TUMOR-NECROSIS-FACTOR-ALPHA AND MICROALBUMINURIA IN PATIENTS WITH INFLAMMATORY BOWEL-DISEASE

Objective: To determine whether tumour necrosis factor-alpha (TNF-alph a) is important in the pathogenesis of microalbuminuria in patients wi th inflammatory bowel disease (IBD). Patients and methods: We measured serum TNF-alpha, interleukin (IL)-6, the erythrocyte sedimentation ra te (ESR), C-reactive protein (CRP) levels and microalbuminuria in 48 p atients with IBD. Serum TNF-alpha was measured by enzyme-linked immuno sorbent assay and microalbuminuria was measured using an immunoturbidi timetric method. Clinical disease activity was quantified using the si mple index of Harvey and Bradshaw. Results: Microalbuminuria was more severe in patients with IBD than in controls, and in patients with act ive versus inactive disease. TNF-alpha levels were higher in patients with IBD than in controls (mean +/- SE 16.4 +/- 1.4 versus 6.6 +/- 1.3 pg/ml, respectively; P < 0.01) and in patients with active versus ina ctive IBD (means+/-SE 20.1+/-2 versus 12.8+/-2.7 pg/ml; respectively P = 0.056). Microalbuminuria correlated strongly with TNF-alpha (r = 0. 60; P < 0.009), ESR (r = 0.67, P < 0.02) and CRP levels (r = 0.935, P < 0.001). TNF-alpha correlated significantly with CRP (r = 0.54, P < 0 .01). IL-6 levels were raised significantly in patients with IBD (7 +/ - 4 pg/ml, controls undetectable; P < 0.05). Patients with active IBD had higher IL-6 levels than those with inactive IBD (mean +/- SE 13 +/ - 8 versus 0.90 +/- 0.35 pg/ml, respectively; P < 0.05). However, IL-6 levels did not correlate with microalbuminuria in patients with IBD ( r = 0.105, P = 0.256). Conclusion: Our findings suggest that TNF-alpha may be important in the pathogenesis of microalbuminuria in patients with IBD, possibly through TNF-induced damage to the glomerular baseme nt membrane. The mechanism for this has not been defined but may relat e to TNF-induced disruption of sulphated glycosaminoglycans.