Calcium Oxalate Relative Supersaturation Research Articles

Effect of Two Different Dietary Weight Loss Strategies on Risk Factors for Urinary Stone Formation and Cardiometabolic Risk Profile in Overweight Women

Overweight has been suggested to increase the risk of kidney stone formation. Although weight reduction might affect risk factors for urolithiasis, findings on the impact of different dietary weight loss strategies are limited. This randomized, controlled study evaluated the effect of a conventional energy-restricted modified diet with (MR group) or without meal replacement (C group) on risk factors for stone formation in overweight women without a history of urolithiasis. Of 105 participants, 78 were included into the per-protocol analysis. Anthropometric, clinical, biochemical, and 24 h urinary parameters were collected at baseline and after 12 weeks. Although both dietary interventions resulted in a significant weight reduction, relative weight loss and rate of responders were higher in the MR group. Weight loss improved cardiometabolic risk profile in both groups. Unfortunately, the benefit of decreased GPT activity in the C group was offset by a significant increase in homocysteine and a decline in GFR. While the relative supersaturation of calcium oxalate decreased significantly in both groups, a significant decline in serum uric acid concentration and relative supersaturation of uric acid was observed only in the MR group. Finally, the energy-restricted modified diet with meal replacement showed significant advantages over the energy-restricted modified diet alone.

Effect of Black Tea Consumption on Urinary Risk Factors for Kidney Stone Formation.

Copious fluid intake is the most essential nutritional measure in the treatment of urolithiasis, and is suggested to be a protective factor in the primary prevention of urinary stone formation. Although the intake of black tea contributes to daily fluid intake, the high oxalate content could outweigh the beneficial effect of urine dilution. The present study investigated the effect of black tea consumption on urinary risk factors for kidney stone formation. Ten healthy men received a standardized diet for a period of ten days. Subjects consumed 1.5 L/day of fruit tea (0 mg/day oxalate) during the 5-day control phase, which was replaced by 1.5 L/day of black tea (86 mg/day oxalate) during the 5-day test phase. Fractional and 24-h urines were obtained. The intake of black tea did not significantly alter 24-h urinary oxalate excretion. Urinary citrate, an important inhibitor of calcium stone formation, increased significantly, while the relative supersaturation of calcium oxalate, uric acid, and struvite remained unchanged. No significantly increased risk for kidney stone formation could be derived from the ingestion of black tea in normal subjects. Further research is needed to evaluate the impact of black tea consumption in kidney stone patients with intestinal hyperabsorption of oxalate.

Increasing Dietary Potassium Chloride Promotes Urine Dilution and Decreases Calcium Oxalate Relative Supersaturation in Healthy Dogs and Cats.

Simple SummaryBladder- and kidney stones are common in dogs and cats, and urine dilution is a strategy often used to decrease the risk of stone and crystal-formation. Pet foods containing sodium chloride (NaCl, table salt) increase drinking with the resultant dilution of urine. The salt substitute potassium chloride (KCl) is a potential alternative for patients that would benefit from dietary sodium restriction, but the effects of KCl on urinary parameters is unknown. This study fed two dry pet foods differing only in KCl to healthy dogs and cats. When fed the diet containing KCl, dogs and cats increased their water intake, and urine volume increased. The urine was more dilute, and measures of calcium oxalate stone risk decreased. A pet food containing KCl is therefore an interesting alternative to NaCl and a novel nutritional strategy for the prevention of urinary stones.Urine dilution is a strategy used to decrease the risk of crystallization in cats and dogs at risk of urolithiasis. Sodium chloride has been used in prescription diets to effectively promote urine dilution, but the effect of the salt-substitute potassium chloride (KCl) on urine parameters has not been extensively investigated. Two diets differing only in KCl (Diet A; K 0.44 g/MJ, Diet B; K 1.03 g/MJ) were fed to 17 cats and 22 dogs for seven days, followed by three days of urine collection. Urinary ion concentrations were determined by ionic chromatography, and SUPERSAT software was used to calculate the relative supersaturation (RSS) value for struvite and calcium oxalate. Water intake and urine volume increased, and USG decreased on diet B (p < 0.001). Urine concentration of potassium increased on diet B, but concentrations of all other ions did not change or decrease in line with urine dilution. Calcium oxalate RSS decreased on diet B (p < 0.05). This short-term study showed that increased dietary KCl in a dry extruded diet effectively dilutes the urine of cats and dogs and therefore offers a novel nutritional strategy for the prevention of urolithiasis. This finding is of interest for patients that would benefit from dietary sodium restriction.

