Enteric hyperoxaluria, recurrent urolithiasis, and systemic oxalosis in patients with Crohn's disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Intestinal oxalate absorption is higher in idiopathic calcium oxalate stone formers than in healthy controls: measurements with the [(13)C2]oxalate absorption test.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: In high oxalate absorbers dietary oxalate has a significant role in oxalate excretion and, therefore, increases the risk of calcium oxalate stone formation.

Effect of oxalate test dose size on absolute and percent oxalate absorption.

The purpose of this pilot study was to establish the dependence or independence of oxalate absorption on the quantity of the test dose of sodium oxalate over a range of test doses corresponding to physiological dietary oxalate intake values. Gastrointestinal oxalate absorption was measured with the [13C2]oxalate absorption test. Six healthy volunteers were always tested under standardized dietary conditions with 63 mg dietary oxalate and 800 mg dietary calcium per day. The volunteers were tested thrice each with sodium oxalate test doses of 25, 50, 200, and 600 mg. Additionally, 1000 mg sodium oxalate was applied once to three of these volunteers. The oxalate absorption of the six volunteers tested under the standardized conditions with 50 mg sodium [13C2]oxalate was 7.2 +/- 2.62 % (mean +/- SD), similar to the 120 volunteers tested previously: 8.0 +/- 4.4 % (mean +/- SD). The tests with sodium [13C2]oxalate doses in the range 25-1000 mg revealed similar percent oxalate absorption values. In conclusion, in healthy volunteers, the amount of oxalate absorbed in the gastrointestinal tract increased proportionally with the higher test doses of oxalate. However, percent oxalate absorption remained unchanged with test doses in the dose range of physiological dietary oxalate intakes.

Hyperoxaluria, hypocitraturia, hypomagnesiuria, and lack of intestinal colonization by Oxalobacter formigenes in a cervical spinal cord injury patient with suprapubic cystostomy, short bowel, and nephrolithiasis.

Although urolithiasis is common in spinal cord injury patients, it is presumed that the predisposing factors for urinary stones in spinal cord injury patients are immobilization-induced hypercalciuria in the initial period after spinal injury and, in later stages, urine infection by urease-producing micro-organisms, e.g., Proteus sp., which cause struvite stones. We describe a patient who sustained C-7 complete tetraplegia in a road traffic accident in 1970, when he was 16 years old. Left ureterolithotomy was performed in 1971 followed by left nephrectomy in 1972. Probably due to adhesions, this patient developed volvulus of the intestine in 1974. As he had complete tetraplegia, he did not feel pain in the abdomen and there was a delay in the diagnosis of volvulus, which led to ischemia of a large segment of the small bowel. All but 1 ft of jejunum and 1 ft of ileum were resected leaving the large bowel intact. In 1998, suprapubic cystostomy was performed. In 2004, this patient developed calculus in the solitary right kidney. Complete stone clearance was achieved by extracorporeal shock wave lithotripsy. Stone analysis: calcium oxalate 60% and calcium phosphate 40%. Metabolic evaluation revealed hyperoxaluria, hypocitraturia, and hypomagnesiuria. Since this patient had hyperoxaluria, the stool was tested for Oxalobacter formigenes, a specific oxalate-degrading, anerobic bacterium inhabiting the gastrointestinal tracts of humans; absence of this bacterium appears to be a risk factor for development of hyperoxaluria and, subsequently, calcium oxalate kidney stone disease. DNA from the stool was extracted using the QIAamp DNA stool Mini Kit (Qiagen, Chatsworth, CA). The genomic DNA was amplified by polymerase chain reaction using specific primers for oxc gene (developed by Sidhu and associates). The stool sample tested negative for O. formigenes. The patient was prescribed potassium citrate mixture; he was advised to avoid oxalate-rich food, maintain recommended levels of calcium in his diet, and take live bio-yogurt. Two months later, 24-h urinary oxalate decreased from 0.618 to 0.411 mmol/day; 24-h urine citrate increased from 0.58 to 1.10 mmol/day. Six months later, an oxalate absorption test was performed. The patient swallowed a capsule, soluble in gastric juice, containing 50 mg (0.37 mmol) sodium [13C2]oxalate corresponding to 33.8 mg of [13C2]oxalic acid. The amount of labeled oxalate, excreted in urine, was measured by a gas chromatographic-mass spectrometric assay. Oxalate absorption, expressed as the percentage of the labeled dose recovered in the 24-h urine after dosing, was 8.3% (reference range: 2.3-17.5%). In addition to other conventional measures, oral administration of O. formigenes or lactic acid bacteria mixture to promote bacterial degradation of oxalate in the gut, and thus combat hyperoxaluria, may play a role in prevention of calcium oxalate kidney stones.

