Marzocco Stefania, Fazeli Gholamreza, Di Micco Lucia, Autore Giuseppina, Adesso Simona, Dal Piaz Fabrizio, Heidland August, Di Iorio Biagio
Department of Pharmacy, University of Salerno, 84084 Fisciano (SA), Italy.
Rudolf Virchow Center, University of Wuerzburg, 97080 Wuerzburg, Germany.
J Clin Med. 2018 Sep 30;7(10):315. doi: 10.3390/jcm7100315.
In end-stage renal disease (ESRD), gut-derived uremic toxins play a crucial role in the systemic inflammation and oxidative stress promoting the excess morbidity and mortality. The biochemical derangement is in part a consequence of an insufficient generation of short-chain fatty acids (SCFA) due to the dysbiosis of the gut and an insufficient consumption of the fermentable complex carbohydrates.
The primary end-point was to evaluate the potential efficacy of SCFA (specifically, sodium propionate (SP)) for patients on maintenance hemodialysis (MHD) on systemic inflammation. Secondary end-points included potential attenuation of oxidative stress markers, insulin resistance and production of gut-derived uremic toxins indoxyl sulfate and p-cresol sulfate, as well as health status after SP supplementation.
We performed a single-center non-randomized pilot study in 20 MHD patients. They received the food additive SP with a daily intake of 2 × 500 mg in the form of capsules for 12 weeks. Pre-dialysis blood samples were taken at the beginning, after six weeks and at the end of the administration period, as well as four weeks after withdrawal of the treatment.
The subjects revealed a significant decline of inflammatory parameters C-reactive protein (-46%), interleukin IL-2 (-27%) and IL-17 (-15%). The inflammatory parameters IL-6 and IFN-gamma showed a mild non-significant reduction and the anti-inflammatory cytokine IL-10 increased significantly (+71%). While the concentration of bacterial endotoxins and TNF-α remained unchanged, the gut-derived uremic toxins, indoxyl sulfate (-30%) and p-cresyl sulfate (-50%), revealed a significant decline. The SP supplementation reduced the parameters of oxidative stress malondialdehyde (-32%) and glutathione peroxidase activity (-28%). The serum insulin levels dropped by 30% and the HOMA-index by 32%. The reduction of inflammatory parameters was associated with a lowering of ferritin and a significant increase in transferrin saturation (TSAT). Four weeks after the end of the treatment phase, all improved parameters deteriorated again. Evaluation of the psycho-physical performance with the short form 36 (SF-36) questionnaire showed an enhancement in the self-reported physical functioning, general health, vitality and mental health. The SP supplementation was well tolerated and without important side effects. No patient had left the study due to intolerance to the medication. The SP supplementation in MHD patients reduced pro-inflammatory parameters and oxidative stress and improved insulin resistance and iron metabolism. Furthermore, SP effectively lowered the important gut-derived uremic toxins indoxyl and p-cresol sulfate. These improvements were associated with a better quality of life. Further controlled studies are required in a larger cohort to evaluate the clinical outcome.
在终末期肾病（ESRD）中，肠道来源的尿毒症毒素在促进过高发病率和死亡率的全身炎症和氧化应激中起关键作用。生化紊乱部分是由于肠道菌群失调导致短链脂肪酸（SCFA）生成不足以及可发酵复合碳水化合物消耗不足所致。
主要终点是评估SCFA（具体为丙酸钠（SP））对维持性血液透析（MHD）患者全身炎症的潜在疗效。次要终点包括氧化应激标志物、胰岛素抵抗以及肠道来源的尿毒症毒素硫酸吲哚酚和对甲酚硫酸盐生成的潜在减轻，以及补充SP后的健康状况。
我们对20例MHD患者进行了一项单中心非随机试验性研究。他们以胶囊形式每日摄入2×500mg的食品添加剂SP，持续12周。在给药期开始时、六周后、结束时以及治疗撤药四周后采集透析前血样。
受试者的炎症参数C反应蛋白（-46%）、白细胞介素IL-2（-27%）和IL-17（-15%）显著下降。炎症参数IL-6和干扰素-γ有轻度非显著性降低，抗炎细胞因子IL-10显著升高（+71%）。虽然细菌内毒素和肿瘤坏死因子-α的浓度保持不变，但肠道来源的尿毒症毒素硫酸吲哚酚（-30%）和对甲酚硫酸盐（-50%）显著下降。补充SP降低了氧化应激参数丙二醛（-32%）和谷胱甘肽过氧化物酶活性（-28%）。血清胰岛素水平下降了30%，胰岛素抵抗指数下降了32%。炎症参数的降低与铁蛋白降低和转铁蛋白饱和度（TSAT）显著升高有关。治疗阶段结束四周后，所有改善的参数再次恶化。用简短健康调查问卷36（SF-36）评估心理-身体表现显示，自我报告的身体功能、总体健康、活力和心理健康有所改善。补充SP耐受性良好，无重要副作用。没有患者因对药物不耐受而退出研究。MHD患者补充SP可降低促炎参数和氧化应激，改善胰岛素抵抗和铁代谢。此外，SP有效降低了重要的肠道来源尿毒症毒素硫酸吲哚酚和对甲酚硫酸盐。这些改善与更好的生活质量相关。需要在更大队列中进行进一步的对照研究以评估临床结局。