The effect of urine acidification on calcium oxalate relative supersaturation in cats.

There is an apparent reciprocal relationship between magnesium ammonium phosphate (MAP, struvite) and calcium oxalate (CaOx) urolithiasis incidence rate in cats. The number of struvite uroliths submitted for analysis over the past 35 years has been decreasing, with an increase in CaOx urolith submissions. Commercial diets aimed to dissolve struvite uroliths are typically acidified, and it has been suggested that dietary acidification increases urinary calcium excretion and the risk of CaOx crystallization. The objective of this study was to assess the effect of urine acidification on the relative supersaturation (RSS) of CaOx in cats, as a representation of crystallization risk. Four diets were extruded to contain identical nutrient contents, but with gradual acidification (0, 0.6, 1.3 and 1.9% sodium bisulphate substituted sodium chloride in diets A, B, C and D respectively). Thirteen adult cats were fed each diet sequentially for a minimum of 10 days. Average urine pH was 6.4, 6.2, 6.0 and 5.9 on diets A, B, C and D respectively (p < 0.0001). Struvite RSS decreased on diets inducing more acidic urine pH (p < 0.0001). Urinary calcium excretion and concentration increased with diets inducing lower urine pH (p < 0.0001), but oxalate excretion and concentration decreased (p < 0.001). CaOx RSS was not different between diets (p = 0.63). These results suggest that a lower diet base excess and resulting urine pH to support struvite dissolution do not increase the risk for CaOx crystallization in the range of urine pH representative of most commercial feline diets. Long‐term studies are needed to confirm this.

Idiopathic calcium nephrolithiasis with pure calcium oxalate composition: clinical correlates of the calcium oxalate dihydrate/monohydrate (COD/COM) stone ratio.

Pure calcium oxalate is the most frequent type of idiopathic kidney stone composition. Fourier transform infrared spectroscopy (FT-IR) allows to detect the ratio of calcium oxalate dihydrate (COD) and monohydrate (COM) crystals in stones, but the clinical significance of this parameter remains uncertain. The objective of this observational study was to verify the association of clinical and laboratory parameters of kidney stone disease with COD/COM ratio in a group of 465 (322M, age 46 ± 14) patients suffering from idiopathic calcium nephrolithiasis with pure calcium oxalate stones (≥ 97%). Each participant underwent a complete clinical examination, serum chemistry, 24-h urine collection for the determination of the profile of lithogenic risk, and had stones analyzed by FT-IR. Most (62%) of the stones had a COD/COM ratio ≤ 0.25, and the urine chemistry of the corresponding patients showed a low prevalence of urinary metabolic abnormalities. With increasing COD/COM ratio intervals (0-0.25, 0.26-0.50, 0.51-0.75, 0.76-1), a significant association was observed for the number of urological procedures, serum calcium, 24-h urinary calcium excretion, prevalence of hypercalciuria and relative calcium oxalate supersaturation, and a negative trend was detected for the age of the first stone episode (all p values < 0.05). A linear regression model showed that the only parameters significantly associated with COD/COM ratio were 24-h urinary calcium excretion (standardized β = 0.464, p < 0.001) and urine pH (standardized β = 0.103, p = 0.013). In pure calcium oxalate idiopathic stones, COD/COM ratio may reflect the presence of urinary metabolic risk factors, and represent a guide for the prescription of urinary analyses.

Short-Term Changes in Urinary Relative Supersaturation Predict Recurrence of Kidney Stones: A Tool to Guide Preventive Measures in Urolithiasis

