Renal tubular damage: an extraintestinal manifestation of chronic inflammatory bowel disease

To investigate whether treatment of inflammatory bowel disease (IBD) with 5-aminosalicylate or sulphasalazine in IBD may induce renal tubular damage.

The urinary enzymes beta-N-acetyl-D-glucosaminidase ( beta-NAG), dipeptidylpeptidase 4 (DPP4) and alanine aminopeptidase (AAP) were measured as markers of renal tubular damage in 104 consecutive patients with Crohn's disease and in 43 consecutive patients with ulcerative colitis (all with normal serum creatinine values). Control values were gained from 65 healthy persons.

The normal values (mean +/- SD) for the urinary enzymes investigated (U/g creatinine in the urine) were: DPP4 4.5 +/- 2.2, beta-NAG 1.6 +/- 1.4, AAP 11.4 +/- 6.5. In 28% of the patients with ulcerative colitis elevated beta-NAG levels of more than the mean + 2 x SD were measured. This pathological enzymuria was nearly exclusively found in patients with active disease (CAI > 6): DPP4 15.6 +/- 25.3, beta-NAG 8.3 +/- 10.1, AAP 24.7 +/- 50.1 (all three enzymes were significantly elevated). The highest values were measured in patients with active ulcerative colitis before start of therapy. Nineteen per cent of the patients with Crohn's disease had elevated beta-NAG levels of more than the mean + 2 x SD. There was no significant difference in enzymuria between patients with active (CDAI > 150) and patients with inactive Crohn's disease (CDAI < or = 150). DPP4 and AAP were normal in both groups. A correlation between the enzymuria and the cumulative doses of 5-aminosalicylic acid, sulphasalazine or prednisolone could not be found. The courses of enzymuria in three patients who presented with the first severe manifestation of IBD are described. They were treated with either corticosteroids and 5-aminosalicylic acid or corticosteroids and sulphasalazine. Before onset of therapy, very high urine enzyme values were measured. They almost normalized in the course of successful medical therapy despite increasing cumulative doses of 5-aminosalicylic acid or sulphasalazine.

Renal tubular damage can frequently be observed in IBD. Our results suggest that this is an extraintestinal manifestation of the disease and not a toxic side-effect of anti-inflammatory therapy using 5-aminosalicylic acid or sulphasalazine.