Effect of Vitamin B2-Deficient Diet on Hydroxyproline- or Obesity-Induced Hyperoxaluria in Mice.

SCOPE: Hyperoxaluria is a major cause of kidney stone disease. Around half of the oxalate in mammals is supplied from the diet and the other half is endogenously synthesized from glyoxylate. Reduction of hepatic glycolate oxidase (GO) activity is one approach to reduce endogenous production of oxalate. However, there are currently few effective dietary approaches to reduce hepatic GO activity. METHODS AND RESULTS: In the present study, it is investigated whether restriction of dietary vitamin B2 (VB2) can reduce hepatic GO activity and oxalate excretion in mice with hyperoxaluria induce by hydroxyproline (Hyp) or obesity. It is found that VB2 restriction significantly reduces hepatic GO activity in both the Hyp- and obesity-induced model of hyperoxaluria in mice. However, VB2 restriction reduces urinary oxalate excretion only in the Hyp-treated mice and not the obese mice. This difference could be due to the contribution of endogenous oxalate production that manifests as increased hepatic GO activity in Hyp-treated mice but not obese mice. CONCLUSION: Together these results suggest that VB2 restriction could be a new dietary approach to improve hyperoxaluria when endogenous production of oxalate is increased.

Urinary lithogenic risk profile in recurrent stone formers with hyperoxaluria: a randomized controlled trial comparing DASH (Dietary Approaches to Stop Hypertension)-style and low-oxalate diets.

BACKGROUND: Patients with nephrolithiasis and hyperoxaluria generally are advised to follow a low-oxalate diet. However, most people do not eat isolated nutrients, but meals consisting of a variety of foods with complex combinations of nutrients. A more rational approach to nephrolithiasis prevention would be to base dietary advice on the cumulative effects of foods and different dietary patterns rather than single nutrients. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: Recurrent stone formers with hyperoxaluria (urine oxalate > 40 mg/d). INTERVENTION: The intervention group was asked to follow a calorie-controlled Dietary Approaches to Stop Hypertension (DASH)-style diet (a diet high in fruit, vegetables, whole grains, and low-fat dairy products and low in saturated fat, total fat, cholesterol, refined grains, sweets, and meat), whereas the control group was prescribed a low-oxalate diet. Study length was 8 weeks. OUTCOMES: Primary: change in urinary calcium oxalate supersaturation. SECONDARY: Changes in 24-hour urinary composition. RESULTS: 57 participants were randomly assigned (DASH group, 29; low-oxalate group, 28). 41 participants completed the trial (DASH group, 21; low-oxalate group, 20). As-treated analysis showed a trend for urinary oxalate excretion to increase in the DASH versus the low-oxalate group (point estimate of difference, 9.0mg/d; 95% CI, -1.1 to 19.1mg/d; P=0.08). However, there was a trend for calcium oxalate supersaturation to decrease in the DASH versus the low-oxalate group (point estimate of difference, -1.24; 95% CI, -2.80 to 0.32; P=0.08) in association with an increase in magnesium and citrate excretion and urine pH in the DASH versus low-oxalate group. LIMITATIONS: Limited sample size, as-treated analysis, nonsignificant results. CONCLUSIONS: The DASH diet might be an effective alternative to the low-oxalate diet in reducing calcium oxalate supersaturation and should be studied more.

Recomendaciones dietéticas en la litiasis de oxalato cálcico / Dietary recommendations in calcium oxalate lithiasis

La dieta puede afectar a los enfermos con litiasis oxálica, aumentando los factores de riesgo para la formación. Una vez completado el estudio metabólico se deben dar algunas normas dietéticas basadas en los datos científicos disponibles. Existen pocos trabajos que hayan analizado de forma completa el contenido de oxalatos en los alimentos de la dieta humana. Se debe insistir en la ingesta hídrica abundante, la reducción de sal y de proteínas animales, manteniendo un correcto aporte de calcio. En el presente trabajo se adjuntan algunas tablas de contenidos de oxalato en diversos alimentos. Los más ricos en oxalato (acelgas, espinacas, coliflor, té, cacao, kiwis) deben ser restringidos