Kidney stone disease is characterized by a relatively high rate of recurrence. In our study we analyzed the association between relative supersaturation and the risk of stone recurrence. Additionally, we examined the association between the risk of recurrence and changes in relative supersaturation and urinary composition after 1 week of medical treatment. We performed a post hoc analysis of data from a previously published randomized controlled trial comparing the effect of 2 diets in 120 men with recurrent calcium oxalate stones and hypercalciuria. Baseline and followup 24-hour urine parameters were used to calculate the relative supersaturation of calcium oxalate, calcium phosphate and uric acid using the EQUIL2, JESS and LithoRisk computer programs. Cox models were used to calculate the estimated association between each baseline relative supersaturation, and 1-week changes and the risk of recurrence during followup. During a 5-year followup 35 patients (34%) experienced recurrence. A reduction in calcium oxalate relative supersaturation at 1 week was significantly associated with a lower risk of recurrence using the EQUIL2 calculation (for every 10% reduction from baseline HR 0.92, 95% CI 0.86-1.00, p = 0.044). However, there was no association for relative supersaturation calculated by other methods or for the relative supersaturation of other salts. Changes in the 24-hour urine excretion of citrate, potassium and magnesium were significantly associated with a risk of recurrence. In recurrent stone formers with hypercalciuria baseline values and changes in the relative supersaturation of calcium oxalate may be associated with the risk of recurrence. Changes in urinary citrate, potassium and magnesium following dietary intervention may also be predictive.

Relative Supersaturation of 24-Hour Urine and Likelihood of Kidney Stones

The relative supersaturation of calcium oxalate, calcium phosphate and uric acid is used clinically in kidney stone prevention. The magnitude of the association between relative supersaturation and stone risk requires further quantification. We performed a cross-sectional study using 24-hour urine collections from the NHS (Nurses' Health Study) I and II, and HPFS (Health Professionals Follow-up Study) cohorts to quantify the association between the relative supersaturation of calcium oxalate, calcium phosphate and uric acid, and the likelihood of stone formation. The OR of being a stone former was 5.85 (95% CI 3.40-10.04) in NHS I, 6.38 (95% CI 3.72-11.0) in NHS II and 6.95 (95% CI 3.56-13.6) in HPFS for the highest category of calcium oxalate relative supersaturation compared with less than 1.0. The OR of being a stone former was 1.86 (95% CI 0.94-3.71) in NHS I, 4.37 (95% CI 2.68-7.10) in NHS II and 3.59 (95% CI 2.04-6.31) in HPFS for the highest category of calcium phosphate relative supersaturation compared with less than 1.0. For uric acid relative supersaturation the OR of being a stone former was 4.30 (95% CI 2.34-7.90) in NHS I and 2.74 (95% CI 1.71-4.40) in NHS II for the highest relative supersaturation category compared with less than 1.0. In HPFS the uric acid relative supersaturation was not significantly associated with the likelihood of stone formation. The likelihood of being a stone former increases with higher relative supersaturation of calcium oxalate and calcium phosphate in men and women, and with higher relative supersaturation of uric acid in women.

Dietary interventions for preventing complications in idiopathic hypercalciuria.

