Oxalate degrading bacteria: new treatment option for patients with primary and secondary hyperoxaluria?

Current treatment options in patients with primary and secondary hyperoxaluria are limited and do not always lead to sufficient reduction in urinary oxalate excretion. Intestinal oxalate degrading bacteria are capable of degrading oxalate to CO₂ and formate, the latter being further metabolized and excreted via the feces. It is speculated, that both endogenously produced, as well as dietary oxalate can be significantly removed via the intestinal tract. Oxalobacter formigenes, an obligate anaerobic microbe normally found in the intestinal tract has one oxalate degrading enzyme, oxalyl-CoA decarboxylase, which is also found in Bifidobacterium lactis. Other bacteria with possible oxalate degrading potency are lactic acid bacteria, as well as Enterococcus faecalis and Eubacterium lentum. However, specific therapeutic studies on humans are scarce and, except for Oxalobacter, data are not congruent. We found the oral application of Oxalobacter successful in patients with primary hyperoxaluria. However, long-term post-treatment follow-up of 1–2 years showed that constant intestinal colonization is not achieved in most patients. In one patient with constant colonization, urinary oxalate excretion normalized over time. Short-term studies with other bacteria such as lactic acid bacteria did not show a specific reduction in urinary oxalate excretion. O. formigenes might be a promising new therapeutic tool in patients with primary and secondary hyperoxaluria.     

Renal and intestinal handling of oxalate following oxalate loading in rats

BACKGROUND: The enteric excretion of oxalate has been established in rats with chronic renal failure induced by 5/6 nephrectomy [Hatch et al.: Regulatory aspects of oxalate secretion in enteric oxalate elimination. JASN 1999;10:S324] and this response is mediated by angiotensin II receptor activation. However, the renal and intestinal handling of oxalate has not been evaluated for other common models of hyperoxaluria that simulate primary hyperoxaluria or oxalate stone disease. METHODS: We assessed the renal clearances of creatinine, oxalate and calcium in three rat models: chronic hyperoxaluria (CH), chronic hyperoxaluria with hyperoxalemia (CHH) and acute hyperoxaluria (AH), and evaluated the transepithelial transport of oxalate and chloride in large intestinal segments of these models and their sensitivity to angiotensin II antagonism. RESULTS: Hyperoxaluria alone (CH) was not associated with changes in colonic oxalate transport, whereas changes in net oxalate transport in distal colon from absorption to net secretion was observed in models with hyperoxalemia (CHH and AH). Angiotensin II receptor antagonism with losartan reduced net colonic oxalate secretion in AH but not CHH. CONCLUSIONS: Colonic secretion of oxalate is stimulated in rat models exhibiting hyperoxalemia suggesting a contribution of this extrarenal pathway to regulation of oxalate mass balance in clinical conditions manifesting hyperoxalemia. The transport avenues and regulatory mechanisms may not be identical to those observed during adaptive enteric oxalate secretion in chronic renal failure models.     

13C2]oxalate absorption in children with idiopathic calcium oxalate urolithiasis or primary hyperoxaluria

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.     

Acute probiotic ingestion reduces gastrointestinal oxalate absorption in healthy subjects

Both a high dietary oxalate intake and increased intestinal absorption appear to be major causes of elevated urine oxalate, a risk factor for kidney stone formation. A number of recent studies have assessed whether daily ingestion of a probiotic containing oxalate-degrading bacteria could lead to sufficient gut colonization to increase oxalate degradation, thereby reducing urinary oxalate. In contrast, the present study assessed whether simultaneous ingestion of oxalate-degrading probiotic bacteria with a 176 mg oxalate load could lead to decreased urinary oxalate in a population of 11 healthy non-stone formers (8 females, 3 males), aged 21-45 years. The results indicated that both the single and double doses of VSL#3(?) probiotic solutions were effective in reducing urinary oxalate and estimated oxalate absorption with no significant difference between the two probiotic doses. The timing of the reduction in urinary oxalate suggested a small intestinal and possibly gastric reduction in oxalate absorption. Similar to what had been reported for chronic or daily probiotic ingestion, individuals characterized by high oxalate absorption were most likely to experience clinically significant reductions in urinary oxalate in response to acute probiotic ingestion.     

