24-hour Urinary Oxalate Excretion Research Articles

Glycolate oxidase inhibition by lumasiran varies between patients with primary hyperoxaluria type 1

Glycolate oxidase inhibition by lumasiran varies between patients with primary hyperoxaluria type 1

Safety, pharmacodynamics, and exposure-response modeling results from a first-in-human phase 1 study of nedosiran (PHYOX1) in primary hyperoxaluria

Primary hyperoxaluria (PH) is a family of ultra-rare autosomal recessive inherited disorders of hepatic glyoxylate metabolism characterized by oxalate overproduction. Nedosiran is an RNA interference agent that inhibits hepatic lactate dehydrogenase, the enzyme responsible for the common, final step of oxalate production in all three genetic subtypes of PH. Here, we assessed in a two-part, randomized, single-ascending-dose, phase 1 study (PHYOX1) the safety, pharmacokinetics, pharmacodynamics, and exposure-response of subcutaneous nedosiran in 25 healthy participants (Group A) and 18 patients with PH1 or PH2 (Group B). Group A received nedosiran (0.3, 1.5, 3.0, 6.0, then 12.0 mg/kg) or placebo, and Group B received open-label nedosiran (1.5, 3.0, or 6.0 mg/kg). No significant safety concerns were identified. Injection site reactions (four or more hours post dose) occurred in 13.3% of participants in Group A and 27.8% of participants in Group B. Mean maximum reduction in 24-hour urinary oxalate excretion from baseline to day 57 (end of study) across Group B dose cohorts was 55% (range: 22%-100%) after single-dose nedosiran, with 33% participants reaching normal 24-hour urinary oxalate excretion. Based on the available modeling and simulation data, a fixed monthly dose of nedosiran 160 mg (free acid; equivalent to 170 mg sodium salt) in adults was associated with the highest proportion of simulated individuals achieving normal or near-normal 24-hour urinary oxalate excretion and fewest fluctuations in urinary oxalate response. Thus, single-dose nedosiran demonstrated acceptable safety and evidence of a pharmacodynamic effect in both PH1 and PH2 subpopulations consistent with its mechanism of action.

Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria Type 1

BackgroundPrimary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate that leads to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. Lumasiran, an investigational RNA interference (RNAi) therapeutic agent, reduces hepatic oxalate production by targeting glycolate oxidase.MethodsIn this double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with PH1 who were 6 years of age or older to receive subcutaneous lumasiran or placebo for 6 months (with doses given at baseline and at months 1, 2, 3, and 6). The primary end point was the percent change in 24-hour urinary oxalate excretion from baseline to month 6 (mean percent change across months 3 through 6). Secondary end points included the percent change in the plasma oxalate level from baseline to month 6 (mean percent change across months 3 through 6) and the percentage of patients with 24-hour urinary oxalate excretion no higher than 1.5 times the upper limit of the normal range at month 6.ResultsA total of 39 patients underwent randomization; 26 were assigned to the lumasiran group and 13 to the placebo group. The least-squares mean difference in the change in 24-hour urinary oxalate excretion (lumasiran minus placebo) was −53.5 percentage points (P<0.001), with a reduction in the lumasiran group of 65.4% and an effect seen as early as month 1. The between-group differences for all hierarchically tested secondary end points were significant. The difference in the percent change in the plasma oxalate level (lumasiran minus placebo) was −39.5 percentage points (P<0.001). In the lumasiran group, 84% of patients had 24-hour urinary oxalate excretion no higher than 1.5 times the upper limit of the normal range at month 6, as compared with 0% in the placebo group (P<0.001). Mild, transient injection-site reactions were reported in 38% of lumasiran-treated patients.ConclusionsLumasiran reduced urinary oxalate excretion, the cause of progressive kidney failure in PH1. The majority of patients who received lumasiran had normal or near-normal levels after 6 months of treatment. (Funded by Alnylam Pharmaceuticals; ILLUMINATE-A ClinicalTrials.gov number, NCT03681184.)

