Oxalate Load Research Articles

Purification of a 90-kDa protein (Band VII) from cardiac sarcoplasmic reticulum. Identification as calnexin and localization of casein kinase II phosphorylation sites.

Purification and sequencing of proteins from cardiac sarcoplasmic reticulum (SR) vesicles have provided a framework for the study of SR function. Included among the SR proteins so far investigated are a collection of intralumenal proteins that stain blue with the protein dye Stains-All in sodium dodecyl sulfate-polyacrylamide gels. A single prominent blue staining SR protein of apparent M(r) = 90,000 (Band VII), however, has remained uncharacterized. In the work described here, purification of Band VII from dog cardiac SR vesicles, along with amino acid sequencing and cDNA cloning, identified this protein as calnexin, a homologue of calreticulin recently described in dog pancreatic microsomes. Using ryanodine-mediated calcium oxalate loading of SR vesicles followed by density gradient centrifugation, we have shown that calnexin is a bona fide SR protein and an integral constituent of both junctional and free SR vesicles. Calnexin was found to be a substrate for casein kinase II and was phosphorylated at two distinct sites localized to the carboxyl- and amino-terminal ends of the molecule. Enrichment of calnexin in cardiac SR vesicles indicates a role for calnexin involving the specialized function of the SR membrane.

Influence of Oxalate Loading on Phosphorus and Aluminum Solubility in Spodosols

AbstractOrganic anions can increase the solubility of P and Al in soils and may influence nutrient availability and soil weathering. In Spodosols of the southeastern USA, oxalate has been identified as the dominant organic anion. Therefore, the objectives of this study were to examine the influence of oxalate on the release of inorganic P, organic P, and Al from A, and Bh horizons of two forested Spodosols from the Lower Coastal Plain. Oxalate loading rates ranging from 0 to 125 mmol kg‐1 soil were examined in a series of batch experiments using single, one‐time additions and repeated sequential additions of oxalate. Oxalate had a negligible effect on P and Al release from the A horizon soils. In contrast, oxalate had a large effect on both inorganic and organic P, as well as Al release from the Bh horizon soils. The effect of sequential additions of oxalate on P and Al release from these soils was found to be cumulative. The amount of Al or P released was primarily controlled by the cumulative oxalate loading rate. In addition, the manner of oxalate loading (single vs. sequential) had relatively little effect. At the same total, cumulative oxalate loading rate, the cumulative amount of Al or P released following sequential additions of oxalate at low concentrations were essentially the same as the amount released following a single addition of oxalate at a much higher concentration. This suggests that a continuous release of even small amounts of organic anions in forest soils could solublize large amounts of P and Al on an annual basis.

Calcium oxalate crystallization in urine: role of urate and glycosaminoglycans.

Increasing the concentration of urate promotes the crystallization of calcium oxalate in human urine. In this study the possibility that this effect might be attributable to the attenuation of the inhibitory activity of urinary glycosaminoglycans (GAGs) was explored. Urine sample were collected from 20 men with no history of urolithiasis and the intact GAGs removed by 10 kDa ultrafiltration. Ten of these specimens, designated type A, spontaneously precipitated calcium oxalate crystals when the median urate concentration was increased from 3.13 to 7.33 mmol/liter by the addition of a saturated solution of sodium urate. In the remaining more dilute urines, which were designated type B, spontaneous calcium oxalate crystallization did not occur when the median urate concentration was raised from 2.20 to 6.40 mmol/liter. In these samples crystallization was induced by a standard load of oxalate above the empirically determined metastable limit. Addition of urate significantly reduced the median metastable limit from the control value of 125 to 46 mumol oxalate, and the volume of calcium oxalate deposited was increased fourfold from 25,000 to 104,000 microns 3/microliters. The median size of the precipitated particles was also increased in the presence of urate from 12.06 microns to 14.3 microns; this was confirmed by scanning electron microscopy, which demonstrated that the crystals precipitated in the presence of added urate, though individually smaller, were markedly more numerous and more highly aggregated than those deposited in the control. Re-ultrafiltration of the urines to which urate had been added did not alter the urate concentration, and SEM examination of the ultrafiltration membranes did not reveal the presence of any particulate material.(ABSTRACT TRUNCATED AT 250 WORDS)

Separation of active and inactive (nonphosphorylating) Ca 2+-ATPase in sacroplasmic reticulum subfractions from low-frequency-stimulated rabbit muscle

Chronic low-frequency stimulation elicits in rabbit fast-twitch muscle a partial inactivation of the sarcoplasmic reticulum (SR) Ca 2+-ATPase and Ca 2+-uptake activities. Inactive Ca 2+-ATPase was enriched in a light microsomal fraction by sucrose density gradient centrifugation after calcium oxalate loading in the presence of ATP. This fraction showed a reduced specific activity and phosphoprotein formation of the Ca 2+-transport ATPase. These results suggest that the inactivation of the Ca 2+-ATPase as induced by increased contractile activity, is confined to a specific SR vesicle population.

