Chronic trimethyltin chloride exposure and the development of kidney stones in rats.

We recently reported that occupational exposure to trimethyltin (TMT) is a risk factor for developing kidney stones. To further examine the association between TMT exposure and the formation of kidney stones, we conducted a 180-day animal study and exposed the randomly grouped Sprague-Dawley (SD) rats to TMT in the drinking water at doses of 0, 8.2, 32.8 and 131.3 µg kg(-1) day(-1). Transient behavioral changes were observed in the high-dose group during the first 2 weeks of exposure. TMT exposure led to a significant dose-dependent inhibition of renal H(+)/K(+)-ATPase and an increase in urinary pH. In comparison to no kidney stones being identified in the control and the lowest dose group, 1 rat in the 32.8 µg kg(-1) day(-1) dose group and 3 out of 9 rats in the 131.3 µg kg(-1) day(-1) dose group were found to have stones in the kidney/urinary tract. Pathological analysis showed that more wide spread calcium disposition was observed in kidneys of rats with TMT exposure compared with the rats in the control group. However, X-ray diffraction (XRD) analysis found that the kidney stones were mainly composed of struvite with the formula: NH4MgPO4 6H2O, while calcium-containing components were also detected. Together, this study further demonstrates through animal studies that chronic exposure to a relatively low level of TMT induces nephrotoxicity and increases the risk for developing kidney stones.

Effect of magnesium dose on amount of pharmaceuticals in struvite recovered from urine.

Phosphorus (P) recovery was carried out through struvite precipitation from urines. Human urine, however, contains not only high nutrients for plants, such as P and nitrogen, but also pharmaceuticals and hormones. In this work, effects of magnesium (Mg) dose (in terms of Mg:P ratio) on P recovery efficiency and pharmaceutical amounts contained in struvite were investigated. Batch-scale experiments of synthetic and human urines revealed that struvite precipitation formed more X-shaped crystals with an increased molar ratio of Mg:P, while the amount of pharmaceuticals (tetracycline, demeclocycline, and oxytetracycline) in struvite decreased with an increased molar ratio of Mg:P. The lowest pharmaceutical amounts in struvite were found at the Mg:P ratio of 2:1 from both samples. Moreover, the maximum P recovery efficiency, quantity and purity of struvite were found in the range of 1.21 to 2:1. It indicated that the molar ratio of Mg:P has a significant impact on struvite precipitation in terms of pharmaceutical amounts in struvite; morphology, quantity and purity of struvite; and P recovery.

Phosphorus recovery: minimization of amount of pharmaceuticals and improvement of purity in struvite recovered from hydrolysed urine.

Struvite (MgNH4PO4·6H2O) is normally used as a fertilizer in agriculture, where struvite crystallization from hydrolysed human urine is a simple and reliable method for phosphorus (P) recovery. Human urine, however, contains high amount of pharmaceuticals, which may cause health risk for applications. This research investigates the possibility of decreasing the amount of pharmaceuticals (tetracycline, demeclocycline and oxytetracycline) in struvite crystals recovered from synthetic and human urines by focusing on storage time, and of increasing the quality of struvite production. Urines were stored for different times up to 15 days prior to recovery of phosphorus by two steps, spontaneous precipitation and struvite crystallization. The morphology of spontaneous precipitates and struvite crystals was observed. Spontaneous precipitation removed around 17-24% of phosphate from synthetic and human urines, while pharmaceuticals were removed with a quite high amount at a short storage time (5 days) and this amount decreased with increasing the storage time (10 and 15 days). Urines with>70% remaining phosphates were re-used for struvite crystallization by adding extra magnesium. It was found that maximum P-recovery efficiency could be achieved from struvite crystallization at 5-day storage time, 70% and 68% of remaining P in the separated supernatant from synthetic and human urines, respectively, whereas less than 1% pharmaceuticals remained in the struvite crystals from both samples. This indicates that the procedure in this work is a good method for phosphorus recovery, in which high struvite purity (>99%) is obtained with low amount of pharmaceuticals.

Effect of magnesium oxide or citrate supplements on metabolic risk factors in kidney stone formers with idiopathic hyperoxaluria: a randomized clinical trial.

