Predictive Factors for Efficacy of AST-120 Treatment in Diabetic Nephropathy: a Prospective Single-Arm, Open-Label, Multi-Center Study

J Korean Med Sci. 2019 Apr 22;34(15):e117. doi: 10.3346/jkms.2019.34.e117.

Abstract

Background: Removal of uremic toxins such as indoxyl sulfate by AST-120 is known to improve renal function and delay the initiation of dialysis in patients with advanced chronic kidney disease. However, it is unclear whether the addition of AST-120 to conventional treatments is effective in delaying the progression of renal dysfunction in patients with diabetic nephropathy.

Methods: A total of 100 patients with type 2 diabetes and renal dysfunction (serum creatinine levels ranging from 1.5 to 3.0 mg/dL) were recruited from eight centers in Korea and treated with AST-120 (6 g/day) for 24 weeks. The primary endpoint was improvement in renal function measured as the gradient of the reciprocal serum creatinine level (1/sCr) over time (i.e., the ratio of 1/sCr time slope for post- to pre-AST-120 therapy). A response was defined as a ratio change of the regression coefficient of 1/sCr ≤ 0.90.

Results: Renal function improved in 80.3% of patients (61/76) after 24 weeks of AST-120 treatment. There were no differences between responder and non-responder groups in baseline characteristics except for diastolic blood pressure (73.5 ± 9.5 mmHg in the responder group vs. 79.3 ± 11.1 mmHg in the non-responder group; P = 0.046). Serum lipid peroxidation level decreased significantly in the responder group (from 2.25 ± 0.56 μol/L to 1.91 ± 0.72 μol/L; P = 0.002) but not in the non-responder group.

Conclusion: The addition of AST-120 to conventional treatments may delay the progression of renal dysfunction in diabetic nephropathy. The antioxidant effect of AST-120 might contribute to improvement in renal function.

Keywords: Antioxidants; Creatinine; Diabetic Nephropathy; Indoxyl Sulfate; Oxidative Stress.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Blood Pressure
  • Carbon / therapeutic use*
  • Creatinine / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / pathology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Lipid Peroxidation
  • Male
  • Middle Aged
  • Oxides / therapeutic use*
  • Prospective Studies
  • Protective Agents / therapeutic use*
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Oxides
  • Protective Agents
  • Carbon
  • AST 120
  • Creatinine