Inclusion of proteins into calcium oxalate crystals precipitated from human urine: a highly selective phenomenon

The abundance of protein in the matrix of calcium oxalate uroliths has fueled speculation regarding its role in stone genesis. In this study, we wanted to characterize the composition of the proteins associated with early stages of calcium oxalate crystallization in urine. Calcium oxalate crystallization was induced in urine from healthy men and women by the addition of an oxalate load. The crystals were harvested and demineralized, and the proteins remaining were separated and characterized by polyacrylamide gel electrophoresis and Western blotting. Most urinary proteins were not detected in the crystals or were present in only small quantities. The most abundant urinary macromolecule, Tamm-Horsfall glycoprotein, was notably absent from the crystal extracts. The predominant protein associated with the crystals, a previously unknown urinary constituent that we call crystal matrix protein (CMP; molecular mass, 30,000 Da), was more prevalent in the crystals derived from female urine. We conclude that most urinary proteins play no direct role in calcium oxalate crystal formation. However, the protein CMP exhibits a remarkable affinity for calcium oxalate crystals and may be important in stone pathogenesis.

Effects of chondroitin sulphate, human serum albumin and Tamm-Horsfall mucoprotein on calcium oxalate crystallization in undiluted human urine

The effects of physiological concentrations of chondroitin sulphate, human serum albumin and Tamm-Horsfall mucoprotein on the crystallization of calcium oxalate in undiluted, ultrafiltered human urine were investigated using particle size analysis and scanning electron microscopy. Neither the amount of oxalate required to induce detectable calcium oxalate crystal nucleation nor crystal morphology was affected by the presence of any of these macromolecules. Chondroitin sulphate had no effect on the amount of crystalline material deposited or on the size of the particles precipitated in response to a standard oxalate load. Human serum albumin slightly reduced the size of the crystal aggregates and caused a small increase in the amount of crystal matter precipitated. By contrast, Tamm-Horsfall mucoprotein significantly inhibited crystal aggregation and markedly increased the volume of matter deposited, although this could not be attributed to a promotion of solute precipitation. It was concluded that chondroitin sulphate, human serum albumin and Tamm-Horsfall mucoprotein cannot account for the inhibitory effects of macromolecules with a relative mass greater than 10 kDa in spun and filtered urine. Nonetheless, Tamm-Horsfall mucoprotein is likely to inhibit crystal aggregation in whole urine in vivo and may therefore be instrumental in preventing calcium oxalate stone formation.

Urinary excretion of oxalate by patients withrenal hypercalciuric stone disease Effect of chronic treatment with hydrochlorothiazide

Hydrochlorothiazide is employed to reduce calcium excretion in patients with urinary stone disease secondary to renal leak hypercalciuria. Because the drug also has been reported to be a competitive inhibitor of oxalate excretion by the renal tubules, we sought to determine whether chronic use indeed affected the amount of oxalate excreted. Patients taking hydrochlorothiazide 50 mg daily did not have a statistically significant reduction in twenty-four-hour urinary oxalate on their customary diets (pretreatment 37 +/- 3 mg/day [mean +/- S.E.M.; N = 22]; at one year 36 +/- 3 mg/day [N = 22]; at two years 37 +/- 3 mg/day [N = 16]). In 12 patients who voluntarily collected twelve-hour urine specimens after dinner on the third day of a low-oxalate diet and again the next day after a 1 g oxalate load, hydrochlorothiazide had no significant effect on oxalate excretion (19 +/- 2.3 mmol oxalate/mol creatinine on hydrochlorothiazide versus 20.6 +/- 2.6 mmol off the drug after low oxalate meal; 50 +/- 7.8 mmol/mol creatinine on hydrochlorothiazide versus 56.2 +/- 7.5 mmol off the drug after an oxalate load). As expected, there was a significant reduction in urinary calcium excretion and thus of calcium oxalate urinary saturation during hydrochlorothiazide administration. Hydrochlorothiazide by itself is not sufficient to reduce oxalate excretion in patients with renal leak hypercalciuria.

