Intestinal Oxalate Absorption Research Articles

Intestinal Oxalate Absorption, Enteric Hyperoxaluria, and Risk of Urinary Stone Formation in Patients with Crohn's Disease.

Nephrolithiasis is a common urologic manifestation of Crohn's disease. The purpose of this study was to investigate the clinical characteristics, intestinal oxalate absorption, and risk factors for urinary stone formation in these patients. In total, 27 patients with Crohn's disease and 27 healthy subjects were included in the present study. Anthropometric, clinical, and 24 h urinary parameters were determined, and the [13C2]oxalate absorption test was performed. Among all patients, 18 had undergone ileal resection, 9 of whom had a history of urinary stones. Compared to healthy controls, the urinary excretion values of calcium, magnesium, potassium, sulfate, creatinine, and citrate were significantly lower in patients with Crohn's disease. Intestinal oxalate absorption, the fractional and 24 h urinary oxalate excretion, and the risk of calcium oxalate stone formation were significantly higher in patients with urolithiasis than in patients without urolithiasis or in healthy controls. Regardless of the group, between 83% and 96% of the [13C2]oxalate was detected in the urine within the first 12 h after ingestion. The length of ileum resection correlated significantly with the intestinal absorption and urinary excretion of oxalate. These findings suggest that enteric hyperoxaluria can be attributed to the hyperabsorption of oxalate following extensive ileal resection. Oral supplementation of calcium and magnesium, as well as alkali citrate therapy, should be considered as treatment options for urolithiasis.

Review of the Role of Enteral Factor in the Development of Secondary Hyperoxaluria

Objectives: Discuss the role of the enteric factor in the hyperoxaluria development.
 Methods: Using the Internet and written materials, the relevant factors of enteral factor; hyperoxaluria; oxalotrophia; Oxalobacter formigenes; kidney stones, and with 36 references, were comprehensively analyzed and studied.
 Results: Under the condition of excessive intake of oxalate and its precursors, increased intestinal absorption of oxalate and imbalance of intestinal flora, resulting in increased urine oxalate and calcium oxalate crystal, which lead to hematuria, proteinuria, recurrent kidney stones and nephrocalcinosis.
 Discussion: Hyperoxaluria is a disease caused by metabolism disorder of oxalic acid and intestinal factors have significant influence on its progression. This disease can occur under the condition of excessive intake of oxalate and its precursors, increased intestinal absorption of oxalate and imbalance of intestinal flora, resulting in increased urine oxalate and calcium oxalate crystal, which lead to hematuria, proteinuria, recurrent kidney stones and nephrocalcinosis. Some patients may further progress to the AKI and CKD. With progressive decline in renal function, oxalate is reduced and deposits in the body can affect other tissues and organs. And adjustment of enteral factors is helpful for the treatment of hyperoxaluria.
 In this article we discuss the role of the enteric factor in the hyperoxaluria development. Hyperoxaluria is a metabolic disease characterized by excessive urinary oxalic acid excretion and calcium oxalate crystal deposition, whose intestinal factors affecting its onset includes the increased intake of oxalic acid and its precursors, the increased intestinal absorption of oxalate and the imbalance of intestinal flora, etc. Severe hyperoxaluria can lead to kidney stones. At present, the influence of intestinal factors on hyperoxaluria has become a research focus, this paper will give a comprehensive description of its related research.

Mechanisms of the intestinal and urinary microbiome in kidney stone disease.

Kidney stone disease affects ~10% of the global population and the incidence continues to rise owing to the associated global increase in the incidence of medical conditions associated with kidney stone disease including, for example, those comprising the metabolic syndrome. Considering that the intestinal microbiome has a substantial influence on host metabolism, that evidence has suggested that the intestinal microbiome might have a role in maintaining oxalate homeostasis and kidney stone disease is unsurprising. In addition, the discovery that urine is not sterile but, like other sites of the human body, harbours commensal bacterial species that collectively form a urinary microbiome, is an additional factor that might influence the induction of crystal formation and stone growth directly in the kidney. Collectively, the microbiomes of the host could influence kidney stone disease at multiple levels, including intestinal oxalate absorption and direct crystal formation in the kidneys.

