Probiotic Lactiplantibacillus plantarum N-1 could prevent ethylene glycol-induced kidney stones by regulating gut microbiota and enhancing intestinal barrier function.

Defective permeability barrier is considered to be an incentive of hyperuricemia, however, the link between them has not been proven. Here, we evaluated the potential preventive effects of Lactiplantibacillus plantarum N-1 (LPN1) on gut microbiota and intestinal barrier function in rats with hyperoxaluria-induced kidney stones. Male rats were supplied with 1% ethylene glycol (EG) dissolved in drinking water for 4 weeks to develop hyperoxaluria, and some of them were administered with LPN1 for 4 weeks before EG treatment as a preventive intervention. We found that EG not only resulted hyperoxaluria and kidney stone formation, but also promoted the intestinal inflammation, elevated intestinal permeability, and gut microbiota disorders. Supplementation of LPN1 inhibited the renal crystalline deposits through reducing urinary oxalic acid and renal osteopontin and CD44 expression and improved EG-induced intestinal inflammation and barrier function by decreasing the serum LPS and TLR4/NF-κB signaling and up-regulating tight junction Claudin-2 in the colon, as well as increasing the production of short-chain fatty acid (SCFAs) and the abundance of beneficial SCFAs-producing bacteria, mainly from the families of Lachnospiraceae and Ruminococcaceae. Probiotic LPN1 could prevent EG-induced hyperoxaluria by regulating gut microbiota and enhancing intestinal barrier function.

Oxalobacter formigenes: A new hope as a live biotherapeutic agent in the management of calcium oxalate renal stones.

Recent advances in understanding the association of gut microbiota with the host have shown evidence of certain bacterial therapeutic potentiality in preventing and treating metabolic diseases. Hyperoxaluria is a severe challenge in nephrology and has led to the novel gut eubiosis as current therapy. The human gut commensal, obligate anaerobic, and intestinal oxalate-degrading strains of Oxalobacter formigenes have drawn a promising significant interest for the next-generation probiotics (NGPs). This nonpathogenic, potential probiotic, and specialist oxalotrophic properties of O. formigenes give a new hope as a live biotherapeutic agent for calcium oxalate renal therapy. Numerous satisfactory outcomes of in vitro and in vivo studies were achieved on evaluating O. formigenes functionality, but the commercial production of this bacterium is yet to be achieved. This bacterium finds diverse application in dietary and endogenous oxalate degradation and the improvement of gut health, on which we concentrated our attention in this review. The relationship between good anaerobic gut bacterial dysbiosis and renal complications is comprehensively discussed to address the need for the development probiotic formulation. However, the commercial production of this bacteria on a broad scale is complex, with numerous obstacles, mainly because they are oxygen-sensitive and difficult to culture. This review will coherently present the current and available methodologies in producing, stabilizing, and delivering these NGPs to treat calcium stones. Moreover, the study presents the extensive work and key milestones achieved in the research on O. formigenes from tale to the truth.

Exosomes from miR-20b-3p-overexpressing stromal cells ameliorate calcium oxalate deposition in rat kidney.

Hyperoxaluria-induced calcium oxalate (CaOx) deposition is the key factor in kidney stone formation, for which adipose-derived stromal cells (ADSCs) have been used as a therapeutic treatment. Studies revealed that miR-20b-3p is down-regulated in hypercalciuric stone-forming rat kidney. To investigate whether ADSC-derived miR-20b-3p-enriched exosomes protect against kidney stones, an ethylene glycol (EG)-induced hyperoxaluria rat model and an in vitro model of oxalate-induced NRK-52E cells were established to explore the protective mechanism of miR-20b-3p. The results showed that miR-20b-3p levels were decreased following hyperoxaluria in the urine of patients and in kidney tissues from animal models. Furthermore, treatment with miR-20b-3p-enriched exosomes from ADSCs protected EG-induced hyperoxaluria rats, and cell experiments confirmed that co-culture with miR-20b-3p-enriched exosomes alleviated oxalate-induced cell autophagy and the inflammatory response by inhibiting ATG7 and TLR4. In conclusion, ADSC-derived miR-20b-3p-enriched exosomes protected against kidney stones by suppressing autophagy and inflammatory responses.

