International Urology and Nephrology

, Volume 45, Issue 6, pp 1569–1576 | Cite as

Clinical and experimental use of probiotic formulations for management of end-stage renal disease: an update

  • Alessandro Di Cerbo
  • Federica Pezzuto
  • Lucia Palmieri
  • Valentina Rottigni
  • Tommaso Iannitti
  • Beniamino Palmieri
Nephrology - Review


Nowadays kidney transplantation and dialysis are the only available therapies for end-stage renal disease management. They imply a considerable increase in plasma concentration of uremic wastes including creatinine, urea and uric acid. These invasive procedures impose high social costs that prevent many low-income countries from adequately treating the patients affected by renal insufficiency. For years, many studies on uremic waste removal through the gut lumen have been published with conflicting results. More recently, microencapsulation of probiotic bacteria has been performed by different research groups. This evidence has opened a new perspective on therapeutic modification of gut bacterial flora in the context of renal disease. This review gives an overview of the experimental and clinical use of probiotic formulations in the context of end-stage renal disease.


End-stage renal disease Microencapsulation Probiotics Dialysis Kidney stones Bacteria Chronic kidney disease 



The authors contributed equally to this work. This review was not supported by grants. The authors thank Professor Decenzio Bonucchi (Nephrology division, Policlinico di Modena, Italy) for his precious advice.

Conflict of interest

The authors certify that they have no conflict of interest with any financial organization regarding the material discussed in this manuscript.