Small-molecule inhibitor of intestinal anion exchanger SLC26A3 for treatment of hyperoxaluria and nephrolithiasis.

Nephrolithiasis is a common and recurrent disease affecting 9% of the US population. Hyperoxaluria is major risk factor for calcium oxalate kidney stones, which constitute two-thirds of all kidney stones. SLC26A3 (DRA, downregulated in adenoma) is an anion exchanger of chloride, bicarbonate, and oxalate thought to facilitate intestinal oxalate absorption, as evidenced by approximately 70% reduced urine oxalate excretion in knockout mice. We previously identified a small-molecule SLC26A3 inhibitor (DRAinh-A270) that selectively inhibited SLC26A3-mediated chloride/bicarbonate exchange (IC50 ~ 35 nM) and, as found here, oxalate/chloride exchange (IC50 ~ 60 nM). In colonic closed loops in mice, luminal DRAinh-A270 inhibited oxalate absorption by 70%. Following oral sodium oxalate loading in mice, DRAinh-A270 largely prevented the 2.5-fold increase in urine oxalate/creatinine ratio. In a mouse model of oxalate nephropathy produced by a high-oxalate low-calcium diet, vehicle-treated mice developed marked hyperoxaluria with elevated serum creatinine, renal calcium oxalate crystal deposition, and renal injury, which were largely prevented by DRAinh-A270 (10 mg/kg twice daily). DRAinh-A270 administered over 7 days to healthy mice did not show significant toxicity. Our findings support a major role of SLC26A3 in intestinal oxalate absorption and suggest the therapeutic utility of SLC26A3 inhibition for treatment of hyperoxaluria and prevention of calcium oxalate nephrolithiasis.

Randomized Placebo-Controlled Trial of Reloxaliase in Enteric Hyperoxaluria

BackgroundEnteric hyperoxaluria is caused by increased intestinal oxalate absorption and can lead to kidney stones, chronic kidney disease, and kidney failure. Reloxaliase is an orally administered recombinant enzyme that degrades oxalate along the gastrointestinal tract, thereby preventing its absorption.MethodsWe randomly assigned participants with enteric hyperoxaluria to reloxaliase or placebo, three to five times per day with food for 4 weeks. The primary end point was percent change from baseline in 24-hour urinary oxalate (UOx) excretion during weeks 1 to 4. Secondary end points included the proportion of participants with more than a 20% reduction in 24-hour UOx and an efficacy assessment in the bariatric surgery subgroup.ResultsA total of 115 patients underwent randomization. The 24-hour UOx decreased from a baseline geometric mean of 83.2 to 67.4 mg/24 hr during weeks 1 to 4 in reloxaliase-treated participants. Corresponding data for placebo-treated participants were 84.2 to 78.1 mg/24 hr. Estimates from the mixed-effect model repeated-measures (MMRM) analysis showed a 22.6% reduction in geometric mean UOx during weeks 1 to 4 for reloxaliase and 9.7% for placebo, a difference of 14.3 percentage points (95% confidence interval [CI], 4.9 to 22.8; P=0.004). A 20% or greater reduction in 24-hour UOx was observed in 48.3% of reloxaliase-treated participants and 31.6% of placebo-treated participants (P=0.06). In the bariatric surgery subgroup, MMRM analysis showed a 21.2% reduction in geometric mean UOx for reloxaliase and a 6.0% reduction for placebo, for a difference of 16.2 percentage points (95% CI, 4.2% to 26.7%). Adverse events occurred in 69% of reloxaliase-treated participants versus 53% of individuals taking placebo and were most commonly gastrointestinal. All but one of the adverse events were grade 1 or 2 in severity; no reloxaliase-treated participants discontinued the study.ConclusionsReloxaliase treatment for 4 weeks reduced UOx excretion in patients with enteric hyperoxaluria; adverse events were relatively common, but not dose-limiting. These data establish the foundation for a clinical trial to determine the impact of reloxaliase on nephrolithiasis in patients with enteric hyperoxaluria. (Funded by Allena Pharmaceuticals; ClinicalTrials.gov number, NCT03456830.)

