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 creatinine 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 micromol/L to 88.7 micromol/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).


CONCLUSIONS
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.
Patel
H
H
University of Toronto, Toronto, Canada.
Barr
A
A
Jeejeebhoy
K N
KN