638 5-Aminosalicylate (5-ASA) Induced Nephrotoxicity in Inflammatory Bowel Disease

Introduction Nephrotoxicity is a rare idiosyncratic reaction to 5-ASA therapy. The precise pathogenic mechanisms are unknown. This study aims to a) describe the clinical features of this rare complication b) explore underlying mechanisms and c) identify clinically useful predictive genetic markers so these drugs can be avoided, or monitoring intensified, in high-risk patients. Here we report the clinical features. Methods Patients were identified and recruited from 185 sites (130 UK). Inclusion criteria included normal renal function prior to commencing 5-ASA, ≥50% rise in creatinine after starting 5-ASA and medical opinion implicating 5-ASA justified drug withdrawal. An adjudication panel assessed causality from case report forms using the validated Liverpool Adverse Drug Reaction Causality Assessment Tool. Results 154 patients were recruited. 19 patients were excluded following adjudication. The cohort included patients with Crohn’s disease, ulcerative colitis and indeterminate colitis (42%, 55%, 4% respectively). 74% of cases were male. Nephrotoxicity was seen with all aminosalicylates including 1 patient treated with topical therapy only. Nephrotoxicity occurred at a median age of 36.5 yrs (range 15.4–88.4 yrs). Two patients had a confirmed family history of 5-ASA-induced nephrotoxicity. 78% were detected by routine blood monitoring. Only 45% of cases recovered completely after drug withdrawal, with 18 requiring renal replacement therapy (14 transplantation). The median time for peak creatinine after commencing 5-ASA was 3.5 yrs (range 0.16–43.4 yrs). There was no evidence that time on 5-ASA treatment was associated with a higher peak creatinine or the likelihood of full recovery (p = 0.87). Women were more likely to reach full recovery than men (p = 0.00148; OR 8.26; CI 2.46–34.94). There was no evidence that early withdrawal of 5-ASA led to a higher likelihood of complete recovery. There was no difference in recovery between the three disease groups on logistic regression analysis. Conclusion This is the largest and most detailed study of 5-ASA induced nephrotoxicity to date. Whilst the incidence is low, the morbidity is high with 13% of patients requiring renal replacement therapy and 55% of patients failing to return to a normal creatinine after 5-ASA withdrawal. The next step is to carry forward these patients to a genome-wide association analysis, to be performed in February 2013. Disclosure of Interest None Declared