Association of Urinary Oxalate Excretion With the Risk of Chronic Kidney Disease Progression

Oxalate is a potentially toxic terminal metabolite that is eliminated primarily by the kidneys. Oxalate nephropathy is a well-known complication of rare genetic disorders and enteric hyperoxaluria, but oxalate has not been investigated as a potential contributor to more common forms of chronic kidney disease (CKD). To assess whether urinary oxalate excretion is a risk factor for more rapid progression of CKD toward kidney failure. This prospective cohort study assessed 3123 participants with stages 2 to 4 CKD who enrolled in the Chronic Renal Insufficiency Cohort study from June 1, 2003, to September 30, 2008. Data analysis was performed from October 24, 2017, to June 17, 2018. Twenty-four-hour urinary oxalate excretion. A 50% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease (ESRD). This study included 3123 participants (mean [SD] age, 59.1 [10.6] years; 1414 [45.3%] female; 1423 [45.6%] white). Mean (SD) eGFR at the time of 24-hour urine collection was 42.9 (16.8) mL/min/1.73 m2. Median urinary excretion of oxalate was 18.6 mg/24 hours (interquartile range [IQR], 12.9-25.7 mg/24 hours) and was correlated inversely with eGFR (r = -0.13, P < .001) and positively with 24-hour proteinuria (r = 0.22, P < .001). During 22 318 person-years of follow-up, 752 individuals reached ESRD, and 940 individuals reached the composite end point of ESRD or 50% decline in eGFR (CKD progression). Higher oxalate excretion was independently associated with greater risks of both CKD progression and ESRD: compared with quintile 1 (oxalate excretion, <11.5 mg/24 hours) those in quintile 5 (oxalate excretion, ≥27.8 mg/24 hours) had a 33% higher risk of CKD progression (hazard ratio [HR], 1.33; 95% CI, 1.04-1.70) and a 45% higher risk of ESRD (HR, 1.45; 95% CI, 1.09-1.93). The association between oxalate excretion and CKD progression and ESRD was nonlinear and exhibited a threshold effect at quintiles 3 to 5 vs quintiles 1 and 2. Higher vs lower oxalate excretion (at the 40th percentile) was associated with a 32% higher risk of CKD progression (HR, 1.32; 95% CI, 1.13-1.53) and 37% higher risk of ESRD (HR, 1.37; 95% CI, 1.15-1.63). Results were similar when treating death as a competing event. Higher 24-hour urinary oxalate excretion may be a risk factor for CKD progression and ESRD in individuals with CKD stages 2 to 4.

Secondary Oxalate Nephropathy: A Systematic Review

IntroductionLittle is known of the clinical outcomes of secondary oxalate nephropathy. To inform clinical practice, we performed a systematic review of case reports and case series to examine the clinical characteristics and outcomes of patients with secondary oxalate nephropathy.MethodsElectronic databases were searched for case reports and case series of individual cases or cohorts of patients with biopsy-proven oxalate nephropathy in native or transplanted kidneys from 1950 until January 2018.ResultsFifty-seven case reports and 10 case series met the inclusion criteria, totaling 108 patients. The case series were meta-analyzed. Mean age was 56.4 years old, 59% were men, and 15% were kidney transplant recipients. Fat malabsorption (88%) was the most commonly attributed cause of oxalate nephropathy, followed by excessive dietary oxalate consumption (20%). The mean baseline serum creatinine was 1.3 mg/dl and peaked at 4.6 mg/dl. Proteinuria, hematuria, and urinary crystals was reported in 69%, 32%, and 26% of patients, respectively. Mean 24-hour urinary oxalate excretion was 85.4 mg/d. In addition to universal oxalate crystal deposition in tubules and/or interstitium, kidney biopsy findings included acute tubular injury (71%), tubular damage and atrophy (69%), and interstitial mononuclear cell infiltration (72%); 55% of patients required dialysis. None had complete recovery, 42% had partial recovery, and 58% remained dialysis-dependent. Thirty-three percent of patients died.ConclusionSecondary oxalate nephropathy is a rare but potentially devastating condition. Renal replacement therapy is required in >50% of patients, and most patients remain dialysis-dependent. Studies are needed for effective preventive and treatment strategies in high-risk patients with hyperoxaluria-enabling conditions.

