Calcium Oxalate Saturation Research Articles

Aspartame ingestion increases urinary calcium, but not oxalate excretion, in healthy subjects.

Aspartame is the artificial sweetener most extensively used as a substitute for glucose or sucrose in the food industry, particularly in soft drinks. As glucose ingestion increases calciuria and oxaluria, the two main determinants of urinary calcium-oxalate saturation, we considered it worthwhile to determine whether aspartame ingestion also affects calcium-oxalate metabolism. Our study compares the effects of the ingestion of similarly sweet doses of aspartame (250 mg) and glucose (75 g) on calcium and oxalate metabolisms of seven healthy subjects. Urinary calcium excretion increased after the intake of both aspartame (+86%; P < 0.01) and glucose (+124%; P < 0.01). This may be due to the rise in calcemia observed after both aspartame (+2.2%; P < 0.05) and glucose ingestion (+1.8%; P < 0.05). The increased calcemia may be linked to the decrease in phosphatemia that occurred after both aspartame (P < 0.01) and glucose (P < 0.01) load. Aspartame did not alter glycemia or insulinemia, whereas glucose intake caused striking increases in both glycemia (+59%; P < 0.001) and insulinemia (+869%; P < 0.01). Although insulin was considered the main calciuria-induced factor after glucose load, it is unlikely that this mechanism played a role with aspartame. Urinary oxalate excretion did not change after aspartame, whereas it increased (+27%; P < 0.05) after glucose load. Thus, as aspartame induced a similar increase in calciuria as did glucose but, conversely, no change in oxaluria, substituting glucose by aspartame in soft drinks may appear to be of some potential benefit.

Urinary Calcium Oxalate Saturation in Healthy Infants and Children

Purpose A number of factors influence the development of renal calculi, the most essential of which is the supersaturation of urine with lithogenic substances. Calcium oxalate stones occur most frequently in adult and pediatric patients with urolithiasis. Therefore, we established normal age and sex related data for urinary calcium oxalate saturation in infancy and childhood to allow a more specific prediction of the risk of (recurrent) stone disease. Materials and Methods We collected 24-hour urine samples from 473 healthy infants and children without a history of renal stones. Urinary lithogenic and stone inhibitory substances were measured, and the urinary calcium oxalate saturation was calculated using a computer program. Results Mean urinary calcium oxalate saturation was always higher in boys than in girls, which was significant in infancy (5.22 versus 2.03, p <0.05) and at ages 7 to 9 years (8.84 versus 5.47, p <0.05). The saturation first increased (p <0.05) until age 7 to 9 years in boys and girls, and remained at high levels at ages 10 to 12 years (7.03 versus 5.49, p <0.05 compared to infancy). Calcium oxalate saturation then decreased until adolescence when values were comparable to those of infancy (5.29 versus 3.35). Conclusions We recommend calculating urinary calcium oxalate saturation for diagnostic purposes as well as for therapy control. Normal age and sex related values must be considered.

Urinary Calcium Oxalate Saturation in Healthy Infants and Children

Urinary Calcium Oxalate Saturation in Healthy Infants and Children

Primary hyperoxaluria type 2.

Primary hyperoxaluria type 2 (PH2) is a rare disease with only 24 patients reported in the literature so far. It should be considered in any patient presenting with urolithiasis or nephrocalcinosis due to hyperoxaluria. The metabolic defect is deficiency of D-glycerate dehydrogenase/glyoxylate reductase leading to characteristic hyperoxaluria and excretion of L-glycerate, the cornerstone of diagnosis of PH 2. Although development of terminal renal failure seems to be less prevalent than in PH 1, recent reports indicate that chronic as well as terminal renal insufficiency may occur. Therefore specific therapeutic measures should aim at reduction of urinary calcium oxalate saturation by potassium citrate or pyrophosphate to reduce the incidence of nephrolithiasis and nephrocalcinosis and thus improve renal survival. Secondary complications (obstruction, urinary tract infections and pyelonephritis) must be avoided. In patients with terminal renal failure isolated renal transplantation seems to carry a high risk of disease recurrence. PH 2 is a rare but important cause of urolithiasis and nephrocalcinosis; long-term follow up is necessary, since the renal prognosis may be worse than previously anticipated.

