Synergistic effect of doxycycline and aqueous extract of irradiated khella on structure of nanobacteria isolated from kidney stones: In vitro and in vivo studies.

Kidney stones have been associated with an increased risk of chronic kidney diseases, end-stage renal failure. This study is devoted to isolate nanobacteria from patients with active urolithiasis and investigate the in vitro and in vivo antinanobacterial activity of some antibiotics alone or in combination with extracts of irradiated herbs from certain medicinal plants. Nanobacteria were detected using scanning (SEM) and transmission (TEM) electron microscopy, protein electrophoresis (SDS-PAGE) and DNA profile. The antimicrobial susceptibility of some biofilm-producing nanobacterial isolates was evaluated. The effect of medicinal plant extracts on growth was tested. A combination treatment between the most potent extracts and antibiotics was tested on biofilm production, protein profile, release of 260 nm absorbing material, protein content, and ultrastructure of the strongest biofilm producers. In vivo study of nanobacteria and its treatment by the most potent agents was evaluated on male rats. Renal function was measured in serum; histological examination and oxidative stress parameters were determined in kidney tissues. Results showed that streptomycin, trimethoprim/sulfamethoxazole, doxycycline, and water extracts of irradiated khella at 6 kGy had antinanobacterial activity. Meanwhile, the synergistic effect of the aqueous extract of irradiated Khella and doxycycline showed higher inhibition activity on microbial growth and biofilm production. They affected dramatically the strength of its cell membrane and subsequently its ultrastructure. Moreover, these results are confirmed by ameliorations in renal function and histological alterations. It could be concluded that the combination of DO and an aqueous extract of irradiated khella has an antinephrotoxic effect against nanobacteria-induced renal toxicity.

Identification of novel inhibitor against human phosphoethanolamine cytidylyltransferase from phytochemicals of Citrus sinensis peel extract by in vitro and in silico approach.

Kidney stone is a major global menace that demands research on nonsurgical treatment involving biological compounds for the benefit of the patients. Among the biological extracts, citric acid is traditionally used to dissolve kidney stones. The current research focuses on evaluating the in vitro anti-urolithiatic activity and in silico study of ethanolic extract of Citrus sinensis (ECS) peel against c: phosphoethanolamine cytidylyltransferase (PCYT). The diuretic activity was evaluated using in vitro model against the synthesized calcium oxalate crystals and cytotoxicity study in Madin-Darby canine kidney cell lines. The phytochemicals were identified using gas chromatography-mass spectroscopy. The interaction mechanism was studied using computational docking studies to confirm their involvement in the dissolution of calcium oxalate kidney stones. Further molecular properties, drug-likeness, ADME (absorption, distribution, metabolism, and excretion), and toxicity analysis were followed for the ligands using software tools. 5-Hydroxymethylfurfural, 2,4-di-tert-butylphenol, 2-methoxy-4-vinylphenol, 6-octen-1-ol, 3,7-dimethyl-, acetate (citronellyl acetate), 3',5'-dimethoxyacetophenone, and ethyl alpha-d-glucopyranoside showed good binding affinities against PCYT. Moreover, the docking studies showed the ligand 3',5'-dimethoxyacetophenone has the highest binding energy (-6.68 kcal/mol) for human CTP. The present investigation concludes that these compounds of C. sinensis peel extract compounds are responsible as novel inhibitors against human CTP and extend their use in the pharmaceutical drug development process.

Prophylactic and curative potential of peppermint oil against calcium oxalate kidney stones.

Mentha piperita L., a well-known traditional herb, constitutes essential oil as one of its important constituent, used for its flavor, aroma and therapeutic applications. Based on the antioxidant, antispasmodic and nephroprotective potential, the essential oil of Mentha piperita was evaluated for its preventive and curative effects against ethylene glycol induced urolithiasis. Peppermint oil (Mp.Eo) was evaluated for its antioxidant potential by DPPH method. Urolithiasis was developed in male rats by the administration of ammonium chloride and ethylene glycol in drinking water. Different doses of Mp.Eo (10, 30 and 50 mg/kg) and cystone, the standard antiurolithic drug (500 mg/kg), were given along with stone-inducing regimen in prophylactic model and after intoxication for the next fourteen days in curative model. Urine and serum were analyzed for various biochemical parameters. One representative kidney from each group was studied for changes in histological parameters. Mp.Eo was found to be effective against urolithiasis-associated changes including crystalluria, polyuria and acidic urine. Mp.Eo also neutralized the altered levels of urinary uric acid, magnesium, total protein, serum creatinine and serum BUN. The data obtained from the present study demonstrated the therapeutic importance of peppermint oil against urolithiasis.

