Advertisement

The Efficacy of Lactobacillus-Containing Probiotic Supplementation in Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

Published:September 05, 2020DOI:https://doi.org/10.1053/j.jrn.2020.07.002

      Objectives

      This study was performed to determine the effects of probiotic supplementation on cholesterol-triglyceride ratio, an indirect marker of insulin resistance, protein-bound uremic toxins, biomarkers of inflammation, and microbial translocation in end-stage renal disease patients on hemodialysis.

      Methods

      Fifty-six patients aged 39–75 years were assigned into two groups to receive either probiotic sachets (n = 28) or a placebo (n = 28) in a randomized double-blinded placebo-controlled clinical trial. The patients in the probiotic group received twice daily sachets that contained a mixture of three viable and freeze-dried strains: Lactococcus lactis subsp. Lactis LL358, Lactobaccillus salivarius LS159, and Lactobaccillus pentosus LPE588 at high dose (100 billion; 1 × 1011 cfu/day) for 6 months.

      Results

      A total of 50 patients were available for final analysis. Probiotic supplementation did not have a significant influence on cholesterol-triglyceride ratio. Probiotic supplementation for 6 months caused a significant decrease in serum levels of indoxyl sulfate. Compared with the placebo, probiotic supplementation did not result in significant changes in hemoglobin levels, blood urea nitrogen, blood glucose, serum p-cresyl sulfate, inflammatory, and microbial translocation markers. No clinically significant changes in body composition were observed between the two groups during the study period. The probiotic supplementation was well tolerated by all subjects with minimal adverse effects during the 6-month-long study.

