that there is no evidence to date that either the test, or the frequency of testing, is effective in identifying these patients at risk of developing 5-ASA-related renal impairment, and therefore there are no firm recommendations, supported by medical evidence, for renal function monitoring (type and frequency) in IBD patients treated with these drugs. Moreover, the aforementioned "recommendations" regarding screening for renal impairment should be considered as "suggestions" and not as medically necessary based on the review of the literature, as there is presently no evidence that such screening or monitoring improves patient outcomes.…”

Section: Recommendations For Renal Function Monitoring In Ibd Patientmentioning

confidence: 99%

See 1 more Smart Citation

5-Aminosalicylates and renal function in inflammatory bowel disease

Gisbert

González-Lama

Maté

2007

Inflammatory Bowel Diseases

199

144

View full text Add to dashboard Cite

Nephrotoxicity has been described in some patients with inflammatory bowel disease (IBD) treated with 5-aminosalicylic acid (5-ASA). Studies with 5-ASA treatment in which serum creatinine or creatinine clearance was measured regularly show that nephrotoxicity is exceptional (mean rate of only 0.26% per patient-year). There have been several case reports, including 46 patients, of renal disease associated with 5-ASA treatment in patients with IBD. 5-ASA treatment-related nephrotoxicity is reported most often within the first 12 months, but also delayed presentation after several years has been shown. The absence of a clear relationship between 5-ASA dose and the risk of nephrotoxicity suggests that this complication is idiosyncratic rather than dose-related. Most of the patients with renal disease associated with 5-ASA treatment suffered interstitial nephritis, with symptoms and signs being nonspecific, which may delay detection for many months. The nephrotoxicity potential of mesalazine and sulfasalazine seems to be similar. The risk with different oral preparations of 5-ASA is probably too small to influence the choice of agent. Mesalazine should be withdrawn when renal impairment manifests in a patient with IBD; if this does not result in a fall in serum creatinine, then renal biopsy should be considered. A trial of high-dose steroid may be recommended in patients whose renal function does not respond to drug withdrawal. The optimal monitoring schedule of serum creatinine in patients receiving 5-ASA treatment remains to be established, as there is no evidence to date that either the test, or the frequency of testing, improves patient outcomes.

show abstract

Section: Epidemiological Studies Evaluating Nephrotoxicity In Ibd Patmentioning

confidence: 90%

Section: Recommendations For Renal Function Monitoring In Ibd Patientmentioning

confidence: 99%

5-Aminosalicylates and renal function in inflammatory bowel disease

Gisbert

González-Lama

Maté

2007

Inflammatory Bowel Diseases

199

144

View full text Add to dashboard Cite

show abstract

“…Finally, in patients the degree of intestinal inflammation affects mesalazine pharmacokinetics [26]. Further research is needed to improve our understanding of the fate of mesalazine in the human body in order to assess a rationale for individual dose optimisation, with the chance to improve the risk/benefit ratio of this drug and maybe also to to reduce the risk for rare adverse effects such as interstitial nephritis [27]. …”

Section: Discussionmentioning

confidence: 99%

Mesalazine pharmacokinetics and NAT2 phenotype

Lück

Kinzig

Jetter

et al. 2008

Eur J Clin Pharmacol

View full text Add to dashboard Cite

BACKGROUND: Mesalazine undergoes extensive metabolism by N-acetylation. While there is some evidence for an involvement of N-acetyltransferase (NAT) type 1, a potential role of NAT type 2 (NAT2) in vivo has not been tested. METHODS: In two studies in healthy young Caucasians, NAT2 phenotyping was carried out using a caffeine metabolic ratio in urine 4-6 h postdose. In study A, 1,000 mg mesalazine doses were given thrice daily for 5 days, and urine and blood samples were drawn during the last dosing interval. In study B, a 1,000 mg single dose was given, and samples were taken for 48 h postdose. Pharmacokinetics of mesalazine and N-acetylmesalazine (LC-MS/MS) were calculated by noncompartmental methods. RESULTS: NAT2 phenotype could be allocated unequivocally in 21 slow and 5 rapid acetylators in study A, and in 9 slow and 8 rapid acetylators in study B. Geometric mean (CV%) values in study A for slow [rapid] acetylators were as follows: mesalazine AUC 11.1 microg/mL.h (51%) [12.0 microg/mL.h (52%)], N-acetylmesalazine AUC 27.7 microg/mL.h (32%) [30.5 microg/mL.h (27%)], mesalazine Ae 8.53% (89%) Statistics provided no evidence for a true difference in mesalazine pharmacokinetics between slow and rapid acetylators, and no significant correlation between NAT2 activity and any mesalazine pharmacokinetic parameter was found. CONCLUSION: NAT2 has no major role in human metabolism of mesalazine in vivo.

show abstract

“…Rarely, patients can develop worsening of their colitis symptoms, sometimes associated with fever and rash [ 8 ]. Nephrotoxicity is also a rare side effect, most often caused by acute or chronic interstitial nephritis with a risk of approximately 1 per 4,000 patients per year, and so renal function should be monitored periodically during therapy [ 9 ].…”

Section: Aminosalicylatesmentioning

confidence: 99%