Diet affect oxalic lithiasis patients, increasing the risk factors for stone formation. Upon completion of the metabolic study should give some dietary guidelines based on scientific data. Few studies have analyzed completely the oxalate content in foods of the human diet. It must be emphatized abundant fluid intake, reducing salt and animal protein, maintaining proper calcium intake. In this paper, some tables about oxalate content in various foods are attached. Most rich in oxalate (chard, spinach, cauliflower, tea, cocoa, kiwis) must be restricted

Dietary management of idiopathic hyperoxaluria and the influence of patient characteristics and compliance.

OBJECTIVE: To assess the efficacy of dietary management for the treatment of idiopathic hyperoxaluria in a large tertiary care center and examine the influence of patient factors, compliance, and follow-up on oxalate reduction, which has not been previously investigated. METHODS: Retrospectively, 149 patients with kidney stones with idiopathic hyperoxaluria who received dietary management at our stone clinic were evaluated. Changes in urinary parameters on 24-hour urine collections were calculated for all patients and those with abnormal values in the overall short-term (30-240 days) and long-term (>240 days) time periods. Changes in urinary oxalate were evaluated with respect to patient characteristics and compliance measures. RESULTS: Urine oxalate and supersaturation of calcium oxalate were significantly (P < .001) reduced by 8.9 ± 19.2 mg/d and 1.7 ± 4.3, respectively. A total of 48.3% of the patients reduced their urinary oxalate to normal. Urine oxalate reductions were similar in the short-term and long-term periods. Women lowered urine oxalate nearly twice as much as men (12.7 ± 2.0 mg/d vs 6.7 ± 2.2 mg/d, P = .022) and body mass index (BMI) negatively correlated with oxalate reduction (Pearson's r = -0.213). Reported noncompliance and keeping follow-up appointments did not affect oxalate, however, there was a significant correlation between increasing urine volume and reducing oxalate (Pearson's r = -0.21). CONCLUSION: This study confirms that meaningful reductions of urine oxalate and supersaturation of calcium oxalate can be achieved with dietary management of hyperoxaluria on a larger clinical scale. Furthermore, we identified that women and patients with low BMIs had greater urine oxalate reductions and urine volume may also be used by clinicians as a measure of dietary compliance.

Effects of dietary interventions on 24-hour urine parameters in patients with idiopathic recurrent calcium oxalate stones.

The aim of this study is to investigate the effects of dietary factors on 24-hour urine parameters in patients with idiopathic recurrent calcium oxalate stones. A total of 108 of idiopathic recurrent calcium oxalate stones were included in the study. A 24-hour urinalysis was performed and metabolic abnormalities were measured for all of the patients. All of the patients were given specialized diets for their 24-hour urine abnormalities. At the end of first month, the same parameters were examined in another 24-hour urinalysis. Hyperoxaluria, hypernatruria, and hypercalciuria were found in 84 (77%), 43 (39.8%), and 38 (35.5%) of the patients, respectively. The differences between the oxalate, sodium, volume, uric acid, and citrate parameters before and after the dietary intervention were significant (p < 0.05). The calcium parameters were not significantly different before and after the intervention. We found that oxalate, sodium, volume, uric acid, and citrate-but not calcium-abnormalities in patients with recurrent calcium oxalate stones can be corrected by diet. The metabolic profiles of idiopathic calcium oxalate stone patients should be evaluated and the appropriate dietary interventions should be implemented to decrease stone recurrence.

[Oxalobacter formigenes--characteristics and role in development of calcium oxalate urolithiasis]. / Oxalobacter formigenes--charakterystyka i rola w rozwoju kamicy szczawianowo-wapniowej.