Simple dietary advice targeting five urinary parameters reduces urinary supersaturation in idiopathic calcium oxalate stone formers

Among 208 kidney stone patients referred within 2 years, 75 patients (66 men, nine women) with truly idiopathic calcium oxalate stones (ICSF) were recruited. Dietary advice (DA) aimed at (1) urine dilution, (2) reduced crystallization promotion (lowering oxalate), and (3) increased crystallization inhibition (increasing citrate). We recommended higher intakes of fluid and calcium with meals/snacks (reducing intestinal oxalate absorption) as well as increased alkali and reduced meat protein (acid) for increasing urinary citrate. The intended effects of DA were elevations in urine volume, calcium (U-Ca) and citrate (U-Cit) as well as reductions in oxalate (U-Ox) and uric acid (U-UA). We retrospectively calculated an adherence score (AS), awarding + 1 point for parameters altered in the intended direction and − 1 point for opposite changes. Calcium oxalate supersaturation (CaOx-SS) was calculated using Tiselius’ AP(CaOx) index EQ. DA induced changes (all p < 0.0001) in urine volume (2057 ± 79 vs. 2573 ± 71 ml/day) and U-Ca (5.49 ± 0.24 vs. 7.98 ± 0.38 mmol/day) as well as in U-Ox (0.34 ± 0.01 vs. 0.26 ± 0.01 mmol/day) and U-UA (3.48 ± 0.12 vs. 3.13 ± 0.10 mmol/day). U-Cit only tendentially increased (3.07 ± 0.17 vs. 3.36 ± 0.23 mmol/day, p = 0.06). DA induced a 21.5% drop in AP(CaOx) index, from 0.93 ± 0.05 to 0.73 ± 0.05 (p = 0.0005). Decreases in CaOx-SS correlated with AS (R = 0.448, p < 0.0005), and highest AS (+ 5) always indicated lowering of CaOx-SS. Thus, simple DA can reduce CaOx-SS which may be monitored by AS.

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.

Enhanced gastrointestinal passive paracellular permeability contributes to the obesity-associated hyperoxaluria.

Most kidney stones (KS) are composed of calcium oxalate and small increases in urine oxalate enhance the stone risk. Obesity is a risk factor for KS, and urinary oxalate excretion increases with increased body size. We previously established the obese ob/ob ( ob) mice as a model (3.3-fold higher urine oxalate) to define the pathogenesis of obesity-associated hyperoxaluria (OAH). The purpose of this study was to test the hypothesis that the obesity-associated enhanced small intestinal paracellular permeability contributes to OAH by increasing passive paracellular intestinal oxalate absorption. ob Mice have significantly higher jejunal (1.6-fold) and ileal (1.4-fold) paracellular oxalate absorption ex vivo and significantly higher (5-fold) urine [13C]oxalate following oral gavage with [13C]oxalate, indicating increased intestinal oxalate absorption in vivo. The observation of higher oxalate absorption in vivo compared with ex vivo suggests the possibility of increased paracellular permeability along the entire gut. Indeed, ob mice have significantly higher fractions of the administered sucrose (1.7-fold), lactulose (4.4-fold), and sucralose (3.1-fold) excreted in the urine, reflecting increased gastric, small intestinal, and colonic paracellular permeability, respectively. The ob mice have significantly reduced gastrointestinal occludin, zonula occludens-1, and claudins-1 and -3 mRNA and total protein expression. Proinflammatory cytokines and oxidative stress, which are elevated in obesity, significantly enhanced paracellular intestinal oxalate absorption in vitro and ex vivo. We conclude that obese mice have significantly higher intestinal oxalate absorption and enhanced gastrointestinal paracellular permeability in vivo, which would likely contribute to the pathogenesis of OAH, since there is a transepithelial oxalate concentration gradient to drive paracellular intestinal oxalate absorption. NEW & NOTEWORTHY This study shows that the obese ob/ob mice have significantly increased gastrointestinal paracellular oxalate absorption and remarkably enhanced paracellular permeability along the entire gut in vivo, which are likely mediated by the obesity-associated increased systemic and intestinal inflammation and oxidative stress. A transepithelial oxalate concentration gradient driving gastrointestinal paracellular oxalate absorption exists, and therefore, our novel findings likely contribute to the hyperoxaluria observed in the ob/ob mice and hence to the pathogenesis of obesity-associated hyperoxaluria.