Intestinal oxalate absorption in patients with continent urinary diversion.

The objective of the study is to evaluate the post-operative effect of an orthotopic ileal neobladder or a Mainz pouch I bladder replacement on the extent of intestinal oxalate absorption. Gastrointestinal oxalate absorption was measured in six patients with an orthotopic ileal neobladder and in six patients with a Mainz pouch I bladder replacement. The function test applied was the [13C2]oxalate absorption test. With a range of 5.1-12.4%, the oxalate absorption of these patients was well within the reference range for healthy volunteers. The results from our small study indicate that such continent urinary diversions present no hazard for oxalate hyperabsorption and subsequent calcium oxalate urolithiasis.

Influence of a high-oxalate diet on intestinal oxalate absorption.

Hyperoxaluria is a major risk factor for renal stones. In most cases, it is sustained by increased dietary loads. In healthy individuals with a normal Western diet, the majority of urinary oxalate is usually derived from endogenous metabolism. However, up to 50% may be derived from the diet. We were interested in the effect of a high-oxalate diet on oxalate absorption, not merely on the frequently studied increased oxalate excretion. In study I, 25 healthy volunteers were tested with the [13C2]oxalate absorption test once while following a low-oxalate (63 mg) and once while following a high-oxalate (600 mg) diet for 2 days each. In study II, four volunteers repeated study I, and afterwards continued with a high-oxalate diet (600 mg oxalate/day) for 6 weeks. In the last week, the [13C2]oxalate absorption test was repeated. After 4 weeks of individual normal diet, the oxalate absorption test with a high-oxalate diet was performed again. The results of study I show that the mean [13C2]oxalate absorption under low-oxalate diet was 7.9 +/- 4.0%. In the presence of oxalate-rich food, the percent absorption for the soluble labelled oxalate almost doubled (13.7 +/- 6.3%). The results of study II show that the mean [13C2]oxalate absorption of the four volunteers under low-oxalate diet was 7.3 +/- 1.4%. The absorption increased to 14.7+/-5.2% under 600 mg oxalate. After 6 weeks under a high-oxalate diet, the [13C2]oxalate absorption was significantly decreased (8.2 +/- 1.7%). After the wash-out phase, the absorption was again high (14.1 +/- 2.2%) under the 600 mg oxalate challenge.

Absorptive hyperoxaluria leads to an increased risk for urolithiasis or nephrocalcinosis in cystic fibrosis.

