A few comments on the recipes against kidney stones in the Croatian prayerbook.
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Biomedical subjects
Publications and source records attributed to H G Tiselius.
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OBJECTIVE: To study the variability in urine composition with respect to factors of importance for the calcium salt crystallization process and to test the reliability of using one or several urine samples in the clinical evaluation. PATIENTS AND METHODS: Twelve patients collected 16-hour daytime and 8-hour night urine samples during 4 days of the same week. The urine was analysed for calcium, oxalate, phosphate, magnesium, citrate and pH, and the ion activity products of CaOx [AP(CaOx) index] and CaP were calculated. The risk of CaOx crystallization, as well as the inhibition of CaOx crystal growth and aggregation, were assessed. RESULTS: There was a good correlation between estimates of the AP(CaOx) index in the different samples, as well as between the AP(CaOx) index and the direct assessment of the risk of CaOx crystallization in the night and daytime urine samples. There was, however, a pronounced intra-individual variation of all variables and parameters. With the assumption that an abnormality would appear in at least one of the four samples, we found that in more than 80% of the cases, two 24-hour (16 + 8 h) urine samples were sufficient to establish whether the patient had a normal or an abnormal urine composition. CONCLUSION: Urine samples collected during two 24-, 16- or 8-hour periods appear to be useful for detecting biochemical abnormalities considered of importance for CaOx stone formation.
Approximate estimates of the ion-acitivity products of calcium phosphate and calcium oxalate in distal tubular urine were derived from the 16-h urinary excretion of calcium, oxalate, citrate, magnesium and phosphate. Urine variables were obtained from 96 normal subjects and 277 calcium stone formers and the calculations were carried out with iterative approximation using the EQUIL2 program. With respect to other ions of importance for the ion-activity products, the urine was assumed to have a fixed composition with pH 6.45. Significantly higher ion-activity products of both calcium phosphate and calcium oxalate were recorded in stone formers. It was concluded that diurnal variations in urine composition and pH might result in peaks of calcium phosphate supersaturation in distal tubular urine whereby a crystallization can occur. In association with abnormalities in terms of promotion and inhibition of calcium salt crystallization, such a precipitation can be of importance for the subsequent formation of calcium renal stones.
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.
In order to reflect the risk of calcium stone formation, risk formulas have been described in the literature with the objective of being able to predict the further course of the stone disease. Some of these formulas are reviewed in this paper. Various results were obtained when different risk expressions were related to the severity of the stone disease. Although a reliable prediction of the future course of the disease most certainly cannot be made by analysis of the variables included in these expressions, several of the risk formulas differed significantly between patients with and without recurrent stone formation during a reasonable follow-up period. Some risk formulas might thus be helpful, at least to some extent, in selecting those patients in whom continuous stone formation can be anticipated and in whom active therapeutic measures should be beneficial and worthwhile. With an increased understanding of the mechanisms of calcium oxalate stone formation and our possibilities of measuring the relevant risk factors, it is likely that improved risk formulas with an increased predictive power can be developed. Until this becomes a reality, in most cases we have to combine important information on the history and clinical observations of the disease with a risk formula that offers a high degree of discrimination with respect to the risk of further stone formation.
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Primary Sjögren's syndrome may be complicated by distal renal tubular acidosis (dRTA) and hypocitraturia, which are risk factors for calcium stone formation. Approached from a different perspective, in patients with urolithiasis and dRTA, autoantibodies and various autoimmune diseases are not uncommon. In search for signs of autoimmune disease, we analysed antinuclear antibodies and total levels of serum IgG in 197 hypocitraturic stone formers (67 women and 130 men). Antinuclear antibodies were present in 1.5% of the men and in 18% of the women. An isolated increase in serum IgG was found in 9% of the men and in 3% of the women. Anti-SS-A antibodies were analysed in a subgroup of 46 women and were estimated to occur in 16% of all hypocitraturic stone forming women. Four of 4 examined women, but no men, fulfilled the criteria of definite or possible primary Sjögren's syndrome. We recommend the analysis of anti-SS-A antibodies in female hypocitraturic stone formers.