      Conclusion

      Our results suggest that high-dose multistrain lactobaccillus probiotic supplementation over 6 months as a monotherapy did not significantly decrease markers of insulin resistance, cholesterol-triglyceride ratio, and most of the studied markers, with the exception of levels of indoxyl sulfate in patients on HD.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and PersonalCorporate R&D Professionals
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Renal Nutrition
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Foley R.N.
        • Parfrey P.S.
        • Sarnak M.J.
        Clinical epidemiology of cardiovascular disease in chronic renal disease.
        Am J Kidney Dis. 1998; 32: S112-S119
        • Tonelli M.
        • Wiebe N.
        • Culleton B.
        • et al.
        Chronic kidney disease and mortality risk: a systematic review.
        J Am Soc Nephrol. 2006; 17: 2034-2047
        • Parfrey P.S.
        • Foley R.N.
        The clinical epidemiology of cardiac disease in chronic renal failure.
        J Am Soc Nephrol. 1999; 10: 1606-1615
        • McClellan W.M.
        • Chertow G.M.
        Beyond Framingham: cardiovascular risk profiling in ESRD.
        J Am Soc Nephrol. 2005; 16: 1539-1541
        • Schiffrin E.L.
        • Lipman M.L.
        • Mann J.F.
        Chronic kidney disease: effects on the cardiovascular system.
        Circulation. 2007; 116: 85-97
        • Ilori T.O.
        • Wang X.
        • Huang M.
        • et al.
        Oxidative balance score and the risk of end-stage renal disease and cardiovascular disease.
        Am J Nephrol. 2017; 45: 338-345
        • Lim P.S.
        • Chen H.P.
        • Chen C.H.
        • et al.
        Association between redox status of serum albumin and peritoneal membrane transport properties in patients on peritoneal dialysis.
        Blood Purif. 2015; 40: 243-249
        • Stenvinkel P.
        • Carrero J.J.
        • Axelsson J.
        • et al.
        Emerging biomarkers for evaluating cardiovascular risk in the chronic kidney disease patient: how do new pieces fit into the uremic puzzle?.
        Clin J Am Soc Nephrol. 2008; 3: 505-521
        • Beberashvili I.
        • Sinuani I.
        • Azar A.
        • et al.
        IL-6 levels, nutritional status, and mortality in prevalent hemodialysis patients.
        Clin J Am Soc Nephrol. 2011; 6: 2253-2263
        • Ikizler T.A.
        • Wingard R.L.
        • Harvell J.
        • et al.
        Association of morbidity with markers of nutrition and inflammation in chronic hemodialysis patients: a prospective study.
        Kidney Int. 1999; 55: 1945-1951
        • Libetta C.
        • Sepe V.
        • Esposito P.
        • et al.
        Oxidative stress and inflammation: implications in uremia and hemodialysis.
        Clin Biochem. 2011; 44: 1189-1198
        • Ori Y.
        • Bergman M.
        • Bessler H.
        • et al.
        Cytokine secretion and markers of inflammation in relation to acidosis among chronic hemodialysis patients.
        Blood Purif. 2013; 35: 181-186
        • Shi K.
        • Wang F.
        • Jiang H.
        • et al.
        Gut bacterial translocation may aggravate microinflammation in hemodialysis patients.
        Dig Dis Sci. 2014; 59: 2109-2117
        • Lau W.L.
        • Savoj J.
        • Nakata M.B.
        • et al.
        Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins.
        Clin Sci (Lond). 2018; 132: 509-522
        • Montemurno E.
        • Cosola C.
        • Dalfino G.
        • et al.
        What would you like to eat, Mr CKD microbiota? A mediterranean diet, please! Kidney.
        Blood Press Res. 2014; 39: 114-123
        • Rossi M.
        • Johnson D.W.
        • Campbell K.L.
        The kidney-gut Axis: implications for nutrition care.
        J Ren Nutr. 2015; 25: 399-403
        • Vaziri N.D.
        • Wong J.
        • Pahl M.
        • et al.
        Chronic kidney disease alters intestinal microbial flora.
        Kidney Int. 2013; 83: 308-315
        • Wong J.
        • Piceno Y.M.
        • DeSantis T.Z.
        • et al.
        Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD.
        Am J Nephrol. 2014; 39: 230-237
        • Kang J.Y.
        The gastrointestinal tract in uremia.
        Dig Dis Sci. 1993; 38: 257-268
        • Vaziri N.D.
        • Freel R.W.
        • Hatch M.
        Effect of chronic experimental renal insufficiency on urate metabolism.
        J Am Soc Nephrol. 1995; 6: 1313-1317
        • Vaziri N.D.
        • Yuan J.
        • Rahimi A.
        • et al.
        Disintegration of colonic epithelial tight junction in uremia: a likely cause of CKD-associated inflammation.
        Nephrol Dial Transpl. 2012; 27: 2686-2693
        • Vaziri N.D.
        • Yuan J.
        • Nazertehrani S.
        • et al.
        Chronic kidney disease causes disruption of gastric and small intestinal epithelial tight junction.
        Am J Nephrol. 2013; 38: 99-103
        • Wu M.J.
        • Chang C.S.
        • Cheng C.H.
        • et al.
        Colonic transit time in long-term dialysis patients.
        Am J Kidney Dis. 2004; 44: 322-327
        • Weiss G.
        Dietary iron supplementation: a proinflammatory attack on the intestine?.
        Gut. 2015; 64: 696-697
        • Ritz E.
        Intestinal-renal syndrome: mirage or reality?.
        Blood Purif. 2011; 31: 70-76
        • Lin C.J.
        • Wu V.
        • Wu P.C.