Pioglitazone decreased renal calcium oxalate crystal formation by suppressing M1 macrophage polarization via the PPAR-γ-miR-23 axis.

Interaction of pioglitazone (PGZ) and macrophages (Mps) in renal crystal formation remains unclear. In the present study, we investigated the possible mechanisms involved with Mps of PGZ in suppressing renal crystal formation. Crystal formation in the mouse kidney was detected using polarized light optical microscopy and Pizzolato staining. Gene expression was detected by Western blot analysis, quantitative RT-PCR, immunohistochemistry, immunofluorescence, and ELISA. Mp phenotypes were identified by flow cytometric analysis. Cell apoptosis was detected with TUNEL assay, and tubular injury was detected with periodic acid-Schiff staining. Interaction of peroxisome proliferator-activated receptor (PPAR)-γ and promoter was determined by chromatin immunoprecipitation assay. Luciferase reporter assay was performed to authenticate target genes of miRNA-23 (miR-23). Recombinant adenovirus was used to elucidate the role of miR-23 in vivo. Renal crystal formation, inflammation, tubular injury, and cell apoptosis were significantly marked in glyoxylic acid-treated groups and significantly decreased in PGZ-treated groups. PGZ significantly reduced Mp infiltration and M1 Mp polarization in the kidney. In vitro, PGZ shifted crystal-stimulated M1-predominant Mps to M2-predominant Mps, which were anti-inflammatory. PPAR-γ could directly bind to one PPAR-γ regulatory element in the promoter of pre-miR-23 to promote expression of miR-23 in Mps. We identified two downstream target genes of miR-23, interferon regulatory factor 1 and Pknox1. Moreover, miR-23 decreased crystal deposition, M1 Mp polarization, and injury in the kidney. This study has proven that PGZ decreased renal calcium oxalate crystal formation and renal inflammatory injury by suppressing M1 Mp polarization through a PPAR-γ-miR-23-interferon regulatory factor 1/Pknox1 axis. PGZ is liable to be a potential therapeutic medicine for treating urolithiasis.

Simultaneous use of oxalate-degrading bacteria and herbal extract to reduce the urinary oxalate in a rat model: A new strategy.

OBJECTIVE: Urinary stones with oxalate composition can cause kidney failure. Recent findings evidenced that probiotics are effective in reducing oxalate absorption in these subjects based on their high colonic absorption levels at baseline. The purpose of this study was to evaluate the effect of the simultaneous use of oxalate-degrading bacteria, Urtica dioica and T. terrestris extract in reducing urinary oxalate. MATERIALS AND METHODS: Anti-urolithiatic activity of Urtica dioica and T. terrestris extract and pro-biotic by using ethylene glycol induced rat model. In this study, 4 strains of Lactobacillus and 2 strains of Bifidobacterium and also 2 strains of L. paracasei (that showed high power in oxalate degrading in culture media) were used. Male Wistar rats were divided into four groups (n=6). The rats of group-I received normal diet (positive control group) and groups-II (negative control group), III, IV rats received diet containing ethylene glycol (3%) for 30 days. Groups III rats re-ceived Urtica dioica and T. terrestris extract. Groups IV rats received extracts + probiotic for 30 days. FINDINGS: The results show that the use of herbal extracts (Urtica dioica and T. terrestris) redu-ced the level of urinary oxalate and other parameters of urine and serum. Also, the accumulation of calcium oxalate crystals in the kidney tissue was significantly reduced. CONCLUSION: Considering that the formation of calcium oxalate crystals can cause inflammation and tissue damage in the kidney, the use of herbal extracts with oxalatedegrading bacteria can be a new therapeutic approach to preventing the formation of kidney stones.