Does Tamm-Horsfall mucoprotein inhibit or promote calcium oxalate crystallization in human urine?

Using two different experimental techniques, Tamm-Horsfall mucoprotein (THM) has been reported both to inhibit and to promote calcium oxalate (CaOx) crystallization in ultrafiltered human urine. In this study, these two techniques were used to compare the effects of THM on CaOx crystallization in the same ultrafiltered urine samples. Urine was collected from 10 healthy men and ultrafiltered (10000 Da). Each sample was divided and to one half was added sufficient human THM to give a final concentration of 35 mg/L. CaOx crystallization was induced in the samples by addition of an oxalate load and by evaporation. Using the evaporation technique THM significantly increased the deposition of CaOx determined as 14C-oxalate, from 9772 cpm to 43652 cpm ( P < 0.01). Using the oxalate load method THM had no effect on the metastable limits of the urine with respect to CaOx, and significantly increased the volume of particulate material deposited from 26000 to 39995 μm 3/μl - an increase of 54%. This increase was reduced to 21% when values were corrected for the volume of THM particles recorded in control samples to which no oxalate load was added. Using 14C-oxalate, it was shown that this increase in volume could not be attributed to an enhanced deposition of crystalline CaOx, but was probably the result of an increased polymerization of THM in the presence of CaOx crystals. Despite this, the average size of the particles precipitated in the presence of THM (6.5 μm) was significantly ( P < 0.01) less than that observed in the absence of THM (12.1 μm). It was concluded that the effect of THM on CaOx crystallization in urine depends upon the methodology used to assess it and that promotion would only be expected in vivo in cases of extreme dehydration. Under usual physiological conditions THM would be expected to inhibit CaOx crystal aggregation and to have little effect, if any, on the amount of crystalline material deposited.

Effect of Urate on Calcium Oxalate Crystallization in Human Urine: Evidence for a Promotory Role of Hyperuricosuria in Urolithiasis

1. The effect of hyperuricosuria, simulated by increasing the concentration of dissolved urate, on the crystallization of calcium oxalate in human urine was examined. 2. Twenty urine samples were studied. Ten of these, designated type A, spontaneously precipitated calcium oxalate dihydrate crystals upon the addition of a solution of sodium urate solution which raised the median urate concentration from 3.1 to 7.0 mmol/l. 3. Adding dissolved urate to the remaining type B samples raised the median urate concentration from 2.2 to 6.2 mmol/l, but did not cause the precipitation of calcium oxalate. This was induced in these samples by the addition of a standard load of oxalate above an empirically determined metastable limit. 4. In the type B urine samples, the addition of urate decreased the median metastable limit from 125 to 66 mumol of oxalate, trebled the median volume of crystalline calcium oxalate deposited from 35,000 to 105,000 microns3/microliters and significantly increased the overall size of the particles precipitated. Calcium oxalate monohydrate was exclusively precipitated, and the individual crystals deposited in the presence of urate were markedly smaller, more numerous, and more highly aggregated than those produced in its absence. 5. These results constitute the most convincing evidence yet obtained that hyperuricosuria may be a powerful promoter of calcium oxalate stone formation.

Urinary oxalate recovery after oral oxalic load: an alternative method to the quantitative determination of stool fat for the diagnosis of lipid malabsorption.

Urinary oxalate concentrations were measured in 45 patients with quiescent Crohn's disease, four patients with chronic pancreatitis and five healthy subjects after a normal oxalate (150 g/day) diet, after a high-fat (150 g/day), normal oxalate diet and after and after a high-oxalate (500 mg/day) diet. Urinary oxalate concentrations were significantly (P less than 0.05) higher in patients with Crohn's disease and steatorrhoea, but not in those with chronic pancreatitis, after administrating a high-oxalate diet compared with healthy subjects. Mean oxalate values were 19.1 mg/24 h in controls compared with 65.8 mg/24 h in Crohn's disease patients. A direct correlation (r = 0.37, P less than 0.01) was established between faecal rats and urinary oxalate after oval oxalate load: this correlation (r = 0.43, P less than 0.01) is closer when only patients with Crohn's disease are considered. The study, therefore, confirmed a correlation between steatorrhoea and hyperoxaluria in patients with Crohn's disease; however, the high percentage of false positive results limits the use of urinary oxalate concentrations as a reliable indicator of lipid malabsorption. It is concluded that, at present, measurement of urinary oxalate cannot be recommended as a valid alternative to the Van de Kamer method for diagnosing lipid malabsorption.