Determination of urinary glycolate by ion chromatography: clinical and experimental implication

Small changes in the oxalate concentration exert a greater impact on the urinary calcium oxalate saturation than those in the calcium concentration. Urinary oxalate arises from ascorbate in 30-40% and glycolate in 50-60%. Glycolic acid plays and intermediate role in glyoxylate metabolism being involved in both its synthesis and degradation. A large variation in urinary glycolate values reported in the literature and a potential key role in calcium oxalate urolithiasis prompted us to measure accurately urinary glycolate. The ion chromatography used was a Model IC-100 lon Chromatoanalyzer (Yokokawa Electric Co., Ltd.), connected to an autosampler, Model KSST-601 (Kyowa Seimitsu Co., Ltd.). The separator column was TSK-gel IC-anion-PW (Tosoh Co., Ltd.). As the eluent, 0.01 mM phthalate and, as the scavenger, 50 mM dodecylbenzenesulfonic acid were used at a flow rate of 2 ml/min. 24-hour urine samples were obtained from 30 normal healthy males, aged from 20 to 57 years, and 20 male Wistar-strain rats (approximately 160 gm.). These samples were treated with charcoal and diluted 100-fold with distilled water for the determination of glycolate. The minimum detectable limit for glycolate was 0.4 mumol/l in a standard solution, and the regression line for the standard curve from 0.4 mumol/l to 2.0 mmol/l glycolate had a significant correlation coefficient (In Y = 0.882 x In X-2.304, r = 0.996, p < 0.01). The intra-run coefficient of variation was 3.44%. The overall intra-run and inter-run coefficient of variation, including the sampling and dilution of urine, were 3.92% and 3.38% respectively. The recovery from the addition of a known amount of glycolate to each 10 urine samples was 100.2 +/- 7.41% (mean +/- S.D.). A comparison of our method with the enzymatic method yielded a significant correlation between the results (r = 0.997, p < 0.01). The 24-hour urinary glycolate excretion in 30 normal men was 0.205 to 1.372 mmol/day (0.746 +/- 0.344 mmol/day, mean +/- S.D.), while that in male Wistar rats was 4.868 to 7.347 mumol/day (6.077 +/- 2.289 mumol/day, mean +/- S.D.), as measured in 20 consecutive rat urine samples. The urinary glycolate determination by ion chromatography is simple and not time consuming, requiring a 100-fold dilution of charcoal treated urine and 20 minutes at most for analysis. This method has been proven to be sensitive, specific and reproducible.

Risk Factors in Urinary Calcium Oxalate Stone Formation and their Relation to Urinary Calcium Oxalate Supersaturation

We studied the effect of potential risk factors of urinary calcium oxalate saturation on calcium oxalate stone formation. Using the Equil2 program, the DG values of calcium oxalate in 390 clinical urine specimens were estimated in 5 healthy male individuals with and without citrate therapy. Critical calcium-oxalate supersaturation (DG value, > 2.8) was noted in 15 out of 390 urine specimens. Of the 15, 14 late night or morning specimens had critical calcium oxalate supersaturation, while only 1 afternoon specimen was supersaturated. Critical calcium oxalate supersaturation was often associated with hyperoxaluria and hypercalciuria, while undersaturation was often associated with hypomagnesiuria, a high Ca/Mg ratio, and hypocitraturia. Hypomagnesiuria, hypocitraturia, and a high Ca/Mg ratio appear to be poor indicators of calcium-oxalate supersaturation, and it is hard to predict the level of calcium-oxalate saturation using single parameters.

Urinary oxalate excretion in premature infants: effect of human milk versus formula feeding

