The composition of four-hour urine samples from patients with calcium oxalate stone disease

Urine collected during a 24-h period between 06.00 and 10.00 h from 25 patients with recurrent CaOx stone disease was analysed with respect to calcium, oxalate, magnesium, citrate and creatinine. Urinary excretion of oxalate in relation to creatinine was slightly higher in 24-h urine but the correlation between 24-h and 4-h values was good. Good correlations were also recorded for calcium and citrate, whereas a more variable result was obtained for magnesium. In terms of the risk of forming a supersaturated urine (CaOx risk index), a good correlation was observed between 24-h and 4-h urine samples, although the highest values were found in 24-h urine. As a result of a low mean urine flow between 06.00 and 10.00 h, the highest supersaturation in terms of the AP (CaOx) index was observed in these samples. When the risk of calcium oxalate crystallisation (CaOx-CR) was determined by means of the increment in oxalate concentration required for precipitation of CaOx, 7 of 11 samples had the highest values in the 4-h urine. Samples collected during a 4-h period might thus be useful in the evaluation and follow-up of CaOx stone formers and further studies will show to what extent they can replace 24-h urine collections.     

Evaluation of urine composition and calcium salt crystallization properties in standardized volume-adjusted 12-h night urine from normal subjects and calcium oxalate stone formers

The volume of 12-h night urine from ten normal men (NM), ten normal women (NW) and 31 male calcium stone formers (SFM) was adjusted to 750 ml and analysed with respect to supersaturation with calcium oxalate (CaOx) and calcium phosphate (CaP), inhibition of CaOx crystal growth and aggregation, as well as the CaOx and CaP crystallization propensity. Concentrations of oxalate and glycosaminoglycans and AP(CaOx) index, an estimate of the CaOx ion-activity product, were higher and the concentration of citrate lower in NM than in NW. In SFM the directly assessed risk of CaOx crystallization was higher and the inhibition of CaOx crystal growth lower than in NM. There were no differences between the groups regarding inhibition of CaOx crystal growth by 74% dialysed urine or inhibition of CaOx crystal aggregation. SFM with mixed CaOxCaP stones had a higher concentration of phosphate and a higher AP(CaP) index at pH 7.0 than SFM with CaOx stones.     

Long-term follow-up of stone formers treated with a low dose of sodium potassium citrate

We evaluated the clinical efficacy of long-term preventive treatment with a single evening dose of alkaline citrate. Information was collected from the files of 52 recurrent stone formers prescribed a daily intake of 3.75-5 g of sodium potassium citrate (SPC; 14-18 mmol of citrate). The annual and cumulative rates of stone formation and the rate of recurrence were compared before and during the treatment. A comparison was also made between the patients with (Group R) and without (Group NR) recurrent stone formation during treatment in terms of urine composition and previous history of the disease. For all patients who started the treatment, the number of stones was smaller during treatment (period tT) than during a period of the same length immediately before treatment (period tB), but greater than the number formed during a corresponding period immediately after the diagnosis (period tA). Via questionnaire we found low treatment compliance, with only 62% of the patients reporting consistent taking of their medication (Group T). The patients in Group T had a smaller cumulated number of stones during period tT than that during periods tA and tB, but the Kaplan-Meier curve of the fraction of patients remaining stone-free during treatment was almost identical to that recorded in 446 recurrent stone formers without medical treatment. No significant differences were recorded in terms of relevant pretreatment urinary risk factors between Groups T(R) and T(NR), but numerically higher values of calcium oxalate (CaOx) supersaturation and calcium/citrate quotients were observed in Group T(R). When 9 patients with a daily intake of SPC and a citrate excretion below 2.5 mmol/day were compared with 16 hypocitraturic patients only given drinking advice, the cumulated percentages of patients without recurrent stone formation in the 2 groups after 3 years were 44% and 48%, respectively. Although the number of patients in this study was small, our results indicate poor long-term protection from recurrent calcium stone formation when a single evening dose of only 3.75-5 g of SPC was taken. The rate of stone formation was apparently slightly reduced, but the fraction of patients free of recurrence was no different from that in patients without medical treatment.     