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.

Association between chronic pancreatitis and urolithiasis: A population-based cohort study.

PurposeChronic pancreatitis (CP) can cause fat or bile acid malabsorption due to exocrine insufficiency. Fat or bile acid malabsorption has been reported to increase the risk of urolithiasis through increased intestinal oxalate absorption. However, no studies have reported an association between CP and urolithiasis.MethodsWe identified 15,848 patients (age: ≥20 years) diagnosed as having CP between 2000 and 2010 from the National Health Insurance Research Database as the study cohort. Beneficiaries without a history of CP were randomly selected and propensity-matched with the study cohort in a 1:4 ratio according to age; sex; comorbidities of hyperlipidemia, diabetes, obesity, hypertension, chronic obstructive pulmonary disease, alcohol-related illness, stroke, and coronary artery disease; and the index date. The prevalence of inflammatory bowel disease (0.44%), hyperparathyroidism (0.10%), or end stage renal disease (1.55%) in CP patients was low, but these comorbidities were also considered in the analysis. All patients were followed until the end of 2011 or withdrawal from the National Health Insurance program to determine the incidence of urolithiasis.ResultsThe cumulative incidence of urolithiasis was higher in the CP cohort than that in the non-CP cohort (log-rank test, P < 0.001) with a 1.89-fold risk of urolithiasis (95% confidence interval [CI] = 1.74–2.06). The prevalence of CP was higher in men (81.9%) and in patients younger than 49 years (63.5%; mean age: 48.5 ± 15.3 years). CP was associated with the development of urolithiasis in each age group (≤49 years: aHR = 2.00, 95% CI = 1.81–2.22; 50–64 years: aHR = 1.71, 95% CI = 1.40–2.09; ≥65 years: aHR = 1.54, 95% CI = 1.20–1.98) and each sex (women: aHR = 2.10, 95% CI = 1.67–2.66; men; aHR = 1.86, 95% CI = 1.70–2.04). Among the patients without comorbidities, the rate of urolithiasis increased from 2.93/1,000 person-years in non-CP patients to 8.28/1,000 person-years in CP patients. Among the patients with comorbidities, the rate of urolithiasis increased from 6.12/1,000 person-years in non-CP patients to 10.9/1,000 person-years in CP patients. The contribution of CP to the relative risk of urolithiasis was greater in patients without comorbidities (without comorbidities: aHR = 2.81, 95% CI = 2.30–3.44) than in those with comorbidities (aHR = 1.76, 95% CI = 1.61–1.94).ConclusionCP is associated with urolithiasis in this population-based cohort study. The contribution of CP to the relative risk of urolithiasis was even greater in patients with a lower risk of urolithiasis, such as those without other comorbidities. Our findings warrant a survey and education on urolithiasis for patients with CP.

Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate Secretion.

Patients with cystic fibrosis have an increased incidence of hyperoxaluria and calcium oxalate nephrolithiasis. Net intestinal absorption of dietary oxalate results from passive paracellular oxalate absorption as modified by oxalate back secretion mediated by the SLC26A6 oxalate transporter. We used mice deficient in the cystic fibrosis transmembrane conductance regulator gene (Cftr) to test the hypothesis that SLC26A6-mediated oxalate secretion is defective in cystic fibrosis. We mounted isolated intestinal tissue from C57BL/6 (wild-type) and Cftr-/- mice in Ussing chambers and measured transcellular secretion of [14C]oxalate. Intestinal tissue isolated from Cftr-/- mice exhibited significantly less transcellular oxalate secretion than intestinal tissue of wild-type mice. However, glucose absorption, another representative intestinal transport process, did not differ in Cftr-/- tissue. Compared with wild-type mice, Cftr-/- mice showed reduced expression of SLC26A6 in duodenum by immunofluorescence and Western blot analysis. Furthermore, coexpression of CFTR stimulated SLC26A6-mediated Cl--oxalate exchange in Xenopus oocytes. In association with the profound defect in intestinal oxalate secretion, Cftr-/- mice had serum and urine oxalate levels 2.5-fold greater than those of wild-type mice. We conclude that defective intestinal oxalate secretion mediated by SLC26A6 may contribute to the hyperoxaluria observed in this mouse model of cystic fibrosis. Future studies are needed to address whether similar mechanisms contribute to the increased risk for calcium oxalate stone formation observed in patients with cystic fibrosis.