To study urinary oxalate excretion in infants fed human milk versus formula, and to compare urinary calcium oxalate and calcium phosphate saturation in premature infants with term infants and adults. We measured urinary oxalate-to-creatinine ratio and urinary oxalate concentration in 15 premature infants fed human milk compared to 16 formula-fed premature infants, and in eight human milk-fed term infants compared to 17 formula-fed term infants. We then studied urinary calcium oxalate and calcium phosphate saturations based on our observations of elevated urinary oxalate excretion in premature infants. Urinary calcium oxalate and calcium phosphate saturations were calculated from urinary concentrations of oxalate, calcium, sodium, potassium, chloride, uric acid, magnesium, phosphorus, and urinary pH. We calculated urinary calcium oxalate and calcium phosphate saturations in nine healthy adults and nine formula-fed term infants to establish control values for urinary saturation. Urinary calcium oxalate and calcium phosphate saturations were determined in nine premature infants receiving a glucose and electrolyte solution, 11 premature infants receiving parenteral nutrition, nine formula-fed premature infants, and 11 human milk-fed premature infants. Urinary oxalate excretion was higher in formula-fed compared to human milk-fed premature infants whether expressed as oxalate-to-creatinine ratio (0.32 +/- 0.04 versus 0.18 +/- 0.03, P < .01) or urinary oxalate concentration (0.047 +/- 0.007 versus 0.022 +/- 0.002 mg/mL, P < .01). Urinary oxalate excretion was higher in formula-fed term infants than in human milk-fed term infants whether expressed as oxalate-to-creatinine ratio (0.14 +/- 0.01 versus 0.07 +/- 0.01, P < .01) or urinary oxalate concentration (0.022 +/- 0.002 versus 0.012 +/- 0.002 mg/mL, P < .01). The urinary calcium oxalate saturation in healthy adults was 2.84 +/- 0.79; the value in formula-fed term infants was 2.12 +/- 0.31. The urinary calcium oxalate saturation was significantly higher in premature infants receiving formula (15.68 +/- 3.15), human milk (15.02 +/- 2.27), or parenteral nutrition (11.38 +/- 2.56) compared to adults or term infants (P < .01). Urinary calcium oxalate saturation in premature infants receiving a glucose and electrolyte solution (2.45 +/- 0.36) was not significantly different from that in adults or term infants. In contrast, urinary calcium phosphate saturation in premature infants as well as term infants and adults was less than 1; precipitation of calcium phosphate is not likely to occur under these conditions. Formula-fed infants have higher urinary oxalate excretion than human milk-fed infants. Premature infants receiving standard nutritional regimens may have urinary calcium oxalate saturation levels at which dissolved calcium oxalate may form nuclei of its solid phase.

Physicochemical effects of a new slow-release potassium phosphate preparation (UroPhos-K) in absorptive hypercalciuria

A new slow-release, neutral potassium phosphate salt (UroPhos-K) has been formulated in order to minimize gastrointestinal side effects and avoid sodium-induced calciuria. It was tested in a prospective randomized, double-blind trial in a group of 21 kidney stone patients with absorptive hypercalciuria type I (AH). Twelve patients allocated to the UroPhos-K group received four tablets twice daily with breakfast and an evening snack providing 1240 mg of phosphorus and 63.5 mEq of potassium daily. Nine patients assigned to the placebo group received placebo tablets of the same appearance containing excipient only. Subjects were studied during a 3-day period in the hospital while consuming a constant metabolic diet containing 400 mg Ca, 100 mEq Na, and 800 mg P per day before and after 3 months of treatment. Treatment with UroPhos-K did not cause any significant gastrointestinal side effects; nor did it raise fasting serum K or phosphorus, or reduce hemoglobin or creatinine clearance. It was associated with a rise in urinary K from 46 +/- 7 to 98 +/- 9 mEq per day and phosphorus from 744 +/- 185 to 1535 +/- 112 mg per day (p < 0.001 each). UroPhos-K treatment reduced urinary Ca from 288 +/- 63 to 171 +/- 49 mg/day (p < 0.001), without altering oxalate excretion. It reduced the urinary saturation of calcium oxalate without altering that of brushite. Moreover, by increasing urinary excretion of inhibitors (citrate and pyrophosphate), it reduced the propensity for spontaneous nucleation of brushite (increased formation product of brushite) and inhibited crystal agglomeration of calcium oxalate.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical significance of assessment of serum calcium oxalate saturation in the hyperoxaluria syndromes.

Estimating calcium oxalate saturation (beta CaOx) in body fluids is proposed as a simple and reproducible procedure to assess the risk of systemic oxalosis in several clinical conditions associated with oxalate retention. beta CaOx was computerized from the measured concentrations of main serum ions. Accurate assay of serum oxalate was crucial for reliability of beta CaOx estimates. However, beta CaOx also depended upon changes of calcium and magnesium concentrations. Patients with end-stage renal failure (ESRF) due to primary or enteric hyperoxaluria had beta CaOx greater than saturation, whereas this happened in only 10 of 25 and two of 24 of those with oxalosis-unrelated ESRF. Bony content of oxalate measured in some of these patients was consistent with these results. In patients with maintained renal function beta CaOx was inversely related to glomerular filtration rate, but the slope was steeper in patients with than in those without hyperoxaluria and beta CaOx reached saturation at earlier stages of renal insufficiency.

