[Show abstract][Hide abstract] ABSTRACT: Secondary hyperoxaluria either based on increased intestinal absorption of oxalate (enteric), or high oxalate intake (dietary), is a major risk factor of calcium oxalate urolithiasis. Oxalate-degrading bacteria might have beneficial effects on urinary oxalate excretion resulting from decreased intestinal oxalate concentration and absorption.
Twenty healthy subjects were studied initially while consuming a diet normal in oxalate. Study participants were then placed on a controlled oxalate-rich diet for a period of 6 weeks. Starting with week 2 of the oxalate-rich diet, participants received 2.6 g/day of a lactic acid bacteria preparation for 5 weeks. Finally, subjects were examined 4 weeks after treatment while consuming again a normal-oxalate diet. Participants provided weekly 24-hour urine specimens. Analyses of blood samples were performed before and at the end of treatment.
Urinary oxalate excretion increased significantly from 0.354 +/- 0.097 at baseline to 0.542 +/- 0.163 mmol/24 h under the oxalate-rich diet and remained elevated until the end of treatment, as did relative supersaturation of calcium oxalate. Plasma oxalate concentration was significantly higher after 5 weeks of treatment compared to baseline. Four weeks after treatment, urinary oxalate excretion and relative supersaturation of calcium oxalate fell to reach initial values.
Persistent dietary hyperoxaluria and increased plasma oxalate concentration can already be induced in healthy subjects without disorders of oxalate metabolism. The study preparation neither reduced urinary oxalate excretion nor plasma oxalate concentration. The preparation may be altered to select for lactic acid bacteria strains with the highest oxalate-degrading activity.
Journal of Translational Medicine 12/2013; 11(1):306. · 3.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: About 75% of urinary stones contain oxalate. As Oxalobacter formigenes is a Gram-negative anaerobic bacterium that degrades oxalate in the intestinal tract, we assessed the role of O. formigenes in oxalate metabolism by evaluating its intestinal absorption, plasma concentration, and urinary excretion. Of 37 calcium oxalate stone formers, 26 tested negative for O. formigenes and were compared with the 11 patients who tested positive. Patients provided 24-h urine samples on both a self-selected and a standardized diet. Urinary oxalate excretion did not differ significantly on the self-selected diet, but was significantly lower in O. formigenes-positive than in O. formigenes-negative patients under controlled, standardized conditions. Intestinal oxalate absorption, measured using [(13)C2]oxalate, was similar in the patients with or without O. formigenes. Plasma oxalate concentrations were significantly higher in noncolonized (5.79 μmol/l) than in colonized stone formers (1.70 μmol/l). Colonization with O. formigenes was significantly inversely associated with the number of stone episodes. Our findings suggest that O. formigenes lowers the intestinal concentration of oxalate available for absorption at constant rates, resulting in decreased urinary oxalate excretion. Thus, dietary factors have an important role in urinary oxalate excretion. The data indicate that O. formigenes colonization may reduce the risk of stone recurrence.Kidney International advance online publication, 27 March 2013; doi:10.1038/ki.2013.104.
Kidney International 03/2013; · 8.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The occurrence of brushite stones has increased during recent years. However, the pathogenic factors driving the development of brushite stones remain unclear.
Twenty-eight brushite stone formers and 28 age-, sex- and BMI-matched healthy individuals were enrolled in this case-control study. Anthropometric, clinical, 24 h urinary parameters and dietary intake from 7-day weighed food records were assessed.
Pure brushite stones were present in 46% of patients, while calcium oxalate was the major secondary stone component. Urinary pH and oxalate excretion were significantly higher, whereas urinary citrate was lower in patients as compared to healthy controls. Despite lower dietary intake, urinary calcium excretion was significantly higher in brushite stone patients. Binary logistic regression analysis revealed pH>6.50 (OR 7.296; p = 0.035), calcium>6.40 mmol/24 h (OR 25.213; p = 0.001) and citrate excretion <2.600 mmol/24 h (OR 15.352; p = 0.005) as urinary risk factors for brushite stone formation. A total of 56% of patients exhibited distal renal tubular acidosis (dRTA). Urinary pH, calcium and citrate excretion did not significantly differ between patients with or without dRTA.
