Login Register Cart 0
Generic placeholder image

Current Nutrition & Food Science

Editor-in-Chief

ISSN (Print): 1573-4013
ISSN (Online): 2212-3881

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Pilot Study of Probiotic Supplementation on Uremic Toxicity and Inflammatory Cytokines in Chronic Kidney Patients

Author(s): Cristina T. Roth-Stefanski, Carla Dolenga, Lia S. Nakao, Roberto Pecoits-Filho, Thyago P. de Moraes and Andrea N. Moreno-Amaral*

Volume 16, Issue 4, 2020

Page: [470 - 480] Pages: 11

DOI: 10.2174/1573401315666190215111402

Price: $65

Abstract

Background: Bacterial metabolism contributes to the generation of uremic toxins in patients with chronic kidney disease (CKD). It has been investigated the use of probiotics in the reduction of uremic toxins intestinal production.

Objective: The aim of this pilot study was to evaluate the effect of probiotic supplementation on reducing the production of uremic toxins and the inflammatory profile of CKD patients.

Methods: We performed a randomized, blind, placebo-controlled, crossover study on patients with CKD stages 3 and 4. The intervention was a probiotic formulation composed of Lactobacillus acidophilus strains given orally three times a day for 3 months. Changes in uremic toxins (p-Cresylsulfate and Indoxyl Sulfate) and serum inflammatory cytokines were the primary endpoints.

Results: Of the 44 patients randomized, 25 completed the study (mean age 51 ± 9.34, 64% female, mean eGFR 36 ± 14.26 mL/min/1.73m², mean BMI 28.5 ± 5.75 kg/m²). At 3 months, there were no significant changes in any of the studied biomarkers including p-cresylsulfate (p = 0.57), Indoxyl sulfate (p = 0.08) and interleukin-6 (p = 0.55).

Conclusion: Lactobacillus acidophilus strains given as probiotic were not able to reduce serum levels of uremic toxins and biomarkers of inflammation in CKD patients in stage 3 and 4.

Keywords: Chronic kidney failure, cytokines, inflammation, Lactobacillus acidophilus, probiotics, uremia.

