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 todetect this complication are not known. The value of immunosuppressionin addition to drug withdrawal is similarly undetermined. METHODS.: Four cases of interstitial nephritis which occurred in associationwith oral Asacol treatment are presented and a further 12 caseswho received similar treatment are reviewed. Clinical trialspublished previously were scrutinized to assess the frequencyof impaired renal function. RESULTS.: The available evidence suggests that renal impairment of anyseverity may occur in up to 1 in 100 patients, but that clinicallysignificant interstitial nephritis occurs in less than 1 in500 patients. This is most reliably detected by an elevatedserum creatinine concentration. If the diagnosis of nephrotoxicityis delayed until 18 months after commencement of medication,restoration of renal function, which is seen on withdrawal ofmedication alone up to 10 months, does not occur and there isno evidence to date to indicate that addition of immunosuppressionconfers any significant advantage at this later stage. CONCLUSIONS.: It is suggested that serum creatinine concentration should bemeasured each month for the first 3 months of treatment, 3-monthlyfor the remainder of the first year and annually thereafter.The use of concurrent immunosuppressive therapy may necessitateextension to the period of intensive monitoring. Any elevationof serum creatinine which cannot be related to a relapse ofinflammatory bowel disease should prompt immediate withdrawalof Asacol and related medications and substitution of alternativetherapy. Neither the lack of urinary abnormalities on routinetesting nor the absence of clinical or laboratory features ofdrug allergy can be relied upon to rule out interstitial nephritisduring oral therapy with these drugs.