Free p-cresylsulphate is a predictor of mortality in patients at different stages of chronic kidney disease
Free p-cresylsulphate is a predictor of mortality in patients at different stages of chronic kidney disease
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DOI：
10.1093/ndt/gfp592
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发表时间：
2010-04-01
影响因子：
6.1
通讯作者：
Massy, Ziad A.
中科院分区：
文献类型：
--
作者：
Liabeuf, Sophie;Barreto, Daniela V.;Massy, Ziad A.
背景。尿毒症毒素被认为是慢性肾病（CKD）患者新出现的死亡风险因素。对甲酚（一种原型蛋白结合尿毒症滞留溶质）已被证明在体外具有毒性作用。最近，已证明对甲酚以其硫酸盐缀合物，对甲酚硫酸盐存在于血浆中。本研究评估了游离和总对甲酚硫酸盐的分布，并试图确定这些参数是否与一组 CKD 患者的血管钙化、动脉僵硬度和死亡风险相关。方法。 139 例 CKD 不同阶段的患者（平均 SD 年龄：67 +/- 12；男性：60%）（2 期 8%、3 期 26.5%、4 期 26.5%、5 期 7% 和 5D 期 32%）纳入本研究。 结果。基线总和游离对甲苯基硫酸盐与肾功能呈负相关，并且与血管钙化显着相关。在研究期间（平均随访时间：779 +/- 185 天），38 名患者死亡[其中 22 人死于心血管 (CV) 原因]。在粗略生存分析中，游离（但不是全部）对甲酚硫酸盐被证明是总体死亡和心血管死亡的预测因子。较高的游离对甲酚硫酸盐水平（>0.051 mg/100 mL；中位数）与死亡率相关，独立于众所周知的生存预测因素，如年龄、血管钙化、贫血和炎症。结论。在 CKD 后期，游离和总对甲酚硫酸盐（对甲酚的主要体内循环代谢物）的血清水平升高。然而，似乎只有游离的对甲酚硫酸盐可以作为 CKD 患者生存的预测因子。
Background. Uraemic toxins are considered to be emerging mortality risk factors in chronic kidney disease (CKD) patients. p-Cresol (a prototype protein-bound uraemic retention solute) has been shown to exert toxic effects in vitro. Recently, it has been demonstrated that p-cresol is present in plasma as its sulphate conjugate, p-cresylsulphate. The present study evaluated the distribution of free and total p-cresylsulphate and sought to determine whether these parameters were associated with vascular calcification, arterial stiffness and mortality risk in a cohort of CKD patients.Methods. One hundred and thirty-nine patients (mean SD age: 67 +/- 12; males: 60%) at different stages of CKD (8% at Stage 2, 26.5% at Stage 3, 26.5% at Stage 4, 7% at Stage 5 and 32% at Stage 5D) were enrolled in this study.Results. Baseline total and free p-cresylsulphate presented an inverse relationship with renal function and were significantly associated with vascular calcification. During the study period (mean follow-up period: 779 +/- 185 days), 38 patients died [including 22 from cardiovascular (CV) causes]. In crude survival analyses, free (but not total) p-cresylsulphate was shown to be a predictor of overall and CV death. Higher free p-cresylsulphate levels (>0.051 mg/100 mL; median) were associated with mortality independently of well-known predictors of survival such as age, vascular calcification, anaemia and inflammation.Conclusions. Serum levels of free and total p-cresylsulphate (the main in vivo circulating metabolites of p-cresol) were elevated in later CKD stages. However, only free p-cresylsulphate seems to be a predictor of survival in CKD.