Hypercalciuria, a diminished citrate excretion and an elevated pH turned out to be the major urinary determinants of brushite stone formation. Interestingly, urinary phosphate was not associated with urolithiasis. The increased urinary oxalate excretion, possibly due to decreased calcium intake, promotes the risk of mixed stone formation with calcium oxalate. Neither dietary factors nor dRTA can account as cause for hypercalciuria, higher urinary pH and diminished citrate excretion. Further research is needed to define the role of dRTA in brushite stone formation and to evaluate the hypothesis of an acquired acidification defect.
PLoS ONE 01/2013; 8(11):e78996. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prevalence of recurrent calcium-oxalate (CaOx) urolithiasis (UL) is up to fivefold higher in Crohn's disease than in the general population. Treatment options are scarce and the risk of recurrent UL or progressive renal CaOx deposition, (oxalosis) based early end-stage renal failure (ESRF), subsequent systemic oxalosis, and recurrence in the kidney graft is pronounced. We aimed to find proof that secondary hyperoxaluria is the main risk factor for the devastating course and correlates with intestinal oxalate absorption.
24-h urines were collected and analyzed for urinary oxalate (Uox) in 27 pediatric (6-18 years) and 19 adult patients (20-62 years). In the 21 patients (8 adults and 13 children) with hyperoxaluria a [(13)C(2)]oxalate absorption test was performed under standardized dietary conditions.
Mean Uox was significantly higher in patients with UL or oxalosis (0.92 ± 0.57) compared with those without (0.53 ± 0.13 mmol/1.73 m(2)/24 h, p<0.05, normal < 0.5). Hyperoxaluria then significantly correlated with intestinal oxalate absorption (p< 0.05).
As UL/oxalosis has major implications for the general health in patients with Crohn's disease (ESRF and systemic oxalosis), new medication, e.g. to reduce intestinal oxalate absorption, is definitely needed.
[Show abstract][Hide abstract] ABSTRACT: Magnesium is suggested to reduce intestinal oxalate absorption and to act as an inhibitor of calcium oxalate crystallization in the urine. However, previous studies have shown only minimal increase in urinary magnesium excretion following oral magnesium supplementation, possibly due to its low bioavailability. This study was performed to examine the bioavailability of magnesium from two different pharmaceutical formulations of magnesium oxide (MgO). Thirteen healthy male volunteers (22-31 years) were recruited from university students and staff, and all completed the study. During the baseline phase, subjects collected two 24-h urines while on their usual diet. Throughout the control and test phases, the subjects consumed a standardized diet calculated according to the recommendations. During the test phases, subjects received two magnesium preparations in a cross-over procedure. With each preparation, MgO-capsules and MgO-effervescent tablets, 450 mg magnesium was supplemented. On the control day and the two test days, fractional urine collection was performed and six corresponding blood samples were taken. In the follow-up phase, subjects continued to take the respective preparation while on their usual diet and collected 24-h urines weekly. With standardized conditions, urinary magnesium excretion increased by 40% after ingestion of the effervescent tablets, and by only 20% after intake of the capsules. The results indicate better bioavailability of magnesium from the effervescent tablets than from the capsules. This may be attributed to the fact that the tablets have to be dissolved in water before ingestion so that magnesium becomes ionized, which is an important precondition for absorption.
Urological Research 04/2011; 39(2):123-7. · 1.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hyperoxaluria is a major risk factor for kidney stone formation. Although urinary oxalate measurement is part of all basic stone risk assessment, there is no standardized method for this measurement.
Urine samples from 24-h urine collection covering a broad range of oxalate concentrations were aliquoted and sent, in duplicates, to six blinded international laboratories for oxalate, sodium and creatinine measurement. In a second set of experiments, ten pairs of native urine and urine spiked with 10 mg/L of oxalate were sent for oxalate measurement. Three laboratories used a commercially available oxalate oxidase kit, two laboratories used a high-performance liquid chromatography (HPLC)-based method and one laboratory used both methods.
Intra-laboratory reliability for oxalate measurement expressed as intraclass correlation coefficient (ICC) varied between 0.808 [95% confidence interval (CI): 0.427-0.948] and 0.998 (95% CI: 0.994-1.000), with lower values for HPLC-based methods. Acidification of urine samples prior to analysis led to significantly higher oxalate concentrations. ICC for inter-laboratory reliability varied between 0.745 (95% CI: 0.468-0.890) and 0.986 (95% CI: 0.967-0.995). Recovery of the 10 mg/L oxalate-spiked samples varied between 8.7 ± 2.3 and 10.7 ± 0.5 mg/L. Overall, HPLC-based methods showed more variability compared to the oxalate oxidase kit-based methods.