Assessment of crystallization risk formulas in pediatric calcium stone-formers

The pathogenesis of calcium urolithiasis involves complex interactions of urinary promoters and inhibitors of crystallization. A variety of risk formulas have been established to approximate these interactions for clinical evaluation, and the aim of our study was to determine their usefulness as predictors of stone formation. The study cohort comprised 126 patients (63 boys and 63 girls) aged 6.7–18 years (mean age 14.1 ± 2.9 years) with calcium urolithiasis (61 with chemically confirmed calcium oxalate stones and 65 children with a strong clinical suspicion of this type of urolithiasis). Of these, 36 children were classified as recurrent stone-formers, whereas the remaining 90 had experienced only one stone episode. The values obtained were compared to those of a control group of 60 age- and gender- matched healthy children. A number of crystallization risk indices were calculated from analytes obtained in 24-h urine: calcium/magnesium ratio (Ca/Mg), calcium/citrate ratio (Ca/Cit), (calcium × oxalate)/(magnesium × citrate) ratio (CaOx/MgCit), relative urinary CaOx supersaturation (RS_CaOx), CaOx activity product index (AP_CaOx), and standardized CaOx activity product index (AP_{CaOx stand}). All indices, except for the AP_CaOx index, were significantly higher in stone-formers than in the controls. The Ca/Mg, Ca/Cit, CaOx/MgCit, AP_CaOx, and AP_{CaOx stand} indices were significantly higher in recurrent stone-formers than in first-episode ones. However, the determination of precise cutoffs between pathological and non-pathological values was problematic due to a considerable overlap of individual values. Based on our results, we conclude that calculation of the majority of risk indices may play a rather supplementary role in the evaluation of children with calcium urolithiasis.     

Magnesium, citrate, magnesium citrate and magnesium-alkali citrate as modulators of calcium oxalate crystallization in urine: observations in patients with recurrent idiopathic calcium urolithiasis

The effects of magnesium (Mg) and citrate on the metastable limit of calcium oxalate (CaOx) solubility (synonym: tolerable oxalate TO) were examined in artificial urine and in postprandial urine of male patients with idiopathic calcium urolithiasis (ICU). In artificial urine increasing pH, Mg and citrate elevate TO, decrease CaOx supersaturation only marginally, but elevate considerably free citrate; the effect of Mg alone was small in comparison with citrate alone, and the effects of both substances appeared additive. In ICU patients, matched for sex, age and CaOx supersaturation to non-stone-forming controls, TO was decreased (mean values 0.33 vs. 0.52 mM/l in controls, P < 0.05). Additional significant (P < 0.05) differences were found between ICU and controls: the former exhibited increased CaOx crystal growth, decreased crystal agglomeration time, a more acidic urinary pH, increased concentrations of free calcium and free Mg, and decreased free oxalate and free citrate. After ingestion of a urine-acidifying test meal, or this meal supplemented with either neutral Mg citrate or Mg-alkali citrate, by three groups of male ICU patients, matched for age and CaOx supersaturation, only the last-named preparation evoked an increase in TO and a decrease in crystal diameter, while the normally occurring pH decline from fasting urine was virtually abolished, and the ratios urinary Mg/citrate and calcium/citrate tended towards low values. In contrast, Mg citrate increased crystal agglomeration time, while changes in the other parameters were only insignificant. The crystals formed in urine were CaOx di- and monohydrate (by electron microscopy), and energy dispersive X-ray analysis showed calcium peaks exclusively. However, chemical analysis of crystals verified the presence not only of oxalate and calcium, but also of Mg, phosphate, citrate, and urate; moreover, these crystal constituents seemed to be influenced by Mg citrate and Mg-alkali citrate in different ways. It was concluded that (1) Mg and citrate are effectors of TO in artificial and natural urine; (2) in ICU, low TO and other disturbed CaOx crystallization parameters appear related to the prevailing low urinary pH and low free citrate; (3) Mg-alkali citrate inhibits CaOx crystallization, probably via actions of the citrate, but not the Mg. Because of the eminent role of Mg in human health and ICU, further studies on crystallization after oral intake of Mg in the form of citrate are warranted. Received: 15 May 1998 / Accepted: 9 October 1998     

Is citrate an inhibitor of calcium oxalate crystal growth in high concentrations of urine?

