Gut microbiota plays a dual role in chronic kidney disease (CKD) and is closely linked to production of uremic toxins. Strategies of reducing uremic toxins by targeting gut microbiota are emerging. It is known that Chinese medicine rhubarb enema can reduce uremic toxins and improve renal function. However, it remains unknown which ingredient or mechanism mediates its effect. Here we utilized a rat CKD model of 5/6 nephrectomy to evaluate the effect of emodin, a main ingredient of rhubarb, on gut microbiota and uremic toxins in CKD. Emodin was administered via colonic irrigation at 5ml (1mg/day) for four weeks. We found that emodin via colonic irrigation (ECI) altered levels of two important uremic toxins, urea and indoxyl sulfate (IS), and changed gut microbiota in rats with CKD. ECI remarkably reduced urea and IS and improved renal function. Pyrosequencing and Real-Time qPCR analyses revealed that ECI resumed the microbial balance from an abnormal status in CKD. We also demonstrated that ten genera were positively correlated with Urea while four genera exhibited the negative correlation. Moreover, three genera were positively correlated with IS. Therefore, emodin altered the gut microbiota structure. It reduced the number of harmful bacteria, such as Clostridium spp. that is positively correlated with both urea and IS, but augmented the number of beneficial bacteria, including Lactobacillus spp. that is negatively correlated with urea. Thus, changes in gut microbiota induced by emodin via colonic irrigation are closely associated with reduction in uremic toxins and mitigation of renal injury.

ObjectivesTo assess the feasibility and acceptability of a randomized controlled trial compared auricular acupressure (AA) on specific acupoints with AA on non-specific acupoints for treating maintenance hemodialysis (MHD) patients with insomnia.MethodsSixty three (63) eligible subjects were randomly assigned into either AA group received AA on specific acupoints (n=32), or sham AA (SAA) group received AA on points irrelevant to insomnia treatment (n=31) for eight weeks. All participants were followed up for 12 weeks after treatments. The primary outcome was clinical response at eight weeks after randomization, defined as a reduction of Pittsburgh Sleep Quality Index (PSQI) global score by 3 points and more.ResultsFifty-eight (58) participants completed the trial and five dropped out. Twenty participants in AA group (62.5%) and ten in SAA group (32.3%) responded to the eight-week interventions (χ2 = 5.77, P = 0.02). PSQI global score declined 3.75 ± 4.36 (95%CI -5.32, -2.18) and 2.26 ± 3.89 (95%CI -3.68, -0.83) in AA group and SAA group respectively. Three participants died during the follow-up period. No evidence supported their deaths were related to the AA intervention. No other adverse event was observed.ConclusionFeasibility and logistics of patient recruitment, randomization procedure, blinding approach, interventions application and outcome assessment had been tested in this pilot trial. The preliminary data appeared to show a favorable result on AA treatment. A full-scale trial is warranted.Trial RegistrationChinese Clinical Trial Registry ChiCTR-TRC-12002272.

Chronic kidney disease (CKD) is often accompanied with colon mucosal barrier damage and gut microbiota disturbance, which strongly associate with up-regulated inflammation and kidney tubulointerstitial fibrosis. However, few interventions could protect the damaged barrier effectively. Rheum palmatum L or rhubarb is a common herbal medicine which is widely used to protect the colon mucosal barrier. In previous studies, we found that rhubarb intervention may reduce renal inflammation and tubulointerstitial fibrosis, via gut microbiota modification. However, whether intestinal barrier function could be improved by rhubarb intervention and the relationship with intestinal flora are still unknown. Therefore, we investigated the effects of rhubarb enema on intestinal barrier, and further analyzed the relationship with gut microbiota in 5/6 nephrectomy rats. Results indicated that rhubarb enema improved the intestinal barrier, regulated gut microbiota dysbiosis, suppressed systemic inflammation, and alleviated renal fibrosis. More specifically, rhubarb enema treatment inhibited the overgrowth of conditional pathogenic gut bacteria, including Akkermansia, Methanosphaera, and Clostridiaceae in CKD. The modification of gut microbiota with rhubarb intervention displayed significant correlation to intestinal barrier markers, TLR4-MyD88-NF-kB inflammatory response, and systemic inflammation. These results revealed that rhubarb enema could restore intestinal barrier by modifying several functional enteric bacteria, which may further explain the renal protection mechanism of the rhubarb enema.

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