Sulfamethoxazole-induced sulfamethoxazole urolithiasis: a case report.

BACKGROUND: Drug-induced urolithiasis falls into two categories: drug-induced and metabolically-induced. Certain antimicrobials are associated with each; sulfonamides are associated with drug- or metabolite-containing calculi when taken in large doses over a long period of time. Trimethoprim-sulfamethoxazole, a member of the sulfonamide family, is a rare cause of drug-induced calculi. Cases of sulfonamide urolithiasis occurring in patients with known stone disease have rarely been reported. CASE PRESENTATION: We report a case of a patient with a brief history of recurrent calcium oxalate nephrolithiasis requiring 2 ureteroscopic procedures whose existing 6 mm lower pole renal stone more than quadrupled in size to form a 4 cm renal staghorn after 4 months of high-dose treatment for Nocardia pneumonia with trimethoprim-sulfamethoxazole. After ureteroscopy with laser lithotripsy and basketing of fragments, the stone was found to be predominantly composed of N4-acetyl-sulfamethoxazole, a metabolite of sulfamethoxazole. CONCLUSION: Stones composed of sulfamethoxazole or its metabolites are rare but have known associated risk factors that should be considered when prescribing this antibiotic. This case report illustrates additional risk factors for consideration, including pre-existing urinary calculi that may serve as a nidus for sulfamethoxazole deposition, and reviews treatment and prevention methods.

Ultra-Mini-Percutaneous Nephrolithotomy for the Treatment of Upper Urinary Tract Stones Sized between 10-20 mm in Children Younger Than 8 Years Old.

PURPOSE: With the invention of miniature devices, it has been advised to apply less aggressive methods for the management of upper urinary tract stones, especially in children. In the recent years, ultra-mini percutaneous nephrolithotomy (UMP) has been used for the treatment of upper urinary tract stones in order to perform surgeries with less complications and more acceptable outcomes. Results reported from different medical centers have been promising. MATERIALS AND METHODS: Twenty-two children aged less than 8 years old with upper urinary stones sized between 10-20 mm underwent UMP. Inclusion criteria was solitary unilateral kidney stone, stone size between 10-20 mm, normal renal function tests, absence of any congenital malformations, and history of previous ESWL failure. Data including age, sex, side of kidney involvement, size of stone, location of stone, duration of surgery, duration of hospitalization, stone composition, need for blood transfusion, damage to adjacent organs, postoperative fever, septicemia after surgery, need for narcotics, further need for a complementary method, stone-free rate, pre and post-operative hemoglobin levels, and urinary leakage from the access tract were extracted from patients' medical files and were recorded. RESULTS: The mean age (± standard deviation) of children was 5.22 (±1.57) years. Fourteen (63.6%) patients were male. Fifteen (68.2%) renal stones were located in the right kidney, and 82% of patients had pelvis stones. 13 (59%) patients' stones were composed of calcium oxalate. Stone-free rate was 95.5%. In none of the cases urinary leakage, septicemia after surgery, injury to adjacent organs, and need for blood transfusions was reported. CONCLUSION: Ultra-mini percutaneous nephrolithotomy is an efficient and safe method for treating urinary stones sized between 10-20 mm in children.

Anti-urolithiatic and anti-inflammatory activities through a different mechanism of actions of Cissus gongylodes corroborated its ethnopharmacological historic.