A Double-Blind, Placebo Controlled, Randomized Phase 1 Cross-Over Study with ALLN-177, an Orally Administered Oxalate Degrading Enzyme

Background: Hyperoxaluria may result from increased endogenous production or overabsorption of dietary oxalate in the gastrointestinal tract leading to nephrolithiasis and, in some, to oxalate nephropathy and chronic kidney disease. ALLN-177 is an oral formulation of a recombinant, oxalate specific, microbial enzyme oxalate decarboxylase intended to treat secondary hyperoxaluria by degrading dietary oxalate in the gastrointestinal tract, thereby reducing its absorption and subsequent excretion in the urine. Methods: This double-blind, placebo controlled, randomized, cross-over, phase 1 study of ALLN-177 evaluated the tolerability of ALLN-177 and its effect on urinary oxalate excretion in 30 healthy volunteers with hyperoxaluria induced by ingestion of a high oxalate, low calcium (HOLC) diet. The primary end point was the difference in the mean 24-hour urinary oxalate excretion during the ALLN-177 treatment period compared with the placebo treatment period. Results: The daily urinary oxalate excretion increased in the study population from 27.2 ± 9.5 mg/day during screening to 80.8 ± 24.1 mg/day (mean ± SD) on the HOLC diet before introducing ALLN-177 or placebo therapy for 7 days. Compared to placebo, ALLN-177 treatment reduced urinary oxalate by 11.6 ± 2.7 mg/day, p = 0.0002 (least squares mean ± SD). Conclusions: In healthy volunteers, with diet-induced hyperoxaluria treatment with ALLN-177, when compared to placebo, significantly reduced urinary oxalate excretion by degrading dietary oxalate in the gastrointestinal tract and thereby reducing its absorption. ALLN-177 may represent a new approach for managing secondary hyperoxaluria and its complications.

Therapeutic effect of inulin on enteric hyperoxaluria in rats.

To observe the therapeutic effect of inulin on enteric hyperoxaluria in rats. In experimental A, 24 healthy male Sprague-Dawley rats received an oxalate-free diet on day 1, a high-oxalate diet (oxalate, 74.82 mg/100 g feed stuffs) on days 2 and 3, and plus 2 g inulin to each rat on day 3. The 24-hour urinary volume, concentrations of urinary oxalate and urine creatinine were measured, and 24-hour urinary oxalate excretion was calculated. In experimental B, 24 healthy male Sprague-Dawley rats were equally randomized into control group and inulin group, Each rat received a high oxalate diet (oxalate, 74.82 mg/100 g feedstuffs), and plus 2 g inulin in inulin group. The 24-hour urinary oxalate excretion was calculated in both two groups. In experimental A, the 24-hour urinary oxalate excretion varied with time (F=11.481, P=0.035). The 24-hour urinary oxalate excretion significantly increased on day 2 compared with that on day 1 (P=0.026) and day 3 (P=0.037); it significantly increased on day 3 compared with day 1 (P=0.004). In experimental B, the 24-hour urinary oxalate excretion significantly decreased in inulin group compared with the control (P=0.011). Inulin may have potential therapeutic effect on enteric hyperoxaluria in rats.

