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Kidney Week

Abstract: TH-PO446

Oral Adsorbent AST-120 Improves Microcirculatory Impairment in Patients with CKD

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Ohtake, Takayasu, Shonan Kamakura General Hospital, Kamakura, KANAGAWA, Japan
  • Mochida, Yasuhiro, Shonan Kamakura General Hospital, Kamakura, KANAGAWA, Japan
  • Ishioka, Kunihiro, Shonan Kamakura General Hospital, Kamakura, KANAGAWA, Japan
  • Moriya, Hidekazu, Shonan Kamakura General Hospital, Kamakura, KANAGAWA, Japan
  • Hidaka, Sumi, Shonan Kamakura General Hospital, Kamakura, KANAGAWA, Japan
  • Kobayashi, Shuzo, Shonan Kamakura General Hospital, Kamakura, KANAGAWA, Japan
Background

Microcirculatory impairment plays an important role at an earlier stage for peripheral arterial disease (PAD) in patients with chronic kidney disease (CKD). To treat PAD as early as possible is mandatory to avoid lower limbs’ amputation. Therefore, we evaluated whether uremic toxin-lowering therapy could improve microcirculatory impairment in patients with CKD.

Methods

Oral charcoal adsorbent AST-120 (Kremezin, Kureha Corporation, Tokyo, Japan) adsorbs indole, a precursor of indoxyl sulfate (IS), in the gastrointestinal tract so that IS does not accumulate in the body. We performed a prospective interventional clinical trial whether AST-120 could improve atherosclerotic surrogates in CKD patients (UMIN no. 000013577). As a primary endpoint, skin perfusion pressure (SPP) of lower limbs, and flow mediated dilation (FMD) were evaluated as surrogate of microcirculatory and macrocirculatory status, respectively. They were evaluated at baseline, 3, 6, and 12 months after AST-120 administration. Serum levels of total IS (free IS and protein-binding IS) and renal function (serum creatinine (sCr), 1/sCr) were also evaluated at baseline, 3, 6, and 12 months after AST-120 administration. Total IS was evaluated using HPLC method and expressed as μM.

Results

We enrolled 30 non-diabetic CKD patients (CKD stage; G3a (n=4), G3b (n=9), G4 (n=14), and G5 (n=3)), and AST-120 6 gram/ day was orally administered for 12 months. Serum creatinine (sCr) levels and 1/sCr at baseline were 2.03±0.85 mg/dL and 0.578±0.226 dL/mg (mean±SD), respectively.
Monthly decline in renal function (slope of 1/sCr) after AST-120 administration did not change compared to that in pre-treatment period. However, serum total IS significantly decreased at 3 months after AST-120 administration (baseline: 11.7±8.6 μM to 3 months: 6.9±5.0 μM, p<0.01). Serum IS levels continued to be decreased for 12 months (p<0.01). Although FMD did not change during study period, SPP values in lower limbs constantly elevated, and was significantly improved at 12 months after AST-120 administration compared to baseline values (69.7 ± 14.6 vs. 78.8 ± 18.9 mmHg, p<0.05).

Conclusion

IS-lowering therapy significantly improved micro-circulatory impairment in non-diabetic pre-dialysis CKD patients.