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Table of Contents
Year : 2019  |  Volume : 5  |  Issue : 1  |  Page : 3-6

Probiotic supplementation and reducing infiammation in hemodialysis patients: A systematic review

1 Dietician, Department of Food and Nutrition, Covenant Healthcare, Mount Pleasant, Michigan, USA
2 Dietician, Department of Food and Nutrition, Central Michigan University, Mount Pleasant, Michigan, USA

Date of Web Publication15-Nov-2019

Correspondence Address:
Dr. Kirsten N Abney
Central Michigan University, 1200 S., Franklin Street, Mount Pleasant 48859, Michigan
Susan J Hewlings
Central Michigan University, 1200 S., Franklin Street, Mount Pleasant 48859, Michigan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jrnm.jrnm_16_19

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Background: Chronic kidney disease (CKD) is a growing health problem worldwide. Uremic toxin buildup caused by protein bacterial metabolites such as indoleamines, urea, and indoxyl sulfate contribute to dysbiosis in the gut microbiome in hemodialysis patients, which contributes to a pro-infiammatory environment. Aims: This systematic review of the literature considers the confiicting evidence on probiotic supplementation and infiammatory status in CKD patients receiving hemodialysis. Methods: PubMed, EBSCO, and Google Scholar were all used to search for control/clinical trials demonstrating the effects of probiotic supplementation on these protein bacterial metabolites and C-reactive protein (CRP) levels. Results: Four of the five studies observed no significant findings in the reduction of infiammatory status in this population. One study demonstrated a significant reduction in CRP levels after 3 months of probiotic supplementation. Many articles varied between using single and multiple strains of bacteria which contributed to limitations to the studies. There was limited supporting evidence to suggest that probiotic supplementation could reduce infiammatory status in hemodialysis patients. Conclusions: Based on the findings, more research is needed before any conclusive recommendations can be made on whether probiotic supplementation would be beneficial for patients receiving hemodialysis treatments.

Keywords: Chronic kidney disease, hemodialysis, probiotics, renal

How to cite this article:
Abney KN, Hewlings SJ. Probiotic supplementation and reducing infiammation in hemodialysis patients: A systematic review. J Renal Nutr Metab 2019;5:3-6

How to cite this URL:
Abney KN, Hewlings SJ. Probiotic supplementation and reducing infiammation in hemodialysis patients: A systematic review. J Renal Nutr Metab [serial online] 2019 [cited 2020 Sep 23];5:3-6. Available from: http://www.jrnm.in/text.asp?2019/5/1/3/271037

  Introduction Top

Chronic kidney disease (CKD) is a growing health problem worldwide. Uremic toxin buildup contributes to dysbiosis in the gut microbiome in hemodialysis patients, which contributes to a pro-infiammatory environment. Therefore, it has been suggested that probiotic supplementation can offset dysbiosis in these patients.[1] Under normal conditions, the gut microbiome plays a role in energy metabolism, absorbing carbohydrates, and micronutrient homeostasis.[2] In hemodialysis patients, dysbiosis can contribute to a life time of systematic and oxidative stress. Probiotics are thought to introduce beneficial microorganisms to restore good bacteria into the gut to reduce infiammatory processes and infections.[2]

Background and objective

The microbiota in healthy human intestines is comprised of more than 100 trillion microbial cells with varying species among its vast community.[3] The microbiome helps to protect against pathogens and regulates the metabolism of carbohydrate and lipids which contribute to nutritional balance.[3] The gut microbiome is heavily infiuenced by the food choices it comes in contact with and can change within a few days based on specific nutrients it encounters.[3] Uremic toxins are a product of partially digested proteins by specific species living within the microbiome. The buildup of protein bacterial metabolites such as indoleamines, urea, and indoxyl sulfate (IS) as a result of CKD induces changes in gut microbiota.[1] Evidence suggest that individuals who have end-stage renal disease have a decreased amount of Bacteroidaceae, Lactobacillus, and Bifidobacterium. This decrease in these bacteria is thought to contribute to elevated uremic toxin concentration which promotes disease progression and adverse outcomes such as cardiovascular disease.[3] The inhibition of uremic toxins has been shown to be effective in terms of reducing infiammation and risk of cardiovascular disease.[4]