The effect of citrate on calcium oxalate (CaOx) crystal growth was studied in a system in which series of samples containing [⁴⁵Ca]calcium chloride were brought to different levels of supersaturation with various concentrations of oxalate. The crystallization was assessed by measuring the amount of isotope remaining in solution 30 min after the addition of CaOx seed crystals to samples containing citrate in concentrations corresponding to those in final urine. The experiments were carried out both in pure salt solutions and in solutions with dialysed urine. Increased concentrations of citrate resulted in a reduced crystallization of CaOx in both the presence and absence of dialysed urine, but with the lowest rate of crystallization in the samples containing urine. The increased concentration of ⁴⁵Ca remaining in solution reflected a reduced crystallization, which could possibly be explained both by a reduced supersaturation and by an increased inhibition of CaOx crystal growth. The direct effects of citrate on CaOx crystal growth were assessed by calculating the ion-activity product of CaOx (AP_CaOx) at corresponding degrees of crystallization. The AP_CaOx recorded at a 30% reduction of the amount of isotope in solution increased with increasing concentrations of citrate between 1.0 and 1.5 mmol/l in samples both with and without dialysed urine. These findings indicate that citrate has a weak direct inhibitory effect on CaOx crystal growth, which adds to the reduced growth rate brought about by urinary macromolecules and a decreased supersaturation.     

Effect of combined supplementation of magnesium oxide and pyridoxine in calcium-oxalate stone formers

A combined supplement of magnesium oxide (300 mg/day) and pyridoxine·HCl (10 mg/day) was given p.o. to 16 recurrent calcium oxalate (CaOx) stone formers, and its therapeutic efficacy was biochemically evaluated by measuring various parameters of blood (Na, K, Mg, urea, creatinine, calcium, phosphate, uric acid, alanine transaminase, aspartate transaminase and alkaline phosphatase) and urine (volume, pH, creatinine, Na, K, Mg, uric acid, calcium, phosphate, oxalate and citrate) at 0, 30, 60, 90 and 120 days of treatment. Serum Mg significantly (P<0.01) increased after 30 days of treatment and remained constant thereafter while other blood parameters were unaltered. Combined treatment led to a significant increase in the urinary excretion of Mg and citrate over pretreatment values while oxalate excretion showed a gradual and significant decline during the therapy. The results confirmed the efficacy of MgO-pyridoxine supplementation in terms of changes in urinary excretion of lithogenic and inhibitory components, leading to a significant (P<0.01) decrease in CaOx risk index from 0.09±0.04 at 0 day to 0.05±0.02 after 120 days of treatment.     

Relevance of the BONN Risk Index for metabolic monitoring of patients with calcium oxalate urolithiasis: a clinical application study of the Urolizer<Superscript>®</Superscript>

The BONN Risk Index (BRI) successfully determines the calcium oxalate (CaOx) crystallization risk from urine samples. The BRI is based on a standardized crystallization test performed on native urine. A BRI-measuring device, the “Urolizer^®”, has been developed, operating automatically and requiring only a minimum of preparative efforts. In this study, the Urolizer^® is evaluated regarding its analytical and diagnostic practicability for metaphylaxis control in the framework of the daily routine of a stone surgery. From 51 CaOx recurrent stone-formers, 24 h urines were collected at the beginning and after 3 months of metaphylaxis. As much as 27 patients were indicated to suffer from “mild hypercalciuria”, low urinary pH or hypocitraturia, and 24 patients from “hypercalciuria”. The former were treated with alkaline citrate (AC), and the latter with hydrochlorothiazide (HCT). Analyses of urines collected before and during treatment, BRI using the Urolizer^®, and urinalysis-based risk indices were evaluated. In both patient groups, BRI decreased significantly, while metaphylaxis (P<0.001) in the AC group decreased from 1.08 (±0.58) to 0.56 (±0.39) L^?1 and in the HCT-group from 3.30 (±1.15) to 1.60 (±0.52) L^?1. In most patients, urinary parameters changed as desired and related risk indices decreased appropriately. The clinical utility of the easy-to-determine BRI is demonstrated. By quantifying the “overall” therapy effect within 15 min, the innovative analysis device may be especially suited for practitioners specializing in urolithiasis treatment.     

