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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

International Urology and Nephrology

Beniamino Palmieri International Urology and Nephrology ISSN 0301-1623 Int Urol Nephrol DOI
Beniamino Palmieri International Urology and Nephrology ISSN 0301-1623 Int Urol Nephrol DOI

ISSN 0301-1623

Int Urol Nephrol DOI 10.1007/s11255-012-0335-5

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Int Urol Nephrol DOI 10.1007/s11255-012-0335-5

NEPHROLOGY - REVIEW

NEPHROLOGY - REVIEW

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

Received: 28 July 2012 / Accepted: 9 November 2012 Springer Science+Business Media Dordrecht 2013

Abstract Nowadays kidney transplantation and

Keywords

End-stage renal disease

dialysis are the only available therapies for end-stage renal disease management. They imply a considerable

Microencapsulation Probiotics Dialysis Kidney stones Bacteria Chronic kidney disease

increase in plasma concentration of uremic wastes including creatinine, urea and uric acid. These inva- sive procedures impose high social costs that prevent many low-income countries from adequately treating the patients affected by renal insufficiency. For years,

End-stage renal disease

many studies on uremic waste removal through the gut lumen have been published with conflicting results. More recently, microencapsulation of probiotic bac- teria 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 over-

End-stage renal disease (ESRD) is the last stage of chronic kidney disease (CKD) [1] and is characterized by a glomerular filtration rate (GFR) fall below 15 ml/ min/1.73 m 2 [2]. Based on 2012 report from United States Renal Data System (USRDS), the rate of new ESRD cases per million population was 348 in 2010

view of the experimental and clinical use of probiotic

[3].

formulations in the context of end-stage renal disease.

Probiotics

A. Di Cerbo F. Pezzuto V. Rottigni B. Palmieri

Department of General Surgery and Surgical Specialties, Surgical Clinic, University of Modena and Reggio Emilia Medical School, Modena, Italy

L. Palmieri

Nephrology and Dialysis Division, University of Modena, Modena, Italy

T. Iannitti ( &)

Department of Physiology, School of Medicine, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA e-mail: tommaso.iannitti@gmail.com

KY 40536-0298, USA e-mail: tommaso.iannitti@gmail.com Over 2,000 species of commensal bacteria live in the human

Over 2,000 species of commensal bacteria live in the human body, the majority of which are in the intestinal tract where they are in a natural balance, namely symbiosis [4]. Among probiotic bacteria belonging to the intestinal ecosystem, bifidobacteria (gram-posi- tive, anaerobes and irregular rod-shaped) are the most abundant and potentially enhance humoral and cellular immune response against antigens [57]. The gut probiotic population is reduced during anti- biotic administration and with age, when pathogenic flora increases [8]. For example, lyophilized

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Bifidobacterium bifidum and Lactobacillus acidophi- lus significantly reduced colonic inflammatory infil- tration, without altering T, B and Leu7? cell percentage in a cohort of patients aged over 70 [9]. At the same time, a significant increase in peripheral blood B cell frequency was also noted. Probiotics also target the bowel immune response through dendritic cell and natural killer cell activity or pro-inflammatory cytokine production and modulation (down-regulation of TNF-a and IL-8 and inhibition of NFjB activation) [1014]. Moreover bifidobacteria decrease ammonia and excess cholesterol in the blood [15, 16]. The probiotics Lactobacillus bulgaricus, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plan- tarum, Streptococcus faecium and Streptococcus thermophilus also assist lactose enzymatic digestion and lipolytic digestive activity with cholesterol-low- ering effects.

ESRD pathophysiology and microbiome

During ESRD, the uremic toxins, consisting in nitro- gen waste products, cause an uremic condition inhib- iting several physiological and biochemical functions [1720]. CKD is also characterized by an alteration in mineral metabolism resulting in a decrease in serum levels of calcium and activated vitamin D versus increased phosphorous and parathyroid hormone [2124]. Chronic renal failure has been associated with small intestinal bacterial overgrowth (SIBO), a path- ological state characterized by a competition between bacteria and the lumen host for nutrients introduced in the body through alimentation [2528]. In this situa- tion, bacteria may also utilize intraluminal proteins in the small bowel that may lead to protein deficiency and excessive production of ammonia by bacteria [29]. The gut microbiome, defined as the bacterial pool of the gut and its genome, undergoes dramatic changes during kidney insufficiency, and harmful bacterial species are allowed to overgrow resulting in an imbalance in the probiotic microenvironment, affect- ing in particular lactobacilli and bifidobacteria [30].