  1. 1.
    Noel D, Landais P (2012) Epidemiology of chronic kidney disease. La Revue du praticien 62(1):38–42PubMedGoogle Scholar
  2. 2.
    National Kidney F (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39(2 Suppl 1):S1–S266Google Scholar
  3. 3.
    United States Renal Data System (USRDS) (2012) Annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States, National Institutes of Health, National Institute of diabetes and digestive and kidney diseases, Bethesda, MDGoogle Scholar
  4. 4.
    Iannitti T, Palmieri B (2010) Therapeutical use of probiotic formulations in clinical practice. Clin Nutr 29(6):701–725PubMedCrossRefGoogle Scholar
  5. 5.
    Yasui H, Shida K, Matsuzaki T, Yokokura T (1999) Immunomodulatory function of lactic acid bacteria. Antonie Van Leeuwenhoek 76:383–389Google Scholar
  6. 6.
    Link-Amster H, Rochat F, Saudan KY, Mignot O, Aeschlimann JM (1994) Modulation of a specific humoral immune response and changes in intestinal flora mediated through fermented milk intake. Fems Immunol Med Microbiol 10:55–63Google Scholar
  7. 7.
    Gill H, Rutherfurd K, Cross M, Gopal P (2001) Enhancement of immunity in the elderly by dietary supplementation with the probiotic Bifidobacterium lactis HN019. Am J Clin Nutrition 74:833–839Google Scholar
  8. 8.
    Hebuterne X (2003) Gut changes attributed to ageing: effects on intestinal microflora. Curr Opin Clin Nutr Metab Care 6(1):49–54Google Scholar
  9. 9.
    De Simone C, Ciardi A, Grassi A, Lambert Gardini S, Tzantzoglou S, Trinchieri V, Moretti S, Jirillo E (1992) Effect of Bifidobacterium bifidum and Lactobacillus acidophilus on gut mucosa and peripheral blood B lymphocytes. mmunopharmacol Immunotoxicol 14(1–2):331–340CrossRefGoogle Scholar
  10. 10.
    Cross ML, Ganner A, Teilab D, Fray LM (2004) Patterns of cytokine induction by gram-positive and gram-negative probiotic bacteria. FEMS Immunol Med Microbiol 42(2):173–180PubMedCrossRefGoogle Scholar
  11. 11.
    Drakes M, Blanchard T, Czinn S (2004) Bacterial probiotic modulation of dendritic cells. Infect Immun 72(6):3299–3309PubMedCrossRefGoogle Scholar
  12. 12.
    Gill HS, Rutherfurd KJ, Cross ML (2001) Dietary probiotic supplementation enhances natural killer cell activity in the elderly: an investigation of age-related immunological changes. J Clin Immunol 21(4):264–271PubMedCrossRefGoogle Scholar
  13. 13.
    Hart AL, Lammers K, Brigidi P, Vitali B, Rizzello F, Gionchetti P, Campieri M, Kamm MA, Knight SC, Stagg AJ (2004) Modulation of human dendritic cell phenotype and function by probiotic bacteria. Gut 53(11):1602–1609PubMedCrossRefGoogle Scholar
  14. 14.
    Hegazy SK, El-Bedewy MM (2010) Effect of probiotics on pro-inflammatory cytokines and NF-kappaB activation in ulcerative colitis. World J Gastroenterol 16(33):4145–4151PubMedCrossRefGoogle Scholar
  15. 15.
    Grill JP, Crociani J, Ballongue J (1995) Effect of bifidobacteria on nitrites and nitrosamines. Lett Appl Microbiol 20(5):328–330PubMedCrossRefGoogle Scholar
  16. 16.
    Ooi LG, Liong MT (2010) Cholesterol-lowering effects of probiotics and prebiotics: a review of in vivo and in vitro findings. Int J Mol Sci 11(6):2499–2522PubMedCrossRefGoogle Scholar
  17. 17.
    Mangione F, Dal Canton A (2011) Chronic kidney disease epidemic: myth and reality. Intern Emerg Med 6(Suppl 1):69–76PubMedCrossRefGoogle Scholar
  18. 18.
    Vanholder R, Argiles A, Baurmeister U, Brunet P, Clark W, Cohen G, De Deyn PP, Deppisch R, Descamps-Latscha B, Henle T et al (2001) Uremic toxicity: present state of the art. Int J Artif Organs 24(10):695–725PubMedGoogle Scholar
  19. 19.
    Vanholder R, De Smet R, Glorieux G, Argiles A, Baurmeister U, Brunet P, Clark W, Cohen G, De Deyn PP, Deppisch R et al (2003) Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int 63(5):1934–1943PubMedCrossRefGoogle Scholar
  20. 20.
    Vanholder R, Van Laecke S, Glorieux G (2008) What is new in uremic toxicity? Pediatr Nephrol 23(8):1211–1221PubMedCrossRefGoogle Scholar
  21. 21.