A hypothesis of calcium stone formation: an interpretation of stone research during the past decades

An interpretation of previous and recent observation on calcium salt crystallization and calcium stone formation provide the basis for formulation of a hypothetical series of events leading to calcium oxalate (CaOx) stone formation in the urinary tract. The various steps comprise a primary precipitation of calcium phosphate (CaP) at high nephron levels, establishment of large intratubular and/or interstitial (sub-epithelial) aggregates of CaP. These crystal masses subsequently might be dissolved during periods with low urine pH. On the denuded surface of subepithelial or intratubularly trapped CaP, release of calcium ions can result in very high ion-activity products of CaOx, particularly during simultaneous periods with peaks of CaOx supersaturation. Crystals of CaOx may result from nucleation in the macromolecular environment surrounding the apatite crystal phase. In the presence of low pH, low citrate and high ion-strength of urine, formation of large CaOx crystal masses can be accomplished by self-aggregation of Tamm–Horsfall mucoprotein. Following dislodgment of the initially fixed CaOx stone embryo, the further development into to clinically relevant stone is accomplished by CaOx crystal growth and CaOx crystal aggregation of the retained stone material. The latter process is modified by a number of inhibitors and promoters present in urine. The retention of the stone is a consequence of anatomical as well as hydrodynamic factors.     

How are urine composition and stone disease affected by therapeutic measures at an outpatient stone clinic?

Urine composition in terms of calcium oxalate (CaOx) supersaturation was studied in 802 patients with calcium stone disease before any intervention and during follow-up. Supersaturation was expressed as the AP(CaOx) index, a simplified estimate of the ion activity product of CaOx, and a similar index calculated for a 24-hour urine volume of 1.5 liters the AP(CaOx) index(s). The AP(CaOx) index was significantly reduced in men with and without medical treatment who remained stone-free during follow-up (p less than 0.001), but not in men who continued to form stones. For the AP(CaOx) index(s), a significant reduction was observed only in patients on medical treatment without new stone formation (p less than 0.01). In women, significantly lower AP(CaOx) index values were recorded in recurrent as well as non-recurrent stone formers on medical treatment, whereas in the group without medical treatment and without recurrences the difference did not reach a statistically significant level. This was similar to the effect on the AP(CaOx) index(s) in non-recurrent women with medical treatment. The small number of women with recurrences might have influenced the result. Significantly reduced levels of the AP(CaOx) index were recorded for patients given thiazide, thiazide + magnesium, magnesium, and alkaline citrate. The AP(CaOx) index(s) was reduced in patients given thiazide + magnesium, magnesium, and alkaline citrate. Comparison between the effects on urine composition and clinical response showed that the reduced CaOx supersaturation observed with thiazide, thiazide + magnesium, and alkaline citrate, corresponded to a low rate of stone formation during follow-up. The inefficiency of allopurinol and orthophosphate in affecting urine supersaturation was reflected in a higher recurrence rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

A critical evaluation of the urinary inhibiting activity in idiopathic calcium oxalate nephrolithiasis

In order to obtain new insights into the relevance of inhibitors in whole urine by focusing on their reciprocal interactions, a statistical approach was followed in 35 controls and 27 calcium oxalate (CaOx) recurrent idiopathic stone formers. The inhibiting activity of CaOx crystal growth and the most widely accepted inhibitors (glycosaminoglycans, citrate, magnesium, pyrophosphate), stone constituents (calcium, oxalate, phosphate, urate) and other normal urinary substances were evaluated. It was seen that the inhibitors played a very small role in total inhibiting activity. On the other hand, considering other normal urinary constituents, almost all the inhibiting power of urine on crystal growth could be explained.     

