Binding of oxalate to mitochondrial inner membranes of rat and human kidney.

Oxalate bound specifically to homogenates of rat kidney and liver but not to homogenates prepared from heart, lung, skeletal muscle, spleen, stomach, small or large intestine. In the renal cortex, binding was localized to the inner mitochondrial membrane where it was enriched fourfold when compared to homogenate. Binding of the oxalate reached equilibrium in two minutes at 23C. Analysis of the binding sites by Scatchard plot indicated that the maximum binding capacity was 49 pmol./mg. protein and the apparent dissociation constant (Kd) was 43 nM. The IC50 of oxalate was 0.25 microM. Among the inhibitors studied the IC50 was in the following order: oxalate less than oxamate less than parabanate less than glyoxalate less than oxaloacetate less than malate less than citrate = glycollate. Heat and treatment with lubrol abolished the binding completely. Binding was not enhanced by the presence of calcium in the incubation medium; neither was it inhibited by the presence of calcium together with its transport inhibitors. A binding substance with some characteristics similar to the rat mitochondrial binding factor was also found in the human renal cortex.

Effect of orchiectomy and ovariectomy on oxalate production, transport and excretion in rats.

The role of sex hormones on oxalate synthesis by liver, transport by renal cortical mitochondria and urinary excretion was studied in adult male and female Sprague-Dawley rats. Orchiectomy decreased the hepatic synthesis of oxalate whereas ovariectomy increased it by 10 per cent. Castration inhibited oxalate transport by the renal mitochondria uncompetitively in both sexes. Urinary levels of oxalate were unaffected after orchiectomy whereas ovariectomy resulted in an initial elevation in the urinary oxalate levels which returned to control values by 21 days. The results are discussed in light of recent data.

Urinary citrate excretion in patients with renal calculi.

Urinary citrate excretion was measured with a specific enzymatic technique in normal subjects and in an unselected group of patients with recurrent calcium oxalate stones. Hypocitraturia (citrate levels less than those present in 95 per cent of the normal population) was detected in 7 of 46 patients with stones (15 per cent). Hypocitraturia was the only metabolic abnormality in 6 patients.

Ion-chromatographic measurement of oxalate in unprocessed urine.

We describe a sensitive, simple technique for determining urinary oxalate. Urine, diluted as necessary with distilled water, is injected into an ion chromatograph. Oxalate is detected conductimetrically as a distinct peak near the tail of the chromatogram. This peak specifically represents oxalate, because it is abolished if the sample is treated with oxalate decarboxylase. We have used this technique to measure oxalate in more than 3000 consecutively received urine samples. It has a CV of 6%.

Oxalate metabolism and renal calculi.

Changes in oxalate excretion (together with changes in urinary volume) constitute the most important factors in altering the probability of renal stone formation. However, investigations on oxalate metabolism have been sparse, perhaps because of the lack of an accurate method for measuring oxalate in biologic fluids. Available data clearly implicate increased urinary oxalate excretion as the etiological factor in stone formation in two groups of patients--those with primary hyperoxaluria and those with gastrointestinal malabsorption. Evidence for the existence of hyperoxaluria in the patient with the "garden" variety of calcium oxalate stones is less persuasive.

Determination of urinary oxalate by ion chromatography: preliminary observation.

The technique of ion chromatography was applied to determine oxalate concentrations in unprocessed urine. The minimal detectable limits of oxalate was 1 microgram./ml. (11 mumole/liter), the within-run imprecision (Sw) was 2.3 per cent and the total imprecision (St) was 4.9 per cent. Ion chromatography can be used for the simple, accurate and direct measurement of urinary oxalate.