ETHNOPHARMACOLOGICAL RELEVANCE: Species Cissus gongylodes has been used in the traditional medicine in South America and India for the treatment of urolithiasis, biliary and inflammatory problems without any scientific evidence. AIM OF THE STUDY: This work was developed to investigate for the first time the anti-inflammatory and anti-urolithiatic activities of leaf decoction of C. gongylodes. MATERIALS AND METHODS: Decoction was subjected to anti-inflammatory evaluation by the in vivo assay of ear oedema and quantification of the main mediators of inflammation PGE2 and LTB4, and the cytokine TNF-α. The decoction's anti-urolithiatic activity was determined by different in vitro assays to evaluate the inhibition and dissolution of the most prevalent types of kidney stones: calcium oxalate (CaOx) and struvite. Diffusion in gel technique and fresh urine of a patient with renal stone were used to investigate the inhibition and dissolution of CaOx, respectively, and the single diffusion gel growth technique was used to evaluate the inhibition and dissolution of struvite crystals. The decoction was chemically characterized by UHPLC-ESI-HRMS analysis. RESULTS: Decoction showed in vivo anti-inflammatory activity by potent decreasing the level of both the main mediators of inflammation and dose-dependent in vitro anti-urolithiatic action by inhibition and dissolution of both type of crystals, CaOx and struvite. CONCLUSIONS: Results obtained corroborate the reports of the traditional use of the decoction of Cissus gongylodes. Besides, it showed multi-target mechanisms actions, inhibition of the main inflammatory pathways, and inhibition/dissolution of the most prevalent types of crystals on urolithiasis. These actions make the decoction a promissory source to the development of new and more efficient drugs.

Vitamin D and Kidney Stones.

This review explores the relationship between vitamin D supplementation and lithogenesis. A causal relationship has been assumed despite myriad studies demonstrating that therapeutic doses of vitamin D do not increase lithogenic risk. Select stone formers may be at increased risk for recurrence with vitamin D supplementation, possibly from CYP24A1 gene mutations. Additionally, the evidence for who is vitamin D deficient, and the benefits of supplementation in those not at risk for rickets, is sparse. Concerns may be avoidable as vitamin D screening appears unnecessary in most patients, and superior pharmacology is available which increases bone density, while decreasing stone formation.

[Nutritional intervention in the control of gallstones and renal lithiasis]. / Intervención nutricional en el control de la colelitiasis y la litiasis renal.

INTRODUCTION: Cholelithiasis and kidney stones are frequent pathologies in developed countries. Gallstones can be pigmentary, cholesterol (75%) or mixed. Age, female sex, obesity, rapid weight loss, consumption of refined sugars, saturated fat, iron deficiency, vitamin D and low intake of fiber and vitamin C are factors associated with an increased risk of cholelithiasis. On the other hand, the intake of ω-3 fatty acids, oleic acid, calcium, magnesium, fiber, fruits and vegetables, dairy products, nuts, coffee, moderate consumption of alcohol, vitamin C supplements, physical exercise and a regular diet have a protective paper. The most frequent kidney stones are calcium oxalate followed by mixed ones (oxalate and calcium phosphate), struvite, uric acid and cystine. A high water intake is recommended (> 2.5 l / day), varying the type of recommended or unadvisable food depending on the type of calculus. In oxalic lithiasis it is recommended to reduce the consumption of meat, moderate that of spinach, Swiss chard, asparagus, chocolate and avoid excessive sodium intake. The administration of oxalate-degrading probiotics (Lactobacillus) may reduce intestinal absorption, although further studies are necessary to corroborate these results. In calcium phosphate acidifying diet is recommended and limit the consumption of coffee and tea. The prevention of uric calculus is based on hydration with alkalizing drinks and vegetarian diet, decreasing foods rich in purines (liver, kidney, fish eggs, anchovies, sardines and seafood) and in calculus of cystine diet is recommended alkalizing. Since the formation of struvite calculi is due to urinary infections, pharmacological treatment and the consumption of acidifying diets, moderation of the intake of phosphate-rich foods and limiting the contribution of fats and citrus fruits are necessary. The nutritional intervention is an effective measure in the prevention of biliary and renal lithiasis and prevent its recurrence.