Oxalobacter sp. reduces urinary oxalate excretion by promoting enteric oxalate secretion

The primary goal of this study was to test the hypothesis that Oxalobacter colonization alters colonic oxalate transport thereby reducing urinary oxalate excretion. In addition, we examined the effects of intraluminal calcium on Oxalobacter colonization and tested the hypothesis that endogenously derived colonic oxalate could be degraded by lyophilized Oxalobacter enzymes targeted to this segment of the alimentary tract. Oxalate fluxes were measured across short-circuited, in vitro preparations of proximal and distal colon removed from Sprague-Dawley rats and placed in Ussing chambers. For these studies, rats were colonized with Oxalobacter either artificially or naturally, and urinary oxalate, creatinine and calcium excretions were determined. Colonized rats placed on various dietary treatment regimens were used to evaluate the impact of calcium on Oxalobacter colonization and whether exogenous or endogenous oxalate influenced colonization. Hyperoxaluric rats with some degree of renal insufficiency were also used to determine the effects of administering encapsulated Oxalobacter lysate on colonic oxalate transport and urinary oxalate excretion. We conclude that in addition to its intraluminal oxalate-degrading capacity, Oxalobacter interacts physiologically with colonic mucosa by inducing enteric oxalate secretion/excretion leading to reduced urinary excretion. Whether Oxalobacter, or products of Oxalobacter, can therapeutically reduce urinary oxalate excretion and influence stone disease warrants further investigation in long-term studies in various patient populations.     

Intestinal absorption of oxalate and calcium in patients with jejunoileal bypass

Jejunoileal bypass (JIB) has been widely performed for treatment of excessive obesity. Formation of calcium oxalate stones is a common side effect. Since, under physiological conditions, the intestinal absorption of calcium and that of oxalate are interrelated, intestinal oxalate and calcium absorption were measured in the present study by isotope techniques in 19 JIB patients and 20 healthy controls. The JIB patients showed pronounced hyperoxaluria and markedly increased absorption of oxalate, with a urinary excretion of 14C-oxalate of 29 +/- 19% (controls 6.2 +/- 3.7%; p less than 0.001). There was a strong correlation between the intestinal absorption and urinary excretion of oxalate in the JIB patients (r = 0.72; p less than 0.001). Furthermore, their oxalate kinetics was altered, with continued urinary excretion of 14C-oxalate for up to 48 hours. The JIB patients also had reduced calcium absorption (36 +/- 9.1% vs. 47 +/- 9.0%; p less than 0.001) and patients with malabsorption of calcium and low urinary calcium had the highest intestinal absorption and urinary excretion of oxalate. It is concluded that hyperoxaluria in JIB patients is due to a significant extent to hyperabsorption of oxalate.     

The urinary response to an oral oxalate load in recurrent calcium stone formers

PURPOSE: Dietary oxalate may contribute up to 50% to 80% of the oxalate excreted in urine. We studied the urinary response to an oral oxalate load in male and female idiopathic recurrent calcium oxalate stone formers with and without mild hyperoxaluria to evaluate the potential pathophysiological significance of dietary oxalate. MATERIALS AND METHODS: A total of 60 recurrent calcium stone formers underwent an oral oxalate load test. Urine samples were obtained after an overnight fast. Each patient then received an oral oxalate load (5 mM. sodium oxalate dissolved in 250 ml. distilled water) and 3, 2-hour urine samples were obtained 2, 4 and 6 hours after the oxalate load. We compared the response to the oxalate load in patients with and without mild hyperoxaluria, and in male and female patients without hyperoxaluria. RESULTS: The peak urinary response occurred 4 hours after the oral oxalate load in all patients. Those with mild hyperoxaluria had a mean fasting urinary oxalate-to-creatinine ratio +/- SE of 0.027 +/- 0.003 and a mean peak urinary oxalate-to-creatinine ratio of 0.071 +/- 0.006. In comparison, patients with normal oxalate excretion had a fasting and peak urinary oxalate-to-creatinine ratio of 0.018 +/- 0.001 and 0.056 +/- 0.004, respectively (p <0.05). The mean 6-hour increment for urinary oxalate excretion after the oxalate load for patients with hyperoxaluria versus those with normal urinary oxalate excretion was 17.2 +/- 1.9 versus 12.1 +/- 0.98 mg. (p <0.05). In the subset of patients with normal urinary oxalate excretion mean 6-hour cumulative urinary oxalate excretion was 16.8 +/- 1.3 and 13.3 +/- 1.4 mg. in males and females, respectively (p not significant). CONCLUSIONS: Recurrent calcium stone formers with mild hyperoxaluria have higher fasting urinary oxalate and an exaggerated urinary response to an oral oxalate load compared with recurrent calcium stone formers with normal urinary oxalate excretion. Men and women stone formers without hyperoxaluria excrete similar fractions of an oral oxalate load. Increased gastrointestinal absorption and renal excretion of dietary oxalate may be a significant pathophysiological mechanism of stone formation in patients with mild hyperoxaluria.     