Two-step transplantation for primary hyperoxaluria: a winning strategy to prevent progression of systemic oxalosis in early onset renal insufficiency cases.

Several transplant strategies for PH1 have been proposed, and LT is performed to correct the metabolic defects. The patients with PH1 often suffer from ESRD and require simultaneous LKT, which leads to a long wait due to the shortage of suitable organ donors. Five patients with PH1 underwent LDLT at our institute. Three of the five patients were under dialysis before LDLT, while the other two patients were categorized as CKD stage 3. An isolated LDLT was successfully performed in all but our first case, who had complicated postoperative courses and consequently died due to sepsis after retransplantation. The renal function of the patients with CKD stage 3 was preserved after LDLT. On the other hand, our second case with ESRD underwent successful LDKT six months after LDLT, and our infant case is waiting for the subsequent KT without any post-LDLT complications after the early establishment of PD. In conclusion, a two-step transplant strategy may be needed as a life-saving option for patients with PH1 and may be possible even in small infants with systemic oxalosis. While waiting for a subsequent KT, an early resumption of PD should be considered from the perspective of the long-term requirement of RRT.

In female rats, ethylene glycol treatment elevates protein expression of hepatic and renal oxalate transporter sat-1 (Slc26a1) without inducing hyperoxaluria.

AIM: To investigate whether the sex-dependent expression of hepatic and renal oxalate transporter sat-1 (Slc26a1) changes in a rat model of ethylene glycol (EG)-induced hyperoxaluria. METHODS: Rats were given tap water (12 males and 12 females; controls) or EG (12 males and 12 females; 0.75% v/v in tap water) for one month. Oxaluric state was confirmed by biochemical parameters in blood plasma, urine, and tissues. Expression of sat-1 and rate-limiting enzymes of oxalate synthesis, alcohol dehydrogenase 1 (Adh1) and hydroxy-acid oxidase 1 (Hao1), was determined by immunocytochemistry (protein) and/or real time reverse transcription polymerase chain reaction (mRNA). RESULTS: EG-treated males had significantly higher (in µmol/L; mean±standard deviation) plasma (59.7±27.2 vs 12.9±4.1, P<0.001) and urine (3716±1726 vs 241±204, P<0.001) oxalate levels, and more abundant oxalate crystaluria than controls, while the liver and kidney sat-1 protein and mRNA expression did not differ significantly between these groups. EG-treated females, in comparison with controls had significantly higher (in µmol/L) serum oxalate levels (18.8±2.9 vs 11.6±4.9, P<0.001), unchanged urine oxalate levels, low oxalate crystaluria, and significantly higher expression (in relative fluorescence units) of the liver (1.59±0.61 vs 0.56±0.39, P=0.006) and kidney (1.77±0.42 vs 0.69±0.27, P<0.001) sat-1 protein, but not mRNA. The mRNA expression of Adh1 was female-dominant and that of Hao1 male-dominant, but both were unaffected by EG treatment. CONCLUSIONS: An increased expression of hepatic and renal oxalate transporting protein sat-1 in EG-treated female rats could protect from hyperoxaluria and oxalate urolithiasis.

Recombinant Lactobacillus plantarum expressing and secreting heterologous oxalate decarboxylase prevents renal calcium oxalate stone deposition in experimental rats.