Role of kidney stones in ESRD

Kidney stones have a high incidence rate world- wide. For example, in the USA, the risk to

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develop kidney stones in ERSD patients is around 51 % [31]. Furthermore, a large clinical study showed a graded association between episodes of kidney stones and risk of renal disease including ESRD [32]. About 80 % of kidney stones are made of calcium oxalate (CaOx), and urinary oxalate is the main risk factor accounting for this condition [33, 34].

Experimental studies of probiotics for management of kidney stones

As a preventive therapeutic approach for kidney stones, a moderate use of oxalate-containing food such as beet, chard, spinaches and cocoa powder, characterized by the highest oxalate levels, is required; however, a microbiological approach may also be effective [35, 36]. From an experimental perspective, a dose-dependent decrease in urinary oxalate was observed in rats affected by dietary- induced chronic hyperoxaluria receiving Oxalobact- er formigenes (a specific oxalate-degrading gram- negative anaerobe which lives in vertebrate gastro- intestinal tract) by esophageal gavage [37]. An in vitro study assessed the oxalate-degrading ability of 31 lactobacilli in a selective medium showing that only Lactobacillus casei HY2743 and Lactobacillus casei HY7201 were able to degrade oxalate [38]. Building upon these findings, an experimental study was conducted in stone-forming Srague-Dawley rats showing that treatment with Lactobacillus casei HY2743 and Lactobacillus casei HY7201 resulted in a decrease in urine oxalate excretion and less abundant crystals in kidneys, if compared to control group [38]. This study suggests an important role for lactobacilli as therapeutic agents for prevention of urinary stones. Another study also analyzed the ability of some Lactobacillus strains, isolated from the canine and feline gastrointestinal tract, to degrade oxalate in vitro, showing that several Lactobacillus animalis and Lactobacillus murinus isolates degraded ammonium oxalate. Lactobacillus animalis 223C, Lactobacillus animalis 5323, Lactobacillus murinus 1222 and Lactobacillus murinus 3133 were also tested in rats, showing that only the two Lactobacillus animalis strains were effective in reducing oxalate excretion, while all the four strains survived gastric transit [39].

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Clinical studies of probiotics for management of kidney stones

Probiotics have already found application in the clinical setting for management of kidney stones. In fact, a 70 % reduction in stone formation has been reported in patients harboring Oxalobacter formigenes in the gut [40]. A study, involving six patients with CaOx urolithiasis and intermediate iperoxaluria ([40 mg/24 h), was designed to determine the effi- cacy of a lyophilized probiotic formulation to reduce oxaluria. They received a daily mixture containing Lactobacillus acidophilus, Lactobacillus brevis, Lac- tobacillus plantarum, Bifidobacterium infantis and Streptococcus thermophilus for 4 weeks. A significant reduction in 24-h oxalate excretion was observed in all 6 patients at the end of the study period and 1 month after the end of treatment. In vitro experiments revealed that Lactobacillus brevis grew into an oxalate-containing medium, but displayed a modest ability to degrade oxalate. On the other hand, Bifido- bacterium infantis not only grew rapidly in oxalate- containing medium, but also showed a quite good ability to degrade oxalate. Lactobacillus acidophilus and Streptococcus thermophilus growth was inhibited by oxalate, and they displayed ability to degrade this metabolite [41]. A further study correlated for the first time the presence of Oxalobacter formigenes in the gut with urinary oxalate levels in 35 patients affected by kidney stones compared to 10 healthy controls without a history of urolithiasis. When fecal samples were analyzed, only 26 % of these patients presented Oxalobacter formigenes, against a value of 60 % observed in controls. Although no significant differ- ence was found in terms of oxalate urinary excretion, among stone-formers, Oxalobacter formigenes-nega- tive patients had significantly higher urinary oxalate levels, if compared with subjects testing positive for this bacterium (41.7 vs. 29.4 mg/day). Moreover, all 10 hyperoxaluric stone-formers ([44 mg/day) tested negative for Oxalobacter formigenes [42]. In the year 2005, Lieske and co-workers studied the efficacy of a probiotic formula, OXADROP , (4 g per dose, VSL Pharmaceuticals), containing Lactobacillus acidophi- lus, Lactobacillus brevis, Streptococcus thermophilus and Bifidobacterium infantis for oxaluria treatment. The different strains were mixed in a 1:1:4:4 ratio and prepared as a granulate. They were chosen based on their ability to degrade oxalate in vitro. Ten male and