Inhibition of calcium oxalate crystallization by urinary macromolecules

Summary The crystallization of calcium oxalate (CaOx) was determined in dialyzed urine samples collected between 0600 and 1000 hours from 18 normal men, 10 normal women and 13 men and 10 women with CaOx stone disease. Each urine samples was supersaturated by the addition of calcium chloride and sodium oxalate, and CaOx crystallization was followed by quantification of the [¹⁴C]-oxalate remaining in solution for 30 min after supersaturation of the sample. The rate of crystallization was compared with that in physiological saline. The surface area delimited by the urine and saline curves was used to express the inhibition of CaOx crystallization by urinary macromolecules (I_UMM). The I_UMM was significantly higher in urine from normal women than in that from stone-forming women (P<0.05), normal men (P<0.005), and stone-forming men (P<0.02). However, there were no significant differences between stoneforming men and stone-forming women, nor was I_UMM higher in normal men than in stone-forming men. A high concentration of inhibitors might protect women from CaOx stone formation and be one factor explaining the lower stone-formation rate in women. Although low values were more predominate in normal men than in normal women, there were no significant differences between the groups when the inhibition was corrected for differences in urinary volumes.     

The effects of citrate on hydroxyapatite induced calcium oxalate crystallization and on the formation of calcium phosphate crystals

Summary The addition of different amounts of hydroxyapatite crystals (HAP) to a solution, metastably supersaturated with respect to calcium oxalate (CaOx) resulted in heterogenous crystallization at seed concentrations exceeding 0.2 mmol/l. The induction period varied between 1 and more than 8 h with the shortest period for a seed concentration of 2 mmol/l. Addition to the system of 1 and 2% of whole urine and citrate in concentrations corresponding to approximately 1% of that found in normal urine inhibited the crystallization for as long as 4 h. In a system supersaturated with respect to calcium phosphate (CaP) the total number of crystals was markedly reduced by citrate concentrations exceeding 0.5 mmol/l. The fractions of medium sized and large crystals were sharply reduced and small crystals predominated at higher citrate concentrations. This might indicate effects of citrate on both crystal growth and crystal aggregation. We conclude that increased citrate concentrations during treatment with alkali leads to a significant inhibition of CaOx growth on HAP as well as to a prevention of the formation of large CaP crystals from solutions supersaturated with respect to CaP.     

Crystallisation properties in stone forming and normal subjects' urine diluted using a standardised procedure to match the composition of urine in the distal part of the distal tubule and the middle part of the collecting duct

Using a standardised procedure, we assessed the crystallisation properties of calcium phosphate in urine with a composition matching that in the distal part of the distal tubules (DTd) and of calcium oxalate in urine with a composition matching that in the mid-collecting duct (CDm). We used 8-h urine samples collected between 2200 h and 0600 h with sodium azide as preservative. Urine from ten patients with recurrent CaOx stone formation and from ten normal subjects was used for the measurements. The DTd and CDm samples were obtained by diluting the voided 8-h urine to 3000 ml and 1750 ml per 1.73 m² body surface area, respectively. The nucleation was studied in DTd urine following supersaturation with CaP. The crystal size distribution was assessed with a Coulter counter both following supersaturation of DTd urine with CaP and of CDm urine with CaOx. The crystallisation of CaP in DTd urine as well as that of CaOx in CDm urine, in the presence of CaP crystals that had been precipitated in DTd urine, was measured with the isotope technique. The inhibition of CaOx and brushite crystal aggregation in standardised diluted aliquots of DTd and CDm urine was assessed spectrophotometrically as the rate of sedimentation. There was a slightly increased sedimentation rate and a lower initial absorbance in DTd urine from stone formers supersaturated with CaP. Although these findings might reflect a state of increased crystal aggregation in stone formers' urine, this could not be confirmed by crystal size measurements in the Coulter counter. The inhibition of brushite crystal aggregation in DTd urine was significantly in stone formers' urine than in normal subjects' urine (P < 0.001). Moreover, all inhibition values in DTd samples from stone formers were negative, suggesting a promoter effect on crystal aggregation. The inhibition of CaOx crystal aggregation in CDm urine also was significantly higher in CDm urine from normal subjects than in CDm urine from stone formers (P < 0.05). For all other variables the level was similar when urine samples from the two groups were compared. Although this series of crystallisation assessments was carried out on a small number of standardised diluted urine samples only, the results nevertheless emphasise a defect in aggregation inhibition as one important determinant for an abnormal calcium salt crystallisation in patients with recurrent stone formations. This difference obviously includes aggregation of both CaP crystals in DTd urine and CaOx crystals in CDm urine. The results also show that assessment of crystallisation properties of this kind can be carried out in standardised, diluted 8-h night urine samples, which accordingly can be used in the routine work-up of patients with calcium stone disease. Such an approach might prove useful in order to get information on the combined effects of the driving force of supersaturation and crystallisation modifying properties accomplished by urinary macromolecules and other modifying agents. Received: 14 September 2000 / Revised: 27 December 2000 / Accepted: 27 December 2000     