Idiopathic hypercalciuria is an inherited metabolic abnormality that is characterised by excessive amounts of calcium excreted in the urine by people whose calcium serum levels are normal. Morbidity associated with idiopathic hypercalciuria is chiefly related to kidney stone disease and bone demineralisation leading to osteopenia and osteoporosis. Idiopathic hypercalciuria contributes to kidney stone disease at all life stages; people with the condition are prone to developing oxalate and calcium phosphate kidney stones. In some cases, crystallised calcium can be deposited in the renal interstitium, causing increased calcium levels in the kidneys. In children, idiopathic hypercalciuria can cause a range of comorbidities including recurrent macroscopic or microscopic haematuria, frequency dysuria syndrome, urinary tract infections and abdominal and lumbar pain. Various dietary interventions have been described that aim to decrease urinary calcium levels or urinary crystallisation. Our objectives were to assess the efficacy, effectiveness and safety of dietary interventions for preventing complications in idiopathic hypercalciuria (urolithiasis and osteopenia) in adults and children, and to assess the benefits of dietary interventions in decreasing urological symptomatology in children with idiopathic hypercalciuria. We searched the Cochrane Renal Group's Specialised Register (23 April 2013) through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE. We included all randomised controlled trials (RCTs) and quasi-RCTs that investigated dietary interventions aimed at preventing complications of idiopathic hypercalciuria, compared with placebo, no intervention, or other dietary interventions regardless of route of administration, dose or amount. Studies were assessed for inclusion and data extracted using a standardised data extraction form. We calculated risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, both with 95% confidence intervals (CI). We included five studies (379 adult participants) that investigated a range of interventions. Lack of similarity among interventions investigated meant that data could not be pooled. Overall, study methodology was not adequately reported in any of the included studies. There was a high risk of bias associated with blinding (although it seems unlikely that outcomes measures were unduly influenced by lack of intervention blinding), random sequence generation and allocation methodologies were unclear in most studies, but selective reporting bias was assessed as low.One study (120 participants) compared a low calcium diet with a normal calcium, low protein, low salt diet for five years. There was a significant decrease in numbers of new stone recurrences in those treated with the normal calcium, low protein, low salt diet (RR 0.77, 95% CI 0.61 to 0.98). This diet also led to a significant decrease in oxaluria (MD 78.00 µmol/d, 95% CI 26.48 to 129.52) and the calcium oxalate relative supersaturation index (MD 1.20 95% CI 0.21 to 2.19).One study (210 participants) compared a low salt, normal calcium diet with a broad diet for three months. The low salt, normal calcium diet decreased urinary calcium (MD -45.00 mg/d, 95% CI -74.83 to -15.17) and oxalate excretion (MD -4.00 mg/d, 95% CI -6.44 to -1.56).A small study (17 participants) compared the effect of dietary fibre as part of a low calcium, low oxalate diet over three weeks, and found that although calciuria levels decreased, oxaluria increased. Phyllanthus niruri plant substrate intake was investigated in a small subgroup with hypercalciuria (20 participants); there was no significant effect on calciuria levels occurred after three months of treatment.A small cross-over study (12 participants) evaluating the changes in urinary supersaturation indices among patients who consumed calcium-fortified orange juice or milk for one month found no benefits for participants.None of the studies reported any significant adverse effects associated with the interventions. Long-term adherence (five years) to diets that feature normal levels of calcium, low protein and low salt may reduce numbers of stone recurrences, decrease oxaluria and calcium oxalate relative supersaturation indexes in people with idiopathic hypercalciuria who experience recurrent kidney stones. Adherence to a low salt, normal calcium level diet for some months can reduce calciuria and oxaluria. However, the other dietary interventions examined did not demonstrate evidence of significant beneficial effects.No studies were found investigating the effect of dietary recommendations on other clinical complications or asymptomatic idiopathic hypercalciuria.

Dietary hyperoxaluria is not reduced by treatment with lactic acid bacteria

BackgroundSecondary 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.MethodsTwenty 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.ResultsUrinary 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.ConclusionsPersistent 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.

Determinants of Urolithiasis in Patients With Intestinal Fat Malabsorption

To investigate the determinants of urinary stone formation in patients with fat malabsorption, because, although the prevalence of urolithiasis is greater in patients with intestinal diseases, the pathogenetic mechanisms and risk factors associated with urolithiasis in this population remain partially unsolved. The present study retrospectively analyzed the determinants of urolithiasis in 51 patients with fat malabsorption due to different intestinal diseases. Anthropometric, clinical, blood, 24-hour urinary parameters, and dietary intake were assessed. The resection rate (ie, pancreatic and/or bowel resection) differed significantly between stone formers (SF; n=10) and nonstone formers (NSF; n=41; 70% vs 29%; P=.027). Urinary citrate was lower (1.606±1.824 vs 3.156±1.968 mmol/24 h; P=.027), while oxalate excretion (0.659±0.292 vs 0.378±0.168 mmol/24 h; P=.002) and the relative supersaturation of calcium oxalate were greater in SF than NSF (8.16±4.61 vs 3.94±2.93; P=.003). Total cholesterol and low-density lipoprotein cholesterol, but also high-density lipoprotein cholesterol, plasma β-carotene, and vitamin E concentrations, were significantly diminished, whereas serum aspartate aminotransferase activity was significantly greater in SF compared with NSF. Binary logistic regression analysis revealed resection status as a major extrarenal risk factor for stone formation (odds ratio 5.639). Increased urinary oxalate and decreased citrate excretion, probably resulting from pancreatic and/or bowel resection with mainly preserved colon, were identified as the most crucial urinary risk factors for stone formation in patients with fat malabsorption. The findings suggest that hyperoxaluria predominantly results from increased colonic permeability for oxalate due to disturbed bile acid metabolism. The impaired status of fat-soluble antioxidants β-carotene and vitamin E indicates severe malabsorptive states associated with an enhanced stone-forming propensity.