« Previous Next »
Graphical Abstract

[1]
Macfarlane GT, Macfarlane S. Bacteria, colonic fermentation, and gastrointestinal health. J AOAC Int 2012; 95(1): 50-60.
[http://dx.doi.org/10.5740/jaoacint.SGE_Macfarlane] [PMID: 22468341]
[2]
Wikoff WR, Anfora AT, Liu J, et al. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci USA 2009; 106(10): 3698-703.
[http://dx.doi.org/10.1073/pnas.0812874106] [PMID: 19234110]
[3]
Evenepoel P, Meijers BK, Bammens BR, Verbeke K. Uremic toxins originating from colonic microbial metabolism. Kidney Int Suppl 2009; (114): S12-9.
[http://dx.doi.org/10.1038/ki.2009.402] [PMID: 19946322]
[4]
Vanholder R, De Smet R, Glorieux G, et al. European Uremic Toxin Work Group (EUTox). Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int 2003; 63(5): 1934-43.
[http://dx.doi.org/10.1046/j.1523-1755.2003.00924.x] [PMID: 12675874]
[5]
Sallée M, Dou L, Cerini C, Poitevin S, Brunet P, Burtey S. The aryl hydrocarbon receptor-activating effect of uremic toxins from tryptophan metabolism: a new concept to understand cardiovascular complications of chronic kidney disease. Toxins (Basel) 2014; 6(3): 934-49.
[http://dx.doi.org/10.3390/toxins6030934] [PMID: 24599232]
[6]
Jourde-Chiche N, Dou L, Cerini C, Dignat-George F, Vanholder R, Brunet P. Protein-bound toxins--update 2009. Semin Dial 2009; 22(4): 334-9.
[http://dx.doi.org/10.1111/j.1525-139X.2009.00576.x] [PMID: 19708977]
[7]
Gryp T, Vanholder R, Vaneechoutte M, Glorieux G. p-Cresyl Sulfate. Toxins (Basel) 2017; 9(2)E52
[http://dx.doi.org/10.3390/toxins9020052] [PMID: 28146081]
[8]
Poesen R, Windey K, Neven E, et al. The influence of CKD on colonic microbial metabolism. J Am Soc Nephrol 2016; 27(5): 1389-99.
[http://dx.doi.org/10.1681/ASN.2015030279] [PMID: 26400570]
[9]
Vanholder R, Van Laecke S, Glorieux G. What is new in uremic toxicity? Pediatr Nephrol 2008; 23(8): 1211-21.
[http://dx.doi.org/10.1007/s00467-008-0762-9] [PMID: 18324423]
[10]
Brunet P, Dou L, Cerini C, Berland Y. Protein-bound uremic retention solutes. Adv Ren Replace Ther 2003; 10(4): 310-20.
[http://dx.doi.org/10.1053/j.arrt.2003.08.002] [PMID: 14681860]
[11]
Meijers BK, Evenepoel P. The gut-kidney axis: indoxyl sulfate, p-cresyl sulfate and CKD progression. Nephrol Dial Transplant 2011; 26(3): 759-61.
[http://dx.doi.org/10.1093/ndt/gfq818] [PMID: 21343587]
[12]
Vaziri ND. CKD impairs barrier function and alters microbial flora of the intestine: a major link to inflammation and uremic toxicity. Curr Opin Nephrol Hypertens 2012; 21(6): 587-92.
[http://dx.doi.org/10.1097/MNH.0b013e328358c8d5] [PMID: 23010760]
[13]
Vaziri ND, Yuan J, Norris K. Role of urea in intestinal barrier dysfunction and disruption of epithelial tight junction in chronic kidney disease. Am J Nephrol 2013; 37(1): 1-6.
[http://dx.doi.org/10.1159/000345969] [PMID: 23258127]
[14]
Vaziri ND, Wong J, Pahl M, et al. Chronic kidney disease alters intestinal microbial flora. Kidney Int 2013; 83(2): 308-15.
[http://dx.doi.org/10.1038/ki.2012.345] [PMID: 22992469]
[15]
Armani RG, Ramezani A, Yasir A, Sharama S, Canziani MEF, Raj DS. Gut microbiome in chronic kidney disease. Curr Hypertens Rep 2017; 19(4): 29.
[http://dx.doi.org/10.1007/s11906-017-0727-0] [PMID: 28343357]
[16]
Rossi M, Klein K, Johnson DW, Campbell KL. Pre-, pro-, and synbiotics: do they have a role in reducing uremic toxins? A systematic review and meta-analysis. Int J Nephrol 2012; 2012673631
[http://dx.doi.org/10.1155/2012/673631] [PMID: 23316359]
[17]
Rossi M, Johnson DW, Campbell KL. The kidney-gut axis: Implications for nutrition care. J Ren Nutr 2015; 25(5): 399-403.
