Department of Microbiology and Immunology, Division of Nephrology, University Hospitals Leuven, B-3000, Leuven, Belgium.
BMC Nephrol. 2014 Jun 9;15:87. doi: 10.1186/1471-2369-15-87.
Serum p-cresyl sulfate (PCS) associates with cardiovascular disease in patients with chronic kidney disease. PCS concentrations are determined by intestinal uptake of p-cresol, human metabolism to PCS and renal clearance. Whether intestinal uptake of p-cresol itself is directly associated with cardiovascular disease in patients with renal dysfunction has not been studied to date.
We performed a prospective study in patients with chronic kidney disease stage 1 - 5 (NCT00441623). Intestinal uptake of p-cresol, under steady state conditions, was estimated from 24 h urinary excretion of PCS. Primary endpoint was time to first cardiovascular event, i.e., cardiac death, myocardial infarction/ischemia, ventricular arrhythmia, cardiovascular surgery, ischemic stroke or symptomatic peripheral arterial disease. Statistical analysis was done using Kaplan-Meier estimates and Cox proportional hazard analyses.
In a cohort of 200 patients, median 24 h urinary excretion of PCS amounted to 457.47 μmol (IQR 252.68 - 697.17). After a median follow-up of 52 months, 25 patients reached the primary endpoint (tertile 1/2/3: 5/6/14 events, log rank P 0.037). Higher urinary excretion of PCS was directly associated with cardiovascular events (univariate hazard ratio per 100 μmol increase: 1.112, P 0.002). In multivariate analysis, urinary excretion of PCS remained a predictor of cardiovascular events, independent of eGFR (hazard ratio 1.120, P 0.002).
In patients with chronic kidney disease, intestinal uptake of p-cresol associates with cardiovascular disease independent of renal function. The intestinal generation and absorption of p-cresol may be therapeutic targets to reduce cardiovascular disease risk in patients with renal dysfunction.
血清对甲酚硫酸盐（PCS）与慢性肾脏病患者的心血管疾病相关。PCS 浓度由肠道摄取对甲酚、人体代谢为 PCS 和肾脏清除决定。目前尚未研究肾功能障碍患者的肠道对甲酚摄取本身是否与心血管疾病直接相关。
我们在慢性肾脏病 1-5 期患者中进行了一项前瞻性研究（NCT00441623）。在稳态条件下，通过 24 小时尿 PCS 排泄来估计对甲酚的肠道摄取。主要终点是首次心血管事件的时间，即心脏死亡、心肌梗死/缺血、室性心律失常、心血管手术、缺血性卒中和有症状的外周动脉疾病。使用 Kaplan-Meier 估计和 Cox 比例风险分析进行统计分析。
在 200 例患者的队列中，中位 24 小时尿 PCS 排泄量为 457.47 μmol（IQR 252.68-697.17）。中位随访 52 个月后，25 例患者达到主要终点（三分位 1/2/3：5/6/14 例事件，对数秩 P=0.037）。更高的 PCS 尿排泄量与心血管事件直接相关（每增加 100 μmol 的单变量风险比：1.112，P=0.002）。在多变量分析中，PCS 的尿排泄量仍然是心血管事件的预测因子，独立于 eGFR（风险比 1.120，P=0.002）。
在慢性肾脏病患者中，肠道对甲酚的摄取与心血管疾病相关，独立于肾功能。肠道生成和吸收对甲酚可能是治疗肾功能障碍患者减少心血管疾病风险的靶点。