Hyperoxaluria Is a Long-Term Consequence of Roux-en-Y Gastric Bypass: A 2-Year Prospective Longitudinal Study

Recent studies suggest that patients undergoing Roux-en-Y gastric bypass (RYGB) for morbid obesity are at risk for hyperoxaluria, nephrolithiasis, and oxalate nephropathy. Our objective was to conduct a long-term prospective longitudinal study to establish the incidence, clinical progression, and severity of hyperoxaluria after RYGB. Patients undergoing RYGB between December 2005 and April 2007 provided 24-hour urine collections for comprehensive stone risk analysis 1 week before and 3 months and 1 and 2 years after surgery. Primary outcomes were changes in 24-hour urinary oxalate excretion and relative supersaturation of calcium oxalate from baseline to 2 years post-RYGB. The cohort consisted of 21 patients, including 5 (24%) men and 16 (76%) women. Mean preoperative age and body mass index (calculated as kg/m(2)) were 48.2 +/- 10.5 years (range 25 to 64 years) and 50.5 +/- 9.1 (range 39.7 to 66.6), respectively. Urinary oxalate excretion increased significantly after RYGB (33 +/- 9 mg/day versus 63 +/- 29 mg/day; p <or= 0.001). De novo hyperoxaluria developed in 11 (52%) patients. Increasing age at the time of surgery was predictive of de novo hyperoxaluria developing (odds ratio = 1.162; 95% CI, 1.002-1.347; p = 0.046). The percentage of patients with hypocitraturia increased from 10% at baseline to 48% at 2 years. The relative supersaturation of calcium oxalate was unchanged (1.73 +/- 0.67 versus 2.20 +/- 2.07; p = 0.27). RYGB is associated with a long-term increase in urinary oxalate excretion and decrease in urinary citrate excretion. Although calcium oxalate relative supersaturation increases early in the postoperative period, this returns to baseline with long-term follow-up. These data suggest that patients who have undergone RYGB are at risk for oxalate nephropathy developing.

1312 HYPEROXALURIA IS A LONG-TERM CONSEQUENCE OF ROUX-EN-Y GASTRIC BYPASS: A TWO-YEAR PROSPECTIVE LONGITUDINAL STUDY

BACKGROUND: Recent studies suggest that patients undergoing Roux-en-Y gastric bypass (RYGB) for morbid obesity are at risk for hyperoxaluria, nephrolithiasis, and oxalate nephropathy. Our objective was to conduct a long-term prospective longitudinal study to establish the incidence, clinical progression, and severity of hyperoxaluria after RYGB. STUDY DESIGN: Patients undergoing RYGB between December 2005 and April 2007 provided 24-hour urine collections for comprehensive stone risk analysis 1 week before and 3 months and 1 and 2 years after surgery. Primary outcomes were changes in 24-hour urinary oxalate excretion and relative supersaturation of calcium oxalate from baseline to 2 years post-RYGB. RESULTS: The cohort consisted of 21 patients, including 5 (24%) men and 16 (76%) women. Mean preoperative age and body mass index (calculated as kg/m 2 ) were 48.2 10.5 years (range 25 to 64 years) and 50.5 9.1 (range 39.7 to 66.6), respectively. Urinary oxalate excretion increased significantly after RYGB (33 9 mg/day versus 63 29 mg/day; p 0.001). De novo hyperoxaluria developed in 11 (52%) patients. Increasing age at the time of surgery was predictive of de novo hyperoxaluria developing (odds ratio 1.162; 95% CI, 1.002–1.347; p 0.046). The percentage of patients with hypocitraturia increased from 10% at baseline to 48% at 2 years. The relative supersaturation of calcium oxalate was unchanged (1.73 0.67 versus 2.20 2.07; p 0.27). CONCLUSIONS: RYGB is associated with a long-term increase in urinary oxalate excretion and decrease in urinarycitrateexcretion.Althoughcalciumoxalaterelativesupersaturationincreasesearlyinthe

Risk of renal stone formation induced by long‐term bed rest could be decreased by premedication with bisphosphonate and increased by resistive exercise