Recent advances in managing and understanding nephrolithiasis/nephrocalcinosis.

Urinary stone disease is a very common disease whose prevalence is still increasing. Stone formation is frequently associated with other diseases of affluence such as hypertension, osteoporosis, cardiovascular disease, metabolic syndrome, and insulin resistance. The increasing concentration of lithogenic solutes along the different segments of the nephron involves supersaturation conditions leading to the formation, growth, and aggregation of crystals. Crystalline aggregates can grow free in the tubular lumen or coated on the wall of the renal tubule. Plugs of crystalline material have been highlighted in the tubular lumen in some patients, but crystalline growth starting from plaques of calcium phosphate within the renal papillae has been demonstrated in others. Urinary supersaturation is the result of a complex interaction between predisposing genetic features and environmental factors. Dietary intake is certainly the most important environmental risk factor. In particular, an insufficient intake of dietary calcium (<600 mg/day) can increase the intestinal absorption of oxalate and the risk of calcium oxalate stone formation. Other possible risk factors that have been identified include excessive intake of salt and proteins. The potential role of dietary acid load seems to play an important role in causing a state of subclinical chronic acidosis; therefore, the intake of vegetables is encouraged in stone-forming patients. Consumption of sugar-sweetened soda and punch is associated with a higher risk of stone formation, whereas consumption of coffee, tea, beer, wine, and orange juice is associated with a lower risk. A high fluid intake is widely recognized as the cornerstone of prevention of all forms of stones. The effectiveness of protein and salt restriction has been evaluated in some studies that still do not allow definitive conclusions to be made. Calcium stone formation can be prevented by the use of different drugs with different mechanisms of action (thiazide diuretics, allopurinol, and potassium citrate), but there is no ideal drug that is both risk free and well tolerated.

Metabolic Evaluation in Paediatric Urolithiasis: A 4-Year Open Prospective Study.

Children with urolithiasis are associated with considerable morbidity and commonly associated with metabolic abnormalities. By treating these abnormalities stone formation is prevented. To study the metabolic risk factors of urolithiasis in children and compare them with literature. In open, prospective and observational study, 75 children were evaluated from August 2010 to June 2014. In all patients' dietary history, water intake and results of laboratory findings were recorded. All urine samples obtained from patients were without dietary restrictions. Reference paediatric 24 hour urinary parameter was used according to western literature. We investigated 75 patients with urolithiasis. Low urine volume was found in 49 patients which is comparable with previous studies indicating simple intervention as to increase water intake. Low calcium intake was found in 44 patients suggesting that low calcium intake is associated with higher incidence of urolithiasis due to increased intestinal oxalate absorption. Hypocalcaemia was found in 32 patients and 24 hour urinary abnormality was found in only 16 patients'. Both these finding does not support previous literature. Stone analysis finding does not correlate with urinary finding. Low urine volume secondary to low water intake is predominant finding. Hypocalcaemia is major metabolic abnormality in contradiction to western literature. There are no nomograms for urinary excretion of Calcium, uric acid, oxalate and citrate in Indian children. Keeping the optimum blood calcium level & increased fluid intake can prevent stone formation in children.

The management of patients with enteric hyperoxaluria.

Enteric hyperoxaluria is a common occurrence in the setting of fat malabsorption, usually due to intestinal resection or intestinal bypass surgery. Enhanced intestinal absorption of dietary oxalate leads to elevated renal oxalate excretion, frequently in excess of 100mg/d (1.14mmol/d). Patients are at increased risk of urolithiasis and loss of kidney function from oxalate nephropathy. Fat malabsorption causes increased binding of diet calcium by free fatty acids, reducing the calcium available to precipitate diet oxalate. Delivery of unabsorbed bile salts and fatty acids to the colon increases colonic permeability, the site of oxalate hyper-absorption in enteric hyperoxaluria. The combination of soluble oxalate in the intestinal lumen and increased permeability of the colonic mucosa leads to hyperoxaluria. Dietary therapy consists of limiting oxalate and fat intake. The primary medical intervention is the use of oral oxalate binding agents such as calcium salts to reduce free intestinal oxalate levels. Bile acid sequestrants can be useful in patients with ileal resection and bile acid malabsorption. Oxalate degrading bacteria provided as probiotics are being investigated but as of yet, no definite benefit has been shown with currently available preparations. The current state of medical therapy and potential future directions will be summarized in this article.

