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.

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.

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.

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.

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.

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.

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

ABSTRACT 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 probiotic 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 received 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) reduced 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 oxalate degrading bacteria can be a new therapeutic approach to preventing the formation of kidney stones.

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.

Designer probiotic Lactobacillus plantarum expressing oxalate decarboxylase developed using group II intron degrades intestinal oxalate in hyperoxaluric rats.

Increased intestinal absorption of oxalate causes hyperoxaluria, a major risk factor for kidney stone disease. Intestinal colonization of recombinant probiotic bacteria expressing oxalate-degrading gene (OxdC) is an effective therapeutic option for recurrent calcium oxalate (CaOx) stone disease. Therefore, we aimed to develop food-grade probiotic L. plantarum secreting OxdC using lactococcal group II intron, Ll.LtrB and evaluate its oxalate degradation ability in vivo. Male Wistar albino rats were divided into four groups. The rats of group I received normal rat chow and drinking water. Groups II, III and IV rats received 5% potassium oxalate containing diet for 28 days. Groups III and IV rats received L. plantarum and food-grade recombinant L. plantarum respectively from 15 to 28 days. Biochemical parameters and crystalluria were analysed in 24 h urine samples. At the end of experimental period, rats were sacrificed; intestine and kidneys were dissected out for colonization studies and histopathological analysis. Herein, we found that the administration of recombinant probiotics significantly reduced the urinary oxalate, calcium, urea, and creatinine levels in rats of group IV compared to group II. Furthermore, colonization studies indicated that recombinant probiotics have gastrointestinal transit and intestinal colonization ability similar to that of wild-type bacteria. In addition, gene expression studies revealed down-regulation of OPN and KIM-1 among group IV rats. Histopathological analysis showed less evidence of nephrocalcinosis in group IV rats. In conclusion, the study demonstrates that food-grade L. plantarum secreting OxdC is capable of degrading intestinal oxalate and thereby prevent CaOx stone formation in experimental rats.

Protective impact of resveratrol in experimental rat model of hyperoxaluria.

PURPOSE: Resveratrol (RES) is a polyphenol with antioxidant, anti-inflammatory, and many other physiological effects on tissues. In the present study, the effect of resveratrol in hyperoxaluria driven nephrolithiasis/nephrocalcinosis is investigated. METHODS: Wistar-Albino rats of 250-300 g (male, n = 24) were included in the present study. The rats were randomized into three groups: Group 1 consisted of the controls (n = 8), Group 2 of hyperoxaluria (1% ethylene glycol (EG), n = 8), and Group 3 of the treatment (1% EG + 10 mg/kg of RES, n = 8) group. At the beginning and fifth week of the study, two rats from each group were placed in metabolic cages for 24 h and their urine was collected. At the end of the study, the rats were killed and their blood was collected from the vena cava inferior. The right kidneys of the rats were used for biochemical and the left ones for immunohistochemical analyzes. Malondialdehyde (MDA), catalase, urea, calcium, oxalate, and creatinine clearance were studied in the blood, urine, and kidney tissues. Moreover, routine histological evaluation, and p38-MAPK and NFkB immunohistochemical analyses were conducted. RESULTS: In the hyperoxaluria group, urinary oxalate levels were higher than the control group; yet, lower in the treatment group compared to hyperoxaluria group (p < 0.05). Serum MDA levels in the hyperoxaluria group were higher than the control group; but in the treatment group it is lower than the hyperoxaluria group (p < 0.05). P38 MAPK activity was higher in the hyperoxaluria group compared to the control (p < 0.05). However, in terms of p38 MAPK activity, there were no statistically significant difference between hyperoxaluria and the treatment group (p < 0.069). Whereas NFkB activity in the hyperoxaluria group is higher than the control (p < 0.001), no statistically significant difference was observed with the treatment group. CONCLUSIONS: In the present study, resveratrol was seen to prevent hyperoxaluria. With preventing oxidative stress factors and Randall plaque formation caused by free oxygen radicals, resveratrol can be an alternative treatment option that can increase the success rate in preventing stone recurrence in the future.

Hiperparatiroidismo en pacientes con litiasis. Influencia del déficit de 25-OH vitamina D / Hyperparathyroidism in patients with stones. Influence of deficit 25-OH vitamin D

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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.

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.

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.

[Nephrolithiasis: metabolic defects and terapeutic implications]. / Nefrolitiasi: aspetti metabolici e implicazioni terapeutiche.

Over the past 10 years, major progress has been made in the knowledge of urinary lithogenesis, including the potential pathogenetic role of Randall's plaques and renal tubular crystal retention. Urine supersaturation is the driving force of this process and can be induced by some risk factors, including low urine volume, high urinary excretion of calcium oxalate and uric acid and low urinary excretion of citrate. Primary hypercalciuria can be due to intestinal overabsorption renal leak and bone reabsorption of calcium. Prophilaxis is mainly conducted with thiazides and low calcium diet which is indicated only in the intestinal form. Primary hyperoxaluria is treated with pyridoxine and may require in the severe forms simultaneous renal and liver transplantation. Enteric hyperoxaluria is secondary to fatty acids malabsorption and requires diet, oral calcium and cholestiramine. Hyperuricosuria is caused by diet endogenous overproduction, mainly due to enzymatic defects or high renal excretion of uric acid. Urine alkalinization with K or K and Mg citrate can prevent stone formation even in idiopathic uric acid nephrolithiasis, in which a defect of urine acidification is supposed to be the main abnormality, and in hypocitraturic patients. Cystinuria is a rare inherited defect with an intense clinical impact. It can be classified in three forms and urinary stone formation is the role. Increased solubility and conversion of cystine in a more soluble form are the main goals of the prophylaxis which includes K citrate and thiol agents administration. Tiopronin is preferred to D-penicillamine due to its lower side effects.

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.

In vitro anti-inflammatory activity of selected oxalate-degrading probiotic bacteria: potential applications in the prevention and treatment of hyperoxaluria.

UNLABELLED: Oxalate (Ox) is a very common component of the human diet, capable to collect in the renal tissue and bind calcium to form calcium oxalate (CaOx) crystals. A supersaturation of CaOx crystal may cause nephrocalcinosis and nephrolithiasis. The inflammation derived from the CaOx crystal accumulation, together with innate or secondary renal alterations, could strongly affect the renal function. In this case a consumption of probiotics with either oxalate-degrading activity at intestinal level and systemic anti-inflammatory activity could be an alternative approach to treat the subjects with excess of urinary oxalate excretion. 11 strains of lactic acid bacteria (Lactobacilli and Bifidobacteria), already included in the list of bacteria safe for the human use, were investigated for their capability to degrade oxalate by mean of RP-HPLC-UV method and modulate inflammation in an in vitro model system based on peripheral blood mononuclear cells. Four promising bacterial strains (Lactobacillus plantarum PBS067, Lactobacillus acidophilus LA-14, Bifidobacterium breve PBS077, Bifidobacterium longum PBS078) were identified as innovative biological tools for the prevention and the therapeutic treatment of hyperoxaluria and the inflammatory events associated to the Ox accumulation. PRACTICAL APPLICATION: The oxalate-degrading activity of some probiotics and their capability to modulate the release of inflammation mediators could be exploited as a new nutraceutical and therapeutic approach for the treatment of oxalate accumulation and the related inflammatory state.