female patients presenting hyperoxaluria ([0.5 mmol/ l/day; [45 mg/day) and gastrointestinal disorders (inflammatory bowel disease in remission, celiac sprue, gastrointestinal resection resulting in short bowel syndrome or chronic pancreatitis) associated with fat malabsorption received increasing doses of OXADROP for a 3-month period. After a month, oxalate urinary excretion fell/remained stable in 7 out of 10 patients (19 % mean decrease from baseline) who received one dose of OXADROP per day. After 2 months, it was reduced by 24 % in 8 out of 10 patients (2 doses per day), but increased toward baseline levels in 4 patients after 3 months (3 doses per day; mean decrease of 2 % from baseline). Interest- ingly, a slight urinary oxalate mean decrease of 20 % was observed during the washout period, if compared to baseline [43]. On the other hand, OXADROP did not show efficacy in another study involving 20 patients affected by calcium stones and idiopathic hyperoxaluria [44]. Ferraz and coworkers tested the efficacy of a bacterial mixture composed of Lactoba- cillus casei and Bifidobacterium breve to lower urinary oxalate in 14 stone-forming patients affected by hyperoxaluria while undergoing an oxalate-rich diet [45]. This mixture showed a variable lowering effect on urinary oxalate excretion. The efficacy of Oxalobacter formigenes in reducing the urinary oxa- late excretion in primary hyperoxaluric patients has also been investigated. After 1–2 years post-treatment follow-up, bacterial gut colonization was not achieved in most of the patients involved in this study. Only in a patient, who showed colonization, the oxalate urinary excretion was normalized over time [46]. In summary, some probiotic bacteria have shown promise in managing hyperoxaluria and kidney stones warranting further investigation in larger clinical trials.

Experimental studies of probiotics in ESRD

In vivo experimental studies have been conducted in rodents and felines to test the hypothesis of therapeutic probiotic administration for management of ESRD. For instance, a study was performed in 36 5/6th Sprague–Dawley nephrectomized rats, a model of chronic renal failure. They were divided into five groups compared to a uremic control group and a non- uremic control group (non-nephrectomized rats). They were fed on a casein-based diet and Bacillus pasteurii

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(group 1), Sporolac (Lactobacillus sporogenes; group 2), Kibow cocktail (Lactobacillus acidophilus, Streptococcus thermophilus, Lactobacillus bulgari- cus, Lactobacillus bifidus, Lactobacillus casei, Lac- tobacillus reuteri, group 3), CHR Hansen Quarto (Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus bifidus, Streptococcus thermophilus, group 4) and ECONORM TM (Saccharomyces boular- dii, group 5). The two control groups received the same diet with no probiotic supplements. Bacillus pasteurii administration, as well as Sporolac supple- mentation enhanced survival of 5/6th nephrectomized rats, slowing down the progress of renal injury. These findings support the idea of clinical efficacy of these bacterial strains for management of ERSD [47]. A further study, performed by the same research group, tested the non-pathogenic soil-borne alkaliphilic ure- ase-positive bacterium Sporosarcina pasteurii for therapeutical purposes to mitigate uremia intoxication in 5/6th nephrectomized rats. Following daily admin- istration of 10 CFU of live Sporosarcina pasteurii, a reduction in blood urea nitrogen levels was observed. Furthermore, this finding coupled with a significantly prolonged lifespan of uremic animals [48]. In sum- mary, contrasting results have been reported in animal studies on ESRD. Different animal species and probiotic strains used may account for these differences.

Clinical studies of probiotic administration to relieve uremia

In recent years, many clinical studies have been performed to assess the efficacy of natural living or genetically-modified bacteria on uremic pathology that often develops in patients affected by ESRD [1720]. For instance, 8 hemodialysis patients, treated with Lactobacillus acidophilus (NCFM TM ), displayed a significant decrease in dimethylamine and nitroso- dimethylamine, two uremic toxins originating from the gut [49]. A further study assessed the effectiveness of 27.9 mg Lebenin (one capsule = Bifidobacterium infantis 1 9 10 8 , Lactobacillus acidophilus 1 9 10 8 and Enterococcus faecalis 1 9 10 8 ) administered in 20 patients twice a day for a month. After 2 weeks, fecal p-cresol and indican, but not phenol levels, were reduced. After 4 weeks, indican plasma levels signif- icantly decreased from 212 ± 40 to 147 ± 25 nmol/

