Kidney-gut axis disruption in chronic kidney disease: causes, consequences and treatment strategies
DOI:
https://doi.org/10.14306/renhyd.21.2.244Keywords:
Renal Insufficiency, Chronic, Gastrointestinal Microbiome, Uremia, Probiotics, Prebiotics, Diet TherapyAbstract
Chronic kidney disease and uremic state are associated with intestinal barrier permeability alterations and changes in gut microbiome composition that increased the production and translocation of uremic toxins such indoxyl sulfate (IS) and p-cresyl sulfate (pCS) and contribute to the immunological response. Uremic toxins and inflammation are associated with and increase on mortality, cardiovascular events and mineral bone disorders. Several nutritional and pharmacological strategies have been studied to modulate the gut microbiota composition and intestinal permeability alterations, including probiotic, prebiotic and symbiotic supplementation, changes in diet composition and use of adsorbent agents. The aim of this study is to review the etiology of intestinal and microbiota alterations analyzing the consequences and interventions studied to date.
References
(1) Kotanko P, Carter M, Levin NW. Intestinal bacterial microflora--a potential source of chronic inflammation in patients with chronic kidney disease. Nephrol Dial Transplant. 2006;21(8):2057-60.
(2) Günzel D, Yu ASL. Claudins and the modulation of tight junction permeability. Physiol Rev. 2013;93(2):525-69.
(3) Vaziri ND, Yuan J, Rahimi A, Ni Z, Said H, Subramanian VS. Disintegration of colonic epithelial tight junction in uremia: a likely cause of CKD-associated inflammation. Nephrol Dial Transplant. 2012;27(7):2686-93.
(4) Vaziri ND, Yuan J, Nazertehrani S, Ni Z, Liu S. Chronic kidney disease causes disruption of gastric and small intestinal epithelial tight junction. Am J Nephrol. 2013;38(2):99-103.
(5) 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.
(6) Vaziri ND, Goshtasbi N, Yuan J, Jellbauer S, Moradi H, Raffatellu M, 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.
(7) Gonçalves S, Pecoits-Filho R, Perreto S, Barberato SH, Stinghen AEM, Lima EGA, et al. Associations between renal function, volume status and endotoxaemia in chronic kidney disease patients. Nephrol Dial Transplant. 2006;21(10):2788-94.
(8) McIntyre CW, Harrison LEA, Eldehni MT, Jefferies HJ, Szeto C-C, John SG, et al. Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease. Clin J Am Soc Nephrol. 2011;6(1):133-41.
(9) Hauser AB, Stinghen AEM, Gonçalves SM, Bucharles S, Pecoits-Filho R. A gut feeling on endotoxemia: causes and consequences in chronic kidney disease. Nephron Clin Pract. 2011;118(2):c165-172; discussion c172.
(10) Machowska A, Carrero JJ, Lindholm B, Stenvinkel P. Therapeutics targeting persistent inflammation in chronic kidney disease. Transl Res. 2016;167(1):204-13.
(11) de Punder K, Pruimboom L. Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability. Front Immunol. 2015;6:223.
(12) Mafra D, Fouque D. Gut microbiota and inflammation in chronic kidney disease patients. Clin Kidney J. 2015;8(3):332-4.
(13) Raj DSC, Carrero JJ, Shah VO, Qureshi AR, Bárány P, Heimbürger O, et al. Soluble CD14 levels, interleukin 6, and mortality among prevalent hemodialysis patients. Am J Kidney Dis. 2009;54(6):1072-80.
(14) Akchurin OM, Kaskel F. Update on inflammation in chronic kidney disease. Blood Purif. 2015;39(1-3):84-92.
(15) Gerritsen J, Smidt H, Rijkers GT, de Vos WM. Intestinal microbiota in human health and disease: the impact of probiotics. Genes Nutr. 2011;6(3):209-40.
(16) Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell. 2012;148(6):1258-70.
(17) Villanueva-Millán MJ, Pérez-Matute P, Oteo JA. Gut microbiota: a key player in health and disease. A review focused on obesity. J Physiol Biochem. 2015;71(3):509-25.
(18) Guinane CM, Cotter PD. Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organ. Therap Adv Gastroenterol. 2013;6(4):295-308.
(19) Vaziri ND, Wong J, Pahl M, Piceno YM, Yuan J, DeSantis TZ, et al. Chronic kidney disease alters intestinal microbial flora. Kidney Int. 2013;83(2):308-15.
(20) 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.
(21) 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.
(22) Kalantar-Zadeh K, Kopple JD, Deepak S, Block D, Block G. Food intake characteristics of hemodialysis patients as obtained by food frequency questionnaire. J Ren Nutr. 2002;12(1):17-31.
(23) Aron-Wisnewsky J, Clément K. The gut microbiome, diet, and links to cardiometabolic and chronic disorders. Nat Rev Nephrol. 2016;12(3):169-81.
(24) Evenepoel P, Meijers BK. Dietary fiber and protein: nutritional therapy in chronic kidney disease and beyond. Kidney Int. 2012;81(3):227-9.
(25) Aronov PA, Luo FJ-G, Plummer NS, Quan Z, Holmes S, Hostetter TH, et al. Colonic contribution to uremic solutes. J Am Soc Nephrol. 2011;22(9):1769-76.
(26) Vanholder R, Glorieux G. The intestine and the kidneys: a bad marriage can be hazardous. Clin Kidney J. 2015;8(2):168-79.
(27) Meijers BKI, Evenepoel P. The gut-kidney axis: indoxyl sulfate, p-cresyl sulfate and CKD progression. Nephrol Dial Transplant. 2011;26(3):759-61.
(28) Vaziri ND, Zhao Y-Y, 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.