The dysbiosis of the intestinal fiora is the main cause of infiammation in hemodialysis patients.[2],[3],[4],[5],[6] Impairment of kidney function and the decreased intake in fruits, vegetables, and dairy products all contribute to alterations in the normal intestinal fiora.[3] CKD is associated with the following: intestinal wall congestion, intestinal wall edema, slow colonic transit, metabolic acidosis, decrease consumption of fiber and iron, and frequent use of antibiotics.[3] These all contribute to intestinal permeability and translocation of bacterial metabolic products across the intestinal barrier.[3] In addition, these consequences of CKD produce an immune response contributing to systematic infiammation in these patients.[3] Probiotics have gained popularity in the last decade and are used widely for various disease states and ailments and are thought to have an positive effect on the systematic infiammatory state in patients with CKD.[3] The exact mechanisms of probiotic therapy are unknown; some suggest they can suppress cellular oxidative stress and free radical production.[4] According to one study, it was observed that hemodialysis patients who were fed Lactobacillus acidophilus had significantly lower blood dimethylamine and nitro dimethylamine (carcinogen) concentrations.[6] The beneficial effects of probiotic supplementation have been well documented on biomarkers of infiammation and oxidative stress among patients who do not have CKD.[6] Due to confiicting evidence on probiotics and infiammatory status in CKD patients receiving hemodialysis, a systematic review of current literature was performed to determine if probiotic supplementation will reduce infiammation in patients receiving hemodialysis treatment.

  Methods Top

Search strategy and literature review

A systematic literature review was completed using PRISMA guidelines to eliminate bias. The following databases were accessed: PubMed, EBSCO, and Google Scholar. While using the databases, the following search terms were used in pairs to retrieve articles: “probiotics,” “chronic kidney disease,” “infiammation,” “dialysis,” and “hemodialysis.” A total of 12 searches were completed on PubMed, EBSCO, and Google Scholar using the search terms in a variety of combinations.

The criteria for article selection included original research published from 2010 to present. Articles were excluded if peritoneal or continuous renal replacement therapy was used, if patients were <18 years of age, and if symbiotic, prebiotic, or concurrent probiotic supplementation was used during the study. Additional exclusion criteria can be found in [Table 1].
Table 1: Inclusion and Exclusion Criteria for Article Selection

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  Results Top

The initial literature searches resulted in a total of 7606 records from the combination of search terms discussed above. Reviewing the references in these articles added an additional three articles to the total number of articles. The records were screened, and many were eliminated if they met one or more of the criteria in the exclusion list. In addition, articles were also eliminated if they were reviews, meta-analysis, or systematic reviews, or focused solely on probiotics and the gut microbiome without inclusion or mention of CKD. While searching the databases, many duplicates were found and were also eliminated. A total of five records were used for this systematic review. When articles included information on hemoglobin, insulin sensitivity, or blood glucose levels, only relevant data discussing infiammatory markers were analyzed. [Figure 1] exemplifies the process of selecting articles. [Table 2] displays the total articles used in the review by author, study type, population, supplementation, duration, and study results.
Figure 1: Prisma fiowsheet depicting article selection. From: Moher D, Liberati A, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6 (7): e1000097. doi: 10.1371/journal.pmed1000097

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Table 2: Characteristics of the RCTs used in this systematic review

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  Discussion Top

In summary, this systematic review observed that there were no significant differences noted in two of the studies that examined serum p-cresol and serum p-cresol phenol.[4],[5] There was also no significant decrease in C-reactive protein (CRP) levels between two of the trials as determined by pre- and post-probiotic supplementation.[7],[8] However, one study was able to demonstrate significant reductions in CRP levels compared to the placebo treatment group.[6] In most of the studies, dietary intake of probiotic containing foods was not assessed; of the two studies that assessed probiotic food consumption, no significant findings were noted in the reduction of infiammatory status.[4],[7]

Nutrition assessment

In the double-blind, randomized, placebo-controlled trial, 23 patients received a probiotic supplement and 23 patients received a placebo.[5] A brief evaluation of the patient's body weight, height, waist, and midarm circumference were documented in order to assess the patient's anthropometric measurements. There was no indication on whether a food recall was performed to determine if patient's food choices were evaluated before and during the study.[5] Similarly, two other studies did not assess probiotic intake from dietary sources.[6],[8] Shariaty et al. had each participant complete a 24-h probiotic food recall questionnaire examining probiotic intake in their diet on weekdays and 1 day of the weekend to ensure probiotic food products were not consumed during the study.[7] Eidi et al. had a similar approach to assessing probiotic food intake by evaluating probiotic supplementation for one hemodialysis weekday, one nonhemodialysis weekday, and one nonhemodialysis weekend day using a visual aid photo album of real foods before and after treatment was utilized.[4]

Predialysis electrolyte status and uremic toxins

Borges et al. focused on predialysis urea and electrolyte status, fecal pH, gut microbiota profile, and IS levels.[5] The individuals received capsules that were to be consumed three times per day for both groups. The probiotic supplement contained three different strains of live bacteria totaling 90 billion colony-forming unit. There was an 82% adherence rate. Blood samples were taken from each individual at the start of dialysis (after overnight fasting), and fecal samples were also collected.[5] Results from the study found that serum urea and potassium plasma levels (P = 0.02) increased after 3 months of probiotic supplementation. A reduction in fecal pH was observed in the probiotic group (P = 0.01), but the gut microbiota of 20 patients (10 from each group) showed that there was no difference between the probiotic or placebo groups.[5] The effects of probiotic supplementation or placebo on plasma levels of toxins indicated that IS plasma levels increased after the probiotic intervention.[5]