Magnesium is one of the recommended treatments for calcium stone formers (CSFs) with hyperoxaluria. In this study, we compared the effect of magnesium oxide (MgO) or magnesium citrate (MgCit) with placebo on 24-hour urine (24-U) metabolites and the calcium oxalate supersaturation index (CaOx SS). In a randomized, double-blind, placebo-controlled clinical trial, 90 CSFs with idiopathic hyperoxaluria were recruited from a tertiary stone prevention clinic. Patients were randomly assigned into three groups: 120 mg MgO, 120 mg MgCit or placebo (supplements were taken three times per day, with meals). Finally, 76 patients were included in the final analysis. Analyses of 24-U were performed at baseline and after eight weeks. Study outcomes included changes in 24-U oxalate, magnesium, citrate, and CaOx SS. Dietary factors were controlled by 24-hour food recalls. Repeated measure ANOVA was used to compare the results. After the intervention, both MgO and MgCit supplements decreased 24-U oxalate excretion (-8.13±16.45 in the MgO group and -16.99±18.02 in the MgCit group) and CaOx SS compared to the placebo, with the effects of MgCit reaching statistical significance (p=0.011 and p=0.010, respectively). An increasing trend was observed for 24-U magnesium and citrate excretion without significant differences among groups. Interestingly, MgCit exhibited a significantly greater inhibitory effect on 24-U oxalate in patients with normal urine magnesium levels (p=0.021). Clinically, both MgO and MgCit reduced 24-U oxalate and CaOx SS compared to placebo. However, MgCit demonstrated a greater effect, especially in patients with normal urine magnesium levels.

X-ray microdiffraction and urine: a new analysis method of crystalluria.

The qualitative and quantitative analyses of crystalluria have clinical significance in the diagnosis and prognosis of urolithiasis. The aim of this paper is to provide a new accurate methodology to get qualitative and quantitative data on urine particulate in patients with renal stone disease.The procedure involves a urine collection, the separation of the solid residual by centrifugation, and its analysis by X-ray diffraction, utilizing a micro-diffractometer in order to analyze very low amounts of residual. The spectrum obtained was converted into 2 θ -I profiles and quantitatively refined by Rietveld method. The proposed methodology has the advantage to accurately quantify all crystalline phases and the amorphous component of the urine; anyway urine samples have to be centrifuged and analysed as soon as possible, because the quantitative results obtained by the X-ray microdiffraction showed that after some days and at room temperature urine increased significantly both amorphous and crystalline phases.

Effect of dietary water intake on urinary output, specific gravity and relative supersaturation for calcium oxalate and struvite in the cat.

It has been reported that daily fluid intake influences urinary dilution, and consequently the risk of urolithiasis in human subjects and dogs. The aim of the present study was to investigate the role of dietary moisture on urinary parameters in healthy adult cats by comparing nutritionally standardised diets, varying only in moisture content. A total of six cats were fed a complete dry food (6.3 % moisture) hydrated to 25.4, 53.2 and 73.3 % moisture for 3 weeks in a randomised block cross-over design. Urinary specific gravity (SG), urine volume, water drunk and total fluid intake were measured daily; relative supersaturation (RSS) for calcium oxalate (CaOx) and struvite was calculated using the SUPERSAT computer program. Cats fed the 73.3 % moisture diet produced urine with a significantly lower SG (P < 0.001) compared with diets containing 53.2 % moisture or lower. Mean RSS for CaOx was approaching the undersaturated zone (1.14 (sem 0.21); P = 0.001) for cats fed the diet with 73.3 % moisture and significantly lower than the 6.3 % moisture diet (CaOx RSS 2.29 (sem 0.21)). The effect of diet on struvite RSS was less clear, with no significant difference between treatment groups. Total fluid intake was significantly increased (P < 0.001) in the 73.3 % moisture diet (144.7 (SEM 5.2) ml, or 30 ml/kg body weight per d) compared with the 6.3 % (103.4 (SEM 5.3) ml), 25.4 % (98.6 (SEM 5.3) ml) and 53.3 % (104.7 (SEM 5.3) ml) moisture diets, despite voluntary water intake decreasing as dietary moisture intake increased. Cats fed the 73.3 % moisture diet had a higher total daily fluid intake resulting in a more dilute urine with a lower risk of CaOx when compared with the lower-moisture diets.

Lithogenic activity and clinical relevance of lipids extracted from urines and stones of nephrolithiasis patients.