Microorganisms are one of the important factors for urinary calculi formation. While urease-positive bacteria and nanobacteria contribute to stone formation, Oxalobacter formigenes rods play a protective role against the development of urolithiasis. Proteus mirabilis alkaline environment of the urinary tract and cause crystallization mainly of struvite (magnesium ammonium phosphate). However, nanobacteria, due to the possibility of apatite deposition on the surface of their cells, have long been considered as an etiological factor of urinary calculi consisting of calcium phosphates. O. formigenes is an anaerobe using oxalate as the main source of carbon and energy and occurs as natural gastrointestinal microflora of humans and animals. These bacteria control the amount of oxalate excretion degrading oxalates and regulating their transport by intestinal epithelium. Lower colonization of the human colon by O. formigenes can cause increased oxalate excretion and lead to the development of oxalate urolithiasis. Due to the positive influence of O. formigenes, there is ongoing research into the use of this microorganism as a probiotic in the prophylaxis or treatment of hyperoxaluria, both secondary and primary. The results of these studies are very promising, but they still require continuation. Future studies focus on the exact characteristics of O. formigenes including their metabolism and the development of methods for applying as a therapeutic agent the bacteria or their enzymes degrading the oxalate.

Pyridoxine and dietary counseling for the management of idiopathic hyperoxaluria in stone-forming patients.

OBJECTIVES: To examine the effects of dietary manipulation and pyridoxine medical management for idiopathic hyperoxaluria in patients with nephrolithiasis. METHODS: A retrospective longitudinal study of the patients treated in our stone clinics from July 2007 to February 2009 was performed. All patients were evaluated with pre- and postintervention 24-hour urine collection and met a registered dietician. Recommendations to keep urine volume above 2 L per day, sodium restriction, protein moderation, increased calcium intake with meals and low oxalate diet combined with oral pyridoxine were given. Initial dosage ranged from 50 to 100 mg per day depending on the baseline oxalate level, and was titrated to a maximum of 200 mg daily. Subjects with at least two 24-hour urine collections were included in the study. RESULTS: Of 314 patients with complete metabolic and urinary profile evaluation, 95 subjects were identified with idiopathic hyperoxaluria. Mean follow-up was 18.4 ± 14.8 months and mean age was 50.3 ± 12.8 years. In patients treated with the combination of dietary counseling and pyridoxine, there was a significant change in urinary parameters in 75% of patients with a significant decrease in urinary oxalate excretion (58.26 ± 27.05 to 40.61 ± 15.04, P < .0001). In all, 39% of the patients had a decrease from a high urine oxalate levels (>40 mg/d) to a normal range urine oxalate (55.30 ± 22.04 to 33.45 ± 3.93, P = .0004). No peripheral neuropathy was reported. CONCLUSIONS: Dietary management and medical treatment using pyridoxine may be an effective first-line therapy to decrease hyperoxaluria in patients who form stones.

Probiotics and dietary manipulations in calcium oxalate nephrolithiasis: two sides of the same coin?

Growing evidence has assigned to oxalate a pivotal role in calcium nephrolithiasis pathophysiology. A better understanding of the mechanisms behind intestinal absorption and renal excretion has led to the identification of new treatments. Among these, diet and probiotics appear promising in terms of safety and rationale. However, the discrepancy between in vitro and in vivo results requires further studies to identify the right patient target, the correct dosage, and the real modification of natural and clinical history of nephrolithiasis.

Diet, but not oral probiotics, effectively reduces urinary oxalate excretion and calcium oxalate supersaturation.

