Schulman Gerald, Berl Tomas, Beck Gerald J, Remuzzi Giuseppe, Ritz Eberhard, Shimizu Miho, Kikuchi Mami, Shobu Yuko
Vanderbilt University School of Medicine, Nashville, TN, USA.
University of Colorado Health Sciences Center, Denver, CO, USA.
Clin Exp Nephrol. 2018 Apr;22(2):299-308. doi: 10.1007/s10157-017-1447-0. Epub 2017 Jul 24.
Two randomized, double-blind, placebo-controlled trials (EPPIC-1 and EPPIC-2) investigated the efficacy and safety of AST-120, an oral spherical carbon adsorbent, in adults with chronic kidney disease (CKD). While the benefit of adding AST-120 to standard therapy was not supported by these trials, we performed a post hoc analysis to focus on CKD progression and to determine the risk factors for the primary endpoint in the EPPIC trial population.
In the EPPIC trials, patients were randomly assigned 1:1 to treatment with AST-120 or placebo. The primary endpoint was a composite of dialysis initiation, kidney transplantation, or doubling of serum creatinine. The EPPIC trial pooled population was evaluated with the same statistical methods used for analysis of the primary and secondary efficacy endpoints. The trials were registered on ClinicalTrials.gov (NCT00500682 [EPPIC-1] and NCT00501046 [EPPIC-2]).
An analysis of the placebo population suggested baseline urinary protein to urinary creatinine ratio (UP/UCr) ≥1.0 and hematuria were independent risk factors for event occurrence and eGFR lowering. Analysis of the high risk patients revealed a difference in the primary endpoint occurrence between treatment groups, if angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers were administered (hazard ratio 0.74, 95% confidence interval 0.56-0.96). Also, the eGFR changes from baseline in the AST-120 group were smaller than that in the placebo group (P = 0.035).
CKD progression may have an association with baseline UP/UCr and hematuria. Treatment with AST-120 may delay the time to the primary endpoint in patients with progressive CKD receiving standard therapy, thus warranting further investigation.
两项随机、双盲、安慰剂对照试验（EPPIC - 1和EPPIC - 2）研究了口服球形碳吸附剂AST - 120对慢性肾脏病（CKD）成人患者的疗效和安全性。虽然这些试验未支持在标准治疗基础上加用AST - 120的益处，但我们进行了一项事后分析，重点关注CKD的进展情况，并确定EPPIC试验人群中主要终点的危险因素。
在EPPIC试验中，患者按1:1随机分配接受AST - 120或安慰剂治疗。主要终点是透析开始、肾移植或血清肌酐翻倍的复合终点。EPPIC试验汇总人群采用与主要和次要疗效终点分析相同的统计方法进行评估。这些试验已在ClinicalTrials.gov上注册（NCT00500682 [EPPIC - 1]和NCT00501046 [EPPIC - 2]）。
对安慰剂组人群的分析表明，基线尿蛋白与尿肌酐比值（UP/UCr）≥1.0和血尿是事件发生和估算肾小球滤过率（eGFR）降低的独立危险因素。对高危患者的分析显示，如果给予血管紧张素转换酶抑制剂和/或血管紧张素受体阻滞剂，治疗组之间主要终点的发生率存在差异（风险比0.74，95%置信区间0.56 - 0.96）。此外，AST - 120组中eGFR相对于基线的变化小于安慰剂组（P = 0.035）。
CKD的进展可能与基线UP/UCr和血尿有关。在接受标准治疗的进展性CKD患者中，AST - 120治疗可能会延迟达到主要终点的时间，因此值得进一步研究。