        • Wu C.J.
        Meta-analysis of the associations of p-cresyl sulfate (PCS) and indoxyl sulfate (IS) with cardiovascular events and all-cause mortality in patients with chronic renal failure.
        PLoS One. 2015; 10: e0132589
        • Meijers B.K.
        • Claes K.
        • Bammens B.
        • et al.
        p-Cresol and cardiovascular risk in mild-to-moderate kidney disease.
        Clin J Am Soc Nephrol. 2010; 5: 1182-1189
        • Wu I.W.
        • Hsu K.H.
        • Hsu H.J.
        • et al.
        Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients-A prospective cohort study.
        Nephrol Dial Transpl. 2012; 27: 1169-1175
        • Gorbach S.L.
        Probiotics and gastrointestinal health.
        Am J Gastroenterol. 2000; 95: S2-S4
        • Liu Q.
        • Duan Z.P.
        • Ha D.K.
        • et al.
        Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis.
        Hepatology. 2004; 39: 1441-1449
        • Chiva M.
        • Soriano G.
        • Rochat I.
        • et al.
        Effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora and bacterial translocation in rats with experimental cirrhosis.
        J Hepatol. 2002; 37: 456-462
        • Taki K.
        • Takayama F.
        • Niwa T.
        Beneficial effects of Bifidobacteria in a gastroresistant seamless capsule on hyperhomocysteinemia in hemodialysis patients.
        J Ren Nutr. 2005; 15: 77-80
        • Rossi M.
        • Johnson D.W.
        • Morrison M.
        • et al.
        Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): a randomized trial.
        Clin J Am Soc Nephrol. 2016; 11: 223-231
        • Guida B.
        • Germano R.
        • Trio R.
        • et al.
        Effect of short-term synbiotic treatment on plasma p-cresol levels in patients with chronic renal failure: a randomized clinical trial.
        Nutr Metab Cardiovasc Dis. 2014; 24: 1043-1049
        • Hyun H.S.
        • Paik K.H.
        • Cho H.Y.
        p-Cresyl sulfate and indoxyl sulfate in pediatric patients on chronic dialysis.
        Korean J Pediatr. 2013; 56: 159-164
        • Borges N.A.
        • Carmo F.L.
        • Stockler-Pinto M.B.
        • et al.
        Probiotic supplementation in chronic kidney disease: a double-blind, randomized, placebo-controlled trial.
        J Ren Nutr. 2018; 28: 28-36
        • Rajkumar H.
        • Mahmood N.
        • Kumar M.
        • et al.
        Effect of probiotic (VSL#3) and omega-3 on lipid profile, insulin sensitivity, inflammatory markers, and gut colonization in overweight adults: a randomized, controlled trial.
        Mediators Inflamm. 2014; 2014: 348959
        • Chen H.S.
        • Lee K.C.
        • Cheng C.T.
        • et al.
        Application of bioimpedance spectroscopy in Asian dialysis patients (ABISAD): serial follow-up and dry weight evaluation.
        Clin Kidney J. 2013; 6: 29-34
      1. Adequacy of dialysis and nutrition in continuous peritoneal dialysis: association with clinical outcomes. Canada-USA (CANUSA) Peritoneal Dialysis Study Group.
        J Am Soc Nephrol. 1996; 7: 198-207
        • Ware J.E.
        • Sherbourne C.D.
        The MOS 36-item short-form health survey (SF-36). I. Conceptual Framework and item Selection.
        Med Care. 1992; 30: 473-483
        • Ware J.E.
        • Kosinski M.
        SF-36 physical and mental health summary scales: a manual for users of version 1.
        2nd ed. QualityMetric Incorporated, Lincoln, RI2001: 2/3
        • Andersen K.
        • Kesper M.S.
        • Marschner J.A.
        • et al.
        Intestinal dysbiosis, barrier dysfunction, and bacterial translocation account for CKD-related systemic inflammation.
        J Am Soc Nephrol. 2017; 28: 76-83
        • Vitetta L.
        • Linnane A.W.
        • Gobe G.C.
        From the gastrointestinal tract (GIT) to the kidneys: live bacterial cultures (probiotics) mediating reductions of uremic toxin levels via free radical signaling.
        Toxins (Basel). 2013; 5: 2042-2057
        • Wang I.K.
        • Wu Y.Y.
        • Yang Y.F.
        • et al.
        The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: a randomised, double-blind, placebo-controlled trial.
        Benef Microbes. 2015; 6: 423-430
        • Soleimani A.
        • Zarrati Mojarrad M.
        • Bahmani F.
        • et al.
        Probiotic supplementation in diabetic hemodialysis patients has beneficial metabolic effects.
        Kidney Int. 2017; 91: 435-442
        • Shariaty Z.
        • Mahmoodi Shan G.R.
        • Farajollahi M.
        • et al.
        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
        • Pisano A.
        • D'Arrigo G.
        • Coppolino G.
        • et al.
        Biotic supplements for renal patients: a systematic review and meta-analysis.
        Nutrients. 2018; 10: 1224
        • Kazemi A.
        • Soltani S.
        • Ghorabi S.
        • et al.
        Effect of probiotic and synbiotic supplementation on inflammatory markers in health and disease status: a systematic review and meta-analysis of clinical trials.
        Clin Nutr. 2020; 39: 789-819
        • Jia L.
        • Jia Q.
        • Yang J.
        • et al.
        Efficacy of probiotics supplementation on chronic kidney disease: a systematic review and meta-analysis.
        Kidney Blood Press Res. 2018; 43: 1623-1635
        • de Faria Barros A.
        • Borges N.A.
        • Nakao L.S.
        • et al.
