The phase II clinical study of rebamipide (mucosta tablet) on chronic glomerulonephritis patients

Abstract

Background: Activated oxygen species, such as superoxide anion and hydroxyl anion, may be generated in immune-mediated glomerulonephritis and give rise to proteinuria. The proteinuria is thought not only to be a result of glomerular damage but also to lead glomerulonephritis to progressive damage. Rebamipide is known as an antiulcer drug and acts as an oxygen radical scavenger or an antioxidant. So, we examine whether rebamipide could reduce the proteinuria in 19 glomerulonephritis patients. Methods: We administered rebamipide 300mg a day via oral route for 12 weeks to the pathologically diagnosed glomerulonephritis patients with proteinuria more than 1g per day-8 membranous nephritis, 7 membranoproliferative glomerulonephritis(2 primary MPGN, 4 hepatitis B virus-associated glomerulonephritis, 1 Henoch-Scholein nephritis), 2 IgA nephritis, 1 Alport's syndrome, and 1 minimal change renal lesion. We excluded the patients with severe renal dysfunction(creatinine clearance<30ml/min or serum creatinine>1.4mg/dl). We evaluated drug side effects and laboratory tests including amount of daily urine protein, malonaldehyde(MDA) as a indication of activity of oxygen radicals, creatinine clearance, and other blood chemistries every 4 weeks for 12 weeks. We compared the amount of proteinuria and MDA at 12th week to these at initiation for determining the effect of rebamipide on glomeruloneprhitis. We defined improvement of proteinuria as decreased amount of proteinuria over 50%, slight improvement as decreased amount of proteinuria from 25% to 50%, no change as decreased amount of proteinuria less than 25% or increased less than 25%, and deterioration as increased amount of proteinuria over 25%. Before medication, there were 7 patients with nephrotic syndrome, among whom two patients recovered from nephrotic syndrome after 12 weeks medication, and any patient did not progress to nephrotic syndrome during medication. Results: There were 2(11.8%) improvement(in 1 primary MPGN and 1 hepatitis B virus associated MPGN), 5(29.4%) slight improvement(in 3 MNs, 1 IgA nephritis, and 1 Alport's syndrome), 6(35.3%) no change, and 4(23.5%) deterioration of proteinuria among 17 patients whose amount of proteinuria could be evaluated. MDA concentration was decreased over 50% in 3 patients and from 25% to 50% in 6 patients and increased over 25% in 3 patients. We could not found any different laboratory findings among improved, slightly improved, no changed, and deteriorated patients(p>0.05, repeated measured ANOVA and Friedman test). We could not find any side effect related to medication of rebamipide. In conclusion: Rebamipide might be safely used as a drug in trying to reduce amount of proteinuria or MDA in chronic nephritis. But it is requested more patients for verifying certain usefulness of rebamipide as a treatment modality in chronic nephritis.