INTRODUCCIÓN: La colelitiasis y litiasis renal son patologías frecuentes en países desarrollados. Los cálculos biliares pueden ser pigmentarios, de colesterol (75%) o mixtos. La edad, el sexo femenino, la obesidad, la pérdida rápida de peso, el consumo de azúcares refinados, la grasa saturada, la deficiencia de hierro y de vitamina D y la baja ingesta de fibra y vitamina C son factores asociados a mayor riesgo de colelitiasis. Por otro lado, la ingesta de ácidos grasos ω-3, ácido oleico, calcio, magnesio, fibra, frutas y verduras, lácteos, frutos secos, café, un consumo moderado de alcohol, suplementos de vitamina C, ejercicio físico y una alimentación regular desempeñan un papel protector. Las litiasis renales más frecuentes son de oxalato cálcico, seguidas de las mixtas (oxalato y fosfato cálcico), estruvita, ácido úrico y cistina. Se aconseja una elevada ingesta hídrica (> 2,5 l/día), variando el tipo de alimentos recomendados o desaconsejados en función del tipo de cálculo. En litiasis oxálica se recomienda reducir el consumo de carne, moderar el de espinacas, acelgas, espárragos, chocolate y evitar el aporte excesivo de sodio. La administración de probióticos degradantes de oxalato (Lactobacillus) podría reducir su absorción intestinal, aunque son necesarios más estudios para corroborar estos resultados. En las de fosfato cálcico se aconseja dieta acidificante y limitar el consumo de café y té. La prevención de cálculos de úrico está basada en la hidratación con bebidas alcalinizantes y dieta vegetariana, disminuyendo los alimentos ricos en purinas (hígado, riñón, huevas de pescado, anchoas, sardinas y mariscos), y en cálculos de cistina se aconseja el consumo de dietas alcalinizantes. Dado que la formación de cálculos de estruvita se debe a infecciones urinarias, es necesario un tratamiento farmacológico y el consumo de dietas acidificantes, moderar la ingesta de alimentos ricos en fosfatos y limitar el aporte de grasas y cítricos. La intervención nutricional es una medida eficaz en la prevención de la litiasis biliar y renal y para evitar su recurrencia.

In vitro effects on calcium oxalate crystallization kinetics and crystal morphology of an aqueous extract from Ceterach officinarum: Analysis of a potential antilithiatic mechanism.

Ceterach officinarum Willd is a plant widespread throughout Europe and used in southern Italy as a diuretic. Beliefs in the benefits of C. officinarum aqueous extract in the treatment of calcium oxalate kidney stones are widely held. Little is known, however, about the actual mechanism of its antilithiatic action. Our results in this in vitro study corroborate C. officinarum aqueous extract as a good source of antioxidants with a high antioxidant effects. Our results also demonstrate a major impact of C. officinarum aqueous extract on in vitro induced calcium oxalate crystallization kinetics and crystal morphology, showing its critical role in kidney stone formation and/or elimination. We show that progressively increasing doses of C. officinarum aqueous extract cause a sequence of effects. A powerful inhibitory action on calcium oxalate monohydrate (COM) growth and aggregation is first observed. C. officinarum aqueous extract also appears highly effective in stimulating nucleation increasing the number and reducing the size of COM crystals, which become progressively thinner, rounded and concave in a dose-dependent manner. These shape-modified COM crystals are known to be less adherent to renal tubular cells and more easily excreted through the urinary tract preventing kidney stone formation. Further, C. officinarum aqueous extract promotes the formation of calcium oxalate dihydrate (COD) rather than the monohydrate so that, at the highest concentrations used, only COD crystals are observed, in significant greater numbers with a clear reduction in their size, in a dose-dependent manner. Furthermore, AFM analyses allowed us to reveal the presence of C. officinarum component(s) on the surfaces of COD and modified COM crystals. The crystal surface adsorbed component(s) are shown to be similarly active as the total aqueous extract, suggesting a trigger factor which may direct crystal modification towards COD forms. In urolithiasis pathogenesis COD crystals are less dangerous than the COM forms due to their lower affinity for renal tubular cells. Our results are important in understanding the mechanisms which guide the modification induced by C. officinarum on the crystallization process. Based on these data, together with no adverse toxic effect being observed on the in vitro model of human intestinal enterocytes, C. officinarum aqueous extract could represent an attractive natural therapy for the treatment of urolithiasis.

[Role of drinking and dietary factors in effective dissolution therapy and recurrence prevention of uric acid kidney stones].