Intestinal Oxalobacter formigenes colonization in calcium oxalate stone formers and its relation to urinary oxalate

BACKGROUND AND PURPOSE: Oxalobacter formigenes is an anaerobic commensal colonic bacterium capable of degrading oxalate through the enzyme oxalyl-CoA decarboxylase. It has been theorized that individuals who lack this bacterium have higher intestinal oxalate absorption, leading to a higher urinary oxalate concentration and an increased risk of calcium oxalate urolithiasis. We performed a prospective, controlled study to evaluate O. formigenes colonization in calcium oxalate stone formers and to correlate colonization with urinary oxalate and other standard urinary stone risk factors. PATIENTS AND METHODS: Thirty-five first-time calcium oxalate stone formers were compared with 10 control subjects having no history of urolithiasis and a normal renal ultrasound scan. All subjects underwent standard metabolic testing by submitting serum and 24-hour urine specimens. In addition, all subjects submitted stool samples for culture and detection of O. formigenes by Xentr(ix) O. formigenes Monitor. RESULTS: Intestinal Oxalobacter was detected in only 26% of the stone formers compared with 60% of the controls (p < 0.05). Overall, the average urinary oxalate excretion by the two groups was similar (38.6 mg/day v 40.8 mg/day). Among stone formers, however, there were statistically higher urinary oxalate concentrations in O. formigenes-negative patients compared with those testing positive (41.7 mg/day v 29.4 mg/day) (p = 0.03). Furthermore, all 10 stone formers with hyperoxaluria (>44 mg/day) tested negative for O. formigenes (p < 0.05). CONCLUSIONS: Calcium oxalate stone formers have a low rate of colonization with O. formigenes. Among stone formers, absence of intestinal Oxalobacter correlates with higher urinary oxalate concentration and an increased risk of hyperoxaluria. Introduction of the Oxalobacter bacterium or an analog of its enzyme oxalyl-CoA decarboxylase into the intestinal tract may be a treatment for calcium oxalate stone disease.     

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.     

Probiotic-induced reduction of gastrointestinal oxalate absorption in healthy subjects

Both a high dietary oxalate intake and increased intestinal absorption appear to be major causes of elevated urine oxalate, a risk factor for kidney stone formation. By favorably altering the gastrointestinal bacterial population, probiotics have the potential to lower oxalate absorption/urinary excretion. This study assessed whether a 4-wk daily consumption of a commercially available probiotic by 11 healthy volunteers (8 females, 3 males), aged 21-36 y, would decrease oxalate absorption. The study involved the ingestion of a probiotic (VSL#3^®) for a 4 wk period followed by a 4 wk washout period. Oxalate load tests, providing a total of 80 mg oxalate, were conducted at baseline (pre-probiotic), and after the probiotic and washout periods. In the total subject population, mean total 22 h oxalate absorption at baseline (30.8 %) was significantly higher than after the probiotic (11.6 %) and washout (11.5 %) periods. However, four subjects identified as high oxalate absorbers at baseline had a particularly marked probiotic-induced reduction in oxalate absorption, which largely accounted for the reduction observed in the total subject population. The overall data suggested that in individuals characterized by high oxalate absorption levels, VSL#3^® ingestion has the potential to reduce gastrointestinal oxalate absorption, which could decrease risk of kidney stones and other disorders related to hyperoxaluria.     

