The intestine and the kidneys: a bad marriage can be hazardous

Raymond Vanholder, Griet Glorieux, Raymond Vanholder, Griet Glorieux

Abstract

The concept that the intestine and chronic kidney disease influence each other, emerged only recently. The problem is multifaceted and bidirectional. On one hand, the composition of the intestinal microbiota impacts uraemic retention solute production, resulting in the generation of essentially protein-bound uraemic toxins with strong biological impact such as vascular damage and progression of kidney failure. On the other hand, the uraemic status affects the composition of intestinal microbiota, the generation of uraemic retention solutes and their precursors and causes disturbances in the protective epithelial barrier of the intestine and the translocation of intestinal microbiota into the body. All these elements together contribute to the disruption of the metabolic equilibrium and homeostasis typical to uraemia. Several measures with putative impact on intestinal status have recently been tested for their influence on the generation or concentration of uraemic toxins. These include dietary measures, prebiotics, probiotics, synbiotics and intestinal sorbents. Unfortunately, the quality and the evidence base of many of these studies are debatable, especially in uraemia, and often results within one study or among studies are contradictory. Nevertheless, intestinal uraemic metabolite generation remains an interesting target to obtain in the future as an alternative or additive to dialysis to decrease uraemic toxin generation. In the present review, we aim to summarize (i) the role of the intestine in uraemia by producing uraemic toxins and by generating pathophysiologically relevant changes, (ii) the role of uraemia in modifying intestinal physiology and (iii) the therapeutic options that could help to modify these effects and the studies that have assessed the impact of these therapies.

Keywords: CKD; creatinine; haemodialysis; systematic review; uraemic toxins.

Figures

Fig. 1.
Fig. 1.
Main metabolic pathways involved in uraemic toxin generation. (A) ingestion via the gastrointestinal tract and direct unmodified uptake via the intestinal wall into the systemic circulation (e.g. advanced glycation end products); (B) gastrointestinal uptake of a precursor (e.g. an amino acid), that is transformed by the intestinal microbiota into another precursor (e.g. indole); after its uptake via the intestinal wall and portal vein, this precursor is further conjugated by the liver (e.g. indoxyl sulphate) before its transfer into the systemic circulation; (C) gastrointestinal uptake of a precursor (e.g. an amino acid), that is transformed by the intestinal microbiota into another precursor (e.g. indole); the precursor is conjugated during its uptake via the intestinal wall (e.g. indoxyl sulphate) and then passes into the systemic circulation via the liver without further modification; (D) endogenous generation without contribution of the gastro-intestinal tract (e.g. β2-microglobulin). Modified from Schepers et al. [12].
Fig. 2.
Fig. 2.
The dual interference between the intestine and uraemia. The intestine is responsible for generating and absorbing uraemic toxins with a deleterious impact on body functions. Uraemia in its turn modifies intestinal functions with a further increase in uraemic toxin generation and pro-inflammatory modifications which again are deleterious to body functions.

References

    1. Turnbaugh PJ, Ley RE, Hamady M, et al. The human microbiome project. Nature 2007; 449: 804–810
    1. Guarner F, Malagelada JR. Gut flora in health and disease. Lancet 2003; 361: 512–519
    1. Choi JJ, Eum SY, Rampersaud E, et al. Exercise attenuates PCB-induced changes in the mouse gut microbiome. Environ Health Perspect 2013; 121: 725–730
    1. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014; 505: 559–563
    1. Lam V, Su J, Koprowski S, et al. Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J 2012; 26: 1727–1735
    1. Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444: 1027–1031
    1. Cesaro C, Tiso A, Del Prete A, et al. Gut microbiota and probiotics in chronic liver diseases. Dig Liver Dis 2011; 43: 431–438