Idiopathic Calcium Oxalate Urinary Lithiasis: Usefulness of Parks’ and Tiselius’ Indices in the Evaluation of the Risk of Stone Formation

Different indices of the risk of urinary calcium oxalate crystallization were compared to determine their usefulness in detecting the stone-formers particularly prone to recurrence. Urine volume and calcium, oxalate, citrate, magnesium or creatinine were determined in 55 patients presenting with an idiopathic calcium oxalate urolithiasis, as well as in 50 control subjects. On 24-hour urine samples, these elements allowed for the calculation and comparison of different indices of lithogenous risk as proposed by Parks and Tiselius. Both Parks' indices and the urinary citrate-calcium ratio varied significantly between the two groups, but conversely Tiselius' indices were statistically comparable. The three Tiselius' indices taking the 24-hour urine volume into account were also strongly correlated. Parks' index and the urinary citrate-calcium ratio are highly discriminating and potentially relevant to select the stone-formers with a high risk of relapse. Tiselius' indices basically reflect urinary calcium oxalate saturation, and can only be used clinically to control the treatment interfering with this. In this respect, the formula based simply on urine volume, calcium and oxalate over 24 h (Ca0.71.Ox.V-1.2) appears to be sufficient.

Urinary Oxalate Excretion in Premature Infants: Effect of Human Milk Versus Formula Feeding

Objective. To study urinary oxalate excretion in infants fed human milk versus formula, and to compare urinary calcium oxalate and calcium phosphate saturation in premature infants with term infants and adults. Methodology. We measured urinary oxalate-to-creatinine ratio and urinary oxalate concentration in 15 premature infants fed human milk compared to 16 formula-fed premature infants, and in eight human milk-fed term infants compared to 17 formula-fed term infants. We then studied urinary calcium oxalate and calcium phosphate saturations based on our observations of elevated urinary oxalate excretion in premature infants. Urinary calcium oxalate and calcium phosphate saturations were calculated from urinary concentrations of oxalate, calcium, sodium, potassium, chloride, uric acid, magnesium, phosphorus, and urinary pH. We calculated urinary calcium oxalate and calcium phosphate saturations in nine healthy adults and nine formula-fed term infants to establish control values for urinary saturation. Urinary calcium oxalate and calcium phosphate saturations were determined in nine premature infants receiving a glucose and electrolyte solution, 11 premature infants receiving parenteral nutrition, nine formula-fed premature infants, and 11 human milk-fed premature infants. Results. Urinary oxalate excretion was higher in formula-fed compared to human milk-fed premature infants whether expressed as oxalate-to-creatinine ratio (0.32 ± 0.04 versus 0.18 ± 0.03, P &amp;lt; .01) or urinary oxalate concentration (0.047 ± 0.007 versus 0.022 ± 0.002 mg/mL, P &amp;lt; .01). Urinary oxalate excretion was higher in formula-fed term infants than in human milk-fed term infants whether expressed as oxalate-to-creatinine ratio (0.14 ± 0.01 versus 0.07 ± 0.01, P &amp;lt; .01) or urinary oxalate concentration (0.022 ± 0.002 versus 0.012 ± 0.002 mg/mL, P &amp;lt; .01). The urinary calcium oxalate saturation in healthy adults was 2.84 ± 0.79; the value in formula-fed term infants was 2.12 ± 0.31. The urinary calcium oxalate saturation was significantly higher in premature infants receiving formula (15.68 ± 3.15), human milk (15.02 ± 2.27), or parenteral nutrition (11.38 ± 2.56) compared to adults or term infants (P &amp;lt; .01). Urinary calcium oxalate saturation in premature infants receiving a glucose and electrolyte solution (2.45 ± 0.36) was not significantly different from that in adults or term infants. In contrast, urinary calcium phosphate saturation in premature infants as well as term infants and adults was less than 1; precipitation of calcium phosphate is not likely to occur under these conditions. Conclusion. Formula-fed infants have higher urinary oxalate excretion than human milk-fed infants. Premature infants receiving standard nutritional regimens may have urinary calcium oxalate saturation levels at which dissolved calcium oxalate may form nuclei of its solid phase.

