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A four-year-old male child was admitted with severe renal failure, apparently recent in onset and he was treated with peritoneal dialysis (PD). A renal biopsy showed interstitial cellular infiltration with crystals within the tubules and sclerotic glomeruli. Type I hyperoxaluria was diagnosed and the child received a liver and kidney transplant after 10 months of dialysis. Two years later, he has normal renal function, and blood and urine oxalate levels are within normal ranges.

An anomaly in erythrocyte oxalate transport has been reported in patients with idiopathic calcium oxalate nephrolithiasis. Even if clinical and experimental evidence suggests a causal role of this cellular anomaly in calcium nephrolithiasis, a definitive answer to this fundamental question is still lacking. We approached this problem by searching for a possible relationship between the erythrocyte oxalate self-exchange anomaly and the renal clearance of this anion in stone formers. In 10 idiopathic calcium-oxalate renal stone formers, and 10 healthy subjects we evaluated the erythrocyte oxalate flux rate, and the renal fractional clearance of oxalate by a recently described enzymathic procedures for plasma oxalate determination. With respect to controls, stone formers had higher oxalate flux rate in erythrocytes, and higher oxalate renal fractional clearance with a significant direct correlation between the two parameters. These data are compatible with a membrane transport abnormality within the kidney of these stone formers, and the existence of a common defect of the oxalate transport shared by both erythrocytes and tubular renal cells. The latter may be crucial in the pathogenesis of calcium oxalate nephrolithiasis, by modifying the renal handling of oxalate.

We use oxalate oxidase from barley seedlings for the colorimetric determination of oxalate in plasma. The oxalate is converted to hydrogen peroxide, which, in the presence of peroxidase, is detected by a Trinder-like chromogenic system. Optimization of the assay, including deproteinization and elimination of interferences from reducing substrates, is described. Ascorbate additions (200 mumol/L) did not affect oxalate concentration in plasma, even after long frozen storage. Mean analytical recovery of oxalate averaged 102% +/- 6.9%, imprecision (CV) at 2.0 mumol/L was 7.2%, and the lower limit of quantification (CV = 20%) was 0.6 mumol/L. Results correlated well with those by chromatography (r = 0.999, Sy/x = 0.29 mumol/L, n = 32, range for x, y = 0-140 mumol/L). Plasma oxalate concentrations measured in 32 healthy subjects ranged from 0.6 to 2.9 mumol/L (mean 1.28, SD 0.71 mumol/L), which agrees with those measurable by using indirect radioisotopic dilution methods. Patients with primary hyperoxaluria and chronic renal failure exhibited markedly greater plasma concentrations of oxalate.

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.

This new procedure for determining oxalic acid in plasma is based on sample deproteinization with hydrochloric acid and acetonitrile and subsequent ion-chromatographic assay of the neutralized supernate. Sample pretreatment produces very clean samples, which ensures long column life. Mean analytical recovery of oxalate (5.0-10.0 mumol/L) added to plasma samples averaged 98.6 +/- 6.2%; imprecision (CV) was 5.2% (at 2.2 mumol/L) and the detection limit was 0.5 mumol/L at a signal-to-noise ratio of 5:1. Ascorbate to oxalate conversion was < 0.2%, indicating that the procedure is free from ascorbate interference. Plasma oxalate concentrations, measured in samples from 31 healthy persons, ranged from 0.8 to 3.4 mumol/L (mean 1.89, SD 0.75 mumol/L), which agrees with results from indirect radioisotopic dilution methods.

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 mumol/kg body weight/d.(ABSTRACT TRUNCATED AT 250 WORDS)