    1. Hopkins MJ, Sharp R, Macfarlane GT. Age and disease related changes in intestinal bacterial populations assessed by cell culture, 16S rRNA abundance, and community cellular fatty acid profiles. Gut 2001; 48: 198–205
    1. Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature 2009; 457: 480–484
    1. Anders HJ, Andersen K, Stecher B. The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease. Kidney Int 2013; 83: 1010–1016
    1. Evenepoel P, Meijers BK, Bammens BR, et al. Uremic toxins originating from colonic microbial metabolism. Kidney Int Suppl 2009; 76(Suppl 114): S12–S19
    1. Schepers E, Glorieux G, Vanholder R. The gut: the forgotten organ in uremia? Blood Purif 2010; 29: 130–136
    1. Ramezani A, Raj DS. The gut microbiome, kidney disease, and targeted interventions. J Am Soc Nephrol 2014; 25: 657–670
    1. Vitetta L, Linnane AW, Gobe GC. 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
    1. Massy ZA, Barreto DV, Barreto FC, et al. Uraemic toxins for consideration by the cardiologist-Beyond traditional and non-traditional cardiovascular risk factors. Atherosclerosis 2010; 211: 381–383
    1. Di Cerbo A, Pezzuto F, Palmieri L, et al. Clinical and experimental use of probiotic formulations for management of end-stage renal disease: an update. Int Urol Nephrol 2013; 45: 1569–1576
    1. Poesen R, Meijers B, Evenepoel P. The colon: an overlooked site for therapeutics in dialysis patients. Semin Dial 2013; 26: 323–332
    1. Glorieux G, Vanholder R, Lameire N. Advanced glycation and the immune system: stimulation, inhibition or both? Eur J Clin Invest 2001; 31: 1015–1018
    1. Koschinsky T, He CJ, Mitsuhashi T, et al. Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc Natl Acad Sci USA 1997; 94: 6474–6479
    1. Smith EA, MacFarlane GT. Enumeration of amino acid fermenting bacteria in the human large intestine: effects of pH and starch on peptide metabolism and dissimilation of amino acids. FEMS Microbiol Ecol 1998; 25: 355–368
    1. Vaziri ND, Wong J, Pahl M, et al. Chronic kidney disease alters intestinal microbial flora. Kidney Int 2013; 83: 308–315
    1. 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
    1. Strid H, Simren M, Stotzer PO, et al. Patients with chronic renal failure have abnormal small intestinal motility and a high prevalence of small intestinal bacterial overgrowth. Digestion 2003; 67: 129–137
    1. Wu MJ, Chang CS, Cheng CH, et al. Colonic transit time in long-term dialysis patients. Am J Kidney Dis 2004; 44: 322–327
    1. Bammens B, Verbeke K, Vanrenterghem Y, et al. Evidence for impaired assimilation of protein in chronic renal failure. Kidney Int 2003; 64: 2196–2203
    1. Wang IK, Lai HC, Yu CJ, et al. Real-time PCR analysis of the intestinal microbiotas in peritoneal dialysis patients. Appl Environ Microbiol 2012; 78: 1107–1112
    1. Wong J, Piceno YM, DeSantis TZ, 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
    1. Bossola M, Sanguinetti M, Scribano D, et al. Circulating bacterial-derived DNA fragments and markers of inflammation in chronic hemodialysis patients. Clin J Am Soc Nephrol 2009; 4: 379–385
    1. de Almeida Duarte JB, de Aguilar-Nascimento JE, Nascimento M, et al. Bacterial translocation in experimental uremia. Urol Res 2004; 32: 266–270
    1. Wang F, Zhang P, Jiang H, et al. Gut bacterial translocation contributes to microinflammation in experimental uremia. Dig Dis Sci 2012; 57: 2856–2862
    1. Wei M, Wang Z, Liu H, et al. Probiotic Bifidobacterium animalis subsp. lactis Bi-07 alleviates bacterial translocation and ameliorates microinflammation in experimental uraemia. Nephrology (Carlton) 2014; 19: 500–506
    1. Magnusson M, Magnusson KE, Sundqvist T, et al. Impaired intestinal barrier function measured by differently sized polyethylene glycols in patients with chronic renal failure. Gut 1991; 32: 754–759
    1. Vaziri ND, Yuan J, Rahimi A, et al. Disintegration of colonic epithelial tight junction in uremia: a likely cause of CKD-associated inflammation. Nephrol Dial Transplant 2012; 27: 2686–2693
    1. 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: 1–6