BACKGROUND: Calcium oxalate (CaOx) is the major constituent of about 75% of all urinary stone and the secondary hyperoxaluria is a primary risk factor. Current treatment options for the patients with hyperoxaluria and CaOx stone diseases are limited. Oxalate degrading bacteria might have beneficial effects on urinary oxalate excretion resulting from decreased intestinal oxalate concentration and absorption. Thus, the aim of the present study is to examine the in vivo oxalate degrading ability of genetically engineered Lactobacillus plantarum (L. plantarum) that constitutively expressing and secreting heterologous oxalate decarboxylase (OxdC) for prevention of CaOx stone formation in rats. The recombinants strain of L. plantarum that constitutively secreting (WCFS1OxdC) and non-secreting (NC8OxdC) OxdC has been developed by using expression vector pSIP401. The in vivo oxalate degradation ability for this recombinants strain was carried out in a male wistar albino rats. The group I control; groups II, III, IV and V rats were fed with 5% potassium oxalate diet and 14th day onwards group II, III, IV and V were received esophageal gavage of L. plantarum WCFS1, WCFS1OxdC and NC8OxdC respectively for 2-week period. The urinary and serum biochemistry and histopathology of the kidney were carried out. The experimental data were analyzed using one-way ANOVA followed by Duncan's multiple-range test. RESULTS: Recombinants L. plantarum constitutively express and secretes the functional OxdC and could degrade the oxalate up to 70-77% under in vitro. The recombinant bacterial treated rats in groups IV and V showed significant reduction of urinary oxalate, calcium, uric acid, creatinine and serum uric acid, BUN/creatinine ratio compared to group II and III rats (P < 0.05). Oxalate levels in kidney homogenate of groups IV and V were showed significant reduction than group II and III rats (P < 0.05). Microscopic observations revealed a high score (4+) of CaOx crystal in kidneys of groups II and III, whereas no crystal in group IV and a lower score (1+) in group V. CONCLUSION: The present results indicate that artificial colonization of recombinant strain, WCFS1OxdC and NC8OxdC, capable of reduce urinary oxalate excretion and CaOx crystal deposition by increased intestinal oxalate degradation.

Dietary interventions for preventing complications in idiopathic hypercalciuria.

BACKGROUND: Idiopathic hypercalciuria is an inherited metabolic abnormality that is characterised by excessive amounts of calcium excreted in the urine by people whose calcium serum levels are normal. Morbidity associated with idiopathic hypercalciuria is chiefly related to kidney stone disease and bone demineralisation leading to osteopenia and osteoporosis. Idiopathic hypercalciuria contributes to kidney stone disease at all life stages; people with the condition are prone to developing oxalate and calcium phosphate kidney stones. In some cases, crystallised calcium can be deposited in the renal interstitium, causing increased calcium levels in the kidneys. In children, idiopathic hypercalciuria can cause a range of comorbidities including recurrent macroscopic or microscopic haematuria, frequency dysuria syndrome, urinary tract infections and abdominal and lumbar pain. Various dietary interventions have been described that aim to decrease urinary calcium levels or urinary crystallisation. OBJECTIVES: Our objectives were to assess the efficacy, effectiveness and safety of dietary interventions for preventing complications in idiopathic hypercalciuria (urolithiasis and osteopenia) in adults and children, and to assess the benefits of dietary interventions in decreasing urological symptomatology in children with idiopathic hypercalciuria. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register (23 April 2013) through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs that investigated dietary interventions aimed at preventing complications of idiopathic hypercalciuria, compared with placebo, no intervention, or other dietary interventions regardless of route of administration, dose or amount. DATA COLLECTION AND ANALYSIS: Studies were assessed for inclusion and data extracted using a standardised data extraction form. We calculated risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, both with 95% confidence intervals (CI). MAIN RESULTS: We included five studies (379 adult participants) that investigated a range of interventions. Lack of similarity among interventions investigated meant that data could not be pooled. Overall, study methodology was not adequately reported in any of the included studies. There was a high risk of bias associated with blinding (although it seems unlikely that outcomes measures were unduly influenced by lack of intervention blinding), random sequence generation and allocation methodologies were unclear in most studies, but selective reporting bias was assessed as low.One study (120 participants) compared a low calcium diet with a normal calcium, low protein, low salt diet for five years. There was a significant decrease in numbers of new stone recurrences in those treated with the normal calcium, low protein, low salt diet (RR 0.77, 95% CI 0.61 to 0.98). This diet also led to a significant decrease in oxaluria (MD 78.00 µmol/d, 95% CI 26.48 to 129.52) and the calcium oxalate relative supersaturation index (MD 1.20 95% CI 0.21 to 2.19).One study (210 participants) compared a low salt, normal calcium diet with a broad diet for three months. The low salt, normal calcium diet decreased urinary calcium (MD -45.00 mg/d, 95% CI -74.83 to -15.17) and oxalate excretion (MD -4.00 mg/d, 95% CI -6.44 to -1.56).A small study (17 participants) compared the effect of dietary fibre as part of a low calcium, low oxalate diet over three weeks, and found that although calciuria levels decreased, oxaluria increased. Phyllanthus niruri plant substrate intake was investigated in a small subgroup with hypercalciuria (20 participants); there was no significant effect on calciuria levels occurred after three months of treatment.A small cross-over study (12 participants) evaluating the changes in urinary supersaturation indices among patients who consumed calcium-fortified orange juice or milk for one month found no benefits for participants.None of the studies reported any significant adverse effects associated with the interventions. AUTHORS' CONCLUSIONS: Long-term adherence (five years) to diets that feature normal levels of calcium, low protein and low salt may reduce numbers of stone recurrences, decrease oxaluria and calcium oxalate relative supersaturation indexes in people with idiopathic hypercalciuria who experience recurrent kidney stones. Adherence to a low salt, normal calcium level diet for some months can reduce calciuria and oxaluria. However, the other dietary interventions examined did not demonstrate evidence of significant beneficial effects.No studies were found investigating the effect of dietary recommendations on other clinical complications or asymptomatic idiopathic hypercalciuria.

