Graduate Program in Medical Sciences, Federal Fluminense University (UFF), Niterói, Rio de Janeiro, Brazil.
Graduate Program in Cardiovascular Sciences, Federal Fluminense University (UFF), Niterói, Rio de Janeiro, Brazil.
J Ren Nutr. 2022 Nov;32(6):685-691. doi: 10.1053/j.jrn.2022.01.010. Epub 2022 Feb 3.
Uremic toxins such as indoxyl sulfate (IS), p-cresyl sulfate (pCS), and indole-3-acetic acid (IAA) produced by the gut microbiota are recognized as risk factors for many comorbidities, including cardiovascular diseases. Patients with chronic kidney disease (CKD) have an accumulation of these toxins, and nutritional strategies have been proposed to mitigate gut dysbiosis and, consequently, reduce these toxins. This study aimed to evaluate the effects of resveratrol supplementation on the plasma levels of IS, pCS, and IAA in nondialyzed patients with CKD.
In this placebo-controlled crossover study, twenty nondialyzed patients were randomly divided into two groups: they received either one capsule/day containing 500 mg of trans-resveratrol (63 ± 7.5 years, glomerular filtration rate [GFR]: 34 ± 14 mL/min, body mass index: 26.8 ± 5.6 kg/m) or a placebo containing 500 mg wheat flour (62 ± 8.4 years, GFR: 34 ± 13 mL/min, body mass index: 28.6 ± 4.4 kg/m) during 4 weeks. After 8 weeks of washout (no supplementation), another 4 weeks of supplementation with crossover was initiated. IS, IAA, and pCS plasma levels were quantified by the reverse phase high-efficiency liquid chromatography method with fluorescent detection. The mRNA expression of nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B in peripheral blood mononuclear cells was evaluated by polymerase chain reaction. C-reactive protein plasma levels were also evaluated.
As expected, the uremic toxin levels were negatively correlated with the GFR, but no effect of trans-resveratrol supplementation was found on levels of IS, IAA, and pCS. There was a positive correlation between IS and nuclear factor erythroid 2-related factor 2 (r = 0.24, P = .03) and also between IS and C-reactive protein (r = 0.21, P = .05).
Supplementation with trans-resveratrol did not reduce the plasma levels of IS, pCS, and IAA in nondialyzed patients with CKD. The interactions among uremic toxins and anti-inflammatory and proinflammatory pathways deserve more studies.
肠道微生物群产生的尿毒症毒素，如硫酸吲哚酚（IS）、对甲酚硫酸盐（pCS）和吲哚-3-乙酸（IAA），被认为是包括心血管疾病在内的许多合并症的危险因素。慢性肾脏病（CKD）患者会积累这些毒素，并且已经提出了营养策略来减轻肠道菌群失调，从而减少这些毒素。本研究旨在评估白藜芦醇补充剂对非透析性 CKD 患者血浆 IS、pCS 和 IAA 水平的影响。
在这项安慰剂对照交叉研究中，20 名非透析患者被随机分为两组：一组每天服用一粒含有 500mg 反式白藜芦醇的胶囊（63±7.5 岁，肾小球滤过率[GFR]：34±14mL/min，体重指数[BMI]：26.8±5.6kg/m2），另一组服用含有 500mg 小麦粉的安慰剂（62±8.4 岁，GFR：34±13mL/min，BMI：28.6±4.4kg/m2），持续 4 周。经过 8 周的洗脱期（无补充），开始进行另一个 4 周的交叉补充期。通过反相高效液相色谱法结合荧光检测定量测定 IS、IAA 和 pCS 血浆水平。通过聚合酶链反应评估外周血单个核细胞中核因子红细胞 2 相关因子 2 和核因子 kappa B 的 mRNA 表达。还评估了 C-反应蛋白的血浆水平。
正如预期的那样，尿毒症毒素水平与 GFR 呈负相关，但白藜芦醇补充剂对 IS、IAA 和 pCS 水平没有影响。IS 与核因子红细胞 2 相关因子 2（r=0.24，P=0.03）和 IS 与 C-反应蛋白（r=0.21，P=0.05）之间呈正相关。
在非透析性 CKD 患者中，白藜芦醇补充剂并未降低 IS、pCS 和 IAA 的血浆水平。尿毒症毒素与抗炎和促炎途径之间的相互作用值得进一步研究。