    1. Vaziri ND, Yuan J, Khazaeli M, et al. Oral activated charcoal adsorbent (AST-120) ameliorates chronic kidney disease-induced intestinal epithelial barrier disruption. Am J Nephrol 2013; 37: 518–525
    1. Niwa T, Emoto Y, Maeda K, et al. Oral sorbent suppresses accumulation of albumin-bound indoxyl sulphate in serum of haemodialysis patients. Nephrol Dial Transplant 1991; 6: 105–109
    1. Einheber A, Carter D. The role of the microbial flora in uremia. I. Survival times of germfree, limited-flora, and conventionalized rats after bilateral nephrectomy and fasting. J Exp Med 1966; 123: 239–250
    1. Yokoyama MT, Tabori C, Miller ER, et al. The effects of antibiotics in the weanling pig diet on growth and the excretion of volatile phenolic and aromatic bacterial metabolites. Am J Clin Nutr 1982; 35: 1417–1424
    1. Holler E, Butzhammer P, Schmid K, et al. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. Biol Blood Marrow Transplant 2014; 20: 640–645
    1. 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: 3698–3703
    1. Wikoff WR, Nagle MA, Kouznetsova VL, et al. Untargeted metabolomics identifies enterobiome metabolites and putative uremic toxins as substrates of organic anion transporter 1 (Oat1). J Proteome Res 2011; 10: 2842–2851
    1. Aronov PA, Luo FJ, Plummer NS, et al. Colonic contribution to uremic solutes. J Am Soc Nephrol 2011; 22: 1769–1776
    1. Patel KP, Luo FJ, Plummer NS, et al. The production of p-cresol sulfate and indoxyl sulfate in vegetarians versus omnivores. Clin J Am Soc Nephrol 2012; 7: 982–988
    1. Ling WH, Hanninen O. Shifting from a conventional diet to an uncooked vegan diet reversibly alters fecal hydrolytic activities in humans. J Nutr 1992; 122: 924–930
    1. Sirich TL, Plummer NS, Gardner CD, 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
    1. Eloot S, Van Biesen W, Glorieux G, et al. Does the adequacy parameter Kt/V(urea) reflect uremic toxin concentrations in hemodialysis patients? PLoS One 2013; 8: e76838.
    1. Sirich T, Meyer TW. Indoxyl sulfate: long suspected but not yet proven guilty. Clin J Am Soc Nephrol 2011; 6: 3–4
    1. Vanholder R, Schepers E, Pletinck A, et al. The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: a systematic review. J Am Soc Nephrol 2014; 25: 1897–1907
    1. Barreto FC, Barreto DV, Liabeuf S, et al. Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clin J Am Soc Nephrol 2009; 4: 1551–1558
    1. Chiu CA, Lu LF, Yu TH, et al. Increased levels of total P-Cresylsulphate and indoxyl sulphate are associated with coronary artery disease in patients with diabetic nephropathy. Rev Diabet Stud 2010; 7: 275–284
    1. Liabeuf S, Barreto DV, Barreto FC, et al. Free p-cresylsulphate is a predictor of mortality in patients at different stages of chronic kidney disease. Nephrol Dial Transplant 2010; 25: 1183–1191
    1. Wang CP, Lu LF, Yu TH, et al. Serum levels of total p-cresylsulphate are associated with angiographic coronary atherosclerosis severity in stable angina patients with early stage of renal failure. Atherosclerosis 2010; 211: 579–583
    1. Wu IW, Hsu KH, Lee CC, et al. p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease. Nephrol Dial Transplant 2011; 26: 938–947
    1. Wu IW, Hsu KH, Hsu HJ, et al. Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients--a Prospective Cohort Study. Nephrol Dial Transplant 2012; 27: 1169–1175
    1. Barnes KJ, Rowland A, Polasek TM, et al. Inhibition of human drug-metabolising cytochrome P450 and UDP-glucuronosyltransferase enzyme activities in vitro by uremic toxins. Eur J Clin Pharmacol 2014; 70: 1097–1106
    1. Pletinck A, Glorieux G, Schepers E, et al. Protein-bound uremic toxins stimulate crosstalk between leukocytes and vessel wall. J Am Soc Nephrol 2013; 24: 1981–1994
    1. Kim YH, Kwak KA, Gil HW, et al. Indoxyl sulfate promotes apoptosis in cultured osteoblast cells. BMC Pharmacol Toxicol 2013; 14: 60.
    1. Sun CY, Young GH, Hsieh YT, et al. Protein-bound uremic toxins induce tissue remodeling by targeting the EGF receptor. J Am Soc Nephrol 2014;
    1. Ng HY, Yisireyili M, Saito S, et al. Indoxyl sulfate downregulates expression of Mas receptor via OAT3/AhR/Stat3 pathway in proximal tubular cells. PLoS One 2014; 9: e91517.