Urine composition and stone formation during treatment with acetazolamide

Twelve patients who formed renal stones during acetazolamide treatment for glaucoma were studied. Calcium phosphate was the dominating component in the stones. Long term treatment with acetazolamide decreased urinary citrate markedly, which will result in an increased ion-activity product of calcium phosphate and a decreased inhibiting property of urine on calcium phosphate crystallization. The treatment also increased urinary oxalate which together with a low citrate might increase the risk of calcium oxalate crystallization. However, an estimate of the ion-activity product of calcium oxalate in urine (AP [CaOx]-index) was unaffected by the treatment and calcium oxalate was a minor component of the stones.     

Stone risk after bladder substitution with the ileal-urethral Kock reservoir

OBJECTIVE: The study was carried out to compare urinary biochemical and physicochemical environments in patients who had undergone bladder substitution with the ileal-urethral Kock reservoir, and who had no actual urinary infection, with those of healthy subjects. MATERIAL AND METHODS: The participants were 23 male patients who had undergone bladder substitution with the ileal-urethral Kock reservoir and 25 healthy men. All subjects had sterile urine at the time of urine collection. Concentrations of calcium, magnesium, phosphorus, creatinine, citrate, oxalate, and ammonia in 24-h urine samples were measured. Estimates of ion activity products of calcium oxalate (CaOx), calcium phosphate (CaP), brushite (Bru), and magnesium ammonium phosphate (MAP) in urine were calculated according to Tiselius. RESULTS: There was no significant difference in 24-h urinary volume between patients with a bladder substitute and the healthy controls. For most of the other measured values the results for patients differed significantly from those for controls. The most striking findings were markedly lower urinary excretion rates of citrate (p < 0.0001) and higher urine pH (p < 0.0001) in patients compared with controls. These findings were reflected in significantly higher levels of urinary supersaturation with respect to CaOx (p < 0.0001), CaP (p <0.0001), Bru (p < 0.0001) and MAP (stuvite) (p < 0.0001) in patients with a bladder substitute compared with healthy subjects. CONCLUSIONS: Hypocitraturia seems to be the main risk factor for calcium stone formation in non-infected Kock reservoir patients, and citrate supplementation appears to be the most obvious choice for stone prophylaxis in patients with intestinal urinary diversion and recurrent renal stone formation.     

Physical chemical studies of calcium oxalate crystallization

The physical chemical approach to the investigation of the calcium oxalate (CaOx) crystallization and urolith formation is the systematic examination of the various aspects of mineral precipitation and growth in pure solution, in the presence of individual urinary components, and in whole urine media. Recent experimental studies have indicated that while small urinary ions such as citrate, magnesium, and phosphocitrate retard the mineralization rate of CaOx, urinary macromolecules may act either as inhibitors of growth or promoters of nucleation. Some CaOx mineralization inhibitors have also been found to influence the growth mechanism of the phase and its flocculation properties. Therefore, urinary macromolecules that are adsorbed on the mineralizing crystals and incorporated into the developing stone may play a significant role in urolithiasis.     

