Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand.
Research Unit for Metabolic Bone Disease in CKD Patients, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
J Nephrol. 2021 Dec;34(6):1805-1817. doi: 10.1007/s40620-020-00955-2. Epub 2021 Jan 23.
Accumulation of protein-bound uremic toxins, including indoxyl sulfate and p-cresyl sulfate, are associated with increased cardiovascular disease and mortality in chronic kidney disease (CKD). We performed a systematic review and meta-analysis to synthesize the available strategies for lowering protein-bound uremic toxin levels in CKD patients.
We conducted a meta-analysis by searching the databases of MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials for observational studies and randomized controlled trials (RCTs) that examined the effect of dietary protein restrictions, biotic supplements (including prebiotics, probiotics, and synbiotics), AST-120, dialysis techniques, and the outcome of preservation of residual renal function (RRF) on indoxyl sulfate and p-cresyl sulfate levels. Random-effect model meta-analyses were used to compute changes in the outcomes of interest.
A total of 38 articles (2,492 patients), comprising 28 RCTs, 8 single-arm or prospective cohort studies, and 2 cross-sectional studies were included in this meta-analysis. When compared with placebo, prebiotics, synbiotics, and AST-120 provided significantly lower levels of both serum indoxyl sulfate and p-cresyl sulfate. There were no significant reductions in serum indoxyl sulfate and p-cresyl sulfate levels in patients receiving probiotics. Preservation of RRF in dialysis patients resulted in lower levels of both of the protein-bound uremic toxins. When compared with conventional hemodialysis, hemodiafiltration significantly decreased serum p-cresyl sulfate alone, whereas a significant change in serum indoxyl sulfate levels was observed only in studies with long-term observation periods. Very low protein diet (VLPD) and other oral medications yielded insignificant differences in protein-bound uremic toxins.
The present meta-analysis demonstrated that prebiotics, synbiotics, and AST-120 can effectively reduce both serum indoxyl sulfate and p-cresyl sulfate in CKD patients when compared with placebo. Preservation of RRF was associated with lower serum indoxyl sulfate and p-cresyl sulfate levels. The effect of biotic supplements was detected only in dialysis patients. For non-dialysis CKD patients, the results were limited due to the small number of studies. Further studies are needed to determine the efficacy in these populations.
蛋白质结合型尿毒症毒素（包括硫酸吲哚酚和硫酸对甲酚）的蓄积与慢性肾脏病（CKD）患者的心血管疾病和死亡率增加有关。我们进行了系统评价和荟萃分析，以综合现有的降低 CKD 患者蛋白质结合型尿毒症毒素水平的策略。
我们通过搜索 MEDLINE、Scopus 和 Cochrane 对照试验中心注册数据库，对观察性研究和随机对照试验（RCT）进行了荟萃分析，这些研究考察了饮食蛋白质限制、生物补充剂（包括益生元、益生菌和合生菌）、AST-120、透析技术以及保留残余肾功能（RRF）的结果对硫酸吲哚酚和硫酸对甲酚水平的影响。使用随机效应模型荟萃分析计算了感兴趣结果的变化。
共有 38 篇文章（2492 名患者），包括 28 项 RCT、8 项单臂或前瞻性队列研究和 2 项横断面研究，被纳入本次荟萃分析。与安慰剂相比，益生元、合生菌和 AST-120 可显著降低血清硫酸吲哚酚和硫酸对甲酚的水平。接受益生菌的患者的血清硫酸吲哚酚和硫酸对甲酚水平没有显著降低。在透析患者中保留 RRF 可降低两种蛋白质结合型尿毒症毒素的水平。与常规血液透析相比，血液透析滤过可显著降低血清硫酸对甲酚，而只有在观察期较长的研究中才观察到血清硫酸吲哚酚水平的显著变化。极低蛋白饮食（VLPD）和其他口服药物在蛋白质结合型尿毒症毒素方面没有显著差异。
本荟萃分析表明，与安慰剂相比，益生元、合生菌和 AST-120 可有效降低 CKD 患者的血清硫酸吲哚酚和硫酸对甲酚水平。保留 RRF 与较低的血清硫酸吲哚酚和硫酸对甲酚水平相关。生物补充剂的作用仅在透析患者中被检测到。对于非透析 CKD 患者，由于研究数量较少，结果有限。需要进一步的研究来确定这些人群的疗效。