Effect of citrate on the urinary excretion of calcium and oxalate: relevance to calcium oxalate nephrolithiasis.

Studies in 24 recurrent oxalate stone-formers have shown that values for urinary calcium excretion for this group on at-home diets vary significantly (P less than 0.001) more than values for creatinine excretions. By placing stone-formers on controlled in-hospital diets and measuring their calcium excretions, we were able to predict probable outpatient hypercalciuria (greater than 7.5 mmol/day) with a sensitivity of 95% and a specificity of 95%. In this study, the renal loss of calcium during low-calcium diets was proportional to the absorptive hypercalciuria during high-calcium diets. Calcium loading experiments in fasted stone-formers and normal subjects indicated that citrate, at citrate:calcium molar ratios ranging from 0.12 to 1, stimulated urinary calcium excretion more than did calcium carbonate loading alone. In addition, citrate also significantly (P less than 0.05) increased the excretion of urinary oxalate by two normal subjects for a given load of calcium oxalate. Malabsorption of citrate and possibly other hydroxycarboxylic acids may thus predispose to oxalate nephrolithiasis by promoting calcium and oxalate absorption.

蓚酸カルシウム結晶形成, 成長, 凝集に対する Sodium Pentosan Polysulfate の阻止作用

The inhibitory effects of sodium pentosan polysulfate (SPP) on the formation, growth and aggregation of calcium oxalate (CaOx) crystals were estimated by means of a Coulter counter TA II by the seed crystal method, whole urine method and infrared spectroscopic method. In the seeded crystal system, the inhibitory activities on aggregation (Ia), growth (Ig) and size (Is) were calculated from the change of the number, volume and diameter of crystals. At above 0.5 microgram/ml, SPP inhibited the aggregation and growth of added CaOx monohydrate (COM) and dihydrate (COD) crystals. In the whole urine system, after determining the metastable limit, the formation and growth of CaOx crystals precipitated in response to a load of sodium oxalate was measured. SPP had a strong inhibitory effect on the formation and growth in the concentration of over 5 micrograms/ml. In infrared spectroscopic study, the ratio of COD/COM formed in whole urine increased with the concentration of SPP. SPP therefore might have prevented the recurrence of stone formation.

Oxalate deposits in the kidney of 5/6 nephrectomised rats supplemented by large doses of vitamin C.

The secondary oxalosis of renal failure has been recognised for more than 20 years (Bennett and Rosenblum, 1961), but details of its prevalence and clinical features have been addressed only recently(Salyer and Keren, 1973; Boer et al., 1984; Pru et al., 1985). Oxalate is a non-metabolisable end product of glycine and ascorbic acid metabolism(Elder and Wyngaarden, 1960) and virtually all of it is excreted by the kidneys. Renal insufficiency can produce oxalate loads that exceed renal excretory capacity. Protein binding of oxalate is minimal and most of it should be removed by hemodialysis. However, hemodialysis does not remove oxalate as fast as it is formed, leaving patients at risk from the complications which result from systemic oxalosis (Landwehr et al., 1987).KeywordsOxalic AcidUrinary OxalateCalcium Oxalate CrystalRemnant KidneyPlasma OxalateThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Postnatal development of Ca2+-sequestration by the sarcoplasmic reticulum of fast and slow muscles in normal and dystrophic mice.

