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To determine the range of normal values, we studied urinary excretion of oxalate and glycolate prospectively and longitudinally in a cohort of 30 healthy term infants. Random urine samples were obtained at 2 days, 2 weeks, and 2, 4, 6, and 9 months of age. The results had a log-normal distribution. The mean oxalate/creatinine ratio, as determined by the oxalate oxidase method, was 0.08 (in milligrams of oxalate to milligrams of creatinine) with a normalized range of 0.02 to 0.31. The mean ratio when oxalates were measured by using the Olthuis assay was 0.13 (range 0.03 to 0.53). The mean glycolate/creatinine ratio was 0.07 (range 0.02 to 0.26). These values did not correlate with increasing age. The oxalate/creatinine ratios were higher in formula-fed infants than in those who were fed human milk (0.14 +/- 0.16 vs 0.08 +/- 0.04; p < 0.01).

Chemical kinetic data, complemented with scanning electron-microscope observations of the crystalline phase, show that seed crystals of hydroxyapatite have the ability to induce the growth of calcium oxalate monohydrate crystals epitaxially from a metastable supersaturated solution of calcium oxalate. The rate of growth of calcium oxalate crystals is dependent on the surface area of the seed material and follows a second-order rate law. It is suggested that there may be a causal relationship between the occurrence of apatite crystals in the urinary tract and the formation of both 'pure' and mixed urinary stones containing calcium oxalate. Under similar experimental conditions, however, seed crystals of calcium oxalate monohydrate appeared unable to induce epitaxially the growth of calcium phosphate crystals from a supersaturated calcium phosphate solution, indicating the absence of an epitaxial relationship between calcium oxalate monohydrate and the initially precipitating calcium phosphate phase(s).

The effect of 1.25-dihydroxyvitamin D [1,25-(OH)2D] on dietary oxalate absorption and postprandial urine supersaturation with calcium oxalate was determined in 11 normal subjects. 1,25-(OH)2D increased the urinary excretion of orally administered [14C]oxalate in the 8 h period after a liquid meal containing 1.875 mmol of calcium and 0.83 mmol of oxalate (P less than 0.01), and during a 48 h period when the subjects ingested a diet containing 25 mmol of calcium and 3.3 mmol of oxalate/day (P less than 0.01); however, 1,25-(OH)2D administration had no effect on [14C]oxalate excretion when calcium was removed from the liquid meal. 1.25-(OH)2D increased 24 h urinary oxalate excretion from 28.7 +/- 2.1 mmol/mol of creatinine to 36.8 +/- 2.6 mmol/mol of creatinine (P less than 0.05) on the 10 mmol/day calcium diet and from 26.4 +/- 2.9 to 33.2 +/- 2.2 mmol/mol of creatinine (P less than 0.1) on the 25 mmol/day calcium diet. A linear correlation (r = 0.72) was found between plasma 1,25-(OH)2D levels and urinary [14C]oxalate excretion after the liquid meal. 1,25-(OH)2D administration produced postprandial supersaturation of urine with calcium oxalate and calcium oxalate crystalluria. These studies suggest that 1,25-(OH)2D increases oxalate absorption (and urinary excretion) by increasing calcium absorption, which results in less binding of calcium to oxalate in the intestine; therefore more oxalate is available for absorption. The combined effect of increased calcium and oxalate absorption results in postprandial supersaturation of urine with calcium oxalate, with resultant crystalluria.

Seed crystals of anhydrous uric acid were shown to epitaxially induce the crystal growth of calcium oxalate monohydrate from its metastable supersaturated solution. Scanning electron microscopic examination of crystalline material isolated from the kinetic experiments supports the chemical evidence that calcium oxalate had been nucleated by uric acid. In spite of close lattice similarities between some of the faces of the two phases, the induction period required for heterogeneous nucleation by the seed material was about half of that required for precipitation in the absence of potential nucleating agents. This has created some doubt as to whether crystalline uric acid has an influence on the formation of calcium oxalate lithiasis.

A method is described for quantitatively determining the inhibitory activity of pure components, isolates, or mixtures of components (such as urine) on the growth of calcium oxalate crystals. Results with known calcium phosphate crystal growth inhibitors--magnesium, citrate, and pyrophosphate--suggest that these components contribute little to the ability to normal urine to inhibit the growth of calcium oxalate crystals. As yet unidentified urinary components seem to be responsible for most of this activity. The urinary crystal growth inhibitors appear to function by adsorbing on the surface of the growing crystals, thereby preventing the further incorporation of lattice ions. The fit of experimental data to the Langmuir absorption isotherm supports this conclusion.

The kinetics of the crystal growth of calcium oxalate monohydrate has been studied using the technique of seeded crystal growth from stable supersaturated solution. The rate law takes the form minus dc/dt equals kN-2 in which the rate of loss of lattice ion from solution is proportional to the square of the supersaturation. It is proposed that the incorporation of lattice ions into the crystal is governed by a bimolecular surface-controlled reaction step. The rate is independent of the hydrodynamics of the system but is proportional to the solid to solution ratio in the supersaturated solution. The specific rate constant, k (M-minus-1 min-minus-1 [mg/dl]minus-1), is nearly independent of the solid to solution ratio, however. The rate of crystal growth was found not to vary with the calcium to oxalate molar ratio in the range 1.5 to 0.75, although the rate did increase at both higher and lower ratios. The method was found to be simple, rapid, and reproducible and lends itself to the quantitative study of inhibitors of crystal growth.

1. Whewellite (calcium oxalate monohydrate) crystals were found to induce epitaxially the heterogeneous nucleation of brushite (calcium monohydrogen phosphate dihydrate) from its metastable supersaturated solution in approximately one-quarter of the time required for spontaneous precipitation in the absence of added nucleating agents. Scanning electron-microscope observation of the crystalline phase showed brushite crystals originating from the whewellite seed crystals. 2. Crystal growth, upon nucleation, proceeded rapidly, and the metastable solutions quickly approached saturation. 3. Brushite crystals also induced the precipitation of calcium oxalate crystals in about one-quarter of the time required for spontaneous precipitation; however, the rate of crystal growth was considerably slower. In support of the chemical data, scanning electron micrographs showed few crystals of calcium oxalate nucleated on the surface of the brushite seed. 4. The results provide some insight into the cause of stones containing calcium oxalate or calcium phosphate (or both), which form in the normally acid environment of human urine.

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California Medical Center, San Francisco. Taken from transcriptions, they are prepared by Drs. Martin J. Cline and Hibbard E. Williams, Assistant Professors of Medicine, under the direction of Dr. Lloyd H. Smith, Jr., Professor of Medicine and Chairman of the Department of Medicine.

The effect of hydroxypyruvate on synthesis of oxalate and glycolate from glyoxylate was studied in in vitro preparations from normal human erythrocytes and leukocytes, rat liver, and with purified lactate dehydrogenase from beef heart. In the presence of reduced nicotinamide adenine dinucleotide, hydroxypyruvate stimulated the oxidation of glyoxylate to oxalate and decreased the reduction of glyoxylate to glycolate. These findings may explain the hyperoxaluria seen in L-glyceric aciduria (type II primary hyperoxaluria).