Analysis and Characterization of Lactobacillus paragasseri and Lacticaseibacillus paracasei: Two Probiotic Bacteria that Can Degrade Intestinal Oxalate in Hyperoxaluric Rats.

In the present study, we characterized the probiotic properties of two commercially available bacterial strains, Lactobacillus paragasseri UBLG-36 and Lacticaseibacillus paracasei UBLPC-87, and evaluated their ability to degrade oxalate in vitro and in a hyperoxaluria-induced nephrolithiasis rat model. UBLG-36 harboring two oxalate catabolizing genes, oxalyl coenzyme A decarboxylase (oxc) and formyl coenzyme A transferase (frc), was previously shown to degrade oxalate in vitro effectively. Here, we show that UBLPC-87, lacking both oxc and frc, could still degrade oxalate in vitro. Both these strains harbored several potential putative probiotic genes that may have conferred them the ability to survive in low pH and 0.3% bile, resist antibiotic stress, show antagonistic activity against pathogenic bacteria, and adhere to epithelial cell surfaces. We further evaluated if UBLG-36 and UBLPC-87 could degrade oxalate in vivo and prevent hyperoxaluria-induced nephrolithiasis in rats. We observed that rats treated with 4.5% sodium oxalate (NaOx) developed hyperoxaluria and renal stones. However, when pre-treated with UBLG-36 or UBLPC-87 before administering 4.5% NaOx, the rats were protected against several pathophysiological manifestations of hyperoxaluria. Compared to the hyperoxaluric rats, the probiotic pre-treated rats showed reduced urinary excretion of oxalate and urea (p < 0.05), decreased serum blood urea nitrogen and creatinine (p < 0.05), alleviated stone formation and renal histological damage, and an overall decrease in renal tissue oxalate and calcium content (p < 0.05). Taken together, both UBLG-36 and UBLPC-87 are effective oxalate catabolizing probiotics capable of preventing hyperoxaluria and alleviating renal damage associated with nephrolithiasis.

Efficacy and safety of Oxalobacter formigenes to reduce urinary oxalate in primary hyperoxaluria.