Regular dialysis treatment (RDT) does not obviate hyperoxalemia of chronic renal failure (CRF). However, there is emerging evidence suggesting that current dialysis prescription is not always associated to progressive oxalate accumulation. In view of the controversy still concerning this issue, we have investigated on plasma profiles and dialysis kinetics of oxalate in patients on RDT. Oxalate was determined by ion chromatography on serum ultrafiltrates and on the whole dialyzate in 23 stable patients on RDT for end-stage renal failure unrelated to primary hyperoxaluria. Nine patients were on traditional hemodialysis (HD) and 14 on soft hemodiafiltration (HDF). Dialysis prescription was set so as to obtain similar KT/V of urea. Mean dialyzer clearance of oxalate (KdOx) was calculated by standard procedures and was compared to urea (KdUrea) and creatinine (KdCr) clearances. Oxalate removal was measured on the whole spent dialyzate. Distribution volume of oxalate (VOx) was estimated by assuming a single-pool model and was used to estimate the oxalate appearance rate (OxAR). Plasma profiles showed that dialysis patients were virtually always hyperoxalemic. However, the threshold of supersaturation for calcium oxalate was exceeded in only 13 of 138 (9.4%) assayed ultrafiltrates, 13% on HD and 7.1% on HDF. Dialysis reduced plasma oxalate by more than 60%. There was a postdialysis oxalate rebound averaging 9.6% at 30 min from the end of dialysis. Plasma oxalate predialysis was independent of sex, age and time on dialysis. KdOx was mildly higher on HDF than on HD, and was lower than both KdUrea and KdCr, irrespective of the dialysis technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Regular dialysis treatment (RDT) does not obviate hyperoxalemia of chronic renal failure (CRF). However, there is emerging evidence suggesting that current dialysis prescription is not always associated with progressive oxalate accumulation. In view of the controversy still concerning this issue we have investigated on plasma profiles and dialysis kinetics of oxalate in patients on RDT. Oxalate was determined by ion chromatography on serum ultrafiltrates and on the whole dialysate in 23 stable patients on RDT for end-stage renal failure unrelated to primary hyperoxaluria. Nine patients were on traditional hemodialysis (HD) and 14 on soft hemodiafiltration (HDF). Plasma profiles showed that dialysis patients were virtually always hyperoxalemic. Dialysis reduced plasma oxalate by more than 60%. There was a post-dialysis oxalate rebound averaging 9.6% at 30 minutes from the end of dialysis. Oxalate dialyzer clearances were mildly higher on HDF than on HD, and were lower than both urea and creatinine clearances, irrespective of the dialysis technique. Distribution space of oxalate was 21.5 1, that is 37.3% of dry body weight, and was quite similar to estimates obtained in normal subjects and in patients with CRF by alternative isotope dilution methods. Oxalate appearance rate averaged 337 +/- 69 mumol/24 h and was not different from the daily oxalate excretion assessed in 40 healthy subjects. Oxalate appearance was significantly related to urea generation and protein catabolic rates. From our results we conclude that, unless metabolic generation of oxalate is increased, current dialysis programs should prevent progressive oxalate accumulation in the majority of the patients.

In an attempt to decrease ascorbate interference on the ion-chromatographic determination of urinary oxalate, we compared the effectiveness of four different methods for ascorbate elimination by analyzing a representative urine pool supplemented with successive ascorbate additions. Two of the methods--treatment with ferric ions or boric acid--have been described elsewhere; treatments with nitrites or ascorbate oxidase (EC 1.10.3.3) are investigated here as possible alternatives. Consideration of the main features, advantages, and drawbacks of the four procedures leads us to conclude that boric acid dilution is a good routine method and that pre-incubation with ascorbate oxidase reliably prevents ascorbate interference in assays of urinary oxalate.

An ion chromatographic procedure for the determination of plasma oxalate is proposed, in which the ultrafiltered sample is injected into an ion-chromatographic system. Sample processing appears effective in avoiding spontaneous oxalogenesis. Sensitivity (down to 1.0 mumol/l) allows determinations in normal and pathological samples; recoveries from plasma ultrafiltration are 94.6 +/- 11.7%. Protein binding was investigated and precautions to improve recoveries from plasma ultrafiltration are proposed. The technique is simple to perform from healthy controls averaged 6.75 +/- 2.62 mumols/l (mean +/- S.D. n = 18); samples from patients with primary hyperoxaluria and chronic renal failure undergoing regular dialysis were also analysed and some of the data obtained are reported and discussed.

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

1. Seventeen healthy controls and 63 patients with idiopathic calcium stone disease of the urinary tract were investigated for urinary calcium and oxalate excretion and for [14C]oxalate intestinal absorption. 2. Under comparable controlled dietary intake a significant increase in calcium excretion as found in patients with stone disease. Oxalate excretion and [14C]oxalate intestinal absorption were mildly but not significantly increased. When patients with stone disease were subdivided into normocalciuric and hypercalciuric subjects, oxalate excretion and [14C]oxalate absorption were significantly increased in the latter. There was a significant direct relationship between calcium excretion and both oxalate excretion and [14C]oxalate absorption. 3. [14C]Oxalate absorption increased significantly in 22 stone-formers when dietary calcium was changed from normal to low. 4. The kinetics of [14C]oxalate intestinal absorption showed that the main difference between normocalciuric and hypercalciuric subjects occurred within the first 6 h after the oxalate-labelled meal. 5. These results confirm that mild hyperoxaluria is a frequent feature of idiopathic calcium stone disease even when patients and controls are studied under controlled dietary conditions. Our data are consistent with the hypothesis that hyperoxaluria is secondary to calcium hyperabsorption and is upper intestinal in origin.