    1. Jourde-Chiche N, Dou L, Cerini C, et al. Protein-bound toxins--update 2009. Semin Dial 2009; 22: 334–339
    1. Mutsaers HA, van den Heuvel LP, Ringens LH, et al. Uremic toxins inhibit transport by breast cancer resistance protein and multidrug resistance protein 4 at clinically relevant concentrations. PLoS One 2011; 6: e18438.
    1. Tsujimoto M, Hatozaki D, Shima D, et al. Influence of serum in hemodialysis patients on the expression of intestinal and hepatic transporters for the excretion of pravastatin. Ther Apher Dial 2012; 16: 580–587
    1. Vanholder R, Van Landschoot N, De Smet R, et al. Drug protein binding in chronic renal failure: evaluation of nine drugs. Kidney Int 1988; 33: 996–1004
    1. Chitalia VC, Shivanna S, Martorell J, et al. Uremic serum and solutes increase post-vascular interventional thrombotic risk through altered stability of smooth muscle cell tissue factor. Circulation 2013; 127: 365–376
    1. Dou L, Sallee M, Cerini C, et al. The cardiovascular effect of the uremic solute indole-3 acetic acid. J Am Soc Nephrol 2014; doi 10.1681/ASN 2013121283
    1. Gondouin B, Cerini C, Dou L, et al. Indolic uremic solutes increase tissue factor production in endothelial cells by the aryl hydrocarbon receptor pathway. Kidney Int 2013; 84: 733–744
    1. Mutsaers HA, Wilmer MJ, Reijnders D, et al. Uremic toxins inhibit renal metabolic capacity through interference with glucuronidation and mitochondrial respiration. Biochim Biophys Acta 2013; 1832: 142–150
    1. Jankowski J, van der Giet M, Jankowski V, et al. Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. J Clin Invest 2003; 112: 256–264
    1. 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: 2388–2396
    1. Glorieux G, Helling R, Henle T, et al. In vitro evidence for immune activating effect of specific AGE structures retained in uremia. Kidney Int 2004; 66: 1873–1880
    1. Uribarri J, Stirban A, Sander D, et al. Single oral challenge by advanced glycation end products acutely impairs endothelial function in diabetic and nondiabetic subjects. Diabetes Care 2007; 30: 2579–2582
    1. Rossi M, Klein K, Johnson DW, et al. 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.
    1. Lieske JC, Tremaine WJ, De Simone C, et al. Diet, but not oral probiotics, effectively reduces urinary oxalate excretion and calcium oxalate supersaturation. Kidney Int 2010; 78: 1178–1185
    1. Birkett A, Muir J, Phillips J, et al. Resistant starch lowers fecal concentrations of ammonia and phenols in humans. Am J Clin Nutr 1996; 63: 766–772
    1. Geboes KP, De Hertogh G, De Preter V, et al. The influence of inulin on the absorption of nitrogen and the production of metabolites of protein fermentation in the colon. Br J Nutr 2006; 96: 1078–1086
    1. De Preter V, Vanhoutte T, Huys G, et al. Baseline microbiota activity and initial bifidobacteria counts influence responses to prebiotic dosing in healthy subjects. Aliment Pharmacol Ther 2008; 27: 504–513
    1. De Preter V, Geboes K, Verbrugghe K, et al. The in vivo use of the stable isotope-labelled biomarkers lactose-[15N]ureide and [2H4]tyrosine to assess the effects of pro- and prebiotics on the intestinal flora of healthy human volunteers. Br J Nutr 2004; 92: 439–446
    1. De Preter V, Vanhoutte T, Huys G, et al. Effects of Lactobacillus casei Shirota, Bifidobacterium breve, and oligofructose-enriched inulin on colonic nitrogen-protein metabolism in healthy humans. Am J Physiol Gastrointest Liver Physiol 2007; 292: G358–G368
    1. Meijers BK, De Preter V, Verbeke K, et al. p-Cresyl sulfate serum concentrations in haemodialysis patients are reduced by the prebiotic oligofructose-enriched inulin. Nephrol Dial Transplant 2010; 25: 219–224
    1. Cloetens L, Broekaert WF, Delaedt Y, et al. Tolerance of arabinoxylan-oligosaccharides and their prebiotic activity in healthy subjects: a randomised, placebo-controlled cross-over study. Br J Nutr 2010; 103: 703–713
    1. Rampton DS, Cohen SL, Crammond VD, et al. Treatment of chronic renal failure with dietary fiber. Clin Nephrol 1984; 21: 159–163
    1. Bliss DZ, Stein TP, Schleifer CR, et al. Supplementation with gum Arabic fiber increases fecal nitrogen excretion and lowers serum urea nitrogen concentration in chronic renal failure patients consuming a low-protein diet. Am J Clin Nutr 1996; 63: 392–398
    1. Younes H, Egret N, Hadj-Abdelkader M, et al. Fermentable carbohydrate supplementation alters nitrogen excretion in chronic renal failure. J Ren Nutr 2006; 16: 67–74
    1. Miranda Alatriste PV, Urbina AR, Gomez Espinosa CO, et al. Effect of probiotics on human blood urea levels in patients with chronic renal failure. Nutr Hosp 2014; 29: 582–590
    1. 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: 634–647
    1. Hida M, Aiba Y, Sawamura S, et al. 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: 349–355
    1. 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: S142–S145
    1. 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
    1. Ando Y, Miyata Y, Tanba K, et al. Effect of oral intake of an enteric capsule preparation containing Bifidobacterium longum on the progression of chronic renal failure. Nihon Jinzo Gakkai Shi 2003; 45: 759–764
    1. 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.