Effect of calcium citrate supplementation on urinary calcium oxalate saturation in female stone formers: implications for prevention of osteoporosis

In 14 women aged 37-68 y with a history of renal calcium calculi, bone densities were 12.0% below those of age-matched control subjects at the L2-4 lumbar spine (P = 0.007) and 6.4% less at the femoral neck (P = 0.095). A low-oxalate diet was supplemented with 1 g Ca/d as citrate. In 6 mo, plasma 1,25(OH)2D concentrations fell from 53.2 +/- 18.8 to 41.9 +/- 15.2 ng/L (P = 0.02) and parathyroid hormone from 39.1 +/- 17.0 to 30.8 +/- 12.5 ng/L (P = 0.02). Calcium oxalate saturation was 2.15 +/- 1.38 at baseline, 2.27 +/- 1.00 at 1 mo, and 2.06 +/- 1.57 at 6 mo. The increase in urinary calcium at 1 mo from 4.411 +/- 1.87 to 6.514 +/- 2.82 mmol/24 h (P = 0.01) was offset by a parallel increase in citrate excretion from 2.909 +/- 1.45 to 3.455 +/- 1.34 mmol/24 h (P = 0.03). Calcium citrate supplementation did not increase the lithogenicity of the women in this protocol.

Limited Risk of Kidney Stone Formation During Long-Term Calcium Citrate Supplementation in Nonstone Forming Subjects

The physiological and physicochemical effects of long-term calcium citrate supplementation (25mmol, calcium per day) were assessed in 7 normal premenopausal women. Calcium citrate increased urinary calcium from 3.27 ± 0.42mmol, per day (standard deviation) before treatment to 5.16 ± 0.75mmol, per day after 1-month of treatment (p <0.0125). After 3 months of treatment urinary calcium decreased from the 1-month value to 4.54 ± 0.67mmol, per day (p <0.0125) but remained higher than the pretreatment value (p <0.0125). Fractional intestinal calcium absorption and serum 1,25-dihydroxyvitamin D levels decreased marginally at 1 month of calcium citrate therapy, from 0.457 ± 0.092 to 0.374 ± 0.035 (p <0.05) and from 103 ± 7 to 77 ± 14 pmol./l. (p <0.05), respectively. After 3 months of treatment fractional intestinal calcium absorption decreased further to 0.341 ± 0.061 (p <0.0125 compared to pretreatment), whereas serum 1,25-dihydroxyvitamin D remained unchanged at 82 ± 14pmol./l.Calcium citrate treatment decreased urinary phosphorus levels significantly from 18.9 ± 3.3 to 15.0 ± 2.5mmol, per day (p <0.0125) and 14.0 ± 2.5mmol, per day (p <0.05) at 1 and 3 months, respectively. Mean urinary oxalate decreased by 15 to 20% and urinary citrate increased marginally during treatment. Urinary saturation of calcium oxalate and brushite did not change during calcium citrate therapy, except at 1 month when the saturation of calcium oxalate increased marginally. The inhibitory activity of urine against spontaneous nucleation of calcium oxalate and brushite (formation product) did not change during treatment.In conclusion, long-term calcium citrate supplementation in normal subjects does not increase the propensity for crystallization of calcium salts in the urine. This protective effect is probably due to the attenuated increase in urinary calcium excretion (from a decrease in fractional intestinal calcium absorption), a decrease in urinary phosphorus and an increase in urinary citrate.

Urinary calcium oxalate saturation in 'stone formers' and normal subjects: an application of the EQUIL2 program.

To produce an index of lithogenic risk which identifies patients at risk of stone recurrence and facilitates the monitoring of prophylactic treatments. The EQUIL2 program provides an evaluation of the state of urinary saturation, particularly of calcium oxalate, based on the pH and total concentrations (mmol/l) of sodium, potassium, calcium, magnesium, uric acid, chloride, ammonium, citrate, phosphate, sulphate, oxalate, pyrophosphate and carbon dioxide. The morning urinary calcium oxalate saturation coefficient was thus calculated for 30 stone-formers (Group 1) and 30 normal control subjects (Group 2). Urine from the majority of individuals was saturated, with no significant difference between the two groups. There appeared to be a correlation between the state of saturation and the urinary calcium oxalate molar product in both stone-formers (r = 0.931) and controls (r = 0.914). In future studies on urinary calcium oxalate saturation, it should be possible to supplement the sophisticated coefficient determined by the EQUIL2 program with the molar product, except in cases where monitoring therapies have little or no effect on urinary oxalate or urinary calcium levels.

Urinary saturation and nephrocalcinosis in preterm infants: effect of parenteral nutrition.

