RENAL TUBULAR DYSFUNCTION IN PATIENTS WITH INFLAMMATORY BOWEL-DISEASETREATED WITH AMINOSALICYLATE

Background-An increasing number of case reports indicate potential nep hrotoxicity of 5-aminosalicylic acid (5-ASA), which shares similaritie s with the chemical structures of both phenacetin and acetylsalicylic acid. Aim-In a point prevalence study the occurrence of sensitive indi ces indicative of early kidney malfunction was assessed in outpatients with inflammatory bowel disease. Methods-Routine indices of kidney fu nction (creatinine clearance, urinary protein content, pH, electrolyte , and microscopy) were investigated in 223 patients with inflammatory bowel disease as well as sensitive markers of glomerular or tubular dy sfunction (microproteinuria by SDS polyacrylamide gel electrophoresis (SDS-PAGE), urinary concentrations of N-acetyl-beta-D-glucosaminidase, alpha 1-microglobulin, gamma-glutamyltransferase (GGT), alkaline phos phatase (AP), and albumin). Histories of exposure to 5-ASA were assess ed by questionnaire.Results-Patients receiving high amounts of 5-ASA, both actual as well as on a lifetime basis, showed an increased preval ence of tubular proteinuria by SDS-PAGE. Raised values for urinary AP and GGT indicate proximal tubular epithelial cells as the source. Ail other kidney function tests were normal. Analysis of covariates indica ted strong associations between disease activity and size of 5-ASA dos es as well as alterations in kidney tubular function. Conclusion-The p ossibility exists that high doses of 5-ASA may be associated with prox imal tubular proteinuria. This point prevalence study cannot dissect t he possible impact of chronic inflammation from high dose 5-ASA treatm ent and further prospective studies are warranted.