[http://dx.doi.org/10.1053/j.jrn.2015.01.017] [PMID: 25812908]
[18]
Vitetta L, Gobe G. Uremia and chronic kidney disease: the role of the gut microflora and therapies with pro- and prebiotics. Mol Nutr Food Res 2013; 57(5): 824-32.
[http://dx.doi.org/10.1002/mnfr.201200714] [PMID: 23450842]
[19]
Patel R, DuPont HL. New approaches for bacteriotherapy: prebiotics, new-generation probiotics, and synbiotics. Clin Infect Dis 2015; 60(Suppl. 2): S108-21.
[http://dx.doi.org/10.1093/cid/civ177] [PMID: 25922396]
[20]
Hida M, Aiba Y, Sawamura S, Suzuki N, Satoh T, Koga Y. Inhibition of the accumulation of uremic toxins in the blood and their precursors in the feces after oral administration of Lebenin, a lactic acid bacteria preparation, to uremic patients undergoing hemodialysis. Nephron 1996; 74(2): 349-55.
[http://dx.doi.org/10.1159/000189334] [PMID: 8893154]
[21]
Takayama F, Taki K, Niwa T. Bifidobacterium in gastro-resistant seamless capsule reduces serum levels of indoxyl sulfate in patients on hemodialysis. Am J Kidney Dis 2003; 41(3)(Suppl. 1): S142-5.
[http://dx.doi.org/10.1053/ajkd.2003.50104] [PMID: 12612972]
[22]
Ranganathan N, Patel BG, Ranganathan P, et al. In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic kidney disease. ASAIO J 2006; 52(1): 70-9.
[http://dx.doi.org/10.1097/01.mat.0000191345.45735.00] [PMID: 16436893]
[23]
Ranganathan N, Ranganathan P, Friedman EA, et al. Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease. Adv Ther 2010; 27(9): 634-47.
[http://dx.doi.org/10.1007/s12325-010-0059-9] [PMID: 20721651]
[24]
Miranda Alatriste PV, Urbina Arronte R, Gómez Espinosa CO, Espinosa Cuevas MdeL. Effect of probiotics on human blood urea levels in patients with chronic renal failure. Nutr Hosp 2014; 29(3): 582-90.
[PMID: 24559003]
[25]
Natarajan R, Pechenyak B, Vyas U, et al. Randomized controlled trial of strain-specific probiotic formulation (Renadyl) in dialysis patients. BioMed Res Int 2014; 2014568571
[http://dx.doi.org/10.1155/2014/568571] [PMID: 25147806]
[26]
Ramezani A, Raj DS. The gut microbiome, kidney disease, and targeted interventions. J Am Soc Nephrol 2014; 25(4): 657-70.
[http://dx.doi.org/10.1681/ASN.2013080905] [PMID: 24231662]
[27]
Rossi M, Johnson DW, Morrison M, et al. Synbiotics easing renal failure by improving gut microbiology (SYNERGY): A randomized trial. Clin J Am Soc Nephrol 2016; 11(2): 223-31.
[http://dx.doi.org/10.2215/CJN.05240515] [PMID: 26772193]
[28]
Guida B, Germanò 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(9): 1043-9.
[http://dx.doi.org/10.1016/j.numecd.2014.04.007] [PMID: 24929795]
[29]
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(1): 77-80.
[http://dx.doi.org/10.1053/j.jrn.2004.09.028] [PMID: 15648012]
[30]
Ranganathan N, Friedman EA, Tam P, Rao V, Ranganathan P, Dheer R. Probiotic dietary supplementation in patients with stage 3 and 4 chronic kidney disease: a 6-month pilot scale trial in Canada. Curr Med Res Opin 2009; 25(8): 1919-30.
[http://dx.doi.org/10.1185/03007990903069249] [PMID: 19558344]
[31]
Wang IK, Wu YY, Yang YF, 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(4): 423-30.
[http://dx.doi.org/10.3920/BM2014.0088] [PMID: 25609654]
[32]
Viramontes-Hörner D, Márquez-Sandoval F, Martín-del-Campo F, et al. Effect of a symbiotic gel (Lactobacillus acidophilus + Bifidobacterium lactis + inulin) on presence and severity of gastrointestinal symptoms in hemodialysis patients. J Ren Nutr 2015; 25(3): 284-91.
[http://dx.doi.org/10.1053/j.jrn.2014.09.008] [PMID: 25455039]