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ml, while p-cresol decreased only slightly, although the fecal accumulation of such toxin resulted inhibited by Lebenin [50]. The therapeutic efficacy of 5-week administration of Bifidobacterium longum in gastro- resistant seamless capsule (3 9 10 9 CFU; Bifina) versus bifidobacteria in powder formulation (2 9 10 7 CFU; Lac B) on indoxyl-sulfate levels in 22 hemodialysis patients has also been tested. In this study, 11 patients received Bifina capsules, while the remaining eleven subjects received Lac B. Indoxyl- sulfate serum levels were significantly reduced in Bifina-treated patients before undergoing dialysis (from 4.5 to 3.8 mg/dl), but not in patients treated with Lac B [51]. In the same year, Ando and coworkers administered Bifidobacterium longum (Bifidus HD)-enteric-coated capsules to 27 patients affected by chronic renal failure for a 6-month period. Although in the treated group no significant variation in biochemical parameters was detected, an ESRD delay in patients with an initial serum creatinine concentration C4.0 mg/dl or inorganic phosphate concentration C4.0 mg/dl was achieved [52]. In the year 2010, Meijers et al. carried out a study to assess the efficacy of a 4-week escalating dose regimen of oligofructose-enriched inulin in 22 maintenance he- modialysis patients (Orafti Synergy 1 = a mixture of oligofructose and Raftiline HP; 10 g per sachet; Orafti, Tienen, Belgium). Probiotic administration significantly reduced p-cresyl sulfate generation rates and serum concentrations in all hemodialysis patients [53]. A further study was conducted by Nakabayashi and coworkers to assess the efficacy of a synbiotic formulation (2 weeks, 3 times a day; SYN), containing Lactobacillus casei Shirota, Bifidobacterium breve Yakult and galacto-oligosaccharides on p-cresol levels in 9 hemodialysis patients. Patients with a high serum p-cresol levels tended to have hard stools with difficulty in defecation. Following SYN treatment, stool quantity increased significantly, while hard, muddy or soft stools tended to be replaced by normal ones. The serum p-cresol levels also decreased significantly [54]. In the context of CKD, in the year 2009, a Canadian study tested the clinical and biochemical efficacy of a probiotic mixture (KB = mixture of Lactobacillus acidophilus KB27, Bifidobacterium longum KB31 and Streptococcus thermophilus KB19 for a total of 1.5 9 10 10 CFU) administration in 13 stage 3 and 4 CKD patients over a 6-month period. During the treatment period, all

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patients showed a significant decrease in mean BUN level, if compared with controls. On the other hand, uric acid levels significantly increased, while serum creat- inine levels did not change [55]. One year later, the same research group performed a 4 nation clinical trial in 46 stage 3 and 4 CKD patients who underwent treatment with KB probiotic mixture. All patients were monthly examined for 3 months [56]. Oral ingestion of KB was well tolerated and safe during the entire trial period at all sites. BUN levels decreased in 29 patients, creatinine levels decreased in 20 patients and uric acid levels decreased in 15 patients. Almost all subjects showed a perceived substantial overall improvement in their

quality of life and absence of serious adverse effects supporting the use of these probiotics for bowel-based toxic solute extraction. In summary, different clinical studies in hemodialysis/CKD patients suggest that administration of a single probiotic or a combination of bacterial strains improve biochemical parameters in these patients and result in a delay in ESRD as shown by Ando and co-wokers [52]. However, further studies comparing different probiotic strains and involving larger cohorts of patients are required to reach a final conclusion. Experimental and clinical studies using probiotic formulations for treatment of ESRD and uremia, respectively, are summarized in Tables 1 and 2.