Urinary lithogenic and inhibitory factors were studied in 27 preterm infants; 16 had total parenteral nutrition (TPN) and 11 had breastmilk with an additional glucose-sodium chloride infusion. Urines were collected for 24 hours on day 2 (period A), day 3 (B), and once between days 4 and 10 (C). Urinary calcium oxalate saturation was calculated by the computer program EQUIL 2. Renal ultrasonography was performed every second week until discharge. The calcium/creatinine ratio increased in infants on TPN (A 0.91; C 1.68 mol/mol) and was significantly higher at period C than that in infants on breastmilk/infusion (A 0.52; C 0.36). The oxalate/creatinine ratio was persistently higher with TPN (203 mmol/mol) than with breastmilk/infusion (98; 137). The citrate/creatinine remained constant with TPN (0.44 mol/mol), whereas it increased significantly with breastmilk/infusion (0.26; 0.49). Calcium/citrate rose considerably with TPN, but decreased with breastmilk/infusion to a significantly lower level than with TPN. The urinary calcium oxalate saturation increased with TPN (2.4; 4.5) and decreased with breastmilk/infusion (2.1; 1.5) to a significantly lower value than with TPN. Nephrocalcinosis developed in two infants on TPN. Mean daily calcium intake was similar in both groups, whereas protein, sodium, and phosphorus intake were significantly higher on TPN. It is concluded that the increase in urinary calcium oxalate saturation observed with TPN is due to the combined effect of an increased urinary calcium excretion and higher urinary oxalate/creatinine and calcium/citrate ratios. The changes observed are likely to be caused by TPN itself, which differs in several respects from breastmilk feeding.

Effect of Orange Juice Consumption on Urinary Stone Risk Factors

The value of orange juice consumption in kidney stone prevention was examined in 8 healthy men and 3 men with documented hypocitraturic nephrolithiasis. They underwent 3 phases of a metabolic study, a placebo phase and 2 treatment phases in which they ingested either 1.2 1. orange juice (containing 60mEq. potassium and 190mEq. citrate per day) with meals or potassium citrate tablets (60mEq. per day) with water and meals. Compared to potassium citrate, orange juice delivered an equivalent alkali load and caused a similar increase in urinary pH (6.48 versus 6.75 from 5.71) and urinary citrate (952 versus 944 from 571mg. per day). Therefore, orange juice, like potassium citrate, decreased urinary undissociated uric acid levels and increased the inhibitor activity (formation product) of brushite (calcium phosphate). However, orange juice increased urinary oxalate and did not alter calcium excretion, whereas potassium citrate decreased urinary calcium without altering urinary oxalate. Thus, orange juice lacked the ability of potassium citrate to decrease urinary saturation of calcium oxalate. Overall, orange juice should be beneficial in the control of calcareous and uric acid nephrolithiasis.

Determinants of Oxalate Balance in Patients on Chronic Peritoneal Dialysis

We assessed plasma levels and removal rates of oxalate in 24 patients on chronic peritoneal dialysis (CPD) for oxalosis-unrelated renal failure. The ion-chromatographic (IC) measurements of oxalate in plasma, dialysate, and urine (in seven patients with residual renal function) were used to calculate peritoneal and renal clearances of oxalate. The serum state of saturation with calcium oxalate was calculated by means of a computer-based model system. Patient data were compared with those from 19 healthy individuals. Peritoneal clearance of oxalate was 6.3 +/- 4.7 mL/min, ie, 8% of the normal renal clearance. As a result, both plasma oxalate and calcium oxalate saturation were higher than in controls and did not overlap. Plasma was supersaturated with calcium oxalate in only two of 24 patients (8%). Removal of oxalate by dialysis was related to the amount of fluid infused. Overall removal of oxalate (dialysate plus urine) was similar to 24-hour excretion of normal subjects and was taken as a measure of its generation. Oxalate generation rate was dependent on protein (whole and animal) intake, but not on caloric intake or pyridoxine status. Pyridoxine supplementation, 75 and 300 mg daily for 1 months, was not effective in reducing plasma levels or generation rates of oxalate. Residual renal function had a minor influence on oxalate patterns. We conclude that current programs are adequate to maintain oxalate balance in patients on CPD under basic conditions.