Sodium Restriction as Initial Conservative Treatment for Urinary Stone Disease

Sodium restriction is widely recommended to prevent urinary stone recurrence. However, the effect of urinary sodium excretion has not been fully evaluated. We investigated the relationship between urinary sodium, urinary metabolite excretion and the risk of recurrence in urinary stone formers. Selected for study were 798 stone formers with no evidence of metabolic disorders as the cause of abnormal urinary solutes. We analyzed the relationship between urinary sodium and other metabolic parameters by gender. Values were adjusted by covariates according to correlation status. Patients were divided into stone formers with hypernatriuresis or normal natriuresis (less than 220 mEq daily) and urinary parameters were compared. Kaplan-Meier analysis was done to determine the cumulative incidence of recurrent stones by urinary sodium. Patients were considered recurrence-free at a minimum followup of 3 years without incidence. In the 492 men and 306 women mean ± SD age was 40.0 ± 11.4 and 45.4 ± 12.7 years, and mean body mass index was 23.9 ± 3.1 and 23.0 ± 3.0 kg/m(2), respectively. Using covariate adjusted partial correlation coefficients urinary sodium was noted to influence volume, pH, calcium, uric acid, oxalate and citrate in men, and volume, pH, calcium, uric acid and citrate in women (each p <0.05). At a median followup of 56.1 months 46 of 98 stone formers (46.9%) with normal natriuresis experienced stone recurrence vs 60 of 93 (64.5%) with hypernatriuresis. Patients with hypernatriuresis also had significantly decreased time to recurrence than those with normal natriuresis (log rank test p = 0.043). Results show that urinary sodium is an important determinant of other stone forming parameters and of the risk of recurrent stones. These findings suggest that a sodium restricted diet should be the initial step when treating stone formers.

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.

Diabetic Kidney Stone Formers Excrete More Oxalate and Have Lower Urine pH Than Nondiabetic Stone Formers

The epidemiological relationship between nephrolithiasis and type 2 diabetes mellitus is well-known. Patients with diabetes mellitus are at increased risk for nephrolithiasis and those with nephrolithiasis are at risk for diabetes mellitus. We examined 24-hour urine composition in stone formers with and without diabetes mellitus. We retrospectively reviewed a database of 462 stone forming patients to examine the relationship between hypertension and 24-hour urine composition. Multivariate linear regression models were adjusted for age, race, gender, body mass index, hypertension, relevant medications and 24-hour urine constituents. On univariate analysis diabetic patients had significantly greater urine volume than nondiabetic patients (2.5 vs 2.1 l daily, p = 0.004). Those with diabetes mellitus also excreted less daily potassium (61.1 vs 68.8 mEq, p = 0.04), phosphate (0.84 vs 1.0 gm, p = 0.002) and creatinine (1405.5 vs 1562.8 mg, p = 0.03), and had significantly lower daily urine pH (5.78 vs 6.09, p <0.001) and CaP supersaturation (0.49 vs 1.20, p <0.001) than nondiabetic patients. On multivariate analysis compared to patients without diabetes mellitus those with type II diabetes mellitus had significantly lower urine pH (-0.34, 95% CI -0.48 to -0.21) and significantly greater urine oxalate (6.43 mg daily, 95% CI 1.26 to 11.60) and volume (0.38 l daily, 95% CI 0.13 to 0.64). Results show that of stone formers patients with type II diabetes mellitus excrete significantly greater urinary oxalate and significantly lower urine pH than those without diabetes mellitus. These findings are important for treating nephrolithiasis since they may influence dietary counseling, medical management and stone prevention.

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

Determinants of 24-hour Urinary Oxalate Excretion

Higher levels of urinary oxalate substantially increase the risk of calcium oxalate kidney stones. However, the determinants of urinary oxalate excretion are unclear. The objective was to examine the impact of dietary factors, age, body size, diabetes, and urinary factors on 24-h urinary oxalate. We conducted a cross-sectional study of 3348 stone forming and non-stone-forming participants in the Health Professionals Follow-up Study (men), the Nurses' Health Study (older women), and the Nurses' Health Study II (younger women). Median urinary oxalate was 39 mg/d in men, 27 mg/d in older women, and 26 mg/d in younger women. Participants in the highest quartile of dietary oxalate excreted 1.7 mg/d more urinary oxalate than participants in the lowest quartile (P trend 0.001). The relation between dietary and urinary oxalate was similar in individuals with and without nephrolithiasis. Participants consuming 1000 mg/d or more of vitamin C excreted 6.8 mg/d more urinary oxalate than participants consuming <90 mg/d (P trend < 0.001). Body mass index, total fructose intake, and 24-h urinary potassium, magnesium, and phosphorus levels also were positively associated with urinary oxalate. Calcium intake and age were inversely associated with urinary oxalate. After adjustment for body size, participants with diabetes excreted 2.0 mg/d more urinary oxalate than those without diabetes (P < 0.01). The impact of dietary oxalate on urinary oxalate appears to be small. Further investigation of factors influencing urinary oxalate may lead to new approaches to prevent calcium kidney stones.