    Kestenbaum B, Belozeroff V (2007) Mineral metabolism disturbances in patients with chronic kidney disease. Eur J Clin Invest 37(8):607–622PubMedCrossRefGoogle Scholar
  22. 22.
    Lund RJ, Davies MR, Mathew S, Hruska KA (2006) New discoveries in the pathogenesis of renal osteodystrophy. J Bone Miner Metab 24(2):169–171PubMedCrossRefGoogle Scholar
  23. 23.
    Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: improving Global Outcomes (KDIGO). Kidney Int 69(11):1945–1953PubMedCrossRefGoogle Scholar
  24. 24.
    Mondry A, Wang Z, Dhar PK (2005) Bone and the kidney: a systems biology approach to the molecular mechanisms of renal osteodystrophy. Curr Mol Med 5(5):489–496PubMedCrossRefGoogle Scholar
  25. 25.
    Karpov PF (1992) Disordered intestinal mechanisms in patients with chronic kidney failure. Ter Arkh 64(6):73–77PubMedGoogle Scholar
  26. 26.
    Rana SV, Bhardwaj SB (2008) Small intestinal bacterial overgrowth. Scand J Gastroenterol 43(9):1030–1037PubMedCrossRefGoogle Scholar
  27. 27.
    Simenhoff ML, Saukkonen JJ, Burke JF, Wesson LG Jr, Schaedler RW, Gordon SJ (1978) Bacterial populations of the small intestine in uremia. Nephron 22(1–3):63–68PubMedCrossRefGoogle Scholar
  28. 28.
    Strid H, Simren M, Stotzer PO, Ringstrom G, Abrahamsson H, Bjornsson ES (2003) Patients with chronic renal failure have abnormal small intestinal motility and a high prevalence of small intestinal bacterial overgrowth. Digestion 67(3):129–137PubMedCrossRefGoogle Scholar
  29. 29.
    Bures J, Cyrany J, Kohoutova D, Forstl M, Rejchrt S, Kvetina J, Vorisek V, Kopacova M (2010) Small intestinal bacterial overgrowth syndrome. World J Gastroenterol 16(24):2978–2990PubMedCrossRefGoogle Scholar
  30. 30.
    Vaziri ND, Wong J, Pahl M, Piceno YM, Yuan J, Desantis TZ, Ni Z, Nguyen TH, Andersen GL (2013) Chronic kidney disease alters intestinal microbial flora. Kidney Int 83(2):308–315Google Scholar
  31. 31.
    Koga N, Nomura G, Yamagata Y, Koga T (1982) Ureteric pain in patients with chronic renal failure on hemodialysis. Diagnostic approach with ultrasonography and computer tomography. Nephron 31:55–58Google Scholar
  32. 32.
    Alexander RT, Hemmelgarn BR, Wiebe N, Bello A, Morgan C, Samuel S, Klarenbach SW, Curhan GC, Tonelli M (2012) Kidney stones and kidney function loss: a cohort study. BMJ 345:e5287Google Scholar
  33. 33.
    Curhan GC, Willett WC, Speizer FE, Stampfer MJ (2001) Twenty-four-hour urine chemistries and the risk of kidney stones among women and men. Kidney Int 59(6):2290–2298PubMedGoogle Scholar
  34. 34.
    Coe FL, Evan A, Worcester E (2005) Kidney stone disease. J Clin Invest 115(10):2598–2608Google Scholar
  35. 35.
    Abratt VR, Reid SJ (2010) Oxalate-degrading bacteria of the human gut as probiotics in the management of kidney stone disease. Adv Appl Microbiol 72:63–87PubMedGoogle Scholar
  36. 36.
    Stewart CS, Duncan SH, Cave DR (2004) Oxalobacter formigenes and its role in oxalate metabolism in the human gut. FEMS Microbiol Lett 230(1):1–7PubMedCrossRefGoogle Scholar
  37. 37.
    Sidhu H, Allison MJ, Chow JM, Clark A, Peck AB (2001) Rapid reversal of hyperoxaluria in a rat model after probiotic administration of Oxalobacter formigenes. J Urol 166(4):1487–1491Google Scholar
  38. 38.
    Kwak C, Jeong BC, Ku JH, Kim HH, Lee JJ, Huh CS, Baek YJ, Lee SE (2006) Prevention of nephrolithiasis by Lactobacillus in stone-forming rats: a preliminary study. Urol Res 34(4):265–270PubMedCrossRefGoogle Scholar
  39. 39.
    Murphy C, Murphy S, O’Brien F, O’Donoghue M, Boileau T, Sunvold G, Reinhart G, Kiely B, Shanahan F, O’Mahony L (2009) Metabolic activity of probiotics-oxalate degradation. Vet Microbiol 136(1–2):100–107PubMedCrossRefGoogle Scholar
  40. 40.
    Kaufman DW, Kelly JP, Curhan GC, Anderson TE, Dretler SP, Preminger GM, Cave DR (2008) Oxalobacter formigenes may reduce the risk of calcium oxalate kidney stones. J Am Soc Nephrol 19(6):1197–1203PubMedCrossRefGoogle Scholar
  41. 41.
    Campieri C, Campieri M, Bertuzzi V, Swennen E, Matteuzzi D, Stefoni S, Pirovano F, Centi C, Ulisse S, Famularo G, De Simone C (2001) Reduction of oxaluria after an oral course of lactic acid bacteria at high concentration. Kidney Int 60(3):1097–1105PubMedCrossRefGoogle Scholar
