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

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.

Figure 1

A flow chart of the literature search and study selection.

Figure 2

(a) A forest plot of data from studies of the effect of AST-120 on the serum IS levels in subgroups of animals (diabetic vs. nondiabetic animals with CKD) (sd: standart deviation; n: number; c: comparator (CKD group); e: experimental (CKD-AST-120 group)). (b) A funnel plot of data from studies of the effect of AST-120 on the serum IS levels in animals with CKD.

Figure 3

(a) A forest plot of data from studies of the effect of AST-120 on the serum creatinine levels in animals with CKD (sd: standart deviation; n: number; c: comparator (CKD group); e: experimental (CKD-AST-120 group)). (b) A funnel plot for studies of the effect of AST-120 on the serum creatinine levels in animals with CKD.

Figure 4

(a) A forest plot of data from studies of the effect of AST-120 on creatinine clearance in animals with CKD (sd: standart deviation; n: number; c: comparator (CKD group); e: experimental (CKD-AST-120 group)). (b) A funnel plot for studies of the effect of AST-120 on creatinine clearance in animals with CKD.

Figure 5

(a) A forest plot of data from studies of the effect of AST-120 on the BUN levels in animals with CKD (sd: standart deviation; n: number; c: comparator (CKD group); e: experimental (CKD-AST-120 group)). (b) A funnel plot of data from studies of the effect of AST-120 on the BUN levels in animals with CKD. (c) A bubble plot of data from studies of the effect of the duration of AST-120 treatment on the BUN levels in animals with CKD.

Figure 5

(a) A forest plot of data from studies of the effect of AST-120 on the BUN levels in animals with CKD (sd: standart deviation; n: number; c: comparator (CKD group); e: experimental (CKD-AST-120 group)). (b) A funnel plot of data from studies of the effect of AST-120 on the BUN levels in animals with CKD. (c) A bubble plot of data from studies of the effect of the duration of AST-120 treatment on the BUN levels in animals with CKD.

Figure 6

(a) A forest plot of data from studies of the effect of AST-120 on proteinuria in animals with CKD (sd: standart deviation; n: number; c: comparator (CKD group); e: experimental (CKD-AST-120 group)). (b) A funnel plot of studies of the effect of AST-120 on proteinuria in animals with CKD.

Figure 7

(a) A forest plot of data from studies of the effect of AST-120 on the serum total cholesterol levels in animal model subgroups (diabetic vs. nondiabetic animals with CKD) (sd: standart deviation; n: number; c: comparator (CKD group); e: experimental (CKD-AST-120 group)). (b) A forest plot of data from studies evaluating the effect of AST-120 on the serum total cholesterol levels in animal species subgroups (rat vs. mouse). (c) A forest plot of data from studies evaluating the effect of AST-120 on the serum total cholesterol levels in subgroups of AST-120 doses (1:8% w/w, 2: 4–5% w/w, and 3: 4 g/kg BW). (d) A funnel plot of studies of the effect of AST-120 on the serum total cholesterol levels in animals with CKD.

Figure 7

(a) A forest plot of data from studies of the effect of AST-120 on the serum total cholesterol levels in animal model subgroups (diabetic vs. nondiabetic animals with CKD) (sd: standart deviation; n: number; c: comparator (CKD group); e: experimental (CKD-AST-120 group)). (b) A forest plot of data from studies evaluating the effect of AST-120 on the serum total cholesterol levels in animal species subgroups (rat vs. mouse). (c) A forest plot of data from studies evaluating the effect of AST-120 on the serum total cholesterol levels in subgroups of AST-120 doses (1:8% w/w, 2: 4–5% w/w, and 3: 4 g/kg BW). (d) A funnel plot of studies of the effect of AST-120 on the serum total cholesterol levels in animals with CKD.

Figure 8

(a) A forest plot of data from studies of the effect of AST-120 on the serum triglyceride levels in animals with CKD (sd: standart deviation; n: number; c: comparator (CKD group); e: experimental (CKD-AST-120 group)). (b) A funnel plot of studies of the effect of AST-120 on serum triglyceride levels in animals with CKD.