        Effects of probiotic supplementation on inflammatory biomarkers and uremic toxins in non-dialysis chronic kidney patients: a double-blind, randomized, placebo-controlled trial.
        J Funct Foods. 2018; 46: 378-383
        • Thongprayoon C.
        • Kaewput W.
        • Hatch S.T.
        • et al.
        Effects of probiotics on inflammation and uremic toxins among patients on dialysis: a systematic review and meta-analysis.
        Dig Dis Sci. 2019; 64: 469-479
        • Natarajan R.
        • Pechenyak B.
        • Vyas U.
        • et al.
        Randomized controlled trial of strain-specific probiotic formulation (Renadyl) in dialysis patients.
        Biomed Res Int. 2014; 2014: 568571
        • Simeoni M.
        • Citraro M.L.
        • Cerantonio A.
        • et al.
        Correction to: an open-label, randomized, placebo-controlled study on the effectiveness of a novel probiotics administration protocol (ProbiotiCKD) in patients with mild renal insufficiency (stage 3a of CKD).
        Eur J Nutr. 2019; 58: 2157
        • Sirich T.L.
        • Plummer N.S.
        • Gardner C.D.
        • et al.
        Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients.
        Clin J Am Soc Nephrol. 2014; 9: 1603-1610
        • Poesen R.
        • Evenepoel P.
        • de Loor H.
        • et al.
        The influence of prebiotic arabinoxylan oligosaccharides on microbiota derived uremic retention solutes in patients with chronic kidney disease: a randomized controlled trial.
        PLoS One. 2016; 11: e0153893
        • Esgalhado M.
        • Kemp J.A.
        • Azevedo R.
        • et al.
        Could resistant starch supplementation improve inflammatory and oxidative stress biomarkers and uremic toxins levels in hemodialysis patients? A pilot randomized controlled trial.
        Food Funct. 2018; 9: 6508-6516
        • Eidi F.
        • Poor-Reza Gholi F.
        • Ostadrahimi A.
        • et al.
        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: 158-164
        • McFarlane C.
        • Ramos C.I.
        • Johnson D.W.
        • et al.
        Prebiotic, probiotic, and synbiotic supplementation in chronic kidney disease: a systematic review and meta-analysis.
        J Ren Nutr. 2019; 29: 209-220
        • Nakabayashi I.
        • Nakamura M.
        • Kawakami K.
        • et al.
        Effects of synbiotic treatment on serum level of p-cresol in haemodialysis patients: a preliminary study.
        Nephrol Dial Transpl. 2011; 26: 1094-1098
        • Ramos C.I.
        • Armani R.G.
        • Canziani M.E.F.
        • et al.
        Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: a randomized controlled trial.
        Nephrol Dial Transpl. 2019; 34: 1876-1884
        • McFarland L.V.
        • Evans C.T.
        • Goldstein E.J.C.
        Strain-specificity and disease-specificity of probiotic efficacy: a systematic review and meta-analysis.
        Front Med (Lausanne). 2018; 5: 124
        • Jeng Y.
        • Lim P.S.
        • Wu M.Y.
        • et al.
        Proportions of proinflammatory monocytes are important predictors of mortality risk in hemodialysis patients.
        Mediators Inflamm. 2017; 2017: 1070959
        • Dai L.
        • Golembiewska E.
        • Lindholm B.
        • et al.
        End-stage renal disease, inflammation and cardiovascular outcomes.
        Contrib Nephrol. 2017; 191: 32-43
        • Lepper P.M.
        • Schumann C.
        • Triantafilou K.
        • et al.
        Association of lipopolysaccharide-binding protein and coronary artery disease in men.
        J Am Coll Cardiol. 2007; 50: 25-31
        • Wang F.
        • Jiang H.
        • Shi K.
        • et al.
        Gut bacterial translocation is associated with microinflammation in end-stage renal disease patients.
        Nephrology (Carlton). 2012; 17: 733-738
        • Awoyemi A.
        • Troseid M.
        • Arnesen H.
        • et al.
        Markers of metabolic endotoxemia as related to metabolic syndrome in an elderly male population at high cardiovascular risk: a cross-sectional study.
        Diabetol Metab Syndr. 2018; 10: 59
        • Lim P.S.
        • Chang Y.K.
        • Wu T.K.
        Serum lipopolysaccharide-binding protein is associated with chronic inflammation and metabolic syndrome in hemodialysis patients.
        Blood Purif. 2019; 47: 28-36
        • Vaziri N.D.
        • Liu S.
        • Lau W.L.
        • et al.
        High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease.
        PLoS One. 2014; 9: e114881
        • Kieffer D.A.
        • Piccolo B.D.
        • Vaziri N.D.
        • et al.
        Resistant starch alters the gut microbiota, uremic retention solutes and xeno-metabolite profiles concurrent with amelioration of chronic kidney disease in rats.
        Am J Physiol Ren Physiol. 2016; 310: F857-F871
        • Tayebi Khosroshahi H.
        • Abedi B.
        • Habibi B.
        • et al.
        The salutary effect of amylose resistant starch (HAM-RS2) supplementation on biomarkers of inflammation and oxidative stress in hemodialysis patients.
        Hemodialysis Int. 2018; 22: 492-500
        • Laffin M.R.
        • Tayebi Khosroshahi H.
        • Park H.
        • et al.
        Amylose resistant starch (HAM-RS2) supplementation increases the proportion of Faecalibacterium bacteria in end-stage renal disease patients: microbial analysis from a randomized placebo-controlled trial.
        Hemodial Int. 2019; 23: 343-347