FP457EFFECT OF AN ORAL ADSORBENT AST-120 ON GLOMERULAR AND TUBULAR INJURY IN METABOLIC SYNDROME/DIABETES RATS

Abstract

Introduction and Aims: Metabolic syndrome is known to be an important risk factor involved in the development of diabetic nephropathy which is a major complication of diabetes and the leading cause of end-stage renal disease. An oral adsorbent AST-120 has been used clinically as a medicine for patients with chronic kidney disease (CKD) to slow down the progression of CKD. However, there is little evidence to support therapeutic efficacy of AST-120 for early stage overt diabetic nephropathy. In this study, we aimed to assess the effect of AST-120 on SHR/NDmcr-cp rats, model rats of metabolic syndrome/ type 2 diabetes. Methods: Male SHR/NDmc-cp (SHR/ND) rats, aged 7 weeks, were administered 0% or 8% AST-120 for 12 weeks in their diets. WKY rats were used as a normal. At every 4 weeks, serum and 24-hour urine samples were collected for biomedical studies. We also investigated the dose-response effect of AST-120 administered at 0%, 1%, 2%, 4% and 8% for SHR/ND rats. The podocyte foot process width (FPW) was measured by Transmission Electron Microscopy as foot process effacement. Monocyte/macrophage infiltration in renal tissues and tubular injury was investigated by ED-1 staining and kidney injury molecule-1 (KIM-1) staining. Results: 8% AST-120-administered SHR/ND rats showed significantly lower levels of urinary protein excretion, urinary albumin excretion, and the FPW as compared with SHR/ND rats. AST-120 also reduced the urinary protein excretion and urinary albumin excretion in a dose-dependent manner. The FPW was significantly correlated with the levels of urinary protein excretion (r = 0.9498) and urinary albumin excretion (r = 0.9532). The number of ED-1 positive cells and KIM-1 positive area in renal tissues were reduced by the administration of AST-120. Conclusions: These results indicate that the administration of AST-120 at an early stage of diabetic nephropathy has a protective effect on the disease progression.