BACKGROUND: Primary hyperoxaluria (PH) is a rare genetic disease, in which high urinary oxalate (Uox) cause recurrent kidney stones and/or progressive nephrocalcinosis, often followed by early end-stage renal disease, as well as extremely high plasma oxalate, systemic oxalosis and premature death. Oxalobacter formigenes, an anaerobic oxalate degrading bacterium, naturally colonizes the colon of most humans. Orally administered O. formigenes (Oxabact) was found to significantly reduce urine and plasma oxalate. We aimed to evaluate its effect and safety in a randomized, double-blind, placebo-controlled multicenter study. METHODS: Oral Oxabact was given to PH patients (>5 years old, Uox > 1.0 mmol/1.73 m(2)/day, glomerular filtration rate (GFR) > 50 mL/min) at nine PH referral sites worldwide. Primary endpoint was the change from baseline in Uox (mmol/1.73 m(2)/day) after 24 weeks of treatment (>20% reduction). RESULTS: Of the 43 subjects randomized, 42 patients received either placebo (23 subjects) or Oxabact (19 subjects). The change in Uox was <20% and not different between groups (P = 0.616). Ad hoc analysis was performed in 37 patients compliant with medication and urine processing. Change in Uox was -19% in subjects given Oxabact and -10% in placebo, (P = 0.288), but -21 and -7% with Uox expressed as molar creatinine ratio (Ox:Cr, mmol/mol, P = 0.06). Reduction of Ox:Cr was more obvious for patients with higher baseline values (>160 mmol/mol, Oxabact -28%, placebo -6%; P < 0.082). No serious adverse events were reported. CONCLUSION: Oxabact was safe and well tolerated. However, as no significant change in Uox was seen, further studies to evaluate the efficacy of Oxabact treatment are needed.

Ethylene glycol induced hyperoxaluria increases plasma and renal tissue asymmetrical dimethylarginine in rats: a new pathogenetic link in hyperoxaluria induced disorders.

PURPOSE: The pathogenesis of kidney stones remains elusive. There is some evidence that hyperoxaluria may effect vascular endothelium and many studies link renal stones to atherosclerosis. Also, renal vascular endothelial cells regulate proximal tubular epithelial cell function. We determined the effect of hyperoxaluria on plasma and tissue levels of asymmetrical dimethylarginine. The secondary aim was to determine the effect of verapamil on asymmetrical dimethylarginine. MATERIALS AND METHODS: A total of 42 Sprague-Dawley rats were included in the study. In groups 1A, 1B and 1C hyperoxaluria was induced with ethylene glycol for 2 weeks. Groups 2A, 2B and 2C received ethylene glycol for 14 days and verapamil for 28 days. Control group 3 received no specific medication but distilled water. Blood samples were obtained at 24 hours and at study end, and kidney samples were obtained at 24 hours, and 7 and 28 days for histopathological evaluation. RESULTS: Plasma asymmetrical dimethylarginine increased early in the hyperoxaluric group (p = 0.0002). The effect was retained at the end of the study period (p = 0.01). There was no increase in asymmetrical dimethylarginine in the verapamil group on short-term and long-term followup. Hyperoxaluria induced a significantly dense staining pattern in renal tissue asymmetrical dimethylarginine vs controls (p = 0.01). Asymmetrical dimethylarginine staining did not differ in the control and verapamil groups. CONCLUSIONS: Increased systemic and local tissue asymmetrical dimethylarginine may help explain the pathogenetic mechanisms of hyperoxaluria induced disorders such as nephrolithiasis and atherosclerosis.

Berberis vulgaris root bark extract prevents hyperoxaluria induced urolithiasis in rats.

Berberis vulgaris is a widely used plant for the treatment of urolithiasis. To evaluate its antiurolithic potential, the crude aqueous-methanol extract of Berberis vulgaris root bark (Bv.Cr) was tested in an animal model of urolithiasis, developed in male Wistar rats by adding 0.75% ethylene glycol in drinking water. Bv.Cr (50 mg/kg) inhibited CaOx crystal deposition in renal tubules and protected against associated changes including polyuria, weight loss, impaired renal function and the development of oxidative stress in kidneys. Activity-guided fractionation revealed the concentration of antiurolithic constituent(s) mainly in the aqueous fraction. These data, indicating the presence of antiurolithic activity in Berberis vulgaris root bark, rationalize its medicinal use for the treatment of urolithiasis.