Significant variability was noted in the quantification of urinary oxalate concentration by different laboratories, which may partially explain the differences of hyperoxaluria prevalence reported in the literature. Our data stress the need for a standardization of the method of oxalate measurement.
[Show abstract][Hide abstract] ABSTRACT: Findings are inconsistent in a few studies of the effect of n-3 fatty acid supplementation on urinary calcium and oxalate excretion in stone formers. We evaluated the physiological effects of supplementation with eicosapentaenoic acid and docosahexaenoic acid on urinary risk factors for calcium oxalate stone formation under standardized conditions.
We studied 15 healthy subjects initially while consuming a standardized diet for 5 days (control phase). During consecutive intervention phases 1-5-day standardized diet, 2-20-day free diet and 3-5-day standardized diet participants received 900 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily. While ingesting the standardized diets, daily 24-hour urine samples were collected.
After short-term supplementation with eicosapentaenoic acid and docosahexaenoic acid in phase 1 we noted no changes in urinary parameters compared to the control phase. After 30-day supplementation with eicosapentaenoic acid and docosahexaenoic acid in phase 3 relative supersaturation with calcium oxalate decreased significantly by 23% from a mean ± SD of 2.01 ± 1.26 to 1.55 ± 0.84 due to significantly decreased urinary oxalate excretion (p = 0.023). Other urinary variables were not affected by supplementation.
Results show that 30-day n-3 fatty acid supplementation effectively decreases urinary oxalate excretion and the risk of calcium oxalate crystallization. The mechanism of the physiological effect may be decreased cellular oxalic acid exchange attributable to an altered fatty acid pattern of membrane phospholipids with concomitant changes in oxalate transporter activity. Calcium oxalate stone formers may benefit from long-term n-3 fatty acid supplementation.
The Journal of urology 02/2011; 185(2):719-24. · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of the study was to analyse the oxalate content of green tea (Camellia sinensis) depending on origin, quality, time of harvest and preparation. Fifty-two green tea samples were received from different regions of China. The oxalate content of each tea infusion was measured using a validated HPLC-enzyme-reactor method. The soluble oxalate content of green tea ranged from 8.3 to 139.8 mg/l. In samples from known provenances, the highest oxalate concentration was found in green tea from Zhe Jiang. Low grade tea showed a tendency to lower oxalate concentration. Leaves reaped in the autumn when grown to full size yielded more oxalate than small and young leaves reaped in the spring. Modifications in steeping duration of tea leaves had no significant influence on the oxalate content of the beverage. Patients at risk for recurrent stone formation should take into account the oxalate content of green tea.
Urological Research 03/2010; 38(5):377-81. · 1.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pathogenesis of calcium oxalate stone formation is not completely understood. Recently, an influence of vascular phenomena like arteriosclerosis on the crystallization process was hypothesized. Thus, stone formation should be more common in patients with diabetes mellitus (DM) who are at risk of developing angiopathy. The aim of the study was to determine the prevalence of urolithiasis (UL) in patients with DM and to identify specific risk factors.
350 patients with DM were evaluated with respect to DM-related history, and a total of 179 patients was included (83 female, 96 male; age 23-84 years). All patients were interviewed to assess the history of stone formation. These data were compared to epidemiological data in Germany.
The overall prevalence of UL in the diabetic group was 7.82% (vs. 4.73% in Germany, p = 0.0485; binominal test). The prevalence was significantly higher in patients with coronary heart disease (25%; p < 0.0001; Fisher's exact test). We could not demonstrate an increased prevalence of UL for patients with occlusive arterial disease or arterial hypertension as diabetic nephropathy was not a risk factor for developing urinary lithiasis (p = 0.7184, p = 1.000, p = 0.6266, respectively; Fisher's exact test). Thiazide medication lowered the prevalence of stone formation (p = 0.0399; Fisher's test). Calcium or magnesium supplementation did not influence stone formation significantly (p = 0.5279; p = 1.000; respectively; Fisher's test).
In Germany, patients with DM are at higher risk of UL compared with patients without diabetes. We demonstrated a significantly higher prevalence of urinary stones in patients with coronary heart disease. These findings are consistent with the hypothesis that urinary stone formation has a vascular pathogenesis in part.