[33]
Koppe L, Mafra D, Fouque D. Probiotics and chronic kidney disease. Kidney Int 2015; 88(5): 958-66.
[http://dx.doi.org/10.1038/ki.2015.255] [PMID: 26376131]
[34]
Medellin-Peña MJ, Wang H, Johnson R, Anand S, Griffiths MW. Probiotics affect virulence-related gene expression in Escherichia coli O157:H7. Appl Environ Microbiol 2007; 73(13): 4259-67.
[http://dx.doi.org/10.1128/AEM.00159-07] [PMID: 17496132]
[35]
Kim Y, Kim SH, Whang KY, Kim YJ, Oh S. Inhibition of Escherichia coli O157:H7 attachment by interactions between lactic acid bacteria and intestinal epithelial cells. J Microbiol Biotechnol 2008; 18(7): 1278-85.
[PMID: 18667857]
[36]
Simenhoff ML, Dunn SR, Zollner GP, et al. Biomodulation of the toxic and nutritional effects of small bowel bacterial overgrowth in end-stage kidney disease using freeze-dried Lactobacillus acidophilus. Miner Electrolyte Metab 1996; 22(1-3): 92-6.
[PMID: 8676836]
[37]
Claro LM, Moreno-Amaral AN, Gadotti AC, et al. The impact of uremic toxicity induced inflammatory response on the cardiovascular burden in chronic kidney disease. Toxins (Basel) 2018; 10(10)E384
[http://dx.doi.org/10.3390/toxins10100384] [PMID: 30249039]
[38]
Borges NA, Barros AF, Nakao LS, Dolenga CJ, Fouque D, Mafra D. Protein-bound uremic toxins from gut microbiota and inflammatory markers in chronic kidney disease. J Ren Nutr 2016; 26(6): 396-400.
[http://dx.doi.org/10.1053/j.jrn.2016.07.005] [PMID: 27751361]
[39]
Meert N, Schepers E, Glorieux G, et al. Novel method for simultaneous determination of p-cresylsulphate and p-cresylglucuronide: clinical data and pathophysiological implications. Nephrol Dial Transplant 2012; 27(6): 2388-96.
[http://dx.doi.org/10.1093/ndt/gfr672] [PMID: 22167586]
[40]
Erthal Leinig C, Pecoits-Filho R, Kunii L, et al. Low-fiber intake is associated with high production of intra-peritoneal inflammation biomarkers. J Ren Nutr 2019; S1051-2276(18): 30253-X.
[41]
Borges NA, Carmo FL, Stockler-Pinto MB, et al. Probiotic supplementation in chronic kidney disease: A double-blind, randomized, placebo-controlled trial. J Ren Nutr 2018; 28(1): 28-36.
[http://dx.doi.org/10.1053/j.jrn.2017.06.010] [PMID: 28888762]
[42]
Hyun HS, Paik KH, Cho HY. p-Cresyl sulfate and indoxyl sulfate in pediatric patients on chronic dialysis. Korean J Pediatr 2013; 56(4): 159-64.
[http://dx.doi.org/10.3345/kjp.2013.56.4.159] [PMID: 23646054]
[43]
Gibson GR, Wang X. Regulatory effects of bifidobacteria on the growth of other colonic bacteria. J Appl Bacteriol 1994; 77(4): 412-20.
[http://dx.doi.org/10.1111/j.1365-2672.1994.tb03443.x] [PMID: 7989269]
[44]
Vaziri ND, Zhao YY, Pahl MV. Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: the nature, mechanisms, consequences and potential treatment. Nephrol Dial Transplant 2016; 31(5): 737-46.
[http://dx.doi.org/10.1093/ndt/gfv095] [PMID: 25883197]
[45]
Moraes C, Borges NA, Mafra D. Resistant starch for modulation of gut microbiota: Promising adjuvant therapy for chronic kidney disease patients? Eur J Nutr 2016; 55(5): 1813-21.
[http://dx.doi.org/10.1007/s00394-015-1138-0] [PMID: 26830416]
[46]
Sirich TL, Plummer NS, Gardner CD, Hostetter TH, Meyer TW. Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients. Clin J Am Soc Nephrol 2014; 9(9): 1603-10.
[http://dx.doi.org/10.2215/CJN.00490114] [PMID: 25147155]
[47]
Krumbeck JA, Maldonado-Gomez MX, Ramer-Tait AE, Hutkins RW. Prebiotics and synbiotics: dietary strategies for improving gut health. Curr Opin Gastroenterol 2016; 32(2): 110-9.
