Severe sepsis is known to cause multiple organ failure, including renal dysfunction. During sepsis, endotoxin targets the renal proximal tubular cells, the function of which can be evaluated on the basis of urinary N-acetyl-beta-glucosaminidase (NAG). We investigated whether urinary NAG activity is altered in patients with severe sepsis and whether treatment with polymyxin B immobilized fibers (PMX-F) affects this activity. Subjects of this study were 120 patients with severe sepsis and 60 healthy volunteers matched for age and gender. Patients were randomly assigned to one of two treatments: PMX-F treatment (n = 70) or conventional treatment (n = 50). The plasma endotoxin level was significantly reduced, from 34.6 +/- 10.2 to 6.8 +/- 2.4 pg/ml (p < 0.01) in patients treated with PMX-F, and the urinary NAG/creatinine ratio was reduced from 46.5 +/- 26.8 U/gm to 18.6 +/- 13.6 U/gm (p < 0.01). The plasma endotoxin level and urinary NAG/creatinine ratio were unchanged in patients who received conventional treatment. The increased urinary NAG/creatinine ratio in patients with severe sepsis may reflect proximal tubular dysfunction. PMX-F is effective in reducing proximal tubular dysfunction, in part owing to reduced plasma endotoxin levels.