Urologia Internationalis 01/2009; 82(3):350-5. · 1.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Treatment of otherwise lethal ethylene glycol poisoning depends on rapid diagnosis, aggressive supportive care, appropriate use of alcohol dehydrogenase inhibitors and, in selected patients, hemodialysis. Next to that, specific measures to prevent renal or systemic calcium-oxalate deposition are important. We report the case of a 12-year-old girl who ingested more than five times the lethal dosis of ethylene glycol in a suicide attempt. At admission her serum ethylene glycol concentration was 88 mg/dl. Under treatment by ethanol infusions to block the alcohol dehydrogenase and by hemodialysis to eliminate ethylene glycol and its toxic metabolites, this level decreased to below 15 mg/dl within 36 h. The plasma oxalate level, however, rose to a maximum of 89 micromol/l (normal <6.3 +/- 1.1) on day 3 and only normalized on day 7 after ingestion. In addition, urinary oxalate excretion was elevated (maximum 1.16 mmol/1.73 m(2)/24 h). Both lead to calcium-oxalate oversaturation and hence to the risk of local (renal) or systemic crystal deposition. Therefore, alkaline citrate was given as a preventive measure to increase urinary oxalate solubility, but nephrocalcinosis still developed. Metabolic acidosis, hypocalcaemia, and neurological symptoms had not occurred. Four weeks after discharge, both plasma and urinary oxalate levels were normal.
[Show abstract][Hide abstract] ABSTRACT: Intestinal oxalate absorption is an important part of oxalate metabolism influencing its urinary excretion and its measurement can be a valuable diagnostic tool in hyperoxaluric disorders. In this study, we use [(13)C(2)]oxalate absorption under standardized dietary conditions to assess intestinal oxalate absorption and its impact on urinary oxalate excretion. Tests were conducted in age-matched pediatric patients that included 60 with idiopathic calcium oxalate urolithiasis, 13 with primary hyperoxaluria, and 35 healthy children. In the idiopathic stone formers, median oxalate absorption was significantly higher than that in the controls or in patients with primary disease. From standardized values obtained in control patients, oxalate hyperabsorption was detected in 23 patients with idiopathic disease but not in any patients with primary hyperoxaluria; therefore, a significant correlation between intestinal absorption and urinary excretion was found only in those with the idiopathic disease. We have shown that increased intestinal oxalate absorption is an important risk factor of idiopathic calcium oxalate urolithiasis. In contrast, low intestinal oxalate absorption in patients with primary hyperoxaluria indicates that only foods with excessive oxalate content be restricted from their diet.
Kidney International 06/2008; 73(10):1181-6. · 8.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare quantitatively the effect of a low- and a high-oxalate vegetarian diet on intestinal oxalate absorption and urinary excretion.
Eight healthy volunteers (three men and five women, mean age 28.6+/-6.3) were studied. Each volunteer performed the [(13)C(2)]oxalate absorption test thrice on a low-oxalate mixed diet, thrice on a low-oxalate vegetarian diet and thrice on a high-oxalate vegetarian diet. For each test, the volunteers had to adhere to an identical diet and collect their 24-h urines. In the morning of the second day, a capsule containing [(13)C(2)]oxalate was ingested.
On the low-oxalate vegetarian diet, mean intestinal oxalate absorption and urinary oxalate excretion increased significantly to 15.8+/-2.9% (P=0.012) and 0.414+/-0.126 mmol/day (P=0.012), compared to the mixed diet. On the high-oxalate vegetarian diet, oxalate absorption (12.5+/-4.6%, P=0.161) and urinary excretion (0.340+/-0.077 mmol/day, P=0.093) did not change significantly, compared to the mixed diet.
A vegetarian diet can only be recommended for calcium oxalate stone patients, if the diet (1) contains the recommended amounts of divalent cations such as calcium and its timing of ingestion to a meal rich in oxalate is considered and (2) excludes foodstuffs with a high content of nutritional factors, such as phytic acid, which are able to chelate calcium.
