Calcium Oxalate Renal Stones Research Articles

Inhibition of calcium oxalate monohydrate crystal aggregation by urine proteins.

Normal urine inhibits both the growth and the aggregation of calcium oxalate monohydrate (COM) crystals but the molecules that inhibit aggregation are not well defined. We have developed a spectrophotometric assay method to measure the aggregation of COM crystals in vitro under conditions that avoid simultaneous crystal growth. At pH 7.2 and 90 mM NaCl, Tamm-Horsfall glycoprotein (THP) and nephrocalcin (NC), a major urinary inhibitor of COM crystal growth, inhibit COM crystal aggregation at concentrations as low as 2 X 10(-9) and 1 X 10(-8) M, respectively. When increasing NaCl to 270 mM or lowering pH to 5.7, inhibition by both glycoproteins, but more markedly by THP, is decreased. Urinary NC from calcium oxalate renal stone formers (SF NC) and NC isolated from calcium oxalate renal stones (stone NC) both inhibit COM crystal aggregation 10-fold less than NC from normal urine. Citrate is ineffective even at millimolar concentrations. Thus THP and NC are two major inhibitors of COM crystal aggregation in normal urine; SF NC and stone NC are defective aggregation inhibitors.

Kinetic factors influencing the dissolution behavior of calcium oxalate renal stones: a constant composition study.

A constant composition method has been used to examine the dissolution kinetics of calcium oxalate renal stones over a wide range of undersaturation in vitro. Demineralization experiments have been carried out with the concentrations of calcium and oxalate ions and ionic strength (hence the solution undersaturation) held constant by the potentiometrically controlled addition of medium electrolyte solution as diluent, triggered by a calcium ion electrode. Kinetic data for renal stones have been compared with results obtained for synthetic calcium oxalate. In addition, constant composition results have been directly compared with results obtained using conventional dissolution methods for both calculi and synthetic calcium oxalate. Overall, calcium oxalate renal stones exhibited markedly different kinetic dissolution behavior as compared with synthetic controls. The renal stone samples dissolved more slowly at all undersaturations, exhibited increased kinetic orders of reaction, and showed reduced sensitivity to solution hydrodynamics. Stones composed of mixed hydrates of calcium oxalate (mono- and di-) came to dihydrate equilibrium in conventional experiments and underwent net dissolution in solutions supersaturated to monohydrate under constant composition conditions. No conversion of di- to monohydrate was observed under these experimental conditions. These results indicate that stone dissolution is strongly influenced by adsorbed inhibitors, presumably including matrix components, which may complicate efforts to develop systemic and/or irrigation measures effective for in situ solubilization.

Isolation From Human Calcium Oxalate Renal Stones of Nephrocalcin, a Glycoprotein Inhibitor of Calcium Oxalate Crystal Growth. Evidence That Nephrocalcin From Patients With Calcium Oxalate Nephrolithiasis is Deficient in γ-Carboxyglutamic Acid

We have determined that the organic matrix of calcium oxalate kidney stones contains a glycoprotein inhibitor ofcalcium oxalate crystal growth (nephrocalcin) that resembles nephrocalcin present in the urine of patients with calcium oxalate stones and differs from nephrocalcin from the urine of normal people. Pulverized calcium oxalate renal stones were extracted with 0.05M EDTA, pH 8.0; nephrocalcin eluted in five peaks using DEAE-cellulose column chromatography, and each peak was further resolved by Sephacryl S-200 column chromatography. Four ofthe fiveDEAE peaks corresponded to those usually found in nephrocalcin from urine; the fifth eluted at a lower ionic strength than any found in urine. Amino acid compositions and surface properties of nephrocalcins isolated from kidney stones closely resembled those of nephrocalcins isolated from urine of stone-forming patients: they differed from normal in lacking y-carboxyglutamic acid residues, and in forming air-water interfacial films that were less stable than those formed by nephrocalcin from normal urine.

Isolation from human calcium oxalate renal stones of nephrocalcin, a glycoprotein inhibitor of calcium oxalate crystal growth. Evidence that nephrocalcin from patients with calcium oxalate nephrolithiasis is deficient in gamma-carboxyglutamic acid.