[http://dx.doi.org/10.1097/MOG.0000000000000249] [PMID: 26825589]
[48]
Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol 2017; 14(8): 491-502.
[http://dx.doi.org/10.1038/nrgastro.2017.75] [PMID: 28611480]
[49]
Anderson AD, McNaught CE, Jain PK, MacFie J. Randomised clinical trial of synbiotic therapy in elective surgical patients. Gut 2004; 53(2): 241-5.
[http://dx.doi.org/10.1136/gut.2003.024620] [PMID: 14724157]
[50]
Urben LM, Wiedmar J, Boettcher E, Cavallazzi R, Martindale RG, McClave SA. Bugs or drugs: are probiotics safe for use in the critically ill? Curr Gastroenterol Rep 2014; 16(7): 388.
[http://dx.doi.org/10.1007/s11894-014-0388-y] [PMID: 24986534]
[51]
Wong J, Piceno YM, DeSantis TZ, Pahl M, Andersen GL, Vaziri ND. 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(3): 230-7.
[http://dx.doi.org/10.1159/000360010] [PMID: 24643131]
[52]
Vaziri ND, Liu SM, Lau WL, et al. High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease. PLoS One 2014; 9(12)e114881
[http://dx.doi.org/10.1371/journal.pone.0114881] [PMID: 25490712]
[53]
Kieffer DA, Piccolo BD, Vaziri ND, et al. Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats. Am J Physiol Renal Physiol 2016; 310(9): F857-71.
[http://dx.doi.org/10.1152/ajprenal.00513.2015] [PMID: 26841824]
[54]
Lau WL, Kalantar-Zadeh K, Vaziri ND. The gut as a source of inflammation in chronic kidney disease. Nephron 2015; 130(2): 92-8.
[http://dx.doi.org/10.1159/000381990] [PMID: 25967288]
[55]
Vaziri ND, Goshtasbi N, Yuan J, et al. Uremic plasma impairs barrier function and depletes the tight junction protein constituents of intestinal epithelium. Am J Nephrol 2012; 36(5): 438-43.
[http://dx.doi.org/10.1159/000343886] [PMID: 23128155]
[56]
Pahl MV, Vaziri ND. The chronic kidney disease - colonic axis. Semin Dial 2015; 28(5): 459-63.
[http://dx.doi.org/10.1111/sdi.12381] [PMID: 25855516]
[57]
Ritz E. Intestinal-renal syndrome: mirage or reality? Blood Purif 2011; 31(1-3): 70-6.
[http://dx.doi.org/10.1159/000321848] [PMID: 21228570]
[58]
Lau WL, Savoj J, Nakata MB, Vaziri ND. Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins. Clin Sci (Lond) 2018; 132(5): 509-22.
[http://dx.doi.org/10.1042/CS20171107] [PMID: 29523750]
[59]
Barros AF, Borges NA, Ferreira DC, et al. Is there interaction between gut microbial profile and cardiovascular risk in chronic kidney disease patients? Future Microbiol 2015; 10(4): 517-26.
[http://dx.doi.org/10.2217/fmb.14.140] [PMID: 25865191]
[60]
Boyle RJ, Robins-Browne RM, Tang ML. Probiotic use in clinical practice: what are the risks? Am J Clin Nutr 2006; 83(6): 1256-64.
[http://dx.doi.org/10.1093/ajcn/83.6.1256] [PMID: 16762934]
[61]
Snydman DR. The safety of probiotics. Clin Infect Dis 2008; 46(Suppl. 2): S104-11.
[http://dx.doi.org/10.1086/523331] [PMID: 18181712]
[62]
Suzuki K, Benno Y, Mitsuoka T, Takebe S, Kobashi K, Hase J. Urease-producing species of intestinal anaerobes and their activities. Appl Environ Microbiol 1979; 37(3): 379-82.
[http://dx.doi.org/10.1128/AEM.37.3.379-382.1979] [PMID: 36839]
[63]
Cook AR. Urease activity in the rumen of sheep and the isolation of ureolytic bacteria. J Gen Microbiol 1976; 92(1): 32-48.
[http://dx.doi.org/10.1099/00221287-92-1-32] [PMID: 812952]
[64]
Lam S, Yeo M. Urease-positive Vibrio parahaemolyticus strain. J Clin Microbiol 1980; 12(1): 57-9.
[http://dx.doi.org/10.1128/JCM.12.1.57-59.1980] [PMID: 7419701]
[65]
Orth D, Grif K, Dierich MP, Würzner R. Prevalence, structure and expression of urease genes in Shiga toxin-producing Escherichia coli from humans and the environment. Int J Hyg Environ Health 2006; 209(6): 513-20.
