An oral adsorbent downregulates renal expression of genes that promote interstitial inflammation and fibrosis in diabetic rats.

BACKGROUND/AIMS: An oral adsorbent, AST-120, removes uremic toxins such as indoxyl sulfate, and delays the progression of renal failure. This study was designed to investigate the effects of AST-120 on the molecular basis of interstitial inflammation and fibrosis, using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of non-insulin-dependent diabetes mellitus.

METHODS

Four weeks after unilateral nephrectomy, the uninephrectomized OLETF (1/2NxOLETF) rats were divided into two groups: AST-120-administered and control 1/2NxOLETF rats. After the administration of AST-120 for 48 weeks, we examined the effects of AST-120 on renal functional, pathological, and gene expressional changes.

RESULTS

The administration of AST-120 to the 1/2NxOLETF rats attenuated the progression of renal dysfunction, proteinuria, glomerular sclerosis, tubular injury, and interstitial inflammation and fibrosis. AST-120 significantly reduced renal expression of intercellular adhesion molecule (ICAM)-1, osteopontin, monocyte chemotactic protein (MCP)-1, and transforming growth factor (TGF)-beta1, as well as clusterin. All the five molecules were expressed mainly in tubular cells. AST-120 also decreased serum and urinary levels of indoxyl sulfate and the overload of indoxyl sulfate in tubular cells.

CONCLUSIONS

AST-120 ameliorates tubulointerstitial injury by reducing renal expression of ICAM-1, osteopontin, MCP-1, TGF-beta1 and clusterin in 1/2NxOLETF rats.