We examined the effect of a controlled diet and two probiotic preparations on urinary oxalate excretion, a risk factor for calcium oxalate kidney stone formation, in patients with mild hyperoxaluria. Patients were randomized to a placebo, a probiotic, or a synbiotic preparation. This tested whether these probiotic preparations can increase oxalate metabolism in the intestine and/or decrease oxalate absorption from the gut. Patients were maintained on a controlled diet to remove the confounding variable of differing oxalate intake from food. Urinary oxalate excretion and calcium oxalate supersaturation on the controlled diet were significantly lower compared with baseline on a free-choice diet. Neither study preparation reduced urinary oxalate excretion nor calcium oxalate supersaturation. Fecal lactobacilli colony counts increased on both preparations, whereas enterococcal and yeast colony counts were increased on the synbiotic. Total urine volume and the excretion of oxalate and calcium were all strong independent determinants of urinary calcium oxalate supersaturation. Hence, dietary oxalate restriction reduced urinary oxalate excretion, but the tested probiotics did not influence urinary oxalate levels in patients on a restricted oxalate diet. However, this study suggests that dietary oxalate restriction is useful for kidney stone prevention.

Case report of paediatric oxalate urolithiasis and a review of enteric hyperoxaluria.

The formation of renal calculi secondary to enteric hyperoxaluria is rare in the paediatric population. We present the case of an 8-year-old boy who had short bowel syndrome resulting in enteric hyperoxaluria which led to the development of urolithiasis and bilateral ureteric strictures, both of which resolved with medical management. We also review the literature on enteric hyperoxaluria.

Diet to reduce mild hyperoxaluria in patients with idiopathic calcium oxalate stone formation: a pilot study.

OBJECTIVES: To assess whether a normal-calcium, low-animal protein, low-salt diet is effective in reducing hyperoxaluria in idiopathic calcium oxalate nephrolithiasis compared with a traditional low-oxalate diet, routinely recommended by clinicians METHODS: We treated 56 patients with idiopathic calcium oxalate stone formation who presented with mild hyperoxaluria (>40 mg/d) while consuming a free diet with a normal-calcium, low-animal protein, low-salt diet for a 3-month period. We compared the results obtained with this diet with those of a historical control group of 20 hyperoxaluric patients treated in the traditional way with a low-oxalate diet RESULTS: After 3 months of therapy, the mean oxaluria level had decreased from 50.2 to 35.5 mg/d with the normal-calcium, low-animal protein, low-salt diet and from 45.9 to 40.2 mg/d with the traditional diet (adjusted difference between post-treatment mean value -7.3 mg/d, 95% confidence interval -12.3 to -2.2, P = .005) CONCLUSIONS: The results suggest that a normal-calcium, low-animal protein, low-salt diet can reduce oxalate excretion in hyperoxaluric patients. This should encourage the undertaking of a randomized-control study to confer more solid evidence in support of our findings.

Diagnostic and therapeutic approaches in patients with secondary hyperoxaluria.

Secondary hyperoxaluria is due either to increased intestinal oxalate absorption or to excessive dietary oxalate intake. Certain intestinal diseases like short bowel syndrome, chronic inflammatory bowel disease or cystic fibrosis and other malabsorption syndromes are known to increase the risk of secondary hyperoxaluria. Although the urinary oxalate excretion is usually lower than in primary hyperoxaluria, it may still lead to significant morbidity by recurrent urolithiasis or progressive nephrocalcinosis. A clear distinction between primary and secondary hyperoxalurias is important. As correct classification may be difficult, appropriate diagnostic tools are needed to delineate the metabolic background as a basis for optimal treatment. We developed an individual approach for the evaluation of patients with suspected secondary hyperoxaluria. First, 24 h urines are examined repeatedly for lithogenic (e.g. calcium, oxalate, uric acid) and stone-inhibitory (e.g. citrate, magnesium) substances, and the patients are asked to fill in a dietary survey form. Urinary saturation is calculated using the computer based program EQUIL2, and the BONN-Risk-index is determined. The measurement of plasma oxalate and of urinary glycolate helps to distinguish between primary and secondary hyperoxalurias. If secondary hyperoxaluria is suspected, the stool is examined for Oxalobacter formigenes, an intestinal oxalate degrading bacterium, as lack or absence may lead to increased intestinal oxalate absorption. The last diagnostic step is to study the intestinal oxalate absorption using [13C2]oxalate. Depending on the results, various therapeutic options are available: 1) a diet low in oxalate, but normal or high in calcium, 2) a high fluid intake (>1.5 L/m2/d), 3) medications to increase the urinary solubility, 4) specific therapeutic measures in patients with malabsorption syndromes, depending on the underlying pathology, and 5) intestinal recolonization of Oxalobacter formigenes or the treatment with other oxalate degrading bacteria.