Distal renal tubular acidosis (dRTA), which occurs in patients with primary Sjögren's syndrome (SS), is a risk factor for the development of urolithiasis. Twenty-seven patients with SS were evaluated with respect to biochemical risk factors of calcium stone formation. Sixteen had no history of urolithiasis (group 1) whereas 11 had such a history (group 2). The stone composition was known for seven of the patients, and calcium phosphate was the major stone constituent in all of them. dRTA was present in all patients in group 2, and in 7 of the 16 patients in group 1. Hypocitraturia was common in both groups, and the urinary excretion of citrate did not differ between the two groups. There was a higher urinary excretion of calcium and urate in group 2 and this group also had a higher urine volume. The risk of forming a urine supersaturated with calcium oxalate (CaOx) expressed in terms of AP(CaOx)index(s), which is an approximate estimate of the ion-activity product of CaOx calculated for a 24-h urine volume of 1500 ml, was higher in stone formers. A similarly derived estimate of the ion-activity product of calcium phosphate, AP(CaP)index(s), was calculated for a urine pH of 7. Although AP(CaP)index(s) was not significantly higher in group 2, there was a good correlation between AP(CaP)index(s) and AP(CaOx)index(s). We conclude that the urine composition in patients with SS, dRTA and urolithiasis is similar to that of other stone-forming patients with dRTA, and recurrence preventive therapy can be designed as for these patients.
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 (APCaOx) at corresponding degrees of crystallization. The APCaOx 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 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.
The effect of macromolecules on the crystallization in solutions with an ion-composition and a pH corresponding to that of urine in the distal part of the distal tubuli was examined by recording the number and volume of crystals in a Coulter Multisizer and by studying the crystal morphology with scanning electron microscopy at different degrees of evaporation. The experiments were carried out with 100 ml samples of salt solutions with and without different concentrations of dialysed urine (dU) from normal subjects. Addition of dU resulted in a greater number of crystals and a reduction in the mean crystal volume (MCV). Under the experimental conditions, the maximal effect of the macromolecules appeared to be accomplished in solutions with an initial dU concentration of 10%. The precipitate was strongly suggestive of calcium phosphate (CaP) as shown by scanning electron microscopy and Raman spectroscopy. This conclusion was further supported by the ion-activity products of calcium oxalate (CaOx) and different CaP salts in those samples in which crystal formation was recorded. The obtained results give support to the view that macromolecules might exert a promotive effect on the nucleation of CaP. The macromolecules also appear to counteract the development of large CaP crystals, but whether this is due to an inhibition of crystal growth, an inhibition of crystal aggregation or both could not be concluded from these experiments. The way in which CaP crystals initially form in the nephron might be of importance for the subsequent crystallization of CaOx and the formation of CaOx containing stones.
The formation of stones in patients with cystinuria can be counteracted by reducing the urinary concentration of cystine and by increasing its solubility. Thirty-one patients with homozygous cystinuria and treated with tiopronin (2-mercaptopropionylglycine) were followed for between 0.4 and 12 years (median 8.8). With the aim of avoiding cystine concentrations above 1200 mumol/l, the daily dose varied between 500 and 3000 mg (median 1500). The therapeutic effect was evaluated from the clinical symptoms and repeated radiographic examinations. The rate of stone formation during the treatment period was reduced by 60% in comparison with the pretreatment period (P < 0.001). The frequency of active stone removal was reduced by 72% (P < 0.05). The formation of new stones was associated with a higher cystine concentration than was the case during periods when stone formation and stone growth were excluded (P < 0.05). The probability of new stone formation increased with increasing concentrations of cystine up to 1100 mumol/l, but stone formation was not accentuated above 1200 mumol/l. There was no significant relationship between the 24 h excretion of cystine and stone formation. It is concluded that the formation of cystine stones can be efficiently counteracted during treatment with tiopronin, guided by analysis of the concentration of urinary cystine.