[http://dx.doi.org/10.1016/j.ijheh.2006.06.003] [PMID: 16877040]
[66]
Esgalhado M, Borges NA, Mafra D. Could physical exercise help modulate the gut microbiota in chronic kidney disease? Future Microbiol 2016; 11: 699-707.
[http://dx.doi.org/10.2217/fmb.16.12] [PMID: 27159232]
[67]
Goto S, Yoshiya K, Kita T, Fujii H, Fukagawa M. Uremic toxins and oral adsorbents. Ther Apher Dial 2011; 15(2): 132-4.
[http://dx.doi.org/10.1111/j.1744-9987.2010.00891.x] [PMID: 21426503]
[68]
Kikuchi K, Itoh Y, Tateoka R, Ezawa A, Murakami K, Niwa T. Metabolomic search for uremic toxins as indicators of the effect of an oral sorbent AST-120 by liquid chromatography/tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2010; 878(29): 2997-3002.
[http://dx.doi.org/10.1016/j.jchromb.2010.09.006] [PMID: 20870466]
[69]
Bolati D, Shimizu H, Niwa T. AST-120 ameliorates epithelial-to-mesenchymal transition and interstitial fibrosis in the kidneys of chronic kidney disease rats. J Ren Nutr 2012; 22(1): 176-80.
[http://dx.doi.org/10.1053/j.jrn.2011.10.015] [PMID: 22200438]
[70]
Shibahara H, Shibahara N. Cardiorenal protective effect of the oral uremic toxin absorbent AST-120 in chronic heart disease patients with moderate CKD. J Nephrol 2010; 23(5): 535-40.
[PMID: 20540030]
[71]
Nakamura T, Sato E, Fujiwara N, et al. Oral adsorbent AST-120 ameliorates tubular injury in chronic renal failure patients by reducing proteinuria and oxidative stress generation. Metabolism 2011; 60(2): 260-4.
[http://dx.doi.org/10.1016/j.metabol.2010.01.023] [PMID: 20189611]
[72]
Ito S, Higuchi Y, Yagi Y, et al. Reduction of indoxyl sulfate by AST-120 attenuates monocyte inflammation related to chronic kidney disease. J Leukoc Biol 2013; 93(6): 837-45.
[http://dx.doi.org/10.1189/jlb.0112023] [PMID: 23362306]
[73]
Niwa T. Role of indoxyl sulfate in the progression of chronic kidney disease and cardiovascular disease: experimental and clinical effects of oral sorbent AST-120. Ther Apher Dial 2011; 15(2): 120-4.
[http://dx.doi.org/10.1111/j.1744-9987.2010.00882.x] [PMID: 21426500]
[74]
Vaziri ND, Yuan J, Khazaeli M, Masuda Y, Ichii H, Liu S. Oral activated charcoal adsorbent (AST-120) ameliorates chronic kidney disease-induced intestinal epithelial barrier disruption. Am J Nephrol 2013; 37(6): 518-25.
[http://dx.doi.org/10.1159/000351171] [PMID: 23689670]
[75]
Akizawa T, Asano Y, Morita S, et al. CAP-KD Study Group. Effect of a carbonaceous oral adsorbent on the progression of CKD: a multicenter, randomized, controlled trial. Am J Kidney Dis 2009; 54(3): 459-67.
[http://dx.doi.org/10.1053/j.ajkd.2009.05.011] [PMID: 19615804]
[76]
Schulman G, Berl T, Beck GJ, et al. Randomized placebo-controlled EPPIC trials of AST-120 in CKD. J Am Soc Nephrol 2015; 26(7): 1732-46.
[http://dx.doi.org/10.1681/ASN.2014010042] [PMID: 25349205]
[77]
Vanholder R, Glorieux G. The intestine and the kidneys: a bad marriage can be hazardous. Clin Kidney J 2015; 8(2): 168-79.
[http://dx.doi.org/10.1093/ckj/sfv004] [PMID: 25815173]
[78]
Tatiana M. Alzbeta Mo, Marina O, Valik Lu. The medical functions of probiotics and their role in clinical nutrition. Curr Nutr Food Sci 2018; 14(1): 3-10.
[http://dx.doi.org/10.2174/1573401313666170405152905]
[79]
Hempel S, Newberry S, Ruelaz A, et al. Safety of probiotics used to reduce risk and prevent or treat disease. Evid Rep Technol Assess (Full Rep) 2011; (200): 1-645.
[PMID: 23126627]

Rights & Permissions Print Cite
Article Metrics
17
5
© 2024 Bentham Science Publishers | Privacy Policy