Table 1

Experimental studies of probiotic administration for treatment of ESRD

 

Authors

Design and treatment

Outcome

36

5/6th Sprague–Dawley nephrectomized rats fed on a

Bacillus pasteurii and Sporolac supplementation enhanced survival of rats while slowing the progress of renal injury

Ranganathan et al. [47]

casein-based diet and Bacillus pasteurii (group 1), Sporolac (Lactobacillus sporogenes; group 2), Kibow cocktail (Lactobacillus acidophilus, Streptococcus thermophilus, Lactobacillus bulgaricus, Lactobacillus bifidus, Lactobacillus casei, Lactobacillus reuteri, group 3), CHR Hansen Quarto (Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus bifidus, Streptococcus thermophilus, group 4) and ECONORM TM (Saccharomyces boulardii, group 5) for 16 weeks

Ranganathan et al. [48]

5/6th Sprague–Dawley nephrectomized rats fed with Sporosarcina pasteurii for 156 days

18

Daily reduction in BUN levels coupled with a significantly prolonged lifespan

Table 2

Clinical studies of probiotic administration for treatment of uremia

Authors

Design and treatment

Outcome

Hida et al.

[50]

uremic patients treated with 27.9 mg Lebenin for 4 weeks

20

Indican plasma levels were significantly decreased, while p- cresol was only slightly decreased

Takayama et al. [51]

hemodialysis patients treated with Bifina and 11 patients treated with Lac B for 5 weeks

11

Indoxyl-sulfate serum levels were significantly reduced in Bifina-treated patients, but not in Lac B-treated subjects

Ando et al.

[52]

patients with chronic renal failure treated with Bifidobacterium longum for 6 months

27

ESRD was delayed

Meijers et al.

[53]

22 hemodialysis patients treated with escalating

dose regimen of oligofructose-enriched inulin for

4 weeks

p-cresyl sulfate generation rates and serum concentrations were decreased

Nakabayashi et al. [54]

9 hemodialysis patients treated with SYN 3 times a day for 2 weeks

Muddy or soft stools tended to be replaced by normal ones and serum p-cresol levels decreased significantly

Ranganathan et al. [55]

stage 3 and 4 CKD patients treated with a KB mixture for 6 months

13

BUN levels decreased while uric acid levels increased. No changes in serum creatinine levels were observed

Ranganathan et al. [56]

46

stage 3 and 4 CKD patients treated with KB mixture for 6 months

BUN levels decreased in 29 patients, creatinine levels decreased in 20 patients, and uric acid levels decreased in 15 patients. An improvement in quality of life was observed. No serious adverse events were noted.

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Conclusions

During the past few years, the interest in therapeutic modification of gut bacterial flora for management of ERSD has gained growing attention. This review gives an overview of the experimental and clinical use of probiotic formulations in the context of ESRD. Experimental studies have focused on the efficacy of bacterial administration to improve kidney insuffi- ciency parameters and symptoms, resulting, at least in some cases, in a positive and promising outcome. On the other hand, clinical trials are still limited and do not involve a sufficient number of participants to draw a final conclusion on the theraputic use of probiotics in ESRD. Clinical studies comparing different probiotic strains, will shed light on the probiotic strains with higher effectiveness for management of this condition.

Acknowledgments 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.

References

1. Noel D, Landais P (2012) Epidemiology of chronic kidney disease. La Revue du praticien 62(1):38–42

2. National Kidney F (2002) K/DOQI clinical practice guide- lines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39(2 Suppl 1):S1–S266

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, MD

4. Iannitti T, Palmieri B (2010) Therapeutical use of probiotic formulations in clinical practice. Clin Nutr 29(6):701–725

5. Yasui H, Shida K, Matsuzaki T, Yokokura T (1999) Immunomodulatory function of lactic acid bacteria. Anto- nie Van Leeuwenhoek 76:383–389

6. Link-Amster H, Rochat F, Saudan KY, Mignot O, Aes- chlimann JM (1994) Modulation of a specific humoral immune response and changes in intestinal flora mediated through fermented milk intake. Fems Immunol Med Microbiol 10:55–63

7. Gill H, Rutherfurd K, Cross M, Gopal P (2001) Enhance- ment of immunity in the elderly by dietary supplementation with the probiotic Bifidobacterium lactis HN019. Am J Clin Nutrition 74:833–839

123

8. Hebuterne X (2003) Gut changes attributed to ageing:

effects on intestinal microflora. Curr Opin Clin Nutr Metab Care 6(1):49–54 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 aci- dophilus on gut mucosa and peripheral blood B lympho- cytes. mmunopharmacol Immunotoxicol 14(1–2):331–340

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):

173–180

11. Drakes M, Blanchard T, Czinn S (2004) Bacterial probiotic modulation of dendritic cells. Infect Immun 72(6):3299–

3309

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):264–271

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):1602–1609

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):4145–4151

15. Grill JP, Crociani J, Ballongue J (1995) Effect of bifido- bacteria on nitrites and nitrosamines. Lett Appl Microbiol

