1 Princess Alexandra Hospital, Brisbane, Queensland, Australia. 2 University of Queensland School of Medicine, Brisbane, Queensland, Australia. 3 Translational Research Institute, Brisbane, Queensland, Australia. 4 Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia. 5 Address correspondence to: Nicole Isbel, Department of Nephrology, Princess Alexandra Hospital, Level 2, ARTS Building, Ipswich Road, Woolloongabba, Brisbane, Queensland 4102, Australia.
Transplantation. 2014 Mar 15;97(5):548-54. doi: 10.1097/01.tp.0000436906.48802.c4.
Emerging evidence suggests that uremic toxins, in particular indoxyl sulfate (IS) and p-cresyl sulfate (PCS), may be involved in the pathogenesis of cardiovascular disease. Despite a significant increase in IS and PCS in patients with established kidney damage, the effect of a nephrectomy in non-chronic kidney disease patients is not yet known.
Forty-two living kidney donors (Caucasian; 76% female [n=32]; 53 ± 10 years) were enrolled in an observational cohort study and followed up annually for 2 years (before nephrectomy, 1 and 2 years after nephrectomy). At each time point, patients underwent measurements of serum total and free IS and PCS (using ultrahigh-performance liquid chromatography), carotid intima-media thickness (a measure of arterial stiffness), brachial artery reactivity (both flow-mediated dilatation and sublingual glycerol trinitrate, markers of endothelial dysfunction), kidney function by Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C, and urate and high-sensitivity C-reactive protein using standard laboratory techniques.
Kidney function decreased by 30% after nephrectomy (absolute change estimated glomerular filtration rate 28 ± 6.9 and 27 ± 7.6 mL/min/1.73 m at 1 and 2 years, respectively), and the concentration of toxin levels increased by 44% to 100%, which remained elevated at 2 years after nephrectomy (all P<0.001). Both toxins were associated with carotid intima-media thickness, brachial artery reactivity-glycerol trinitrate, serum urate, and C-reactive protein levels (all P<0.03). Further, IS and urate were found to be independent predictors of change in kidney function, from baseline at 2 years after nephrectomy (both P<0.03).
This study demonstrated significant and sustained increases in nephrovascular toxins, IS and PCS, after nephrectomy. Levels of both toxins were associated with clinically relevant markers of cardiovascular and renal risk, warranting further research in this area.
新出现的证据表明，尿毒症毒素，特别是硫酸吲哚酚（IS）和对甲酚硫酸（PCS），可能与心血管疾病的发病机制有关。尽管在有明确肾脏损害的患者中，IS 和 PCS 显著增加，但在非慢性肾病患者中肾切除术的效果尚不清楚。
42 名活体供肾者（白种人；76%为女性[ n = 32]；53 ± 10 岁）被纳入一项观察性队列研究，并在肾切除术前、术后 1 年和 2 年每年进行随访。在每个时间点，患者接受血清总游离 IS 和 PCS（使用超高效液相色谱法）、颈动脉内膜中层厚度（动脉僵硬度的测量指标）、肱动脉反应性（血流介导的扩张和舌下甘油三硝酸酯，内皮功能障碍的标志物）、慢性肾脏病协作组肌酐胱抑素 C 评估的肾功能以及尿酸和高敏 C 反应蛋白的检测，所有检测均采用标准实验室技术。
肾切除术后肾功能下降 30%（估计肾小球滤过率绝对值变化分别为 28 ± 6.9 和 27 ± 7.6 mL/min/1.73 m2，分别在术后 1 年和 2 年），毒素浓度增加 44%至 100%，术后 2 年仍持续升高（均 P < 0.001）。两种毒素均与颈动脉内膜中层厚度、肱动脉反应性-甘油三硝酸酯、血清尿酸和 C 反应蛋白水平相关（均 P < 0.03）。此外，IS 和尿酸被发现是术后 2 年肾功能变化的独立预测因子（均 P < 0.03）。
本研究表明，肾切除术后肾血管毒素 IS 和 PCS 显著且持续增加。两种毒素的水平均与心血管和肾脏风险的临床相关标志物相关，这在该领域值得进一步研究。