To clarify the influence of long-term bed rest on renal stone formation and to analyze the mechanism of bed-rest-induced stone formation and prevention by bisphosphonate and bed-rest exercise. Twenty-five men aged 26-48 years and divided into control (CON: n = 9), exercise (EX: n = 9), and pamidronate (PMD: n = 7) groups, rested on a 6 degrees head-down tilt bed for 90 days. The exercise group carried out resistive exercise every 3 days. Pamidronate (60 mg) was intravenously given 2 weeks before the initiation of bed rest. Abdominal X-ray examination and urine biochemistry were carried out during 90 days of bed rest and 90 days of reloading. Renal stone formation was observed in two (22.2%) and four (44.4%) subjects in the control and exercise groups, respectively. No stone was seen in the pamidronate group. In the exercise group, urinary oxalate and phosphate excretion were significantly higher than in the control group. In the pamidronate group, urinary calcium excretion and relative supersaturation of calcium oxalate and brushite were lower than in the control group throughout the bed-rest and recovery period. Long-term bed-rest-induced renal stone formation was found to be induced by increased urinary calcium and subsequent crystal formation of calcium oxalate and calcium phosphate. Exercise during bed rest for the prevention of bone mineral loss and contracture might increase the risk of renal stone formation. Pamidronate is useful for the prevention of renal stone formation during and after bed rest.

Roux-en-Y Gastric Bypass is Associated with Early Increased Risk Factors for Development of Calcium Oxalate Nephrolithiasis

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. 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. 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. 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.

Renal response to lithogenic and anti-lithogenic supplement challenges in a stone-free population group

Objective In South Africa, urolithiasis is extremely rare in the black population, but is common in the white population. The objective of this study was to investigate the individual effects of 5 different dietary and supplemental challenges (high dietary calcium, calcium supplement, vitamin B6 supplement, L-glutamine supplement, and L-cysteine supplement) on the urinary risk factors for calcium oxalate urolithiasis in subjects from both race groups. Design Complete Latin Square design. Setting University research laboratory. Subjects Subjects were recruited from the student cohort of the University of Cape Town (10 male subjects from each race group). Selection criteria were no history of renal or metabolic diseases, and no chronic or acute medication. Subjects served as their own controls. Intervention After 7 days on a self-selected standardized diet, a 24-hour baseline urine sample was collected. A second 24-hour urine sample was collected after 5 days on the prescribed dietary or supplemental challenge. These were analyzed for biochemical and physicochemical risk factors. Additionally, 24-hour dietary recall questionnaires were recorded at baseline and after the 5-day test period, and were analyzed using a food analysis program. Statistical analysis of variance was performed on all of the data. Main outcome measures Urine composition, relative supersaturation of urinary salts, calcium oxalate metastable limit, and Tiselius risk index. Results None of the protocols altered any of the urinary biochemical or physicochemical risk factors in black subjects. In white subjects, the calcium diet significantly increased urinary potassium ( P = .0001) and decreased the relative supersaturation of brushite ( P = .035); the calcium supplement significantly decreased the Tiselius risk index ( P = .014); vitamin B6 supplement significantly decreased urinary calcium ( P = .016), urinary phosphate ( P = .027), and the relative supersaturation of brushite ( P = .004); L-glutamine supplement significantly decreased relative supersaturation of calcium oxalate ( P = .01); L-cystine supplement significantly decreased urinary calcium ( P = .031) and the Tiselius risk index ( P = .013). Conclusions Because none of the challenges had an effect on the urinary risk factors in black subjects, it is speculated that a renal or gastrointestinal homeostatic adjustment occurs in this group, thereby keeping urinary concentration of substances in balance.

The relative effects of supplemental dietary calcium and oxalate on urine composition and calcium oxalate relative supersaturation in healthy adult dogs

The aim of this study was to establish the relative effects of dietary calcium and oxalate (in the form of oxalic acid) on the composition of urine produced by healthy adult Cairn Terriers and Miniature Schnauzers. A nutritionally complete dry dog food was fed to 7 dogs (4 Cairn terriers and 3 Miniature schnauzers) for 24 weeks. The dogs were fed the diet alone, or supplemented with six different combinations of dietary calcium (as carbonate and sulphate) and oxalate (as oxalic acid) commonly found in dry commercially prepared dog foods. Urine pH, volume, specific gravity, and concentrations of 12 analytes were measured for each dog; urinary relative supersaturation (RSS) with calcium oxalate (CaOx) was calculated from these values. The effects of supplemental calcium and oxalate were established using two-way analysis of variance and multiple range tests (least significant difference); P<0.05 was considered significant. The lowest level of dietary calcium and oxalate resulted in the lowest CaOx RSS. The high calcium, low oxalate diet resulted in the highest CaOx RSS, a low calcium diet with increased dietary oxalate also tended to increase CaOx RSS although results were highly variable. Urinary calcium concentration increased significantly with dietary calcium; urinary oxalate increased, although inconsistently, with dietary oxalic acid only when dietary calcium was low. Measures to reduce both calcium and oxalate should be considered when implementing dietary changes to reduce the risk of calcium oxalate formation in dogs. A reduction in dietary calcium without a concomitant decrease in dietary oxalate may increase the risk of CaOx crystallisation in susceptible dogs.

