Strict control of blood glucose and blood pressure levels sometimes fail to delay the development of diabetic nephropathy, and effective therapy for diabetic nephropathy is not yet available. AST-120, a spherical adsorptive carbon preparation, absorbs uremic toxins, such as indoxyl sulfate, in the gut. Since indoxyl sulfate can generate profibrotic cytokines, the accumulation of uremic toxins is toxic to the kidney. The removal of indoxyl sulfate by the adsorptive carbon should be renoprotective (1). AST-120 decreases circulating indoxyl sulfate in patients with chronic kidney diseases (2). In a nonrandomized study, we sought to determine whether AST-120 can delay the progression of diabetic nephropathy.
We explained the clinical usefulness of AST-120 for diabetic nephropathy to type 2 diabetic outpatients who also had overt proteinuria with increased serum creatinine levels (>1.3 mg/dl), and 2.0 g AST-120 was administered three times a day between meals to those choosing to receive it. Serum creatinine and blood pressure levels were measured every month for 6 months. In control subjects not taking AST-120 (n = 12), serum creatinine levels significantly increased (before 2.50 ± 0.26 mg/dl, after 6 months 3.27 ± 0.34 mg/dl, P < 0.005). In contrast, serum creatinine levels were not changed in AST-120–treated patients (n = 9) (before 2.63 ± 0.36 mg/dl, after 6 months 2.40 ± 0.20 mg/dl, NS). The 1/serum creatinine slope was significantly (P < 0.01) higher in AST-120–treated subjects (0.0043 ± 0.0036 dl · mg−1 · week−1) than in control subjects (−0.0174 ± 0.0043 dl · mg−1 · week−1). AST-120 did not affect HbA1c levels (control subjects: before 7.4 ± 0.2%, after 6 months 7.5 ± 0.2%, NS, vs. AST-120–treated subjects: before 7.0 ± 0.4%, after 6 months 6.8 ± 0.4%; NS) or systolic and diastolic blood pressure levels (control subjects: before 136.4 ± 4.9/67.0 ± 4.4 mmHg, after 6 months 136.1 ± 3.6/70.9 ± 1.9 mmHg, NS, vs. AST-120–treated subjects: before 131.5 ± 4.3/63.8 ± 5.5 mmHg, after 6 months 130.3 ± 2.5/69.8 ± 3.0 mmHg, NS).
Since AST-120 in the gut did not adsorb creatinine in the blood, and there is no exchange of serum creatinine levels between the gut and blood (3), the observed attenuation of increase of serum creatinine levels by AST-120 should not be attributable to the excretion of creatinine into the feces. Although the results are limited because of the nonrandomized self-selection study design, our findings indicate that AST-120 should contribute to the delay of the development of renal dysfunction in type 2 diabetic patients.