BACKGROUND: Hyperoxaluria has been incriminated to account for the increased incidence of urolithiasis or nephrocalcinosis in patients with cystic fibrosis (CF). Hyperoxaluria presumably is caused by fat malabsorption and the absence of such intestinal oxalate-degrading bacteria as Oxalobacter formigenes. To better elucidate its pathophysiological characteristics, we prospectively studied patients with CF by determining these parameters and performing renal ultrasonography twice yearly. METHODS: In addition to routine tests in urine (lithogenic and stone-inhibitory substances), the presence of O formigenes was tested in stool, plasma oxalate was measured, and a [13C2]oxalate absorption test was performed in 37 patients with CF aged 5 to 37 years (15 females, 22 males) who were constantly hyperoxaluric before the study. RESULTS: Hyperoxaluria (oxalate, 46 to 141 mg/1.73 m2/24 h [0.51 to 1.57 mmol/1.73 m2/24 h]; normal, < 45 mg/1.73 m2/24 h [< 0.5 mmol/1.73 m2/24 h]) was now found in 24 patients (64.8%). Plasma oxalate levels were elevated in 6 patients (7.92 to 19.5 micromol/L; normal, 6.3 +/- 1.1 micromol/L). Oxalobacter species were detected in only 1 patient. Intestinal oxalate absorption was elevated (11.4% to 28.5%; normal, < 10%) in 23 patients. Hypocitraturia was present in 17 patients (citrate, 0.35 to 2.8 g/1.73 m2/24 h [0.2 to 1.1 mmol/1.73 m2/24 h]; normal female, > 2.8 mg/1.73 m2/24 h [> 1.6 mmol/1.73 m2/24 h]; male, > 3.3 mg/1.73 m2/24 h [> 1.9 mmol/1.73 m2/24 h]). Urine calcium oxalate saturation was elevated in 17 patients (5.62 to 28.9 relative units; normal female, < 5.5 relative units; male, < 6.3 relative units). In 16% of patients, urolithiasis (n = 2) or nephrocalcinosis (n = 4) was diagnosed ultrasonographically. CONCLUSION: Absorptive hyperoxaluria and hypocitraturia are the main culprits for the increased incidence of urolithiasis and nephrocalcinosis in patients with CF. We advocate high fluid intake, low-oxalate/high-calcium diet, and alkali citrate medication, if necessary. Additional studies are necessary to determine the influence of Oxalobacter species or other oxalate-degrading bacteria on oxalate handling in patients with CF.

The efficacy of dietary intervention on urinary risk factors for stone formation in recurrent calcium oxalate stone patients.

PURPOSE: Nutrition is suggested to be the major environmental risk factor in idiopathic calcium oxalate stone disease. The study was designed to evaluate the effect of dietary intervention on urinary risk factors for recurrence in calcium oxalate stone formers. MATERIALS AND METHODS: A total of 76 men and 31 women with idiopathic calcium oxalate stone disease collected 24-hour urine on their habitual, self-selected diets and after 7 days on a balanced standardized diet according to the recommendations for calcium oxalate stone formers. RESULTS: On the usual diet, a urine volume of less than 2.0 l per 24 hours was present in 57.9%, hypercalciuria in 25.2%, hypomagnesuria in 18.7%, hyperoxaluria in 14.0%, hyperuricosuria in 41.3% and hypocitraturia in 57.0% of patients. The frequency of metabolic abnormalities and the risk of calcium oxalate stone formation decreased significantly on the ingestion of the balanced diet, due to the significant increase in urinary volume, pH and citrate excretion and the significant decrease in urinary calcium and uric acid excretion. No change occurred in urinary oxalate and magnesium excretion. CONCLUSIONS: The evaluation of urinary risk profiles of the patients on their usual dietary habits revealed a high risk for calcium oxalate stone formation. A low fluid intake and an increased intake of protein and alcohol were identified as the most important dietary risk factors. The shift to a nutritionally balanced diet according to the recommendations for calcium oxalate stone formers significantly reduced the stone forming potential.

Importance of magnesium in absorption and excretion of oxalate.

INTRODUCTION: Magnesium treatment for calcium oxalate urolithiasis is discussed controversially. The aim of this study was to investigate the influence of magnesium supplementation on the oxalate absorption. MATERIALS AND METHODS: The [13C2]oxalate absorption test was always performed three times in 6 healthy volunteers under standardized conditions, with one 10-mmol magnesium supplement together with the labeled oxalate and with two 10-mmol magnesium supplements given in 12-hour intervals. RESULTS: The mean intestinal oxalate absorption under standard conditions was 8.6 +/- 2.83%. The oxalate absorption with one 10-mmol magnesium supplement was 5.2 +/- 1.40% and with two supplements 5.5 +/- 1.62%. Both decreases were statistically significant relative to the standard test, however, not significantly different from each other. CONCLUSIONS: The results show that magnesium administration decreases the oxalate absorption, when magnesium is taken together with oxalate. However, magnesium administration does not decrease the oxalate absorption, when magnesium and oxalate intake differ by 12 h.