Effect of dietary moisture and sodium content on urine composition and calcium oxalate relative supersaturation in healthy miniature schnauzers and labrador retrievers

The aim of this series of studies was to evaluate two possible feeding strategies as methods for reducing the risk of calcium oxalate (CaOx) formation in two breeds of healthy dog. The studies compared the effect of dietary moisture (Study 1) and dietary sodium (Na), (Study 2) on urine composition of labrador retrievers (LR) and miniature schnauzers (MS). A nutritionally complete dry dog food was fed to 16 dogs (eight LR, eight MS; Study 1) and 15 dogs (seven LR, eight MS; Study 2) for 24 days (Study 1), or 36 days (Study 2). The dogs were fed the diet alone (7% moisture, 0.06 g Na/100 kcal), or supplemented with deionised water to 73% moisture (Study 1), or dietary Na, to deliver 0.20 or 0.30 g Na per 100 kcal (Study 2). Urine pH, volume, specific gravity, and concentrations of 12 analytes were measured for each dog. Urinary relative supersaturations (RSS) with CaOx were calculated from these values. The effects of supplemental Na or water were established using t tests (Study 1) or analysis of variance, and multiple range tests (least significant difference) (Study 2); P<0.05 was considered significant. Increasing dietary moisture significantly increased total moisture intake ( P=0.001), and reduced urine specific gravity ( P=0.003), urinary oxalate concentration ( P=0.04), and CaOx relative supersaturation ( P=0.04) in the MS. Urinary parameters remained unchanged in the LR, indicating that feeding a high moisture diet may reduce the risk of CaOx formation in high-risk breeds. Increasing dietary Na led to production of urine with a significantly lower CaOx RSS in both breeds, indicating that sodium supplementation to dry diet formats may reduce the risk of CaOx formation. These feeding strategies should be considered when evaluating methods for preventing CaOx formation within high-risk groups.

Citric acid or citrates in urine: which should we focus on in the prevention of calcium oxalate crystals and stones?

In order to distinguish between normocitraturia and hypocitraturia, the 24 h urine excretion value of citric acid is evaluated in relation to the established limit value of 2.5 mmol/day. We propose changing this widely-used excretion value to a "minimum contribution" of citric acid to the total urine's ionic strength, since the inhibitory effect of citric acid on crystallization depends on citrate anions being available to complex calcium ions or to associate with the crystal surface. A total of 71424 h-urine samples, taken from 74 healthy persons and 58 calcium stone formers, were investigated for pH, citric acid concentration ([CA]), and related relative calcium oxalate supersaturation (RS). Based on the Henderson-Hasselbalch-equation, the individual concentrations of the differently charged citrate anion species in each of the urines were calculated from the urinary pH and [CA]. From the anion concentrations determined, the contribution of the urine's citric acid to the total urine's ionic strength, ISCA, was calculated. Referring to the limit value of 2.5 mmol/day and assuming an average urine volume of 1.5 l/day, a hypothetical concentration limit of 1.67 mmol/l can be obtained. Grouping the samples into "stone-formers" and "non-stone-formers" as well as into three different ranges of RS revealed: (1). that the groups' median [CA]-values were below 1.67 mmol/l, and (2). that [CA] was not inversely associated with the risk of stone formation. Within the pH-range of 5 and 7, the ISCA-values which are related to, for example, [CA]=1.67 mmol/l, vary considerably by a factor of nearly three between 2.48 mmol/l and 6.64 mmol/l. The use of a fixed citric acid excretion level for the distinction of normocitraturia from hypocitraturia does not take into account the different citrate species which actually modify the urine's crystallization behaviour. The proposed ISCA approach takes this fact into consideration. From this parameter, a desirable "minimum impact of citric acid" can be derived. In a first approach, a potential ISCA-limit value, which currently distinguishes between urines indicated by a "normo-protective" impact and those indicated by a "hypo-protective" impact with respect to calcium oxalate precipitation, may be set at 2.48 mmol/l.

