Renal Effects of Long-Term Treatment with 5-Aminosalicylic Acid
BACKGROUND: A number of case reports link the use of 5-aminosalicylic acid (5-ASA) to interstitial nephritis in patients with inflammatory bowel disease (IBD).OBJECTIVE: To investigate whether the long-term use of 5-ASA has harmful effects on renal function in patients with IBD.METHODS: A retrospective analysis of 171 consecutive outpatients with Crohn’s disease or ulcerative colitis was conducted. Serum creati-nine levels and body weight were measured before and after treatment to calculate the creatinine clearance (CrCl) rate.RESULTS: In 171 patients (93 women, 78 men), the mean (± SD) dose of 5-ASA was 3.65±0.85 g/day with a cumulative dose of 11±7.7 kg over an interval of 8.4±5.9 years. Serum creatinine concentrations increased from 76.8 μmol/L to 88.7 μmol/L (n=171; P<0.0001) and the CrCl rate fell significantly from 104.6 mL/min to 93.1 mL/min (n=81; P<0.0001). There was one case of interstitial nephritis reported. Treatment groups included mesalamine (74.3%), sulfasalazine (15.2%) and combination (sulfalsalazine/mesalamine [10.5%]) with treatment durations of 7.2±4.5, 12.3±8.7 and 11.2±6.7 years, respectively. The duration of treatment was the most important covariate for change in CrCl and when analyzed by treatment group, those treated with sulfasazine had a strong correlation (r=−0.54, P=0.0145), while nonsignificant in the mesalamine group (r=0.06, P=0.7017). The decline in CrCl was negatively correlated with the pretreatment CrCl rate (r=−0.34; P=0.0024) and positively correlated with the mean daily dose of 5-ASA (r=0.32; P=0.0034).CONCLUSION: The present study is the first to demonstrate a significant dose- and treatment duration-dependant decline in CrCl. The risks need to be further evaluated because 5-ASA is widely used for long-term maintenance therapy in patients with IBD.