During the randomized controlled double-blind clinical trial, Eidi et al. used a single strain Lactobacillus rhamnosus for 4 weeks.[4] It was demonstrated that there was no significant difference in serum electrolytes between the probiotic and placebo groups after supplementation.[4] However, serum p-cresol levels decreased compared to baseline (P = 0.034), and serum p-cresol levels phenol (P = 0.009) also decreased after the 4 week period.[4]

Effects of probiotics on C-reactive protein

Three of the five studies focused mainly onCRP. One study used a probiotic supplement containing seven different strains of bacteria [Table 2].[7] Serum CRP levels were assessed in the intervention and control groups before the intervention and then, 30, 60, and 90 days after the beginning of the intervention.[7] The findings showed no significant difference between the two groups in either pre- or post-intervention CRP levels (P = 0.239).[7] Another study used a probiotic supplement containing three different strains of bacteria [Table 2]. There was no statistically significant changes observed in the levels of total indoxyl glucuronide (P > 0.058) or CRP levels (P<0.071) on the participants consuming the probiotic supplement.[8] CRP levels before and after administration of a three-strain probiotic were also evaluated in a comparison study.[6] Compared with placebo, probiotic supplementation resulted in significant reductions in serum CRP (P = 0.03).[6]


The main limitations to the findings are that most of the trials had a short duration ranging from 1 to 6 months with small sample sizes consisting of 16–28 patients. It is evident that larger studies with a longer duration are needed to determine if infiammatory status could be reduced in hemodialysis patients by taking probiotic supplements. Furthermore, multiple to single strain probiotic formulas were used which made it difficult to determine if a specific strain or multistrain probiotic was more effective at decreasing infiammatory status among this population.

  Conclusions Top

Based on the results from this systematic review, patients with CKD receiving hemodialysis treatments would find no significant benefits from taking probiotic supplements. However, as Soleimani et al. demonstrated, there was a significant improvement in CRP levels after 3 months of supplementation using L.acidophilus, Lactobacilluscasei, and Bifidobacteriumbifidum for 12 weeks. Further studies are needed to evaluate the long-term effects of probiotics on hemodialysis patients and the potential reduction on infiammatory proteins.

Financial support and sponsorship


Confiicts of interest

There are no confiicts of interest.

  References Top

Bland J. Chronic kidney disease: The gut-kidney connection? Integr Med 2017;16:14-6.  Back to cited text no. 1
Vaziri ND, Wong J, Pahl M, Piceno YM, Yuan J, DeSantis TZ, et al. Chronic kidney disease alters intestinal microbial fiora. Kidney Int 2013;83:308-15.  Back to cited text no. 2
Chen YY, Chen DQ, Chen L, Liu JR, Vaziri ND, Guo Y, et al. Microbiome-metabolome reveals the contribution of gut-kidney axis on kidney disease. J Transl Med 2019;17:5.  Back to cited text no. 3
Eidi F, Poor-Reza Gholi F, Ostadrahimi A, Dalili N, Samadian F, Barzegari A. Effect of Lactobacillus rhamnosus on serum uremic toxins (phenol and P-cresol) in hemodialysis patients: A double blind randomized clinical trial. Clin Nutr ESPEN 2018;28:158-64.  Back to cited text no. 4
Borges NA, Carmo FL, Stockler-Pinto MB, de Brito JS, Dolenga CJ, Ferreira DC, et al. Probiotic supplementation in chronic kidney disease: A double-blind, randomized, placebo-controlled trial. J Ren Nutr 2018;28:28-36.  Back to cited text no. 5
Soleimani A, Zarrati Mojarrad M, Bahmani F, Taghizadeh M, Ramezani M, Tajabadi-Ebrahimi M, et al. Probiotic supplementation in diabetic hemodialysis patients has beneficial metabolic effects. Kidney Int 2017;91:435-42.  Back to cited text no. 6
Shariaty Z, Mahmoodi Shan GR, Farajollahi M, Amerian M, Behnam Pour N. The effects of probiotic supplement on hemoglobin in chronic renal failure patients under hemodialysis: A randomized clinical trial. J Res Med Sci 2017;22:74.  Back to cited text no. 7
[PUBMED]  [Full text]  
Natarajan R, Pechenyak B, Vyas U, Ranganathan P, Weinberg A, Liang P, et al. Randomized controlled trial of strain-specific probiotic formulation (Renadyl) in dialysis patients. Biomed Res Int 2014;2014:568571.  Back to cited text no. 8


  [Figure 1]

  [Table 1], [Table 2]


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