In an attempt to improve the diagnostic value of urine analysis in patients with homozygous cystinuria, we studied the diurnal variation in urine composition. A simplified estimate of the ion-activity product of cystine was used to increase the probability of identifying patients with a particular risk of stone formation. Eight 6-h urine samples were collected during two 24-h periods. The highest urinary excretion of cystine was recorded between 1200 and 1800 hours and the lowest between 0000 and 0600 hours, whereas the urinary cystine concentration was highest between 0000 and 0006 hours and lowest between 1200 and 1800 hours. The approximate ion-activity product of cystine had a maximal level between 0000 and 0600 hours but a minimal level between 0600 and 1200 hours. The differences between different periods were numerically more pronounced in terms of the ion-activity product of cystine than in terms of concentration. The peak concentrations of cystine in 6-h samples were about 90% higher than the corresponding concentrations in 24-h urine samples. It is concluded that the analysis of cystine in 6-h urine samples reveals transient episodes of cystine supersaturation that otherwise will remain undetected. Further studies are, however, needed to establish its usefulness in clinical practice.
A procedure is described to avoid problems with stents that either have been inserted too far in the ureter or have migrated to a level above the bladder and to solve this problem easily if it nevertheless occurs. A knot is tied on the pulling thread at the end of the stent to create a loop of approximately 2 cm. With such a pre-caution, the loop usually remains in the bladder in case of limited stent retraction. For stents that retract to a higher level in the ureter, a special extraction device was constructed from a standard ureteral catheter. These two procedures have so far made it possible to easily remove or adjust the position of 13 of those 15 stents (87%) in 225 patients in whom the distal end became positioned proximal to the ureteral orifice. The procedure was in all cases undertaken without regional or general anesthesia and without the need for ureteroscopy.
PURPOSE: We determine whether stone formers and normal subjects can be distinguished in terms of supersaturation with calcium oxalate, and inhibition of calcium oxalate growth and aggregation. MATERIALS AND METHODS: An estimate of the ion activity product of calcium oxalate was obtained from the analysis of calcium, oxalate, citrate and magnesium in 16-hour urine samples obtained between 6 a.m. and 10 p.m. The inhibition of calcium oxalate crystal growth and aggregation was assessed in 8-hour urine specimens obtained between 10 p.m. and 6 a.m. RESULTS: The ion activity product of calcium oxalate was higher and inhibition of crystal aggregation was lower in stone formers than in normal subjects. Inhibition of crystal growth was lower only in male stone formers. Quotient 1 (10(2) x ion activity product of calcium oxalate/inhibition of crystal growth), quotient 2 (10(2) x ion activity product of calcium oxalate/inhibition of crystal aggregation) and quotient 3 (10(4) x ion activity product of calcium oxalate/[inhibition of crystal growth x inhibition of crystal aggregation]) were significantly higher in stone formers. CONCLUSIONS: The biochemical risk situation in calcium oxalate stone formers can be summarized by quotient 2 or 3.
A routine programme for investigation of patients with renal stone disease is presented. The different steps in this process are determined by the stone composition and the patient's previous history of stone formation. Assessment of the supersaturation and the crystallization properties are carried out in urine collected during a 24-hour period in one 16-hour and one 8-hour sample. The programme described in this paper has been formulated with a therapeutic goal in mind, whereby expensive and unnecessary procedures are avoided.
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The rate of crystal sedimentation in a suspension of calcium oxalate monohydrate (COM) crystals was determined spectrophotometrically in the presence and absence of dialysed urine and citrate. A reduced rate of crystal sedimentation after stirring was recorded in suspensions containing citrate in concentrations between 0.33 and 1.67 mmol/l. The sedimentation rate was reduced in the presence of a 0.3-3.3% concentration of dialysed urine, with increased inhibition of crystal sedimentation when the concentration of urine was increased. A comparison of the inhibition of COM crystal sedimentation in whole urine and in dialysed urine from normal subjects and stone-formers disclosed significantly higher values (P < 0.05) in the dialysed urine. The results support previous observations that physiological concentrations of citrate might efficiently inhibit the aggregation of COM crystals. Furthermore even low concentrations of both whole urine and dialysed urine are apparently very efficient inhibitors of COM crystal aggregation.
Stone and urine composition were analysed in 75 men and 40 women with recurrent calcium oxalate stone disease (group R) and in 48 men and 19 women who had formed only one calcium-oxalate-containing stone (group S). Patients who had developed stones with a large fraction of calcium phosphate were significantly more frequent in group R than in group S. There was furthermore a higher excretion of calcium and higher calcium oxalate supersaturation levels in patients with stones containing more than 25% calcium phosphate. It was concluded from these observations that the calcium phosphate content of renal stones might be a useful factor in predicting the future course of the disease.