Division of Nephrology, Department of Internal Medicine, Shinmatsudo Central General Hospital, Chiba 270-0034, Japan.
Metabolism. 2011 Feb;60(2):260-4. doi: 10.1016/j.metabol.2010.01.023. Epub 2010 Mar 1.
AST-120 is an oral adsorbent that attenuates the progression of chronic renal failure (CRF) and improves the prognosis of the patients under dialysis. Although tubulointerstitial injury is more important than glomerulopathy in terms of renal prognosis in patients with CRF, effect of AST-120 on tubular injury in CRF patients remains unknown. In this study, we examined whether and how AST-120 treatment could improve tubular damage in nondiabetic CRF patients. Fifty nondiabetic CRF patients were enrolled in the present study and divided into 2 groups: one was the AST-120-treated group (15 men and 10 women) and the other was the age-, sex-, and clinical variables-matched non-AST-120-treated control group. Patients were followed up for 12 months. We investigated the effects of AST-120 on serum levels of interleukin-6 (IL-6), proteinuria, and urinary excretion levels of 8-hydroxydeoxyguanosine (8-OHdG) and L-fatty acid binding protein (L-FABP), markers of oxidative stress and tubular injury, respectively. AST-120 treatment (6 g/d), but not control treatment, for 12 months significantly reduced IL-6, proteinuria, and urinary excretion levels of L-FABP and 8-OHdG, and inhibited the increase in serum creatinine in CRF patients. In univariate analyses, L-FABP levels were correlated with age, proteinuria, 8-OHdG, and IL-6. In multiple stepwise regression analysis, proteinuria and urinary 8-OHdG levels were independently related to L-FABP levels (R² = 0.605). Our present study demonstrated for the first time that AST-120 improved tubular injury in nondiabetic CRF patients. AST-120 may exert beneficial effects in CRF patients by protecting tubular damage partly via reduction of proteinuria and oxidative stress generation.
AST-120 是一种口服吸附剂,可减缓慢性肾衰竭(CRF)的进展并改善透析患者的预后。尽管在 CRF 患者的肾脏预后方面,肾小管间质性损伤比肾小球病变更为重要,但 AST-120 对 CRF 患者肾小管损伤的影响尚不清楚。在这项研究中,我们研究了 AST-120 治疗是否以及如何改善非糖尿病 CRF 患者的肾小管损伤。本研究共纳入 50 例非糖尿病 CRF 患者,分为 AST-120 治疗组(15 例男性,10 例女性)和年龄、性别和临床变量匹配的非 AST-120 治疗对照组。患者随访 12 个月。我们研究了 AST-120 对血清白细胞介素 6(IL-6)、蛋白尿以及尿液 8-羟基脱氧鸟苷(8-OHdG)和 L-脂肪酸结合蛋白(L-FABP)排泄水平的影响,这分别是氧化应激和肾小管损伤的标志物。AST-120 治疗(6 g/d)而非对照组治疗 12 个月后,可显著降低 CRF 患者的 IL-6、蛋白尿、L-FABP 和 8-OHdG 的尿液排泄水平,并抑制血清肌酐的增加。在单因素分析中,L-FABP 水平与年龄、蛋白尿、8-OHdG 和 IL-6 相关。在多元逐步回归分析中,蛋白尿和尿液 8-OHdG 水平与 L-FABP 水平独立相关(R²=0.605)。本研究首次表明,AST-120 可改善非糖尿病 CRF 患者的肾小管损伤。AST-120 通过减少蛋白尿和氧化应激的产生,可能对 CRF 患者发挥有益作用,从而部分保护肾小管损伤。