General and dietary oxalate restriction advice reduces urinary oxalate in the stone clinic setting.

BACKGROUND: Idiopathic hyperoxaluria is a risk factor for developing calcium oxalate nephrolithiasis. Dietary oxalate's effect on urinary oxalate is not well studied. The aim of this study is to assess the effect of advice focused on reducing dietary oxalate in a cohort of idiopathic hyperoxaluric patients. METHODS: Patients referred to the Groote Schuur Hospital Stone Clinic from 2015 to 2017 were considered eligible, if they were an idiopathic hyperoxaluric stone former, excreting > 40 mg/d of urinary oxalate on a pre-intervention 24-hour stone study urinalysis. Patients were asked to adhere to a diet sheet which included general stone prevention advice (low salt diet, increased fluid intake and moderate protein intake) and specific low oxalate diet advice. A post-intervention 24-hour urinalysis was performed at six weeks. RESULTS: Nineteen patients had hyperoxaluria (eight men and 11 women) with a mean age of 49 years (range 25-76 years). The mean BMI of the group was 28.4 kg/m2 (17.4-50). All patients had mean number of 1.9 range prior stone episodes (range 1-6 stone episodes). Fourteen (14/19) patients completed the study. The mean pre-dietary advice urinary oxalate was 53.2 mg/24 hours (n = 14), SD while the post-intervention was 29.6 mg/24 hours SD (p = 0.0002). Only 3/14 patients who completed the assessment failed to normalise their urinary oxalate on the diet. CONCLUSION: In the stone clinic setting, general advice of low salt diet, increased water intake, moderate protein intake and specific oxalate restriction can significantly reduce oxalate excretion in hyperoxaluric stone formers. Sustained reduction of oxalate excretion and longitudinal clinical benefit are worthy of study in larger cohorts.

Dietary Recommendations for Bariatric Patients to Prevent Kidney Stone Formation.

Bariatric surgery (BS) is one of the most common and efficient surgical procedures for sustained weight loss but is associated with long-term complications such as nutritional deficiencies, biliary lithiasis, disturbances in bone and mineral metabolism and an increased risk of nephrolithiasis, attributed to urinary metabolic changes resultant from low urinary volume, hypocitraturia and hyperoxaluria. The underlying mechanisms responsible for hyperoxaluria, the most common among all metabolic disturbances, may comprise increased intestinal oxalate absorption consequent to decreased calcium intake or increased dietary oxalate, changes in the gut microbiota, fat malabsorption and altered intestinal oxalate transport. In the current review, the authors present a mechanistic overview of changes found after BS and propose dietary recommendations to prevent the risk of urinary stone formation, focusing on the role of dietary oxalate, calcium, citrate, potassium, protein, fat, sodium, probiotics, vitamins D, C, B6 and the consumption of fluids.

A critical analysis of the role of gut Oxalobacter formigenes in oxalate stone disease.

Hyperoxaluria is a major risk factor for the formation of calcium oxalate stones, but dietary restriction of oxalate intake might not be a reliable approach to prevent recurrence of stones. Hence, other approaches to reduce urinary oxalate to manage stone disease have been explored. The gut-dwelling obligate anaerobe Oxalobacter formigenes (OF) has attracted attention for its oxalate-degrading property. In this review we critically evaluate published studies and identify major gaps in knowledge. Recurrent stone-formers are significantly less likely to be colonized with OF than controls, but this appears to be due to antibiotic use. Studies in animals and human subjects show that colonization of the gut with OF can decrease urinary oxalate levels. However, it remains to be determined whether colonization with OF can affect stone disease. Reliable methods are needed to detect and quantify colonization status and to achieve durable colonization. New information about oxalate transport mechanisms raises hope for pharmacological manipulation to decrease urinary oxalate levels. In addition, probiotic use of lactic acid bacteria that metabolize oxalate might provide a valid alternative to OF.