(29) Moraes C, Fouque D, Amaral ACF, Mafra D. Trimethylamine N-Oxide From Gut Microbiota in Chronic Kidney Disease Patients: Focus on Diet. J Ren Nutr. 2015;25(6):459-65.
(30) Mafra D, Lobo JC, Barros AF, Koppe L, Vaziri ND, Fouque D. Role of altered intestinal microbiota in systemic inflammation and cardiovascular disease in chronic kidney disease. Future Microbiol. 2014;9(3):399-410.
(31) 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(7):e0132589.
(32) Wu I-W, Hsu K-H, Lee C-C, Sun C-Y, Hsu H-J, Tsai C-J, et al. p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease. Nephrol Dial Transplant. 2011;26(3):938-47.
(33) Ramezani A, Raj DS. The gut microbiome, kidney disease, and targeted interventions. J Am Soc Nephrol. 2014;25(4):657-70.
(34) Black AP, Cardozo LFMF, Mafra D. Effects of Uremic Toxins from the Gut Microbiota on Bone: A Brief Look at Chronic Kidney Disease. Ther Apher Dial. 2015;19(5):436-40.
(35) Tang WHW, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368(17):1575-84.
(36) Tang WHW, Wang Z, Kennedy DJ, Wu Y, Buffa JA, Agatisa-Boyle B, et al. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015;116(3):448-55.
(37) World Health Organization, Food and Agriculture Organization of the United Nations. Probiotics in food: Health and nutritional properties and guidelines for evaluation. Roma, Italia: FAO/WHO; 2006.
(38) Koppe L, Mafra D, Fouque D. Probiotics and chronic kidney disease. Kidney Int. 2015;88(5):958-66.
(39) Wang I-K, Wu Y-Y, Yang Y-F, Ting I-W, Lin C-C, Yen T-H, 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.
(40) 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.
(41) Miranda Alatriste PV, Urbina Arronte R, Gómez Espinosa CO, Espinosa Cuevas M de los Á. Effect of probiotics on human blood urea levels in patients with chronic renal failure. Nutr Hosp. 2014;29(3):582-90.
(42) Rossi M, Johnson DW, Campbell KL. The Kidney-Gut Axis: Implications for Nutrition Care. J Ren Nutr. 2015;25(5):399-403.
(43) 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.
(44) 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;2012:673631.
(45) Chiavaroli L, Mirrahimi A, Sievenpiper JL, Jenkins DJA, Darling PB. Dietary fiber effects in chronic kidney disease: a systematic review and meta-analysis of controlled feeding trials. Eur J Clin Nutr. 2015;69(7):761-8.
(46) Guida B, Germanò R, Trio R, Russo D, Memoli B, Grumetto L, 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.
(47) Viramontes-Hörner D, Márquez-Sandoval F, Martín-del-Campo F, Vizmanos-Lamotte B, Sandoval-Rodríguez A, Armendáriz-Borunda J, 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.
(48) Cruz-Mora J, Martínez-Hernández NE, Martín del Campo-López F, Viramontes-Hörner D, Vizmanos-Lamotte B, Muñoz-Valle JF, et al. Effects of a symbiotic on gut microbiota in Mexican patients with end-stage renal disease. J Ren Nutr. 2014;24(5):330-5.
(49) Rossi M, Johnson DW, Morrison M, Pascoe EM, Coombes JS, Forbes JM, et al. Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial. Clin J Am Soc Nephrol. 2016;11(2):223-31.
(50) Marzocco S, Dal Piaz F, Di Micco L, Torraca S, Sirico ML, Tartaglia D, et al. Very low protein diet reduces indoxyl sulfate levels in chronic kidney disease. Blood Purif. 2013;35(1-3):196-201.
(51) Rossi M, Johnson DW, Xu H, Carrero JJ, Pascoe E, French C, et al. Dietary protein-fiber ratio associates with circulating levels of indoxyl sulfate and p-cresyl sulfate in chronic kidney disease patients. Nutr Metab Cardiovasc Dis. 2015;25(9):860-5.
(52) Montemurno E, Cosola C, Dalfino G, Daidone G, De Angelis M, Gobbetti M, et al. What would you like to eat, Mr CKD Microbiota? A Mediterranean Diet, please! Kidney Blood Press Res. 2014;39(2-3):114-23.
(53) Díaz-López A, Bulló M, Martínez-González MÁ, Guasch-Ferré M, Ros E, Basora J, et al. Effects of Mediterranean diets on kidney function: a report from the PREDIMED trial. Am J Kidney Dis. 2012;60(3):380-9.
(54) Huang X, Jiménez-Moleón JJ, Lindholm B, Cederholm T, Arnlöv J, Risérus U, et al. Mediterranean diet, kidney function, and mortality in men with CKD. Clin J Am Soc Nephrol. 2013;8(9):1548-55.
(55) Patel KP, Luo FJ-G, Plummer NS, Hostetter TH, Meyer TW. The production of p-cresol sulfate and indoxyl sulfate in vegetarians versus omnivores. Clin J Am Soc Nephrol. 2012;7(6):982-8.
(56) Kandouz S, Mohamed AS, Zheng Y, Sandeman S, Davenport A. Reduced protein bound uraemic toxins in vegetarian kidney failure patients treated by haemodiafiltration. Hemodial Int. 2016;20(4):610-7.
(57) Schulman G, Vanholder R, Niwa T. AST-120 for the management of progression of chronic kidney disease. Int J Nephrol Renovasc Dis. 2014;7:49-56.
(58) Schulman G, Berl T, Beck GJ, Remuzzi G, Ritz E, Arita K, et al. Randomized Placebo-Controlled EPPIC Trials of AST-120 in CKD. J Am Soc Nephrol. 2015;26(7):1732-46.
This journal 