Role for “uremic toxin” in the progressive loss of intact nephrons in chronic renal failure

Abstract

We studied the effect on the progression of glomerular sclerosis of two different experimental maneuvers, peritoneal dialysis and oral adsorbent, which remove circulating substances in different fashions. Munich-Wistar rats with established glomerular sclerosis, verified by renal biopsy analysis at seven weeks after subtotal nephrectomy, were treated for four weeks with either peritoneal dialysis (PD) or oral charcoal adsorbent (AST-120). Treatment was initiated at eight weeks. Rats were paired in treatment and control groups according to the similarity in the degree of sclerosis determined at biopsy with a minimum of 50 glomeruli analyzed. Systolic blood pressure and BUN and creatinine clearance, measured at seven to eight weeks, were not different among groups. In Group 2 rats, PD was performed with 1.5% dextrose for eight one-hour cycles, six days per week, while Group 1 control rats had zero indwelling time of the dialysate. Group 4 rats received AST-120, an oral adsorbent charcoal, mixed 5% by weight with standard rat chow and given ad libitum from 8 to 12 weeks after subtotal nephrectomy, while control Group 3 rats received only rat chow. Whole kidney GFR at 12 weeks was significantly higher in Group 2 PD versus Group 1 control (0.50 +/- 0.08 vs. 0.30 +/- 0.05 ml/min, P less than 0.05). There was no statistical difference for BUN and whole kidney creatinine or inulin clearance in Group 4 AST-120 treated versus Group 3 control rats. Light microscopic studies in autopsy specimens revealed that both PD and AST-120 attenuated progression of glomerular sclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Quenching of Nitric Oxide by an Oral Carbonaceous Adsorbent.

“…It has been shown to adsorb uremic molecules by an enteral exchange of molecules through the epitheli um. The agent is not absorbed or decomposed during the passage through the gastrointestinal tract, does not affect digestive enzymes, and is excreted unaltered when orally administered (4). These characteristics of AST-120 have shown to be advantageous over conventional charcoal powder for use as a luminal adsorbent for uremic toxins.…”

“…Carbonaceous molecules such as activated charcoal are an adsorbent of gaseous and non-gaseous molecules (2). AST-120 (Cremedin®), which consists of spherical porous car bonaceous particles with a diameter of 0.2 to 0.4 mm, has been used clinically as an enteral adsorbent of uremic toxins in progressive renal disease (3,4). We hypothesized that such a non-specific adsorbent may quench NO be cause AST-120 is an analog of activated charcoals that are widely used as an adsorbent of NOX in industry.…”

Molecular Mechanisms and Therapeutic Strategies of Chronic Renal Injury: The Role of Nuclear Factor κB Activation in the Development of Renal Fibrosis

“…Circulating uremic toxins, such as indoxyl sulfate, are proposed to be involved in the progression of chronic renal failure (CRF) (18). Oral carbonaceous adsorbent, AST-120 (Kremezin ® ), removes uremic toxins by interfering with intestinal absorption of uremic toxins and their precursors (such as indole) (19) and retards the progression of CRF in uremic rats (20).…”

An Oral Adsorbent, AST-120 Protects Against the Progression of Oxidative Stress by Reducing the Accumulation of Indoxyl Sulfate in the Systemic Circulation in Renal Failure

“…The toxin is thought to be involved in the progression of CRF because it is present in high levels in the serum of patients with CRF and causes tubulointerstitial injuries in rodent models (12,13). Several researchers have recently reported that IS has the potential to produce oxidative stress in renal proximal tubular cells and mesangial cells (10,14).…”