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.

Reduction of oxaluria after an oral course of lactic acid bacteria at high concentration

Hyperoxaluria is a major risk factor for renal stones, and in most cases, it appears to be sustained by increased dietary load or increased intestinal absorption. Previous studies have shown that components of the endogenous digestive microflora, in particular Oxalobacter formigenes, utilize oxalate in the gut, thus limiting its absorption. We tested the hypothesis of whether oxaluria can be reduced by means of reducing intestinal absorption through feeding a mixture of freeze-dried lactic acid bacteria. Six patients with idiopathic calcium-oxalate urolithiasis and mild hyperoxaluria (>40 mg/24 h) received daily a mixture containing 8 x 10(11) freeze-dried lactic acid bacteria (L. acidophilus, L. plantarum, L. brevis, S. thermophilus, B. infantis) for four weeks. The 24-hour urinary excretion of oxalate was determined at the end of the study period and then one month after ending the treatment. The ability of bacteria to degrade oxalate and grow in oxalate-containing media, and the gene expression of Ox1T, an enzyme that catalyzes the transmembrane exchange of oxalate, also were investigated. The treatment resulted in a great reduction of the 24-hour excretion of oxalate in all six patients enrolled. Mean levels +/- SD were 33.5 +/- 15.9 mg/24 h at the end of the study period and 28.3 +/- 14.6 mg/24 h one month after treatment was interrupted compared with baseline values of 55.5 +/- 19.6 mg/24 h (P < 0.05). The treatment was associated with a strong reduction of the fecal excretion of oxalate in the two patients tested. Two bacterial strains among those used for the treatment (L. acidophilus and S. thermophilus) proved in vitro to degrade oxalate effectively, but their growth was somewhat inhibited by oxalate. One strain (B. infantis) showed a quite good degrading activity and grew rapidly in the oxalate-containing medium. L. plantarum and L. brevis showed a modest ability to degrade oxalate even though they grew significantly in oxalate-containing medium. No strain expressed the Ox1T gene. The urinary excretion of oxalate, a major risk factor for renal stone formation and growth in patients with idiopathic calcium-oxalate urolithiasis, can be greatly reduced with treatment using a high concentration of freeze-dried lactic acid bacteria. We postulate that the biological manipulation of the endogenous digestive microflora can be a novel approach for the prevention of urinary stone formation.

Clofibrate feeding to Sprague-Dawley rats increases endogenous biosynthesis of oxalate and causes hyperoxaluria

The effects of clofibrate feeding (5 g/kg diet) on oxalate metabolism were investigated in male and female rats. Following clofibrate feeding, 24-hour urinary excretion of oxalate increased until 4 days and then reached a plateau. Whereas the contribution of dietary oxalate (1.4 g/kg diet, as potassium salt) to urinary oxalate was less than 5% in both control and clofibrate-treated male rats, the contribution of dietary glycolate (1.0 g/kg diet, as sodium salt) to urinary oxalate was six times higher in clofibrate-treated male rats compared with controls, indicating that the clofibrate-induced hyperoxaluria is due to increased endogenous biosynthesis of oxalate. This was supported by the increased lactate dehydrogenase (LDH) activity observed in liver supernatants of clofibrate-treated rats compared with controls, and the increased rate of conversion of glycolate and glyoxylate to oxalate by clofibrate-treated male rat liver supernatants. Female rats had lower excretion of urinary oxalate and lower levels of liver glycolic acid oxidase (GAO) as compared with males. Clofibrate-treated female rat liver supernatants had higher LDH levels and produced more oxalate from glyoxylate. Thus, it can be concluded that the increase in LDH activity may be the cause of the increased endogenous biosynthesis of oxalate leading to increased urinary excretion of oxalate in male and female rats treated with clofibrate.