    1. Hoppe B, Dittlich K, Fehrenbach H, et al. Reduction of plasma oxalate levels by oral application of Oxalobacter formigenes in 2 patients with infantile oxalosis. Am J Kidney Dis 2011; 58: 453–455
    1. Campieri C, Campieri M, Bertuzzi V, et al. Reduction of oxaluria after an oral course of lactic acid bacteria at high concentration. Kidney Int 2001; 60: 1097–1105
    1. Lieske JC, Goldfarb DS, De Simone C, et al. Use of a probiotic to decrease enteric hyperoxaluria. Kidney Int 2005; 68: 1244–1249
    1. Ferraz RR, Marques NC, Froeder L, et al. Effects of Lactobacillus casei and Bifidobacterium breve on urinary oxalate excretion in nephrolithiasis patients. Urol Res 2009; 37: 95–100
    1. Goldfarb DS, Modersitzki F, Asplin JR. A randomized, controlled trial of lactic acid bacteria for idiopathic hyperoxaluria. Clin J Am Soc Nephrol 2007; 2: 745–749
    1. 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 Transplant 2011; 26: 1094–1098
    1. 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
    1. Pavan M. Influence of prebiotic and probiotic supplementation on the progression of chronic kidney disease. Minerva Urol Nefrol 2014; in press
    1. Lieske JC, Regnier C, Dillon JJ. Use of sevelamer hydrochloride as an oxalate binder. J Urol 2008; 179: 1407–1410
    1. Brandenburg VM, Schlieper G, Heussen N, et al. Serological cardiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study. Nephrol Dial Transplant 2010; 25: 2672–2679
    1. Schulman G, Agarwal R, Acharya M, et al. A multicenter, randomized, double-blind, placebo-controlled, dose-ranging study of AST-120 (Kremezin) in patients with moderate to severe CKD. Am J Kidney Dis 2006; 47: 565–577
    1. Akizawa T, Asano Y, Morita S, et al. Effect of a carbonaceous oral adsorbent on the progression of CKD: a multicenter, randomized, controlled trial. Am J Kidney Dis 2009; 54: 459–467
    1. Konishi K, Nakano S, Tsuda S, et al. AST-120 (Kremezin) initiated in early stage chronic kidney disease stunts the progression of renal dysfunction in type 2 diabetic subjects. Diabetes Res Clin Pract 2008; 81: 310–315
    1. Shoji T, Wada A, Inoue K, et al. Prospective randomized study evaluating the efficacy of the spherical adsorptive carbon AST-120 in chronic kidney disease patients with moderate decrease in renal function. Nephron Clin Pract 2007; 105: c99–107
    1. Schulman G, Berl T, Beck GJ, et al. Randomized placebo-controlled EPPIC trials of AST-120 in CKD. J Am Soc Nephrol 2014;
    1. Wu IW, Hsu KH, Sun CY, et al. Oral adsorbent AST-120 potentiates the effect of erythropoietin-stimulating agents on Stage 5 chronic kidney disease patients: a Randomized Crossover Study. Nephrol Dial Transplant 2014; 29: 1719–1727
    1. Anraku M, Tanaka M, Hiraga A, et al. Effects of chitosan on oxidative stress and related factors in hemodialysis patients. Carbohydr Polym 2014; 112: 152–157
    1. Evenepoel P, Bammens B, Verbeke K, et al. Acarbose treatment lowers generation and serum concentrations of the protein-bound solute p-cresol: a Pilot Study. Kidney Int 2006; 70: 192–198
    1. Cummings JH, Hill MJ, Bone ES, et al. The effect of meat protein and dietary fiber on colonic function and metabolism. II. Bacterial metabolites in feces and urine. Am J Clin Nutr 1979; 32: 2094–2101
    1. Gibson G, Scott K, Rastall R. Dietary Prebitoics: current status and new defintion. IFRS Functional FoodsBulletin 2010; 7: 1–19