Intestinal and renal handling of oxalate loads in normal individuals and stone formers

The renal handling and intestinal absorption of dietary oxalate are believed to be risk factors for calcium oxalate stone formation. In this study, we have examined the time and dose effects of soluble oxalate loads on the intestinal absorption and renal handling of oxalate in six stone formers (SF) and six normal individuals (N) who consumed diets controlled in oxalate and other nutrients. Urinary and plasma oxalate changes were monitored over 24 h after ingestion of 0, 2, 4, and 8 mmole oxalate loads, containing a mixture of ¹²C- and ¹³C₂-oxalate. There were significant time and dose dependent changes in urinary oxalate excretion and secretion after these loads. However, there were no significant differences between SF and N in both the intestinal absorption and the renal handling of oxalate loads, as measured by the urinary excretion of oxalate (P = 0.96) and the ratio of oxalate to creatinine clearance (P = 0.34). ¹³C₂-oxalate absorption studies showed three of the subjects, two SF and one N, had enhanced absorption with the 8 mmole load. A clear difference in absorption was demonstrated in these individuals during the 8–24 h interval, suggesting that in these individuals there was greater oxalate absorption in the large intestine as compared to the other subjects. This enhanced absorption of oxalate warrants further characterization. This research was supported in part by NIH grants RO1 DK62284 and MO1 RR07122.     

The genetic composition of Oxalobacter formigenes and its relationship to colonization and calcium oxalate stone disease

Oxalobacter formigenes is a unique intestinal organism that relies on oxalate degradation to meet most of its energy and carbon needs. A lack of colonization is a risk factor for calcium oxalate stone disease. Protection against calcium oxalate stone disease appears to be due to the oxalate degradation that occurs in the gut on low calcium diets with a possible further contribution from intestinal oxalate secretion. Much remains to be learned about how the organism establishes and maintains gut colonization and the precise mechanisms by which it modifies stone risk. The sequencing and annotation of the genomes of a Group 1 and a Group 2 strain of O. formigenes should provide the informatic tools required for the identification of the genes and pathways associated with colonization and survival. In this review we have identified genes that may be involved and where appropriate suggested how they may be important in calcium oxalate stone disease. Elaborating the functional roles of these genes should accelerate our understanding of the organism and clarify its role in preventing stone formation.     

Association of absence of intestinal oxalate degrading bacteria with urinary calcium oxalate stone formation

AIM: Urinary concentration of oxalate is considered an important factor in the formation of renal stones. Dietary oxalate is a major contributor to urinary oxalate excretion in most individuals. Furthermore, oxalate degrading bacteria have been isolated from human feces. We investigated the significance of oxalate degrading bacteria for urinary oxalate excretion and urinary stone formation. METHODS: Twenty-two known calcium oxalate stone-forming patients (stone formers) and 34 healthy volunteers (non-stone formers) were included in the study. Stool specimens were inoculated into pepton yeast glucose (PYG) medium supplemented with oxalate under anaerobic condition at 37 C for one week. After the incubation period, each colony was checked for the loss of oxalate from the culture medium. A 24-h urine sample was collected in 43 individuals and analyzed for oxalate excretion. RESULTS: Twenty-eight of 34 (82%) healthy volunteers and 10 of 22 (45%) calcium oxalate stone formers were colonized with oxalate degrading bacteria. Calcium oxalate stone formers were more frequently free of oxalate degrading bacteria (P < 0.01). Urinary excretion of oxalate in those with oxalate degrading bacteria was significantly less than in those without oxalate degrading bacteria (P < 0.05). Hyperoxaluria (> 40 mg/day) was found in four of 27 individuals (15%) with oxalate degrading bacteria compared to seven of 16 (44%) without oxalate degrading bacteria (P < 0.05), suggesting an association between the absence of oxalate degrading bacteria and the presence of hyperoxaluria. CONCLUSION: The absence of oxalate degrading bacteria in the gut could promote the absorption of oxalate, thereby increasing the level of urinary oxalate excretion. The absence of oxalate degrading bacteria from the gut appears to be a risk factor for the presence of absorptive hyperoxaluria and an increased likelihood of urolithiasis.     

Net intestinal transport of oxalate reflects passive absorption and SLC26A6-mediated secretion

