The Ability of AST-120 to Lower the Serum Indoxyl Sulfate Level Improves Renal Outcomes and the Lipid Profile in Diabetic and Nondiabetic Animal Models of Chronic Kidney Disease: A Meta-Analysis

Toxins (Basel). 2024 Dec 16;16(12):544. doi: 10.3390/toxins16120544.

Abstract

The therapeutic benefit of the oral adsorbent drug AST-120 in chronic kidney disease (CKD) is related to an indoxyl sulfate (IS)-lowering action. Diabetes and dyslipidemia might worsen kidney damage in CKD. However, it is not known whether AST-120 influences lipid abnormalities as well as renal function in patients with CKD and diabetes. The objective of the present meta-analysis was to evaluate the efficacy of AST-120 treatment in CKD using data from preclinical studies. Mixed-effect or random-effect models were used to estimate the standardized mean difference (SMD) and the 95% confidence interval (CI). Publication bias was assessed with a funnel plot and Egger's test. The potential influence of some variables (the dose and duration of AST-120 treatment, the animal species, and the CKD model's diabetic status) was evaluated in subgroup analyses. Treatment with AST-120 was associated with a significantly lower IS level in animals with CKD (SMD = -1.75; 95% CI = -2.00, -1.49; p < 0.001). Significant improvements in markers of renal function and the lipid profile were also observed. In subgroup analyses of the cholesterol level, the diabetic status, the AST-120 dose, and the animal species were found to be influential factors. AST-120 lowered serum IS and triglyceride levels and improved renal function in animal models of CKD independent of diabetes status. However, AST-120's ability to lower the total cholesterol level was more prominent in animals with diabetic CKD.

Keywords: AST-120; cholesterol; chronic kidney disease; diabetes; indoxyl sulfate; meta-analysis; mouse; rat; renal function markers; triglyceride.

Publication types

  • Meta-Analysis

MeSH terms

  • Animals
  • Carbon*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / drug therapy
  • Disease Models, Animal
  • Humans
  • Indican* / blood
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / physiopathology
  • Lipids* / blood
  • Oxides* / therapeutic use
  • Renal Insufficiency, Chronic* / blood
  • Renal Insufficiency, Chronic* / drug therapy
  • Silicon / pharmacology
  • Silicon / therapeutic use

Substances

  • AST 120
  • Indican
  • Oxides
  • Carbon
  • Lipids
  • Silicon