METABOLIC RISK FACTORS FOR STONE FORMATION IN PATIENTS WITH CYSTIC FIBROSIS

Cystic fibrosis is characterized by chronic pulmonary disease, insufficient pancreatic and digestive function, and abnormal sweat concentrations. Patients with cystic fibrosis also have an increased incidence of nephrolithiasis. We compared the results of metabolic evaluation in patients with cystic fibrosis with and without nephrolithiasis. A total of 496 patients were evaluated at our center, including 98 with a mean age of 25 years who had cystic fibrosis and complete metabolic evaluation available between 1996 and 2000. Of these patients 13 (13%) had a history of nephrolithiasis. The records were reviewed for clinical characteristics and all patients underwent metabolic evaluation, including serum electrolyte measurement and 24-hour urine collection. Statistical analysis was done to compare the stone versus nonstone groups. The incidence of nephrolithiasis in our study was 3%. We identified 13 patients 16 to 41 years old (mean age 27) with nephrolithiasis, of whom 62% had had multiple episodes. Flank pain was the presenting symptom in 9 of the 13 cases (69%). Renal ultrasound and computerized tomography were the most common imaging modalities. In 9 cases stones were passed without intervention, extracorporeal shock wave lithotripsy was required in 2 and ureteroscopy with stone extraction was done in 2. Calcium oxalate was the dominant stone composition in the 9 patients in whom stone analysis was performed. Metabolic evaluation of the stone versus no stone groups showed elevated urinary oxalate (45.5 versus 42.5 mg./24 hours), relative calcium oxalate supersaturation (5.3 versus 7.2) and decreased urinary citrate in the 2 groups. There was a statistical difference in citrate excretion with lower levels in stone formers (102 versus 218 mg./24 hours, p = 0.0007). Patients with cystic fibrosis have an increased incidence of nephrolithiasis and are at high risk for recurrence. Metabolic evaluation is indicated in all patients with cystic fibrosis and urolithiasis since most have hyperoxaluria, urinary calcium oxalate supersaturation and decreased urinary citrate. Correcting detected stone risk factors in these cases may decrease stone recurrence.

Metabolic risk factors for stone formation in patients with cystic fibrosis.

Cystic fibrosis is characterized by chronic pulmonary disease, insufficient pancreatic and digestive function, and abnormal sweat concentrations. Patients with cystic fibrosis also have an increased incidence of nephrolithiasis. We compared the results of metabolic evaluation in patients with cystic fibrosis with and without nephrolithiasis. A total of 496 patients were evaluated at our center, including 98 with a mean age of 25 years who had cystic fibrosis and complete metabolic evaluation available between 1996 and 2000. Of these patients 13 (13%) had a history of nephrolithiasis. The records were reviewed for clinical characteristics and all patients underwent metabolic evaluation, including serum electrolyte measurement and 24-hour urine collection. Statistical analysis was done to compare the stone versus nonstone groups. The incidence of nephrolithiasis in our study was 3%. We identified 13 patients 16 to 41 years old (mean age 27) with nephrolithiasis, of whom 62% had had multiple episodes. Flank pain was the presenting symptom in 9 of the 13 cases (69%). Renal ultrasound and computerized tomography were the most common imaging modalities. In 9 cases stones were passed without intervention, extracorporeal shock wave lithotripsy was required in 2 and ureteroscopy with stone extraction was done in 2. Calcium oxalate was the dominant stone composition in the 9 patients in whom stone analysis was performed. Metabolic evaluation of the stone versus no stone groups showed elevated urinary oxalate (45.5 versus 42.5 mg./24 hours), relative calcium oxalate supersaturation (5.3 versus 7.2) and decreased urinary citrate in the 2 groups. There was a statistical difference in citrate excretion with lower levels in stone formers (102 versus 218 mg./24 hours, p = 0.0007). Patients with cystic fibrosis have an increased incidence of nephrolithiasis and are at high risk for recurrence. Metabolic evaluation is indicated in all patients with cystic fibrosis and urolithiasis since most have hyperoxaluria, urinary calcium oxalate supersaturation and decreased urinary citrate. Correcting detected stone risk factors in these cases may decrease stone recurrence.