Dietary risk factors for hyperoxaluria in calcium oxalate stone formers.

BACKGROUND: Hyperoxaluria is a major predisposing factor in calcium oxalate urolithiasis. The aim of the present study was to clarify the role of dietary oxalate in urinary oxalate excretion and to assess dietary risk factors for hyperoxaluria in calcium oxalate stone patients. METHODS: Dietary intakes of 186 calcium oxalate stone formers, 93 with hyperoxaluria (>or=0.5 mmol/day) and 93 with normal oxalate excretion (<0.4 mmol/day), were assessed by a 24-hour weighed dietary record. Each subject collected 24-hour urine during the completion of the food record. Oxalate content of foods was measured by a recently developed analytical method. RESULTS: The mean daily intakes of energy, total protein, fat and carbohydrates were similar in both groups. The diets of the patients with hyperoxaluria were estimated to contain 130 mg/day oxalate and 812 mg/day calcium as compared to 101 mg/day oxalate and 845 mg/day calcium among patients without hyperoxaluria. These differences were not significant. The mean daily intakes of water (in food and beverages), magnesium, potassium, dietary fiber and ascorbic acid were greater in patients with hyperoxaluria than in stone formers with normal oxalate excretion. Multiple logistic regression analysis revealed that urinary oxalate excretion was significantly associated with dietary ascorbate and fluid intake, and inversely related to calcium intake. Differences of estimated diet composition of both groups corresponded to differences in urinary parameters. CONCLUSIONS: These findings suggest that hyperoxaluria predominantly results from increased endogenous production and from intestinal hyperabsorption of oxalate, partly caused by an insufficient supply or low availability of calcium for complexation with oxalate in the intestinal lumen.

Conjugated bile acid replacement therapy reduces urinary oxalate excretion in short bowel syndrome.

BACKGROUND: Patients with short bowel syndrome (SBS) have steatorrhea, in part because of bile acid malabsorption that causes decreased bile acid secretion into the duodenum and consequent fat maldigestion. In SBS patients with colon in continuity, luminal calcium forms calcium fatty acid soaps rather than precipitating as insoluble calcium oxalate. Soluble oxalate is hyperabsorbed by the colon leading to hyperoxaluria and an increased risk for renal calcium oxalate stones and deposits. The authors hypothesized that oral ingestion of conjugated bile acids would increase fat absorption and thereby decrease calcium fatty acid soap formation and oxalate hyperabsorption. METHODS: The effect of conjugated bile acid replacement therapy (9 g/d) on fecal fat excretion and urine oxalate excretion was measured in an appropriate patient, utilizing the metabolic balance technique. The effects of chronic bile acid replacement therapy on oxalate excretion and nutritional status also were measured in a 3-month outpatient study. RESULTS: Natural conjugated bile acid replacement therapy reduced fecal fat excretion from 119 to 79 g/d (Delta40 g/d), and urinary oxalate excretion from 87 to 64 mg/d (966 to 710 micromol/d; Delta23 mg/d). Cholylsarcosine, a synthetic conjugated bile acid, had similar but less powerful effects. During a 3-month outpatient trial of natural conjugated bile acids (9 g/d), urine oxalate decreased to normal levels (27 mg/d) in association with weight gain, decreased hunger, and decreased hyperphagia. CONCLUSION: Conjugated bile acid replacement therapy reduced fecal fat excretion, reduced urinary oxalate excretion, and improved nutritional status in a patient with SBS with colon in continuity, hyperoxaluria, and oxalate nephrolithiasis.