Management of primary hyperoxaluria: efficacy of oral citrate administration

The prognosis of primary hyperoxaluria (PH) is not only related to endogenous oxalate production and the response (if any) to pyridoxine (in type I), but is greatly influenced by extrarenal factors like dehydration. The earlier the diagnosis of PH, the better the chances of improving the prognosis in individual patients. Measures to enhance the solubility of calcium oxalate are important. Besides ensuring at all times a generous fluid intake (> 2 l/m2), administration of alkali citrate (0.15 g/kg), which has not been advocated so far in PH, appears very promising. We studied the effect of sodium citrate in six patients with PH. Mean urinary citrate excretion (mmol/day per 1.73 m2) without oral citrate was very low (0.57) and rose to 2.49 with citrate administration. This was accompanied by a significant decrease in the calcium oxalate saturation (calculated by equil 2) from 11.7 to 6.9 (P < 0.05). Treatment in five patients over 10-36 months resulted in improved (1) or stabilized (4) renal function and reduced passage of stones. Additional measures include restriction of salt and of oxalate-rich food. We conclude that long-term administration of alkali citrate is beneficial in patients with PH.

Thresholds of serum calcium oxalate supersaturation in relation to renal function in patients with or without primary hyperoxaluria

Systemic oxalosis is a constant feature in patients with primary hyperoxaluria type 1 (PH1) and chronic renal failure (CRF) and is not prevented by regular dialysis (RDT), because removal cannot keep up with retention and overproduction of oxalate. These patients are candidates to kidney and/or liver transplantation, which should be ideally planned prior to the development of oxalosis. However, methods to detect the presence and extent of oxalosis are invasive and poorly reproducible, and only indirect approaches are feasible. Because supersaturation of body fluids is an essential condition for oxalotic deposits to form, we have assessed serum calcium oxalate saturation (beta CaOx) in 12 patients with PH1 and 26 with PH1-unrelated renal diseases and varying degrees of CRF. Nineteen healthy individuals were taken as controls. beta CaOx was closely dependent on oxalate serum levels. Serum oxalate and beta CaOx were increased in patients with CRF as compared to controls, and were inversely related to GFR, assessed as creatinine clearance. However, at any level of GFR, both were always greater in PH1 patients. From the slopes of the regression of beta CaOx over ClCr, saturation was predicted to be obtained at ClCr ranging 24-34 and 8-11 ml/min/1.73 m2 in PH1 and non-PH1 patients respectively. Based on the dependence of beta CaOx on oxalate, saturation was associated with serum oxalate between 44 and 46 mumol/l, irrespective of either the prevailing GFR or the underlying disease. These simple procedures represent a valuable non-invasive tool to define the risk of systemic oxalosis and may assist in timing of transplantation.

Oxalate Balance Studies in Patients on Hemodialysis for Type I Primary Hyperoxaluria

Primary hyperoxaluria type I (PH1) always leads to end-stage renal failure (ESRF) due to deposition of calcium oxalate in the kidney. Regular dialysis therapy (RDT) can not overcome the excess production of oxalate, hence, systemic oxalate deposition occurs. The extent of tissue deposition and the rate at which oxalate accumulates influence the quality of life and survival of the patients. Therefore, an estimate of the oxalate balance needs to be made for patients on RDT. In this study, we suggest a simple model by which some of the main parameters of oxalate turnover can be assessed without using radioactive materials. Levels of oxalate, glycolate, and urea, and degrees of calcium oxalate saturation, were assessed on plasma ultrafiltrates from two patients with PH1, sampled before, at the end of a dialysis session, and over the entire interdialytic interval. In patients with PH1, oxalate increased linearly during the early phases and then the curve flattened at a concentration corresponding to approximately threefold saturation. The initial phase of the relationship was used to estimate generation rate of oxalate. The delayed phase was ascribed to the deposition of newly generated oxalate out of its miscible pool. Conversely, the relationship for glycolate and urea remained linear. This was also different from the values obtained in four patients with oxalosis-unrelated ESRF, whose oxalate levels increased linearly over the entire interdialytic interval. In the two patients with PH1, the overall oxalate generation was assessed at 4 to 7 mmol/d. The difference between generation and dialysis removal indicated that tissue deposition was greater than 50 δmol/kg body weight/d. Pyridoxine therapy produced some improvement in only one of these patients. On the contrary, all of the patients with oxalosis-unrelated ESRF maintained oxalate balance with the current dialysis schedules. We suggest that this simple model may represent a valuable and reproducible means to routinely perform oxalate balance studies on patients on RDT for PH1.