Abstract
A potent aldose reductase inhibitor, ONO-2235 (Ono Pharmaceuticals, Osaka, Japan) helps prevent peripheral nerve dysfunction in diabetes mellitus. To determine whether this compound is effective against diabetic renal damage, we compared urinary albumin excretion measured by radioimmunoassay and urinary N-acetyl-β-D-glucosaminidase (NAG) activity before and after treatment with ONO-2235. Urinary albumin excretion and NAG activity were measured twice with an interval of 5 months in diabetic patients without clinical proteinuria as determined with a reagent strip test. Fifteen patients who had both high urinary albumin excretion and high NAG activity in the two assays were given 150 mg of ONO-2235 daily by mouth for 8 weeks. The urinary albumin level significantly decreased in 11 patiens whose level was 200 mg per gram of creatinine or less 8 weeks after the treatment started (74.4±57.3 vs. 19.5±16.9 mg/g of creatinine, mean±SD, p<0.02). Four weeks after the treatment ended, urinary albumin excretion was measured in 7 of these patients, and each showed an elevation in urinary albumin which had been decreased by the aldose reductase inhibitor. However urinary albumin in 4 patients with albuminuria of over 200 was not decreased 8 weeks after the treatment started.
There was no significant difference in urinary NAG before and after treatment (10.4±3.6 vs. 11.8±4.8 U/g of creatinine). Neither fasting blood glucose nor hemoglobin A1c changed during the study.
These results suggest that impaired polyol metabolism may participate in the development of diabetic renal disease and that aldose redutase inhibitor may be effective against diabetic renal damage.