Sensitivity to meat protein intake and hyperoxaluria in idiopathic calcium stone formers.

BACKGROUND: High protein intake is an accepted risk factor for renal stone disease. Whether meat protein intake affects oxaluria, however, remains controversial in healthy subjects and in stone formers. This study was designed (1) to test the oxaluric response to a meat protein load in male recurrent idiopathic calcium stone formers (ICSFs) with and without mild metabolic hyperoxaluria (MMH and non-MMH, respectively), as well as in healthy controls, and (2) to seek for possible disturbed vitamin B(6) metabolism in MMH, in analogy with primary hyperoxaluria. METHODS: Twelve MMH, 8 non-MMH, and 13 healthy males were studied after five days on a high meat protein diet (HPD; 700 g meat/fish daily) following a run-in phase of five days on a moderate protein diet (MPD; 160 g meat/fish daily). In both diets, oxalate-rich nutrients were avoided, as well as sweeteners and vitamin C-containing medicines. Twenty-four-hour urinary excretion of oxalate was measured on the last day of each period, along with 4-pyridoxic acid (U(4PA)) and markers of protein intake, that is, urea, phosphate, uric acid, and sulfate. Serum pyridoxal 5' phosphate (S(P5P)) was measured after protein loading. RESULTS: Switching from MPD (0.97 +/- 0.18 g protein/kg/day) to HPD (2.26 +/- 0.38 g protein/kg/day) led to the expected rise in the urinary excretion rates of all markers of protein intake in all subjects. Concurrently, the mean urinary excretion of oxalate increased in ICSFs taken as a whole (+73 +/- 134 micromol/24 h, P = 0.024) as well as in the MMH subgroup (+100 +/- 144 micromol/24 h, P = 0.034) but not in controls (-17 +/- 63 micromol/24 h). In seven ICSFs (4 MMH and 3 non-MMH) but in none of the healthy controls (P = 0.016, chi square), an increment in oxaluria was observed and considered as significant based on the intra-assay coefficient of variation at our laboratory (8.5%). There was no difference in S(P5P)nd U(4PA)etween the groups after protein loading. CONCLUSION: Approximately one third of ICSFs with or without so-called MMH are sensitive to meat protein in terms of oxalate excretion, as opposed to healthy subjects. Mechanisms underlying this sensitivity to meat protein remain to be elucidated and do not seem to involve vitamin B(6) deficiency.

Hyperoxaluria in patients with recurrent calcium oxalate calculi: dietary and other risk factors.

The presence of mild hyperoxaluria in recurrent calcium oxalate stone formers is controversial. The aim of this study was to identify recurrent stone formers with mild hyperoxaluria and to classify them further by assessing their response to a low oxalate diet. In addition, the prevalence of other risk factors for stone formation in this group of patients was investigated. A total of 207 consecutive patients with recurrent renal calculi were screened and 40 (19%) were found to have mild hyperoxaluria. Of these, 18 (45%) responded to dietary oxalate restriction by normalising their urinary oxalate. The remaining 22 patients were classified as having idiopathic hyperoxaluria and were subdivided into those in whom urinary oxalate excretion was consistently elevated in all specimens measured and those in whom the elevation was intermittent in nature. Dietary oxalate restriction had a partially beneficial effect in lowering oxalate excretion in the patients with persistent hyperoxaluria. No difference in urinary oxalate excretion was found after dietary restriction in the patients with intermittent hyperoxaluria. Other risk factors, including dietary, absorptive and renal hypercalciuria and hypocitraturia, were documented, the prevalence of which (65%) was not significantly different from that (62.5%) found in 40 age- and sex-matched calcium stone formers without hyperoxaluria. The prevalence of hyperuricosuria was significantly greater in patients with hyperoxaluria when compared with stone controls. Further studies are required to elucidate the underlying mechanisms of hyperoxaluria in recurrent stone formers.