Effect of a carbonaceous adsorbent on the progression of CKD

Background: AST-120 (Kureha Chemical, Tokyo, Japan) is an oral spherical carbonaceous adsorbent, which was approved for use in delaying the initiation of dialysis and ameliorating the symptoms of uremia in patients with progressive chronic kidney disease (CKD). It adsorbs the precursor of indoxyl sulfate in the intestines and prevents indoxyl sulfate production. Indoxyl sulfate, initially identified as a major uremic toxin that causes uremic symptoms, contributes to CKD progression. Although international multicenter prospective trials of AST-120 did not slow progression of CKD in patients with moderate to severe CKD, present study evaluated the efficacy of AST-120 in preventing the progression of CKD and its indication in our Japanese cohort. Methods: Antihypertensive therapy using renin-angiotensin-aldosterone inhibitor (RAS-i) and a low-protein diet is conventionally used to treat patients with CKD. We retrospectively recruited 218 patients with CKD treated with AST-120 from 2014 to 2015. Changes of serum levels of blood urea nitrogen (BUN) and eGFR were analyzed for 4 years, from 1 year before medication. Moreover, we elucidated the recommended timing of initiation of AST-120 administration. Results: The mean eGFR and BUN at the baseline were 24.1 ml/min/1.73m2 and 35.9 mg/dL, respectively. Decline of eGFR before AST-120 treatment was -4.9 ml/min/1.73m2/ year. After 1-year and 3-year medication with AST-120, the decline of eGFR was significantly improved to -0.7 and -0.9 ml/min/1.73m2/year, respectively. Increase slope of BUN also improved +4.7 to +1.9 mg/dl/year after 3-year administration with AST-120. We next divided patients into 3 groups depending on baseline eGFR, i.e., >50 eGFR ≥40, >40 eGFR ≥30 and eGFR<30 ml/min/1.73m2 groups. The effect of AST-120 to prevent progression of CKD was the highest in >50 eGFR ≥40 group in which decline of eGFR was -9.9 to -1.2 ml/min/1.73m2/year during intervention period. Conclusions: Present study suggests that treatment with AST-120 may delay progression of CKD. Especially, AST-120 administration is recommended to initiate relatively maintained renal function (>50 eGFR ≥40). Those findings provided insight into management of CKD patients.