Tranilast Slows the Progression of Advanced Diabetic Nephropathy

Abstract

Background: Tranilast, N-(3,4-dimethoxycinnamoyl) anthranilic acid, suppresses collagen synthesis by various cells, including macrophages and fibroblasts, by interfering with the actions of transforming growth factor-beta 1. We investigated the effect of tranilast on progression of diabetic nephropathy (DN), since this process is associated with accumulation of collagens in the glomerulus and interstitium. Methods: Tranilast (100 mg, 3 times daily) was administered to 9 outpatients with advanced DN who were receiving an angiotensin-converting enzyme inhibitor or an angiotensin II receptor antagonist and who exhibited a progressive decline in renal function. The decline in renal function before and during tranilast treatment was evaluated for each patient on the basis of the slope in reciprocal serum creatinine (1/S_Cr) over time. Urinary type IV collagen (U-IV·C) and protein (U-P) excretions were measured just before commencement of tranilast treatment and every 2 months during the treatment. Results: One male patient dropped out soon after commencement of tranilast treatment due to development of lung cancer, and hemodialysis was introduced in one female patient 6 months after the start of treatment. In the 8 patients who did not drop out, 1/S_Cr was significantly less steep during tranilast treatment than before treatment (–0.00748 ± 0.00700 vs. –0.01348 ± 0.00636 dl/mg/month, respectively; p = 0.0374). U-IV·C and U-P tended to decrease with time, although the decrease was statistically insignificant. Conclusions: Our data suggest that tranilast treatment may suppress accumulation of collagens in renal tissue and may be therapeutically useful for reducing the progression of advanced DN.