We have determined that the organic matrix of calcium oxalate kidney stones contains a glycoprotein inhibitor of calcium oxalate crystal growth (nephrocalcin) that resembles nephrocalcin present in the urine of patients with calcium oxalate stones and differs from nephrocalcin from the urine of normal people. Pulverized calcium oxalate renal stones were extracted with 0.05 M EDTA, pH 8.0; nephrocalcin eluted in five peaks using DEAE-cellulose column chromatography, and each peak was further resolved by Sephacryl S-200 column chromatography. Four of the five DEAE peaks corresponded to those usually found in nephrocalcin from urine; the fifth eluted at a lower ionic strength than any found in urine. Amino acid compositions and surface properties of nephrocalcins isolated from kidney stones closely resembled those of nephrocalcins isolated from urine of stone-forming patients: they differed from normal in lacking gamma-carboxyglutamic acid residues, and in forming air-water interfacial films that were less stable than those formed by nephrocalcin from normal urine.

The Effect of Monosodium Urate on the Capacity of Urine, Chondroitin Sulphate and Heparinl to Inhibit Calcium Oxalate Crystal Growth and Aggregation

In order to investigate the possibility of interaction between urinary glycosaminoglycans and particulate monosodium urate, growth and aggregation rates of calcium oxalate seed crystals were measured in the presence of heparin, chondroitin sulphate and normal urine after preincubation with and without monosodium urate (0.5mg./ml.). Rates of crystal aggregation in the presence of heparin and chondroitin sulphate were significantly (p < 0.0005) increased after pretreatment with sodium urate, indicating a reduction in the inhibitory potency of heparin and chondroitin sulphate by this salt. A similar effect was observed with the rate of crystal growth in the presence of heparin (p < 0.01). In contrast, the rate of growth in the presence of chondroitin sulphate was unaffected. Pretreatment with sodium urate had an inconsistent effect on the rate of crystal growth in the presence of 10 normal human urine samples, but significantly (p < 0.001) raised the rate of crystal aggregation.It was concluded that the influence of urate on crystal aggregation in the presence of urine may be a result of its binding to endogenous chondroitin sulphate, but may not be of practical consequence in the pathogenesis of calcium oxalate renal stones.

Inhibitory activity of whole urine: A comparison of urines from stone formers and healthy subjects

The inhibitory activity of whole urines from 32 healthy subjects and 50 calcium oxalate renal stone formers was assessed in terms of (a) their ability to withstand increasing quantities of oxalate before undergoing spontaneous nucleation of calcium oxalate, and (b) their response to a standard 30-μmol challenge of oxalate above their measured metastable limits. The concentrations of calcium ( p <0.05), oxalate ( p <0.05), urate ( p <0.01) and glycosaminoglycans ( p < 0.005) were significantly lower in the stone formers than in the controls and were associated with a significantly higher 24-h urinary volume ( p < 0.001). The majority of urine samples precipitated envelope crystals of calcium oxalate dihydrate, while the remainder precipitated the monohydrate. A significantly ( p < 0.02) greater proportion of the urines from stone formers than from controls deposited calcium oxalate monohydrate, and this was attributed to a lower concentration of calcium in these urines. The minimum amounts of oxalate necessary to induce crystal nucleation did not differ between the two groups, but when the measured metastable limits were expressed as the product of the total (i.e. endogenous + that added to induce nucleation) concentrations of oxalate and calcium at which precipitation occurred, then these limits were significantly lower ( p < 0.05) in the stone formers than in the healthy subjects. However, when the metastable limits of a subgroup of stone formers and controls matched for 24-h urinary volume and calcium and urate concentrations were compared, no differences between the groups could be discerned. The urines from the two groups of subjects were indistinguishable with respect to their responses to the oxalate load, whether these were expressed as rate of crystal growth, total amount of calcium oxalate deposited during a given time or size of the precipitated crystals. It was concluded that the lower metastable limits of the stone formers were a consequence of reduced concentration, rather than output, of urinary inhibitors.

Determination of Urinary Oxalate by Ion Chromatography

Abstract The factors which are important for calcium oxalate renal stone formation may be studie, in vitro, using the constant composition mineralization method (Gaur and Nancollas, Kidney Int., 26, 767 (1984). Since the molar calcium/oxalate rations in vivo are relatively high (normal range, 5–50) the rates of these seeded crystallization reactions at constant supersaturations are markedly dependent upon the concentrations of oxalate ion. Kinetic studies therefore require a rapid and reliable method for the analysis of this ion. A Dionex QIC analyzer incorporating an anion fiber suppressor unit and conductometric detector has been used to develop a method for the determination of urinary oxalate. The eluent, consisting of a mixture of 3.23 × 10−3 mol L−1 NaHCO3 and 2.41 × 10−3 mol L1 Na2CO3, was used isocratically at a flow rate of 2.2 cm3 min−1. The 14 min analysis time was considerably shorter than that reported for previous ionchromatographic methods. The minimum detectactable oxalate in urine was 0.1...