Mice lacking the oxalate transporter SLC26A6 develop hyperoxalemia, hyperoxaluria, and calcium-oxalate stones as a result of a defect in intestinal oxalate secretion, but what accounts for the absorptive oxalate flux remains unknown. We measured transepithelial absorption of [(14)C]oxalate simultaneously with the flux of [(3)H]mannitol, a marker of the paracellular pathway, across intestine from wild-type and Slc26a6-null mice. We used the anion transport inhibitor DIDS to investigate other members of the SLC26 family that may mediate transcellular oxalate absorption. Absorptive flux of oxalate in duodenum was similar to mannitol, insensitive to DIDS, and nonsaturable, indicating that it is predominantly passive and paracellular. In contrast, in wild-type mice, secretory flux of oxalate in duodenum exceeded that of mannitol, was sensitive to DIDS, and saturable, indicating transcellular secretion of oxalate. In Slc26a6-null mice, secretory flux of oxalate was similar to mannitol, and no net flux of oxalate occurred. Absorptive fluxes of both oxalate and mannitol varied in parallel in different segments of small and large intestine. In epithelial cell lines, modulation of the charge selectivity of the claudin-based pore pathway did not affect oxalate permeability, but knockdown of the tight-junction protein ZO-1 enhanced permeability to oxalate and mannitol in parallel. Moreover, formation of soluble complexes with cations did not affect oxalate absorption. In conclusion, absorptive oxalate flux occurs through the paracellular "leak" pathway, and net absorption of dietary oxalate depends on the relative balance between absorption and SLC26A6-dependent transcellular secretion.     

Roux-en-Y gastric bypass is associated with early increased risk factors for development of calcium oxalate nephrolithiasis

BACKGROUND: Patients treated for obesity with jejunoileal bypass (JIB) experienced a marked increased risk of hyperoxaluria, nephrolithiasis, and oxalate nephropathy developing. Jejunoileal bypass has been abandoned and replaced with other options, including Roux-en-Y gastric bypass (RYGB). Changes in urinary lithogenic risk factors after RYGB are currently unknown. Our purpose was to determine whether RYGB is associated with elevated risk of developing calcium oxalate stone formation through increased urinary oxalate excretion and relative supersaturation of calcium oxalate. STUDY DESIGN: A prospective longitudinal cohort study of 24 morbidly obese adults (9 men and 15 women) recruited from a university-based bariatric surgery clinic scheduled to undergo RYGB between December 2005 and April 2007. Patients provided 24-hour urine collections for analysis 7 days before and 90 days after operation. Primary outcomes were changes in 24-hour urinary oxalate excretion and relative supersaturation of calcium oxalate from baseline to 3 months post-RYGB. RESULTS: Compared with their baseline, patients undergoing RYGB had increased urinary oxalate excretion (31 +/- 10 mg/d versus 41 +/- 18 mg/d; p = 0.026) and relative supersaturation of calcium oxalate (1.73 +/- 0.81 versus 3.47 +/- 2.59; p = 0.030) 3 months post-RYGB in six patients (25%). De novo hyperoxaluria developed. There were no preoperative patient characteristics predictive of development of de novo hyperoxaluria or the magnitude of change of daily oxalate excretion. CONCLUSIONS: This prospective study indicates that RYGB is associated with an earlier increase in urinary oxalate excretion and relative supersaturation of calcium oxalate than previously reported. Additional studies are needed to determine longterm post-RYGB changes in urinary oxalate excretion and identify patients that might be at risk for hyperoxaluria developing.     

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.     

Enteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy: potentially serious and unappreciated complications of Roux-en-Y gastric bypass.

BACKGROUND: Neither the presence nor prevalence of enteric hyperoxaluria has been recognized after Roux-en-Y gastric bypass (RYGBP). We have noted a high rate of oxalate nephrolithiasis and even 2 patients with oxalate nephropathy in this patient population postoperatively. Our aim was to determine the frequency of the occurrence and effects of enteric hyperoxaluria after RYGBP. METHODS: Retrospective review of all patients at our institution diagnosed with calcium oxalate nephrolithiasis or oxalate nephropathy after standard (n = 14) or distal (n = 9) RYGBP. The mean postoperative follow-up was 55 months. RESULTS: A total of 23 patients (14 men and 9 women; mean age 45 years; mean preoperative body mass index 55 kg/m(2)) developed enteric hyperoxaluria after RYGBP, defined by the presence of oxalate nephropathy (n = 2) or calcium oxalate nephrolithiasis (n = 21) and increased 24-hour excretion of urinary oxalate and/or calcium oxalate supersaturation. Enteric hyperoxaluria was recognized after a mean weight loss of 46 kg at 29 months (range 2-85) after RYGBP. Two patients developed renal failure and required chronic hemodialysis. Of the 21 patients with nephrolithiasis, 14 had no history of nephrolithiasis preoperatively, and 19 of 21 required lithotripsy or other intervention. Of the 23 patients, 20 tested had increased oxalate excretion, and 14 of 15 tested had high urine calcium oxalate supersaturation. CONCLUSION: Enteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy must be considered with the other risks of RYGBP. Efforts should be made to identify factors that predispose patients to developing hyperoxaluria.     