20(5):328–330

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):2499–2522

17. Mangione F, Dal Canton A (2011) Chronic kidney disease epidemic: myth and reality. Intern Emerg Med 6(Suppl 1):

69–76

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):695–725

19. Vanholder R, De Smet R, Glorieux G, Argiles A, Baur- meister U, Brunet P, Clark W, Cohen G, De Deyn PP, Deppisch R et al (2003) Review on uremic toxins: classifi- cation, concentration, and interindividual variability. Kid- ney Int 63(5):1934–1943

20. Vanholder R, Van Laecke S, Glorieux G (2008) What is new in uremic toxicity? Pediatr Nephrol 23(8):1211–1221

21. Kestenbaum B, Belozeroff V (2007) Mineral metabolism disturbances in patients with chronic kidney disease. Eur J Clin Invest 37(8):607–622

22. Lund RJ, Davies MR, Mathew S, Hruska KA (2006) New discoveries in the pathogenesis of renal osteodystrophy. J Bone Miner Metab 24(2):169–171

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 osteodys- trophy: a position statement from Kidney Disease:

improving Global Outcomes (KDIGO). Kidney Int 69(11):

1945–1953

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):489–496

Author's personal copy

Int Urol Nephrol

25. Karpov PF (1992) Disordered intestinal mechanisms in patients with chronic kidney failure. Ter Arkh 64(6):73–77

26. Rana SV, Bhardwaj SB (2008) Small intestinal bacterial overgrowth. Scand J Gastroenterol 43(9):1030–1037

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):63–68

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 preva- lence of small intestinal bacterial overgrowth. Digestion

67(3):129–137

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):2978–2990

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):308–315

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 31:55–58

32. Alexander RT, Hemmelgarn BR, Wiebe N, Bello A, Mor- gan C, Samuel S, Klarenbach SW, Curhan GC, Tonelli M (2012) Kidney stones and kidney function loss: a cohort study. BMJ 345:e5287

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–

2298

34. Coe FL, Evan A, Worcester E (2005) Kidney stone disease. J Clin Invest 115(10):2598–2608

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 72:63–87

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):1–7

37. Sidhu H, Allison MJ, Chow JM, Clark A, Peck AB (2001) Rapid reversal of hyperoxaluria in a rat model after probi- otic administration of Oxalobacter formigenes. J Urol

166(4):1487–1491

38. Kwak C, Jeong BC, Ku JH, Kim HH, Lee JJ, Huh CS, Baek YJ, Lee SE (2006) Prevention of nephrolithiasis by Lacto- bacillus in stone-forming rats: a preliminary study. Urol Res

34(4):265–270

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 degrada- tion. Vet Microbiol 136(1–2):100–107

40. Kaufman DW, Kelly JP, Curhan GC, Anderson TE, Dretler SP, Preminger GM, Cave DR (2008) Oxalobacter formig- enes may reduce the risk of calcium oxalate kidney stones.

J Am Soc Nephrol 19(6):1197–1203

41. Campieri C, Campieri M, Bertuzzi V, Swennen E, Mat- teuzzi 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):1097–1105

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):173–176

43. Lieske JC, Goldfarb DS, De Simone C, Regnier C (2005) Use of a probiotic to decrease enteric hyperoxaluria. Kidney Int 68(3):1244–1249

44. Goldfarb DS, Modersitzki F, Asplin JR (2007) A random- ized, controlled trial of lactic acid bacteria for idiopathic hyperoxaluria. Clin J Am Soc Nephrol 2(4):745–749

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 excre- tion in nephrolithiasis patients. Urol Res 37(2):95–100

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):372–375

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 5:652–660

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):70–79

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):92–96

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):349–355

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–S145

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 Bifidobacte- rium longum on the progression of chronic renal failure. Nihon Jinzo Gakkai shi 45(8):759–764

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 oli- gofructose-enriched inulin. Nephrol Dial Transplant

25(1):219–224

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–

1098

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

123

Author's personal copy

Int Urol Nephrol

6-month pilot scale trial in Canada. Curr Med Res Opin

25(8):1919–1930

56. Ranganathan N, Ranganathan P, Friedman EA, Joseph A, Delano B, Goldfarb DS, Tam P, Rao AV, Anteyi E, Musso

123

CG (2010) Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease. Adv ther 27(9):634–647