Prevalence of hyperoxaluria in idiopathic calcium oxalate kidney stone disease.

Urinary excretion of oxalate, calcium and urate has been investigated in 88 patients affected by idiopathic calcium oxalate stone disease and in 20 normal subjects. Of these ions, only oxalate was found significantly higher in stone formers. Defining hyperoxaluria as urinary oxalate excretion greater than 2 SD above normal, 50% of stone-forming people were found to be hyperoxaluric. When stone formers were classified in normo- and hyperoxaluric, the prevalence of hypercalciuria, hyperuricuria, family history of stone disease and recurrencies in stone formation was the same in both groups. It is concluded that hyperoxaluria is a frequent finding in finding in idiopathic calcium oxalate renal stone disease.

Effect of thiazides on the urinary calcium oxalate stone-forming potential in normal males.

We studied the effect of bendroflumethiazide on a risk factor index, COSP, reflecting the stone-forming potential of urinary calcium oxalate. This index includes the concentrations of three stone promotors: calcium, oxalate, and uric acid in its numerator, and two stone inhibitors: magnesium and citrate, in its denominator. These risk factors were measured in 4-hour and 24-hour urinary specimens obtained under fixed conditions of food and fluid intake. Eight normal males were studied before and after two and four weeks of continued thiazide treatment. Thiazide 2.5 mg b.i.d. was given for two weeks, followed by 2.5 mg t.i.d. for another two weeks. Before treatment COSP exhibited a pronounced diurnal variation with peaks between 8 a.m. and noon, and 8 p.m. and midnight. After four weeks of thiazide treatment suppression of two stone promotors, calcium (p less than 0.01) and uric acid (p less than 0.02), and reduced COSP by 36 to 95% in each subject (median: -71%, p less than 0.01). Moreover, thiazide abolished the diurnal variation of COSP. After the initial two weeks of thiazide 2.5 mg b.i.d., almost identical effects were observed. Nearly all the changes in COSP were explained by the effects on urinary calcium. This marked suppression of COSP supports the theory that thiazides may be useful in the prevention of renal calcium oxalate stone formation.

PROCEEDINGS OF THE AUSTRALIAN SOCIETY FOR MEDICAL RESEARCH

PROCEEDINGS OF THE AUSTRALIAN SOCIETY FOR MEDICAL RESEARCH

Growth and Characterization of Calcium Oxalate Dihydrate Crystals (Weddellite)

Conditions are given for the growth of calcium oxalate dihydrate crystals (weddellite) in aqueous solution. The crystals obtained were characterized by scanning electron microscopic, spectroscopic, and thermal methods. The dissolution kinetics and electrophoretic mobility were determined; the thermodynamically unstable calcium oxalate dihydrate had a higher dissolution rate and a lower zeta potential than the monohydrate and underwent a phase transformation into the more stable calcium oxalate monohydrate. The results obtained on the chemical stability and the surface charge of calcium oxalate dihydrate offered additional information for assessing the current theories on the formation of calcium oxalate renal stones.

Dissolution of calcium oxalate renal stones in patient with jejunoileal bypass and after reanastomosis

A patient formed multiple calcium oxalate renal stones after jejunoileal bypass. Following reanastomosis of the small bowel, she was placed on a high fluid intake and a thiazide diuretic which resulted in a urine undersaturated for calcium oxalate. Stone dissolution occurred in situ.

Interaction of hyperuricuria and hyperoxaluria on renal calcium oxalate stone formation.

There is increasing evidence that excessive urinary excretion of uric acid plays a role in the genesis of renal calcium oxalate stones. 17 percent of our stone formers show a hyperuricuria, a much higher frequency than in normal people. Robertson (1) describes an inhibitory effect on acid mucopo1ysaccarides, which serve as inhibitors of crystal aggregation.KeywordsUric AcidRenal TissueStone FormationCalcium OxalateDuodenal TubeThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Familial idiopathic hypercalciuria.

The frequency of hypercalciuria was determined in the families of nine hypercalciuric patients with idiopathic hypercaliuria who formed recurrent calcium oxalate renal stones. Idiopathic hypercalciuria occurred in 26 of 73 relatives, in three consecutive generations of two families and in two successive generations of four other families. Multiple siblings or children of the probands were affected in three families. Nineteen of 44 first-degree relatives (43 per cent) had idiopathic hypercalciuria, as compared to seven of 29 (29 per cent) other relatives; there was no relation to age or sex. Renal stones were formed by 19 of the 44 first-degree relatives but by none of the others; nine of the 19 were women. We conclude that there is a familial form of hypercalciuria, which appears to be transmitted as an autosomal dominant trait. Stone disease is frequent in first-degree relatives, and affects both sexes equally.