Dietary oxalate and calcium oxalate nephrolithiasis

PURPOSE: Patients with calcium oxalate kidney stones are advised to decrease the consumption of foods that contain oxalate. We hypothesized that a cutback in dietary oxalate would lead to a decrease in the urinary excretion of oxalate and decreased stone recurrence. We tested the hypothesis in an animal model of calcium oxalate nephrolithiasis. MATERIALS AND METHODS: Hydroxy-L-proline (5%), a precursor of oxalate found in collagenous foods, was given with rat chow to male Sprague-Dawley rats. After 42 days rats in group 1 continued on hydroxy-L-proline, while those in group 2 were given chow without added hydroxy-L-proline for the next 21 days. Food and water consumption as well as weight were monitored regularly. Once weekly urine was collected and analyzed for creatinine, calcium, oxalate, lactate dehydrogenase, 8-isoprostane and H(2)O(2). Urinary pH and crystalluria were monitored. Rats were sacrificed at 28, 42 and 63 days, respectively. Renal tissue was examined for crystal deposition by light microscopy. RESULTS: Rats receiving hydroxy-L-proline showed hyperoxaluria, calcium oxalate crystalluria and nephrolithiasis, and by day 42 all contained renal calcium oxalate crystal deposits. Urinary excretion of lactate dehydrogenase, 8-isoprostane and H(2)O(2) increased significantly. After hydroxy-L-proline was discontinued in group 2 there was a significant decrease in urinary oxalate, 8-isoprostane and H(2)O(2). Half of the group 2 rats appeared to be crystal-free. CONCLUSIONS: Dietary sources of oxalate can induce hyperoxaluria and crystal deposition in the kidneys with associated degradation in renal biology. Eliminating oxalate from the diet decreases not only urinary oxalate, but also calcium oxalate crystal deposits in the kidneys and improves their function.     

Effect of animal and vegetable protein intake on oxalate excretion in idiopathic calcium stone disease

Oxalate excretion was measured in healthy subjects and idiopathic calcium stone-formers on dietary regimens which differed in the type and amount of protein allowed; 24-h urine collections were obtained from 41 practising vegetarians and 40 normal persons on a free, mixed, "mediterranean" diet. Twenty idiopathic calcium stone-formers were also studied while on two low calcium, low oxalate diets which differed in that animal protein was high in one and restricted in the other. Vegetarians had higher urinary oxalate levels than controls and although the calcium levels were markedly lower, urinary saturation with calcium/oxalate was significantly higher. This mild hypercalciuria was interpreted as being secondary to both a higher intake and increased fractional intestinal absorption of oxalate. Changing calcium stone-formers from a high to a low animal protein intake produced a significant decrease in calcium excretion but there was no variation in urinary oxalate. As a result, the decrease in calcium oxalate saturation was only marginal and not significant. It was concluded that dietary animal protein has a minimal effect on oxalate excretion. Mild hyperoxaluria of idiopathic calcium stone disease is likely to be intestinal in origin. Calcium stone-formers should be advised to avoid an excess of animal protein but the risks of a vegetable-rich diet should also be borne in mind.     

Pyridoxamine lowers oxalate excretion and kidney crystals in experimental hyperoxaluria: a potential therapy for primary hyperoxaluria

In order to prevent kidney stones and nephrolithiasis in hyperoxaluria, a new treatment that specifically reduces oxalate production and therefore urinary oxalate excretion would be extremely valuable. Pyridoxamine(PM) could react with the carbonyl intermediates of oxalate biosynthesis, glycolaldehyde and glyoxylate, and prevent their metabolism to oxalate. In PM treated rats, endogenous urinary oxalate levels were consistently lower and became statistically different from controls after 12 days of experiment. In ethylene glycol-induced hyperoxaluria, PM treatment resulted in significantly lower (by ~50%) levels of urinary glycolate and oxalate excretion compared to untreated hyperoxaluric animals, as well as in a significant reduction in calcium oxalate crystal formation in papillary and medullary areas of the kidney. These results, coupled with favorable toxicity profiles of PM in humans, show promise for the therapeutic use of PM in primary hyperoxaluria and other kidney stone diseases.