Determination of oxalate excretion in spot urines of healthy children by ion chromatography

Summary: Evidence for the suitability of Spot urines for selective screening in children was obtained by comparing the 24-hour urinary oxalate excretion with the ratio of urinary oxalate to creatinine [mmol/mol] in spontaneously voided urine samples. Spot urines of 169 healthy children aged l day to 13 years were analysed in order to establish reference values for the urinary oxalate/creatinine ratio in relation to age and body surface area. Oxalate was measured by automated ion chroraatography. Results showed an inverse relationship between the oxalate/creatinine ratio and age. The highest ratios, 131 ± 57 mmol/mol (mean ± 2 SD), were found in infants. At age two years, the ratio was 84 ± 55, at age five years 56 ± 35, and for children older than ten years 42 ± 31. This finding can be explained by the gain of muscle mass and hence increased creatinine productiori with increasing age. Data for the urinary oxalate/creatinine ratio are presented according to body surface area for the assessment of children with abnormal growth. In 19 urine samples from nine patients with primary hyperoxaluria, the oxalate/creatinine ratio greatly exceeded (286—2022 mmol/mol) the above reference ranges. We therefore propose the determination of the oxalate/creatinine ratio in spot urines for the selective screening for hyperoxaluria in children with nephrocalcinosis or urolithiasis.

Effects of Magnesium Salts in Preventing Experimental Oxalate Urolithiasis in Rats

Magnesium oxide, magnesium hydroxide, magnesium sulfate, magnesium trisilicate, and magnesium citrate were added to a calcium-oxalate lithogenic diet in order to determine their effects in preventing lithogenesis. Male Wistar-strain rats which had been fed the glycolic-acid diet developed marked urinary calculi within four weeks. Rats in the magnesium-hydroxide, magnesium-citrate, and magnesium-trisilicate groups, however, had almost no stones in the urinary system. Rats in the magnesium-oxide and magnesium-sulfate groups showed significantly less effect than those in the former three groups. During the experimental period, the 24-hour urinary oxalate excretion and concentration were higher in the glycolic-acid group than in the other groups. The urinary citrate excretion and concentration were the highest in the magnesium-hydroxide and magnesium-citrate groups and higher in the magnesium-trisilicate and magnesium-oxide groups than in the magnesium-sulfate and glycolic-acid groups. Similar trends were observed in the urinary magnesium excretion and in its concentration. The urinary calcium excretion and concentration were higher in the experimental groups than in the glycolic-acid group. The urinary calcium/magnesium ratio remained mostly unchanged. Therefore, it can be concluded that alkaline magnesium salts increase the urinary calcium and magnesium concentrations, without changing the calcium/magnesium ratio, and inhibit urinary calculi formation, most likely by increasing the urinary citrate concentration. (J. Urol, 144: 385-389, 1990)

Tea Consumption as a Possible Risk Factor in Urolithiasis: A Preliminary Report

ABSTRACT The relationship between tea consumption and increased risk of urolithiaisis was studied in seven volunteers, four men and three women. All subjects were put on a tea-free diet for one wee...

Acquired hyperoxaluria, nephrolithiasis, and intestinal disease. Description of a syndrome.

Abstract In seven patients with resection of the distal ileum, calcium oxalate nephrolithiasis and increased urinary excretion of oxalate (64 to 135 mg per 24 hours) developed. Cholestyramine therapy (4 g four times a day) lowered the 24-hour urinary excretion of oxalate to normal in the four patients in whom it was used. Urinary excretion of oxalate was measured in an additional 42 patients with various types of intestinal disorders without evidence of nephrolithiasis. Five of 18 patients with ileal resection, two of seven with bacterial over-growth, and six of 15 with miscellaneous conditions, including nontropical sprue and cirrhosis, had hyperoxaluria.