We investigated contents and classes of urinary and stone matrix lipids, and evaluated their clinical relevance in nephrolithiasis patients. Lithogenic role of major lipid classes was explored. Urine (24 h) and stone samples were collected from 47 patients with nephrolithiasis. Control urines were obtained from 29 healthy subjects. Urinary 8-hydroxy-deoxyguanosine (8-OHdG), malondialdehyde (MDA), N-acetyl-ß-glucosaminidase (NAG) activity and total proteins were measured. Total lipids were extracted from centrifuged urines (10,000 rpm, 30 min) and stones by chloroform/methanol method. Major classes of lipids were identified using multi-one-dimensional thin-layer chromatography (MOD-TLC). Influence of each lipid class purified from stone matrices on stone formation was evaluated using crystallization and crystal aggregation assays. Urinary NAG activity and 8-OHdG were significantly elevated in nephrolithiasis patients. Total lipids in centrifuged urines of the patients were not significantly different from that of controls. In nephrolithiasis, urinary excretion of total lipids was linearly correlated to urinary MDA, 8-OHdG, NAG activity and total proteins. Lipid contents in stone matrices varied among stone types. Uric acid stone contained lower amount of total lipids than calcium oxalate and magnesium ammonium phosphate stones. MOD-TLC lipid chromatograms of healthy urines, nephrolithiasis urines and stone matrices were obviously different. Triacylglyceride was abundant in urines, but scarcely found in stone matrices. Stone matrices were rich in glycolipids and high-polar lipids (phospholipids/gangliosides). Partially purified glycolipids significantly induced crystal aggregation while cholesterol was a significant inducer of both crystal formation and agglomeration. In conclusion, total lipids in centrifuged urines did not differ between nephrolithiasis and healthy subjects. Our finding suggests that the significant sources of lipids in patients' urine may be large lipids-containing particles, which are removed in centrifuged urines. However, urinary lipid excretion in nephrolithiasis patients was associated with the extent of oxidative stress and renal tubular injury. Triacylglyceride was abundant in urines, but rarely incorporated into stones. Glycolipids were principal lipid constituents in stone matrices and functioned as crystal aggregator. Cholesterol purified from stone matrices bared crystal nucleating and aggregating activities.

Risk factors for the incidence of calcium oxalate uroliths or magnesium ammonium phosphate uroliths for dogs in Ontario, Canada, from 1998 to 2006.

OBJECTIVE: To investigate individual- and community-level contextual variables as risk factors for submission of calcium oxalate (CaOx) uroliths or magnesium ammonium phosphate (ie, struvite) uroliths for dogs to a national urolith center, as determined on the basis of urolith submission patterns. SAMPLE POPULATION: Records of 7,297 dogs from Ontario, Canada, with CaOx or struvite uroliths submitted to the Canadian Veterinary Urolith Centre from 1998 through 2006. PROCEDURES: Data were analyzed via multilevel multivariable logistic regression. RESULTS: Individual-level main effects and interactions significantly associated with the risk of submission of CaOx uroliths rather than struvite uroliths included age, sex, breed group, neuter status, body condition, dietary moisture content, diet type, sex-neuter status interaction, sex-age interaction, body condition-age interaction, and breed group-dietary moisture content interaction. In addition, median community family income and being located within a major urban center (ie, Toronto) were significant risk factors for submission of CaOx uroliths, compared with submission of struvite uroliths. CONCLUSIONS AND CLINICAL RELEVANCE: Individual-level and dietary factors for dogs affected the risk of submission of CaOx uroliths, relative to that of struvite uroliths. Interactions among these variables need to be considered when assessing the impact of these risk factors. In addition, community-level or contextual factors (such as community family income and residing in a densely populated area of Ontario) also affected submission patterns, although most of the variance in the risk for submission of CaOx uroliths, compared with the risk for submission of struvite uroliths, was explained by individual-level factors.

Factors affecting struvite (MgNH4PO4.6H2O) crystallization in feline urine.

Factors affecting struvite, a magnesium-ammonium-phosphate complex (MgNH(4)PO(4).6H(2)O), in feline urine were evaluated. Incubation of just "urine mineral (UM)" solution, in which mineral concentrations are compatible with those in feline urine, for 4 h at 37 degrees C did not induce the formation of crystals. Similarly, incubation of urine alone did not produce crystals. However, struvite crystals were formed by the addition of urine to UM solution. Mg, NH(3) and P were all required for urine-induced struvite crystallization. The lower molecular weight (LMW) fraction of urine was essential for struvite crystal formation, and the higher molecular weight (HMW) fraction enhanced formation of LMW-induced struvite crystals. The effects of urine proteins further fractionated by column chromatography were examined. A protein at >250 kDa and cauxin, a major urine protein recently identified as a regulator of felinine production, potentiated struvite crystal formation induced by the LMW fraction. In contrast, Tamm-Horsfall glycoprotein, a urine protein thought to promote struvite crystallization, did not have this activity. The present study reveals a novel mechanism of feline struvite crystallization.