Eric J. Will

Growth kinetics of calcium oxalate monohydrate: I. Method and validation

Abstract A method is presented for measuring the growth kinetics of a calcium oxalate monohydrate (whewellite) seed suspension, based on the direct uptake of 45Ca tracer into the crystals. Measurements were highly reproducible when standardized methods of seed crystal preparation and inoculation were employed. The reliability of the isotope measurements was confirmed by isotope balances, measurements of the depletion of calcium from solution, and a conductivity method. Composite growth curves could be described by a simple hyperbola. Statistical analysis of the growth parameters was straightforward. The method is compared with other systems used to measure whewellite growth.

Growth kinetics of calcium oxalate monohydrate: II. The variation of seed concentration

Abstract With a tracer system described earlier, the influence of the variation of the seed concentration s on the growth kinetics of CaC 2 O 4 ·H 2 O at 37°C was investigated. The observed variation of the process parameters U ∞ and m m with s was explained and quantitated. The growth curves were described by a simple formula, containing the time dependence of the growth in the (closed) system as one term, and the time-independent initial growth rate as another. The relationship between measured growth and equilibrium conditions was established. A parameter [ t m ] was defined, characteristic of the agglomeration of a certain suspension, containing all the uncertain factors in a particular growth experiment. The solubility product based on activities, was found to be 2.82 × 10 -9 M 2 and was constant in the ionic strength region I = 0-0.16M. The dependence of the growth rate on s pointed to agglomeration being one of the essential processes is suspension growth systems. This effect could be quantitated.

Primary oxalosis: clinical and biochemical response to high-dose pyridoxine therapy.

Although pyridoxine hydrochloride (vitamin B6) is known to reduce the endogenous production of oxalate in some individuals with primary oxalosis, the dose for a satisfactory trial of treatment is not established. We report two cases of primary oxalosis on a daily regimen of 1 g pyridoxine hydrochloride, in which 24-hr urinary oxalate excretion decreased by 60% and 70%, respectively, with corresponding clinical benefit. The responses have been sustained up to 2.5 yr in one case, and 20 mo in the other. In the patient with renal failure, serum creatinine decreased from 243 to 146 mumole/liter after 15 mo of treatment. The decrease in glycollic acid excretion in both patients was consistent with an increase of glyoxalate transaminase activity by the vitamin. Supranormal levels of erythrocyte glutamic oxaloacetate transaminase (egot) activity were observed during therapy, and these may be useful as a measure of the effective dose of pyridoxine.

Growth kinetics of calcium oxalate monohydrate: III. Variation of solution composition

The influence of the variations of initial supersaturation, ionic strength and calcium-to-oxalate ratio on the growth kinetics of calcium oxalate monohydrate from suspension at 37°C have been investigated in an isotopic system. All experiments can be described with a single growth formula, containing three constants: kA (growth rate constant), La (thermodynamic solubility product) and [t m] (a parameter describing the agglomeration of any seed suspension). This formula is able to predict any growth curve when the initial concentrations of seed, oxalate and indifferent electrolyte are known. Comparisons with datak from the literature are discussed.

Inhibition of Calcium Oxalate Crystal Growth-A Simple Method of Measurement and Preliminary Results

The mechanisms which govern the development of renal calculi composed largely of calcium oxalate remain obscure1. Robertson et al2,3 have shown that urine is usually supersaturated with respect to calcium oxalate, and that when the formation product is exceeded a crystalline deposit may be found in fresh urine. Stone-forming patients differ, however, from controls in producing larger, faceted crystals and crystal aggregates. Urine contains inhibitors of calcium oxalate crystal growth and aggregation1–6 and a relative deficiency of inhibitory activity has been described7. Progress has been hampered by the paucity of convenient methods for measuring inhibition of crystal growth. We have combined the use of a seeded system and radioisotopes in an effort to increase both convenience and precision8.

Renal Physiology and the Phosphate Ion

Phosphate enters or leaves the kidneys by three main routes. The one main route of entry is by glomerular filtration. The rate of phosphate entry is not subject to modulation other than that due to variations of plasma phosphate concentration and of glomerular filtration rate. Despite about 13% protein binding of the plasma phosphate, the phosphate concentration in the glomerular filtrate equals the plasma phosphate concentration1,2,3. This is because in assessing plasma phosphate concentration the volume of proteins is not taken into account and because the presence of plasma proteins on only one side of the ultrafiltering glomerular membrane induces an electrochemical gradient across it, resulting in unequal distribution of phosphate ions over the two sides. These factors happen to cancel each other out and therefore the filtration rate of phosphate can conveniently be calculated as the product of plasma phosphate concentration and glomerular filtration rate.

Routine Measurements of the Inhibition of Calcium Oxalate Crystal Growth— an Evaluation

Whatever the initiating mechanisms, renal calculi grow by the deposition of crystalline material on a surface bathed in urine. Sixty per cent contain calcium oxalate, and it is important to be able to measure the properties of urine which counter the usually prevailing supersaturation of the salt (1). Current methods of measuring calcium oxalate crystal growth are unsuitable for routine laboratory use. Complicated equipment, inconveniently large volumes of solution, and extended incubation periods are necessary to make comparable observations. Where the inhibitory effects of additives have been investigated it has been difficult to make a large number of measurements in order to explore the relationship between additive concentration and inhibition.

Inhibition, diminution and retardation, and the growth of calcium oxalate crystals

One quarter of all urine stones is composed of calcium oxalate. Growth of these stones should be possible when urine is supersaturated with respect to calcium and oxalate. Urine has an inhibiting effect on calcium oxalate crystal growth. This inhibition can be effected either by diminution of supersaturation — for instance by altering ion activity or the solubility product — or ba retarding the crystal growth rate that is typical for a given supersaturation through binding of inhibitors to the crystal surface. The solubility product could be altered by an effect of inhibitors on the growing crystal phase.

Voraussage der Wachstumskinetik von Calciumoxalat Monohydrat

In den vorgehenden Jahren haben wir von einigen Beitragen zur Untersuchung des Wachstumsprozesses von Calciumoxalat Monohydrat (Whewellit) berichtet (1), (2), (3), (4). Die schwierige Beschreibung des Wachstumssystems bei der Messung der Inhibierung (1), (2), notigte eine systematische Untersuchung der Wachstumskinetik ohne Additive. Deswegen wurde vorher untersucht wie die Kritstallkonzentration das Wachstumsbenehmen beeinfluste (3), und wurde das Loslichkeitsprodukt bestimmt (4). Aber nicht nur diese zwei Faktoren beeinflussen die Kristallisation von Whewellit im Harn. Auch die Ubersattigung, die Ionenstarke und das Calcium/Oxalatverhaltnis variieren grundsatzlich in vivo. Deswegen wurden die Einflusse dieser Grosen auf die Wachstumskinetik in der vorliegenden Veroffentlichung untersucht. Es erwies sich, das eine einfache Gleichung gefunden werden kann, die unter beliebigen Umstanden jede Wachstumskurve voraussagt.