The effect of oral administration of calcium and magnesium on intestinal oxalate absorption in humans.

Calcium oxalate (CaOx) urolithiasis is the most common urinary stone disease (70-75 % of all stones consist of CaOx in countries with western diet). Oxalate is the most lithogenic substance in CaOx crystallisation in urine. Oxalate is either synthesized within the body or absorbed from food. As oxalate is not metabolized in the human body, it appears unchanged in urine. Conventional analysis methods cannot distinguish between endogenous and exogenous oxalate. Our [13C2]oxalate absorption test enabled measurement of intestinal oxalate absorption and quantification of the influence of Ca- and Mg-supplementation on it. The effects of the oral administration of these supplements were compared in order to obtain valid data for recommendations for CaOx urolithiasis patients. A 10 mmol supplement of both ions decreased the oxalate absorption significantly, calcium being more than twice as effective.

Dependence of oxalate absorption on the daily calcium intake.

Two to 20% of ingested oxalate is absorbed in the gastrointestinal tract of healthy humans with a daily 800 mg calcium intake. Calcium is the most potent modifier of the oxalate absorption. Although this has been found repeatedly, the exact correlation between calcium intake and oxalate absorption has not been assessed to date. Investigated was oxalate absorption in healthy volunteers applying 0.37 mmol of the soluble salt sodium [(13)C(2)]oxalate in the calcium intake range from 5 mmol (200 mg) calcium to 45 mmol (1800 mg) calcium. Within the range of 200 to 1200 mg calcium per day, oxalate absorption depended linearly on the calcium intake. With 200 mg calcium per day, the mean absorption (+/- SD) was 17% +/- 8.3%; with 1200 mg calcium per day, the mean absorption was 2.6% +/- 1.5%. Within this range, reduction of the calcium supply by 70 mg increased the oxalate absorption by 1% and vice versa. Calcium addition beyond 1200 mg/d reduced the oxalate absorption only one-tenth as effectively. With 1800 mg calcium per day, the mean absorption was 1.7% +/- 0.9%. The findings may explain why a low-calcium diet increases the risk of calcium oxalate stone formation.

Reference range for gastrointestinal oxalate absorption measured with a standardized [13C2]oxalate absorption test.

PURPOSE: Hyperoxaluria is a prominent risk factor for calcium oxalate urinary stones. Oxalate in urine is synthesized in the body or absorbed from food in the gastrointestinal tract. The amount of oxalate absorbed by patients with calcium oxalate stones may vary from a few percent to 50% of the dietary intake. Reference values for oxalate absorption measured under a standardized diet have never been attained in sufficient numbers from healthy individuals. Therefore, to our knowledge we collected for the first time the values required to interpret test results in patients with recurrent urinary stones. MATERIALS AND METHODS: A total of 120 healthy volunteers, including 60 females and 60 males, received an identical standard diet on 2 consecutive days. On the morning of day 2 a capsule containing 0.37 mmol. sodium [13C2]oxalate (not radioactive) was ingested with water. Urinary oxalate was measured by gas chromatography-mass spectrometry. Absorption at a fixed 800 mg. daily Ca input is expressed as a percent of the labeled oxalate dose. RESULTS: For the standardized [13C2]oxalate absorption test the reference range in 95% of the 120 volunteers was 2.2% to 18.5% (mean +/- SD 7.9% +/- 4.0%). The repeatability of the standardized test was determined in 26 of the 120 volunteers by repeating the test twice. The mean intra-individual SD was 3.39% +/- 1.68%. CONCLUSIONS: We assessed reference values of intestinal oxalate absorption using a standardized diet. Interindividual and intra-individual variance was high.