Allopurinol in the Prevention of Calcium Oxalate Renal Stones

The authors report their preliminary results using allopurinol as prophylactic treatment in 30 patients suffering from recurrent calcium oxalate renal stones. The results obtained were generally good, but a longer follow-up period and a larger patient population are required before definite conclusions can be drawn.

Oxalic acid and the hyperoxaluric syndromes

Because calcium oxalate renal stones are the most common type of renal calculus found in this country, a discussion of oxalic acid and abnormalities associated with its synthesis and excretion seems warranted in a symposium of this sort. Although calcium metabolism and excretion have been investigated extensively in syndromes associated with recurrent nephrolithiasis, relatively little attention has been paid to oxalate in these conditions. Nevertheless, information now available, particularly concerning the known hyperoxaluric conditions, has led to greater understanding of idiopathic calcium oxalate nephrolithiasis and more rational treatment of this condition. In this review, the physicochemical and metabolic aspects of oxalic acid will be reviewed, followed by a discussion of the hyperoxaluric syndromes and the role of oxalate in idiopathic calcium oxalate stone disease.

Scanning Electron Microscopic Study of Calcium Oxalate Concretions Grown in Gel System and Calcium Oxalate Stones

Calcium oxalate concretions grown in gelatin gel medium, and calcium oxalate renal stones were studied by polarized light and scanning electron microscopy. In both cases, the results obtained confirm that the surface crystals have random axial orientation and that the gross configuration seems to be determined by the fibrous organic matrix. In vitro concretions grown in the gelatin gel medium are more resistant to EDTA demineralization and to ultrasonic irradiation than calcium oxalate stones.

The contribution of dietary purine over-consumption to hyperuricosuria in calcium oxalate stone formers

Excessive urine uric acid excretion appears to play a causal role in calcium oxalate stone formation and excessive purine intake is a major factor producing hyperuricosuria. We have studied spontaneous dietary purine intake in 10 hyperuricosuric men with recurrent calcium oxalate renal stones in order to define the basis for their purine over-consumption and the precise relationship that exists between purine intake and urine uric acid excretion. Diet diaries, kept by patients, were used to assess purine intake. The stone patients consumed more purine than five matched control subjects eating isocaloric diets. Steak, poultry and roast beef were the main sources of surplus purine. Urine uric acid excretion was linearly related to purine intake in both normal subjects and patients, and uric acid excretion on a purine-free diet predicted by the linear regression equation derived from diet diaries corresponded well with measured values, an observation confirming the accuracy of the dietary measurements employed. Stone patients who excreted normal amounts of uric acid on a purine-free diet displayed a relationship between uric acid excretion and dietary purine intake indistinguishable from normal.

Dissolution and growth of calcium oxalate monohydrate. I. Effect of magnesium and pH.

Abstract The rate of dissolution of calcium oxalate monohydrate and of a calcium oxalate renal stone was measured in 0.9% NaCl solution at different levels of magnesium concentration and pH. The growth of calcium oxalate obtained by chemical reaction between Ca2+ and oxalate ions at a concentration similar to that existing in normal urine was also investigated as a function of pH and magnesium concentration. It was found that both magnesium and pH exert a fine kinetic control on the precipitation and growth of calcium oxalate monohydrate. Magnesium had no effect on the dissolution. The possible role of magnesium and pH in calcium oxalate urolithiasis has been discussed in the light of previous reports and of the data presented in this study.

Effect of Daily MgO and Vitamin B6 Administration to Patients with Recurring Calcium Oxalate Kidney Stones

Patients with histories of recurring calcium oxalate renal stone formation have been given daily oral supplements of 200 mg of MgO and 10 mg of pyridoxine for extended periods of time. Thirty of 36 patients maintained on this program for 5 years or more have shown no recurrence or decreased recurrence of stone formation. After 1 year on this regimen, urines obtained from 51 patients showed a marked increase in their capacity to maintain calcium oxalate in solution, significantly raised calcium and citric acid levels, and decreased xanthurenic acid levels. No significant changes were observed in urinary magnesium, oxalic acid, phosphate-P or pyrophosphate-P values. Decreases in serum β-lipoproteins were also observed in a group of 25 of these subjects.