Nephrology Dialysis Transplantation Mesalazine - associated interstitial nephritis

Background. When used for oral treatment of inflammatory bowel disease, Asacol (a coated form of mesalazine = 5-aminosalicylic acid) can cause interstitial nephritis. The spectrum of severity, frequency of occurrence and the best renal function test to detect this complication are not known. The value of immunosuppression in addition to drug withdrawal is similarly undetermined. Methods. Four cases of interstitial nephritis which occurred in association with oral Asacol treatment are presented and a further 12 cases who received similar treatment are reviewed. Clinical trials published previously were scrutinized to assess the frequency of impaired renal function. Results. The available evidence suggests that renal impairment of any severity may occur in up to 1 in 100 patients, but that clinically significant interstitial nephritis occurs in less than 1 in 500 patients. This is most reliably detected by an elevated serum creatinine concentration. If the diagnosis of nephrotoxicity is delayed until 18 months after commencement of medication, restoration of renal function, which is seen on withdrawal of medication alone up to 10 months, does not occur and there is no evidence to date to indicate that addition of immunosuppression confers any significant advantage at this later stage. Conclusions. It is suggested that serum creatinine concentration should be measured each month for the first 3 months of treatment, 3-monthly for the remainder of the first year and annually thereafter. The use of concurrent immunosuppressive therapy may necessitate extension to the period of intensive monitoring. Any elevation of serum creatinine which cannot be related to a relapse of inflammatory bowel disease should prompt immediate withdrawal of Asacol and related medications and substitution of alternative therapy. Neither the lack of urinary abnormalities on routine testing nor the absence of clinical or laboratory features of drug allergy can be relied upon to rule out Correspondence and offprint requests to: M. J. World BSc, MD, FRCP, Professor of Military Medicine, Royal Army Medical College, 45 Millbank, London SW1P4RJ, UK. interstitial nephritis during oral therapy with these drugs.