Ca2+-uptake activities of the sarcoplasmic reticulum (SR) were determined with a Ca2+-sensitive electrode in homogenates from fast- and slow-twitch muscles from both normal and dystrophic mice (C57BL/6J strain) of different ages. Immunochemical quantification of tissue Ca2+-ATPase content allowed determination of the specific Ca2+-transport activity of the enzyme. In 3-week-old mice of the dystrophic strain specific Ca2+ transport was already significantly lower than in the normal strain. It progressively decreased with maturation and reached only 40-50% and 30-50% of the normal values in fast- and slow-twitch muscles of adult dystrophic animals, respectively. Tissue contents of calsequestrin were reduced in both types of muscle leading to an increased Ca2+-ATPase to calsequestrin protein ratio. Equal amounts of the Ca2+-ATPase protein (detected by Coomassie blue staining of polyacrylamide gels) were present in SR vesicles isolated by Ca2+-oxalate loading from adult normal and dystrophic fast-twitch muscles. However, the specific ATP-hydrolysing activity of the enzyme was approximately 50% lower in dystrophic than in normal SR. The reduced ATP-hydrolysing activity was correlated with decreased Ca2+-transport activity, phosphoprotein formation and fluorescein isothiocyanate labeling as determined in total microsomal and heavy SR fractions. Although the Ca2+ and ATP affinities of the enzyme were unaltered, its ATPase activity was reduced at all levels of ATP in the dystrophic SR. Taken together, these findings point to a markedly impaired function of the SR and an increase in the population of inactive SR Ca2+-ATPase molecules in murine muscular dystrophy.

Intestinal Oxalate-Degrading Bacteria Reduce Oxalate Absorption and Toxicity in Guinea Pigs

Previous studies have provided evidence that an anaerobic bacterium, which degrades dietary oxalate to CO2 and formate, is present in colonic contents of a number of herbivorous species, laboratory rodents and humans. The present study examines the possibility that these bacteria degrade significant amounts of oxalate and can influence colonic oxalate absorption. Guinea pigs adapted to a diet containing 2% sodium oxalate or fed a normal diet were challenged with 67, 135, 170 or 200 mg of sodium oxalate containing 0.5 microCi of [14C]oxalate, which was injected into the cecum. Adapted animals excreted approximately 2% of the 14C in the urine, regardless of the dose, whereas unadapted animals excreted significantly higher amounts in the urine at the two lower doses and died at the two higher doses. Conversely, antibiotic treatment of adapted guinea pigs reduced the ability of their cecal flora to degrade oxalate, and a correspondingly greater percentage of an injected oxalate load was excreted in the urine. Oxalate degradation rates in cecal fluid were depressed by the secondary bile salt deoxycholate, and in vitro studies with pure isolates of guinea pig and human strains of oxalate degraders confirmed that these bacteria were highly sensitive to low concentrations of deoxycholate. Results indicate that these bacteria may be important in preventing excess absorption of oxalate and raise the possibility that the hyperoxaluria associated with bile salt malabsorption of ileal disease in part may be due to suppression of these bacteria by the bile salts.

Influence of Calcium Content in Mineral Water on Chemistry and Crystallization Conditions in Urine of Calcium Stone Formers

19 idiopathic recurrent calcium stone formers were examined on a constant diet supplemented with mineral water of high (386 mg/l) and low (10 mg/l) calcium content. The effects of calcium and oxalate loading were studied separately. Ingestion of mineral water with high calcium content lead to an increase of urinary calcium and a decrease of urinary oxalate compared to mineral water with low calcium content. On the calcium-rich mineral water, urinary saturation with Whewellite was lower and it hardly reached the critical level for calcium oxalate crystallization after oxalate loading, which was in contrast to the results on low calcium mineral water. Urinary Brushite saturation was generally low and showed no significant differences between the two mineral waters.

Dietary Protein Levels Affect the Excretion of Oxalate and Calcium in Patients with Absorptive Hypercalciuria Type II

A total of 12 patients with absorptive hypercalciuria type II and 11 normal controls participated in a study to evaluate the effects of dietary protein levels on urinary calcium and oxalate excretion before and after a 1 gm. dose of oxalate. Two test periods were used during which calcium (less than 400mg. per day) and oxalate were restricted. The first test was done under conditions of low dietary protein (12 per cent total caloric intake, 60 gm.) and the second test was done at a high protein level (25 per cent, 125 gm. protein). Twelve-hour urine specimens were obtained after dinner on day 3 of each diet (low and high protein) and again on day 4 when 1 gm. oxalate (spinach) was added to the dinner meal. The specimens were analyzed for calcium, oxalate and relative calcium oxalate saturation (concentration product ratio). There were no significant differences between the controls and subjects with absorptive hypercalciuria type II in oxalate excretion before the oxalate load on the low protein (controls 31.4 ± 4.2 standard error, expressed as mmol, oxalate per mol. creatinine, and absorptive hypercalciuria type II 23.1 ± 3.1) and high protein (controls 30.4 ± 4.2 and absorptive hypercalciuria type II 28.8 ± 5.9) diets. After the oxalate bolus the positive changes in oxalate excretion were 11.8 ± 4.8 (low protein) and 17.8 ± 4.7 (high protein) for controls, and 11.4 ± 4.4 (low protein) and 31.8 ± 5.2 (high protein) for patients with absorptive hypercalciuria type II. Thus, the increases in post-load urinary oxalate levels observed for controls and patients were greater on the high protein than on the low protein diets. After the oxalate load the increases in urinary oxalate and calcium oxalate supersaturation were significantly greater for patients with absorptive hypercalciuria type II than for control subjects for the high protein but not the low protein diets (p less than 0.05).

