Oral adsorbent AST-120 potentiates the effect of erythropoietin-stimulating agents on Stage 5 chronic kidney disease patients: a randomized crossover study

BACKGROUND: Indoxyl sulfate (IS) suppresses erythropoietin (EPO) activity and exerts renal damage. The oral adsorbent AST-120 reduces IS load and has antioxidant and renoprotective properties; however, its roles in the treatment of anemia remain unclear in chronic kidney disease (CKD) patients. METHODS: Fifty-one Stage 5 predialysis CKD patients with hemoglobin <10 g/dL were randomly assigned to receive two period treatments with AST-120 plus once-monthly administration of continuous EPO receptor activator (CERA, A) and CERA alone (B), with a 4-week washout period in between. Mean changes of serum creatinine, estimated glomerular filtration rate (eGFR) and hemoglobin levels from the baseline were compared between two treatments. RESULTS: The baseline and postintervention mean creatinine levels were 5.48 and 5.36 mg/dL in the Treatment A, and 5.14 mg/dL and 5.61 g/dL in the Treatment B group, respectively (treatment effect P = 0.025, period effect P = 0.467, carryover effect P = 0.384). The baseline and postintervention mean hemoglobin levels were 9.27 and 10.47 g/dL in the Treatment A, and 9.63 g/dL and 9.54 g/dL in the Treatment B group, respectively (treatment effect P = 0.039, period effect P = 0.001, carryover effect P = 0.060). Use of AST-120 significantly reduced IS and p-cresyl sulfate (PCS) levels. Hierarchical regression showed that eGFR was an independent predictor for hemoglobin after adjustment of serum free IS and PCS levels (B = 0.049, P = 0.005). CONCLUSIONS: Use of adjuvant AST-120 may improve renal function and hemoglobin levels than use of CERA alone in late-stage CKD patients. The change of eGFR might play an intermediate role between serum IS/PCS and improve hemoglobin levels. The finding offered insight into novel therapeutic strategies of anemia for late-stage CKD patients.