    1. Koppe L, Pillon NJ, Vella RE, et al. p-Cresyl sulfate promotes insulin resistance associated with CKD. J Am Soc Nephrol 2013; 24: 88–99
    1. Furuse SU, Ohse T, Jo-Watanabe A, et al. Galacto-oligosaccharides attenuate renal injury with microbiota modification. Physiol Rep 2014; 2
    1. Younes H, Alphonse JC, Behr SR, et al. Role of fermentable carbohydrate supplements with a low-protein diet in the course of chronic renal failure: experimental bases. Am J Kidney Dis 1999; 33: 633–646
    1. Sanders ME. Probiotics: definition, sources, selection, and uses. Clin Infect Dis 2008; 46(Suppl 2): S58–S61
    1. Mandal A, Mandal S, Roy S, et al. Assessment of efficacy of a potential probiotic strain and its antiuremic and antoxidative activities. e-SPEN J 2013; 8: e155–e163
    1. Mandal A, Das K, Roy S, et al. In vivo assessment of bacteriotherapy on acetaminophen-induced uremic rats. J Nephrol 2013; 26: 228–236
    1. 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: 70–79
    1. Ranganathan N, Patel B, Ranganathan P, et al. Probiotic amelioration of azotemia in 5/6th nephrectomized Sprague-Dawley rats. Scientific World J 2005; 5: 652–660
    1. Jankowski J, Westhof T, Vaziri ND, et al. Gases as uremic toxins: is there something in the air? Semin Nephrol 2014; 34: 135–150
    1. Rossi M, Johnson DW, Morrison M, et al. SYNbiotics easing renal failure by improving Gut microbiologY (SYNERGY): a protocol of placebo-controlled randomised cross-over trial. BMC Nephrol 2014; 15: 106.
    1. Barna MM, Kapoian T, O'Mara NB. Sevelamer carbonate. Ann Pharmacother 2010; 44: 127–134
    1. Kays MB, Overholser BR, Mueller BA, et al. Effects of sevelamer hydrochloride and calcium acetate on the oral bioavailability of ciprofloxacin. Am J Kidney Dis 2003; 42: 1253–1259
    1. Phan O, Ivanovski O, Nguyen-Khoa T, et al. Sevelamer prevents uremia-enhanced atherosclerosis progression in apolipoprotein E-deficient mice. Circulation 2005; 112: 2875–2882
    1. Kikuchi K, Itoh Y, Tateoka R, et al. 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: 2997–3002
    1. 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
    1. Ueda H, Shibahara N, Takagi S, et al. AST-120, an oral adsorbent, delays the initiation of dialysis in patients with chronic kidney diseases. Ther Apher Dial 2007; 11: 189–195
    1. Lekawanvijit S, Kumfu S, Wang BH, et al. The uremic toxin adsorbent AST-120 abrogates cardiorenal injury following myocardial infarction. PLoS One 2013; 8: e83687.
    1. Saito H, Yoshimura M, Saigo C, et al. Hepatic sulfotransferase as a nephropreventing target by suppression of the uremic toxin indoxyl sulfate accumulation in ischemic acute kidney injury. Toxicol Sci 2014; 141: 206–217
    1. Vanholder R, De Smet R, Waterloos MA, et al. Mechanisms of uremic inhibition of phagocyte reactive species production: characterization of the role of p-cresol. Kidney Int 1995; 47: 510–517
    1. Saigo C, Nomura Y, Yamamoto Y, et al. Meclofenamate elicits a nephropreventing effect in a rat model of ischemic acute kidney injury by suppressing indoxyl sulfate production and restoring renal organic anion transporters. Drug Des Devel Ther 2014; 8: 1073–1082
    1. Levey AS, Adler S, Caggiula AW, et al. Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study. Am J Kidney Dis 1996; 27: 652–663

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다