Vitamin C with metabolites reduce oxalate levels compared to ascorbic acid: a preliminary and novel clinical urologic finding.

The incidence and prevalence of kidney stones are notable and are projected to increase over the next decade. Risk factors for kidney stones abound, but a prominent risk factor is hyperoxaluria, which has numerous etiologies, including vitamin C (ascorbic acid) dietary supplement intake. This randomized, double-blind, crossover study examined the effects of two different vitamin C formulations and found that vitamin C with metabolites (Ester-C) significantly reduced urine oxalate levels compared to ascorbic acid. This is a potential novel finding that requires further clinical evaluation.

[Effects of mangesium salts and their combinations with vitamin B6 on oxalates crystalluria in rats fed with pyridoxine-deficient diet].

We studied the effects of oral magnesium (Mg) salts either alone or in combination with pyridoxine hydrochloride in rats on pyridoxine-deficient diet. Fifty-four male rats were randomized into two groups and were fed either a standard diet or a pyridoxine-deficient diet for 3 weeks. A significant rise of the EGOT index ( > 1.5), oxaluria (from 74.8 +/- 5.2 to 117.9 +/- 12.3 mcM/l, p = 0.035), and crystalluria in rats fed with pyridoxine deficient diet were revealed. Oral Mg chloride, Mg L-aspartate either alone or in combination with pyridoxine in comparison with magnesium sulfate, magne B6 (Mg lactate with pyridoxine) and pyridoxine alone were administered (50 mg of magnesium and/or 5 mg of pyridoxine per kg body weight). Magnesium salts in combination with pyridoxine lowered an oxalate level and crystalluria whereas magnesium salts alone reduced only crystalluria. Antilithis effects of Mg L-aspartate and Mg chloride in combination with pyridoxine were comparable with those observed in magne B6 or pyridoxine treatment and were significantly higher than in magnesium sulfate treatment.

Mitochondrial dysfunction in an animal model of hyperoxaluria: a prophylactic approach with fucoidan.

Oxalate/calcium oxalate toxicity is mediated through generation of reactive oxygen species in a process that partly depends upon events that induce mitochondrial damage. Mitochondrial dysfunction is an important event favoring stone formation. The objective of the present study was to investigate whether mitochondria is a target for oxalate/calcium oxalate and the plausible role of naturally occurring glycosaminoglycans from edible seaweed, fucoidan in ameliorating mitochondrial damage. Male albino rats of Wistar strain were divided into four groups and treated as follows: Group I: vehicle treated control, Group II: hyperoxaluria was induced with 0.75% ethylene glycol in drinking water for 28 days, Group III: fucoidan from F. vesiculosus (5 mg/kg b.wt, s.c) from the 8th day of the experimental period, Group IV: ethylene glycol+fucoidan treated rats. The tricarboxylic acid (TCA) cycle enzymes like succinate dehydrogenase, isocitrate dehydrogenase, malate dehydrogenase and respiratory complex enzyme activities were assessed to evaluate mitochondrial function. Oxidative stress was assessed based on the activities of antioxidant enzymes, level of reactive oxygen species, lipid peroxidation and reduced glutathione. Mitochondrial swelling was also analyzed. Ultra structural changes in renal tissue were analyzed with electron microscope. Hyperoxaluria induced a decrease in the activities of TCA cycle enzymes and respiratory complex enzymes. The oxidative stress was evident by the decrease in antioxidant enzymes, glutathione and an increase in reactive species and lipid peroxidation in mitochondria. Mitochondrial damage was evident by increased mitochondrial swelling. Administration of fucoidan, decreased reactive oxygen species, lipid peroxidation (P<0.05), mitochondrial swelling and increased the activities of antioxidant enzymes and glutathione levels (P<0.05) and normalized the activities of mitochondrial TCA cycle and respiratory complex enzymes (P<0.05). From the present study, it can be concluded that mitochondrial damage is an essential event in hyperoxaluria, and fucoidan was able to effectively prevent it and thereby the renal damage in hyperoxaluria.