Improvement of microcirculatory impairment in patients with predialysis chronic kidney disease after AST-120 administration

Abstract

BackgroundEndothelial dysfunction starts at an earlier stage in patients with chronic kidney disease (CKD), and induces macro- and microcirculatory impairments. We evaluated whether uremic toxin-lowering therapy could improve endothelial function in patients with CKD.MethodsWe performed a prospective interventional trial with 30 predialysis non-diabetic CKD patients who were administered oral adsorbent AST-120 (6 g/day) for 12 months. Surrogate markers of endothelial function including flow-mediated dilation (FMD) and skin perfusion pressure (SPP) were serially evaluated along with serum indoxyl sulfate (IS) levels and renal function. Renal function was evaluated based on blood urea nitrogen, serum creatinine (sCr) levels, and estimated glomerular filtration ratio (eGFR).ResultsMonthly decline in renal function (slope of reciprocal sCr) after AST-120 administration did not change compared to that during the pre-treatment period. However, serum IS levels significantly decreased at 3 months after AST-120 administration (p < 0.01), and it was sustained during the period of AST-120 administration (p < 0.01). Although FMD did not improve, SPP was constantly elevated after AST-120 administration, and was significantly higher at 12 months compared with baseline value (69.7 ± 14.6 vs. 78.8 ± 18.9 mmHg, p < 0.05). A significant correlation between the change of IS and SPP from baseline values was shown at 6 months after AST-120 administration (r = − 0.558, p = 0.02).ConclusionMicrocirculatory impairment was improved after AST-120 administration in patients with predialysis CKD.Trial registrationUMIN, UMIN000013577. Registered on March 31, 2014,