Detection of crystallization inhibitory activity of whole urine with a gel model

Summary The inhibitory activity of urine on calcium oxalate crystallization was measured as an inhibitory index using a gel model modified from Schneider et al. [8]. Urine samples from 36 recurrent stone formers and 21 controls in 3 separate periods (morning, afternoon and evening) were tested. Mean inhibitory indices of >0 were observed among normal controls in the 3 sampled periods and among stone formers in the morning and afternoon samples. A significantly lower (negative) value was observed in the evening samples of stone formers, indicating a higher tendency towards crystallization than normal. The gel method may be applied to identify individuals at risk of stone formation if sufficient numbers of period-defined urine samples from the individual are tested for a statistically significant mean inhibitory index but whether this is practical in a clinical laboratory will need further evaluations.     

Effects of urinary pH and acid-base balance on the formation of calcium oxalate stone

The effects of urinary pH and acid-base balance on the calcium oxalate stone formation was investigated by two experiments. 24-hr urine samples were collected from 15 recurrent CaOx stone formers, 9 single stone formers and 6 age-matched controls. Inhibitory effect of 1% urine in various pH (4.0-9.0) were calculated by a seed crystal method. In the seed crystal system, there were no significant differences in the inhibitory activity of aggregation (Ia) and in the inhibitory activity of size (Is) for each pH of metastable solution between the stone former group and the control group. However, the value of Ia and Is showed a tendency of rise in proportion to a rise in pH. Rats model for calcium oxalate urolithiasis were fed with three different diets (1% NH4Cl, 5% NaHCO3 and 8% NaHCO3 diet) for three weeks. On the fourth week, 24-hr urine samples were collected. In the animal experiment, calcium oxalate stone formations were predominantly recognized in the kidney of the 1% NH4Cl diet group. The biochemical data showed an increase of urinary calcium and oxalate, and a decrease of urinary citrate. These results suggest that low urinary pH and metabolic acidosis are promoters of the calcium oxalate stone formation.     

Relationship between supersaturation and calcium oxalate crystallization in normals and idiopathic calcium oxalate stone formers

BACKGROUND: In an earlier study on recurrent CaOx stone formers with no detectable abnormalities, we found that the urine of these subjects had a lower tolerance to oxalate load than controls and that the removal of urinary macromolecules with a molecular weight greater than 10,000 D improved their tolerance to oxalate. METHODS: The effects on CaOx crystallization of reduced urinary supersaturation of calcium oxalate (CaOx), induced by night water load, were studied in 12 normal males and in 15 male OxCa stone formers who were free from urinary metabolic abnormalities. The effect of the macromolecules, purified and retrieved from the natural and diluted urine, were analyzed in a metastable solution of CaOx. RESULTS: The water load caused an increase in urine volume (from 307 +/- 111 to 572 +/- 322 ml/8 hr, P = 0.014 in normal subjects, and from 266 +/- 92 to 518 +/- 208 ml/8 hr, P = 0.001 in the stone formers) and a concomitant reduction of the relative CaOx supersaturation (from 8.7 +/- 2.5 to 5.1 +/- 2.5 ml/8 hr, P = 0.001 in normal subjects, and from 10.4 +/- 3.5 to 5.0 +/- 2.7 ml/8 hr, P = 0.001 in the stone formers). The decrease in CaOx supersaturation was accompanied by an increase of the permissible increment in oxalate, both in normal subjects (from 43.8 +/- 10.1 to 67.2 +/- 30. 3 mg/liter, P = 0.018) and in the stone formers (from 25.7 +/- 9.4 to 43.7 +/- 17.1 mg/liter, P = 0.0001), without any significant variations of the upper limit of metastability for CaOx (from 21.6 +/- 5.3 to 20.5 +/- 4.2 mg/liter in normal subjects, and from 18.7 +/- 4.5 to 17.1 +/- 3.7 mg/liter in the stone formers). The inhibitory effect of urinary macromolecules with molecular weight greater than 10,000 Daltons did not undergo any change when the latter were recovered from concentrated or diluted urine, either in normal subjects or in the stone formers. CONCLUSIONS: Reduced CaOx supersaturation by means of water load has a protective effect with regards to CaOx crystallization in subjects who do not present any of the common urinary stone risk factors.