Effect of An Oral Absorbent AST-120 in Late-stage Chronic Kidney Disease (CKD) Patients.

Recent research work has directed especial attention toward a distinct group of uremic retension molecules, called "protein-bound uremic toxins". The prototypes of this group of uremic toxins are indoxyl sulfate and p-cresol. These uremic toxins can promote production of free radical and impair antioxidant system and exerts direct toxicity on different cells and organs, including mesangial, tubular, endothelial cell and osteoblasts. Accumulation of these protein bound uremic toxins results in glomerular sclerosis and interstitial fibrosis of kidneys of uremic rats and confer skeletal resistance to parthyroid hormone in uremic patients. In hemodialysis, high serum p-cresol level is associated with higher cardiovascular mortality. AST-120 (Kremezin) is a carbonated oral absorbent extensively used in Japan and Korea. It has superior adsorption ability for certain small-molecular weight organic compounds known to accumulate in patients with CKD. In uremic rats and CKD patients, oral administration of AST-120 decreased the elevated pretreatment levels of serum indoxyl sulfate. In Japan, it was reported that AST-120 suppressed the increase in serum creatinine levels, prevented proteinuria, improved uremic symptoms, and, consequently, led to the postponement of dialysis therapy. Value of AST-120 on the outcome of late-stage CKD patients is still unknown. We hypothesized AST-120 through reduction of level of indoxyl sulfate and p-cresol can improved the morbidity- mortality of CKD patients. The principal aim of this prospective cohort study is to investigate the effectiveness of AST-120 in incidence of dialysis and mortality of late-stage CKD patients. Determination of this relationship can help to establish new therapeutic strategy in the treatment of late-stage CKD patients.

Inclusion Criteria: adults aged > 18 year-old or < 85 year-old eGFR or CCR < 60 ml/min hemoglobin < 10 g/dL, ESA-naïve, had adequate iron storage (serum ferritin > 200 ng/dL and transferrin saturation > 20%) no spontaneous renal improvement or progression in past 3 months. Exclusion Criteria: renal transplant recipients, liver cirrhosis, bone marrow disorder blood pressure > 170/80 mmHg in 3 occasions recent cardiovascular disease (Coronary artery disease, myocardial ischemia, cerebrovascular disease or peripheral artery disease) or gastrointestinal bleeding in past 3 months acute tubular necrosis in the past 3 months unwilling to participate in the trial