2,8-Dihydroxyadenine (DHA) crystalluria – A rare cause of recurrence after kidney transplant

Increased intestinal oxalate absorption leads to increased urinary oxalate excretion (secondary hyperoxaluria) and calcium oxalate crystal formation, contributing to nephrocalcinosis/lithiasis. Lanthanum carbonate is an intestinal phosphate binder that is orally administered to patients on dialysis to treat hyperphosphatemia. It is hypothesized that lanthanum can also bind oxalate, in addition to phosphate. We evaluated this in vitro and in vivo.In vitro oxalate binding was evaluated by oxalate precipitation from a solution by lanthanum. In vivo oxalate absorption kinetics and the effect of lanthanum carbonate on nephrocalcinosis development were assessed in male Sprague-Dawley® rats that received 1) 1,000 mg lanthanum carbonate and oxalate, 2) carboxymethylcellulose and oxalate or 3) carboxymethylcellulose by gavage for up to 12 hours (kinetics) or 7 days (nephrocalcinosis). Plasma and urinary oxalate concentrations were measured at several time points after gavage. The degree of nephrocalcinosis was assessed histomorphometrically on von Kossa stained sections and by measuring total calcium content in renal tissue.In vitro lanthanum bound oxalate in a pH range comparable to the range of the intestine. In vivo oxalate administration in untreated animals resulted in a biphasic pattern of increased plasma oxalate levels, which was almost abolished in lanthanum treated rats. In the urine of treated rats oxaluria and calcium oxalate crystalluria were blunted. Moreover, significantly decreased nephrocalcinosis was observed compared with that in untreated rats.Lanthanum carbonate is a promising agent for the future prevention/treatment of secondary hyperoxaluria.

Primary and secondary hyperoxaluria: Understanding the enigma.

Hyperoxaluria is characterized by an increased urinary excretion of oxalate. Primary and secondary hyperoxaluria are two distinct clinical expressions of hyperoxaluria. Primary hyperoxaluria is an inherited error of metabolism due to defective enzyme activity. In contrast, secondary hyperoxaluria is caused by increased dietary ingestion of oxalate, precursors of oxalate or alteration in intestinal microflora. The disease spectrum extends from recurrent kidney stones, nephrocalcinosis and urinary tract infections to chronic kidney disease and end stage renal disease. When calcium oxalate burden exceeds the renal excretory ability, calcium oxalate starts to deposit in various organ systems in a process called systemic oxalosis. Increased urinary oxalate levels help to make the diagnosis while plasma oxalate levels are likely to be more accurate when patients develop chronic kidney disease. Definitive diagnosis of primary hyperoxaluria is achieved by genetic studies and if genetic studies prove inconclusive, liver biopsy is undertaken to establish diagnosis. Diagnostic clues pointing towards secondary hyperoxaluria are a supportive dietary history and tests to detect increased intestinal absorption of oxalate. Conservative treatment for both types of hyperoxaluria includes vigorous hydration and crystallization inhibitors to decrease calcium oxalate precipitation. Pyridoxine is also found to be helpful in approximately 30% patients with primary hyperoxaluria type 1. Liver-kidney and isolated kidney transplantation are the treatment of choice in primary hyperoxaluria type 1 and type 2 respectively. Data is scarce on role of transplantation in primary hyperoxaluria type 3 where there are no reports of end stage renal disease so far. There are ongoing investigations into newer modalities of diagnosis and treatment of hyperoxaluria. Clinical differentiation between primary and secondary hyperoxaluria and further between the types of primary hyperoxaluria is very important because of implications in treatment and diagnosis. Hyperoxaluria continues to be a challenging disease and a high index of clinical suspicion is often the first step on the path to accurate diagnosis and management.

Dietary habits may influence oxalate degradation by intestinal bacteria commentary on: the role of Oxalobacter formigenes colonization in calcium oxalate stone disease.