  42. 42.
    Troxel SA, Sidhu H, Kaul P, Low RK (2003) Intestinal Oxalobacter formigenes colonization in calcium oxalate stone formers and its relation to urinary oxalate. J Endourol 17(3):173–176PubMedCrossRefGoogle Scholar
  43. 43.
    Lieske JC, Goldfarb DS, De Simone C, Regnier C (2005) Use of a probiotic to decrease enteric hyperoxaluria. Kidney Int 68(3):1244–1249PubMedCrossRefGoogle Scholar
  44. 44.
    Goldfarb DS, Modersitzki F, Asplin JR (2007) A randomized, controlled trial of lactic acid bacteria for idiopathic hyperoxaluria. Clin J Am Soc Nephrol 2(4):745–749PubMedCrossRefGoogle Scholar
  45. 45.
    Ferraz RR, Marques NC, Froeder L, Menon VB, Siliano PR, Baxmann AC, Heilberg IP (2009) Effects of Lactobacillus casei and Bifidobacterium breve on urinary oxalate excretion in nephrolithiasis patients. Urol Res 37(2):95–100PubMedCrossRefGoogle Scholar
  46. 46.
    Hoppe B, von Unruh G, Laube N, Hesse A, Sidhu H (2005) Oxalate degrading bacteria: new treatment option for patients with primary and secondary hyperoxaluria? Urol Res 33(5):372–375PubMedCrossRefGoogle Scholar
  47. 47.
    Ranganathan N, Patel B, Ranganathan P, Marczely J, Dheer R, Chordia T, Dunn SR, Friedman EA (2005) Probiotic amelioration of azotemia in 5/6th nephrectomized Sprague-Dawley rats. Sci World J 5:652–660CrossRefGoogle Scholar
  48. 48.
    Ranganathan N, Patel BG, Ranganathan P, Marczely J, Dheer R, Pechenyak B, Dunn SR, Verstraete W, Decroos K, Mehta R et al (2006) In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic kidney disease. ASAIO J 52(1):70–79PubMedCrossRefGoogle Scholar
  49. 49.
    Simenhoff ML, Dunn SR, Zollner GP, Fitzpatrick ME, Emery SM, Sandine WE, Ayres JW (1996) 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 22(1–3):92–96PubMedGoogle Scholar
  50. 50.
    Hida M, Aiba Y, Sawamura S, Suzuki N, Satoh T, Koga Y (1996) 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 74(2):349–355PubMedCrossRefGoogle Scholar
  51. 51.
    Takayama F, Taki K, Niwa T (2003) Bifidobacterium in gastro-resistant seamless capsule reduces serum levels of indoxyl sulfate in patients on hemodialysis. Am J Kidney Dis 41(3 Suppl 1):S142–S145PubMedCrossRefGoogle Scholar
  52. 52.
    Ando Y, Miyata Y, Tanba K, Saito O, Muto S, Kurosu M, Homma S, Kusano E, Asano Y (2003) Effect of oral intake of an enteric capsule preparation containing Bifidobacterium longum on the progression of chronic renal failure. Nihon Jinzo Gakkai shi 45(8):759–764PubMedGoogle Scholar
  53. 53.
    Meijers BK, De Preter V, Verbeke K, Vanrenterghem Y, Evenepoel P (2010) p-Cresyl sulfate serum concentrations in haemodialysis patients are reduced by the prebiotic oligofructose-enriched inulin. Nephrol Dial Transplant 25(1):219–224PubMedCrossRefGoogle Scholar
  54. 54.
    Nakabayashi I, Nakamura M, Kawakami K, Ohta T, Kato I, Uchida K, Yoshida M (2011) Effects of synbiotic treatment on serum level of p-cresol in haemodialysis patients: a preliminary study. Nephrol Dial Transplant 26(3):1094–1098PubMedCrossRefGoogle Scholar
  55. 55.
    Ranganathan N, Friedman EA, Tam P, Rao V, Ranganathan P, Dheer R (2009) 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 25(8):1919–1930PubMedCrossRefGoogle Scholar
  56. 56.
    Ranganathan N, Ranganathan P, Friedman EA, Joseph A, Delano B, Goldfarb DS, Tam P, Rao AV, Anteyi E, Musso CG (2010) Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease. Adv ther 27(9):634–647PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Alessandro Di Cerbo
    • 1
  • Federica Pezzuto
    • 1
  • Lucia Palmieri
    • 2
  • Valentina Rottigni
    • 1
  • Tommaso Iannitti
    • 3
  • Beniamino Palmieri
    • 1
  1. 1.Department of General Surgery and Surgical Specialties, Surgical ClinicUniversity of Modena and Reggio Emilia Medical SchoolModenaItaly
  2. 2.Nephrology and Dialysis DivisionUniversity of ModenaModenaItaly
  3. 3.Department of Physiology, School of MedicineUniversity of Kentucky Medical CenterLexingtonUSA

Personalised recommendations