The effect of serum on the crystallization of calcium oxalate in whole human urine: inhibition disguised as apparent promotion.

The effect of serum on calcium oxalate crystallization was studied in whole human urine. At concentrations between 0.005% to 0.10% (v/v), serum had no effect on the metastable limit of urine as detected by the Coulter Counter. However, serum caused a marked increase in the number and volume of calcium oxalate crystals deposited in response to an oxalate load. That this increase in volume reflected true deposition of calcium oxalate was confirmed by determining calcium concentration and by including control urines containing added serum but no exogenous oxalate. Analysis of particle size distributions showed that the crystals deposited in the presence of serum were smaller than those occurring in the control. Since serum did not affect the limit of metastability, the enhancement of crystal volume is unlikely to be a result of heterogeneous nucleation. We hypothesize that the apparent promotion effect of serum is due to its inhibition of crystal aggregation which increases the crystal surface area available for calcium oxalate deposition.

A Method for Studying Inhibitory Activity in Whole Urine

A method has been developed for inducing and quantifying calcium oxalate crystallisation in whole human urine. The propensity of a given urine to induce crystal formation was described in two ways: its ability to resist spontaneous nucleation of calcium oxalate crystals was assessed by titrating 20 mls of the urine with increasing quantities of sodium oxalate (0-150 mumol) to determine its practical metastable limit. This limit was inversely related to the endogenous calcium concentration; its capacity to inhibit crystal growth was quantified by determining the rate of growth of calcium oxalate crystals precipitated in response to a fixed oxalate load (30 mumol) above its metastable limit. The crystals produced were predominantly calcium oxalate dihydrate and were morphologically identical to those occurring naturally in urine. Citrate had no effect on the metastable limits of 3 urines examined, but markedly inhibited crystal growth. Pyrophosphate had a similar effect on crystal growth, and in addition, raised the metastable limit of one of the urine samples.

An inheritable anomaly of red-cell oxalate transport in "primary" calcium nephrolithiasis correctable with diuretics.

We measured the rate of oxalate flux across the red-cell membrane in the steady state in 114 patients with a history of calcium oxalate kidney stones and in 25 controls. Of the patients, 98 had recurrent, "idiopathic" kidney stones, 8 had primary hyperparathyroidism, 7 had renal or urinary tract malformations, and 1 had primary hyperoxaluria. Oxalate exchange was significantly higher in the 98 patients with idiopathic stone formation than in the controls (-1.10 +/- 0.95 [SD] X 10(-2) min-1 vs. -0.31 +/- 0.12 X 10(-2); P less than 0.001); it was above the upper limits of normal in 78 of these patients. All 8 patients with hyperparathyroidism and the patient with primary hyperoxaluria had values in the normal range; 2 of the patients with renal or urinary tract malformation had values at the upper normal limit. A study of five families indicated that the abnormality is an autosomal monogenic dominant trait with complete penetrance and variable expressivity. Oxalate-tolerance tests were carried out in five pairs of brothers. One brother in each pair had the abnormality in oxalate flux, and had a significantly higher percentage of oxalate excretion at two hours after oxalate loading (18.09 +/- 3.07 [SD] vs. 10.37 +/- 3.08 percent; t = 3.97; P less than 0.005) and four hours (14.87 +/- 2.91 vs. 9.89 +/- 2.93 percent; t = 2.70; P less than 0.05). Treatment with oral hydrochlorothiazide (50 mg per day) or amiloride (5 mg per day) or both restored normal or nearly normal red-cell oxalate exchange in all of 33 patients who initially had increased rates. We conclude that an inherited cellular defect in oxalate transport may be a factor in "primary" calcium oxalate stone formation and that this defect may be corrected with diuretics.