The purpose of this article was to assess the role of Oxalobacter formigenes (O formigenes) on the intestinal absorption, plasma concentration, and urinary excretion of oxalate in calcium oxalate stone formers and to better understand oxalate metabolism in the presence or absence of this bacterial species.

Helicobacter pylori and urinary system stones: Endoluminal damage as sub-hypothesis to support the current stone theory

Helicobacter pylori (H. pylori) is a atypical gram-negative bacteria preferring gastric mucosa which also have bizarre multisystem effects extended to some malignancies, hematologic and vascular disorders through some not well defined pathophysiologic pathways. Our pioneer data was pointing that the urinary system stone existence was seemed to be high in the group of H. pylori+cases. While the explanation of the reason of the coincidence of renal-gall bladder stones, it was previously suggested that there may be a shift mechanism of intestinal microbial flora, from Oxalobacter formigenes that may reduce the risk of renal stone by consuming intestinal oxalate, to H. pylori which is known to induce gallstone by unknown mechanism. This hypothesis is an indirect one and highly controversial for the effect of H. pylori in the renal stone formation because intestinal absorption of oxalate is not significant when it is compared with the endogen oxalate. The present preliminary unique data in connection with our hypothesis claimed that a possible relation between H. pylori and renal stones. We think that this detrimental effect is due to the possible systemic influence such as vascular and/or endoluminal sickness due to the H. pylori other than directs bacteriologic colonization. There is strong evidence that H. pylori have some role in the atherosclerotic procedure. The vascular theory of Randall plaque formation at renal papilla and subsequent calcium oxalate stone development that suggests microvascular injury of renal papilla in an atherosclerotic-like fashion results in calcification near vessel walls that eventually erodes as a calculus format into the urinary system. Briefly, theories of stone and atherosclerosis seemed to be overlap and H. pylori is one of the factor of both processes. In addition to our hypothesis, we claimed that H. pylori might have same detrimental effect on endoluminal surfaces of urinary and genital systems and resulting in some special pathologies as Hunner’s ulcers in interstitial cystitis and even posttesticular infertility. The accumulating knowledge about extragastric sequelae of H. pylori may open new aspects on therapeutic and the prevention strategies of urolithiasis and even this progress may reach to chronic pelvic pain syndromes and idiopathic infertility.

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

BackgroundCalcium 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.ResultsRecombinants 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.ConclusionThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-014-0086-y) contains supplementary material, which is available to authorized users.

Factors contributing to the variation in feline urinary oxalate excretion rate1

This study aimed to identify factors (season, animal, and diet) contributing to the variation in urinary oxalate (Uox) excretion rate, Uox concentration, and urine volume in healthy adult cats. A data set (1,940 observations) containing information on Uox excretion rate of 65 cats fed 252 diets (i.e., each diet was fed to a group of 6 to 8 cats), with known dietary oxalate concentrations, collected over a 6 yr period at a feline nutrition facility, were retrospectively analyzed. Data related to season, animal (i.e., age, gender, body weight, and breed), and diet (i.e., nutrient content) characteristics were subjected to stepwise multivariate regression analysis to identify factors significantly correlated to Uox excretion rate (μmol/(kg BW(0.67)·d)) and concentration (mmol/L) as well as urine volume (mL/(kg BW(0.67)·d)). Independent factors significantly (P < 0.05) associated with lower Uox concentration (mmol/L) included greater ash, Ca, and Na intake and lower nitrogen-free extract, total dietary fiber, P, and oxalate intake, and a body weight <5 kg. Factors significantly associated with lower Uox excretion rate (μmol/(kg BW(0.67)·d)) included greater crude fat and Ca intake and lower CP, total dietary fiber, P, and oxalate intake. However, a considerable part of the variation in Uox excretion rate remained unexplained. The majority of the unexplained variation in Uox excretion rate is likely to be related to factors involved in endogenous oxalate synthesis, as the majority of the dietary factors involved in intestinal oxalate absorption were included in the model. Apparent intestinal oxalate absorption was estimated to be 6.2% on average; however, much variation was present. Future research on Uox excretion rate in cats should focus on the influence of dietary protein sources, amino acid composition, vitamin C (that was not included in the present study), and variations in apparent intestinal oxalate absorption.