European Journal of Clinical Nutrition 08/2007; 62(9):1090-7. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Xanthinuria type I is a rare disorder of purine metabolism caused by xanthine oxidoreductase or dehydrogenase (XDH) deficiency. We report a family with two affected children out of 335 pediatric stone patients studied since 1991 in Armenia. The propositus, a 13-month-old boy, presented with abdominal pain and urinary retention followed by stone passage (0.9x0.6 cm). Infrared spectroscopy in Yerevan revealed a pure xanthine stone. Family examination in the parents and brother was normal, but the propositus and his 8-year-old asymptomatic sister had hypouricemia, hypouricosuria, and high urinary excretion of hypoxanthine and xanthine. Ultrasonography in the index patient showed bilateral stones requiring pyelolithotomy. High fluid intake and purine restriction did not prevent further stone passages. The affected asymptomatic sister had a small pelvic stone (4 mm). Mutation analysis revealed a heterozygous novel base pair substitution in exon 25 of the XDH gene (c.2810C>T), resulting in an amino acid substitution (p.Thr910Met). The second mutation could not be detected. Despite this, the heterozygous mutation, the chemical findings, and the positive allopurinol test altogether prove xanthinuria type I, which may present wide clinical intrafamilial variation. Diagnosis is suspected usually from low serum uric acid. No specific therapy is available.
[Show abstract][Hide abstract] ABSTRACT: The prevalence and incidence of urolithiasis have markedly increased over the past several decades. Inappropriate dietary habits, overweight, and lifestyle are considered to be important risk factors for stone formation. The primary goal of metaphylaxis of stone disease is to correct the individual biochemical risk profile. A reduction in the risk of stone formation and recurrence rate can already be achieved by appropriate dietary treatment. One of the most effective dietary measures is a sufficient circadian fluid intake of suitable beverages. The reduction of overweight is suggested to additionally contribute to a decrease in the risk of recurrent stone formation.
Der Urologe 12/2006; 45(11):1392, 1394-8. · 0.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primary hyperoxaluria is characterized by severe urolithiasis, nephrocalcinosis, and early renal failure. As treatment options are scarce, we aimed for a new therapeutic tool using colonic degradation of endogenous oxalate by Oxalobactor formigenes. Oxalobacter was orally administered for 4 weeks as frozen paste (IxOC-2) or as enteric-coated capsules (IxOC-3). Nine patients (five with normal renal function, one after liver-kidney transplantation, and three with renal failure) completed the IxOC-2 study. Seven patients (six with normal renal function and one after liver-kidney transplantation) completed the IxOC-3 study. Urinary oxalate or plasma oxalate in renal failure was determined at baseline, weekly during treatment and for a 2-week follow-up. The patients who showed >20% reduction both at the end of weeks 3 and 4 were considered as responders. Under IxOC-2, three out of five patients with normal renal function showed a 22-48% reduction of urinary oxalate. In addition, two renal failure patients experienced a significant reduction in plasma oxalate and amelioration of clinical symptoms. Under IxOC-3 treatment, four out of six patients with normal renal function responded with a reduction of urinary oxalate ranging from 38.5 to 92%. Although all subjects under IxOC-2 and 4 patients under IxOC-3 showed detectable levels of O. formigenes in stool during treatment, fecal recovery dropped directly at follow up, indicating only transient gastrointestinal-tract colonization. The preliminary data indicate that O. formigenes is safe, leads to a significant reduction of either urinary or plasma oxalate, and is a potential new treatment option for primary hyperoxaluria.
Kidney International 10/2006; 70(7):1305-11. · 8.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We assessed the importance of oxalate hyperabsorption for idiopathic calcium oxalate urolithiasis, oxalate absorption in healthy volunteers and recurrent calcium oxalate stone formers was compared.
The [(13)C2]oxalate absorption test, a standardized, radioactivity-free test, was performed. On 2 days 24-hour urine was collected and an identical standard diet containing 800 mg Ca daily was maintained. On the morning of day 2 a capsule containing 0.37 mmol sodium [(13)C2]oxalate was ingested. A total of 120 healthy volunteers (60 women and 60 men) and 120 patients (30 women and 90 men) with idiopathic CaOx urolithiasis (60% or greater CaOx) were tested.
Mean intestinal oxalate absorption in the volunteers was 8.0 +/- 4.4%, and in the patients was 10.2 +/- 5.2% (p <0.001). There was no significant difference in mean absorption values between men and women within both groups. A high overlap between the absorption values of volunteers and patients was found. Only in the patient group did absorption values greater than 20% occur. Oxalate absorption correlated with oxalate excretion in the patients, r = 0.529 (p <0.01) and in the volunteers, r = 0.307 (p <0.01).
In high oxalate absorbers dietary oxalate has a significant role in oxalate excretion and, therefore, increases the risk of calcium oxalate stone formation.
The Journal of Urology 06/2006; 175(5):1711-5. · 3.75 Impact Factor