The use of alkaline mineral waters leads to alkalization of urine and an increase in level of urinary citrate, which represent important factor inhibiting the formation of urinary stones. Combination of alkaline mineral waters with citrates facilitates the achievement of target urine pH level not only during dissolution therapy, but also during recurrence prevention. Alkalization of urine and reducing of the influence of alimentary factor dont preclude drug therapy. Patients should be counselled about complex strategies aimed to modifiable risk factors for urinary stone disease.

Hydroxycitrate: a potential new therapy for calcium urolithiasis.

Alkali supplements are used to treat calcium kidney stones owing to their ability to increase urine citrate excretion which lowers stone risk by inhibiting crystallization and complexing calcium. However, alkali increases urine pH, which may reduce effectiveness for patients with calcium phosphate stones and alkaline urine. Hydroxycitrate is a structural analog of citrate, widely available as an over-the-counter supplement for weight reduction. In vitro studies show hydroxycitrate has the capacity to complex calcium equivalent to that of citrate and that it is an effective inhibitor of calcium oxalate monohydrate crystallization. In fact, hydroxycitrate was shown to dissolve calcium oxalate crystals in supersaturated solution in vitro. Hydroxycitrate is not known to be metabolized by humans, so it would not be expected to alter urine pH, as opposed to citrate therapy. Preliminary studies have shown orally ingested hydroxycitrate is excreted in urine, making it an excellent candidate as a stone therapeutic. In this article, we detail the crystal inhibition activity of hydroxycitrate, review the current knowledge of hydroxycitrate use in humans, and identify gaps in knowledge that require appropriate research studies before hydroxycitrate can be recommended as a therapy for kidney stones.

Variation in Kidney Stone Composition Within the United States.

INTRODUCTION AND OBJECTIVES: Kidney stone incidence has been known to vary with temperature and climate. However, little is known about any variation in the composition of kidney stones across different regions of the United States. We attempted to evaluate whether stone composition changes depending on region. METHODS: We were given access to de-identified data from LABCORPs database of kidney stone composition from August 1, 2016, to October 24, 2016, for states in seven representative areas of the country: Virginia, Minnesota, Florida, Arizona, Colorado, California, and Texas. We analyzed each component of kidney stones with optical microscopy supplemented with Fourier-transform infrared spectroscopy (FT-IR) spectrometry using both the percentage of the stone that was composed of that component as well as a binary variable coded none vs any. Univariate associations between component and state were examined using chi-square or Fisher's exact test for the binary indicator, and analysis of variance for the continuous percentage. The same set of analyses was used for decade of age vs each component. The association between age and state was examined using analysis of variance. RESULTS: Data were available for 4335 kidney stones, from patients in the 7 states mentioned. The most common components across all stones were calcium oxalate monohydrate and calcium phosphate (both present in 93% of stones), calcium oxalate dihydrate (in 57% of stones), and uric acid (in 12% of stones). Stone composition did not vary widely across regions, except for uric acid stones, which were more prevalent in Florida compared to other states, with an odds ratio of 1.43 (95% confidence interval 1.12, 1.83). CONCLUSION: Kidney stone composition does not vary widely by region within the United States. Although temperature and humidity play a role in stone incidence, there does not appear to be a large variation between different climates, with the exception of uric acid stone formation in Florida.

Inhibitory effects of taraxasterol and aqueous extract of Taraxacum officinale on calcium oxalate crystallization: in vitro study.

OBJECTIVE: We investigated and compared the effects of taraxasterol, aqueous extract of T. officinale (AET) aerial part, and potassium citrate (PC) on calcium oxalate (CaOx) crystallization in vitro. MATERIALS AND METHODS: CaOx crystallization was induced by adding sodium oxalate to synthetic urine. Taraxasterol (2.5, 5, 7.5 and 12.5 µg/mL), extract (1, 2, 4 and 8 mg/mL), and PC (100, 150, 200 and 350 mg/mL) were subjected to anti-crystallization activities. The absorbance and %inhibition of nucleation of CaOx crystals were evaluated by spectrophotometer at 2, 4, 6, 8, 10, 20, 30, 40, 50 and 60 min and the number and morphology of crystals were studied by light microscopy after 60 min. RESULTS: Presence of taraxasterol, extract and PC decreased absorbance in experimental samples compared to control, significantly. The nucleation of crystals is inhibited by taraxasterol, extract, and PC (26-64, 55-63 and 60-70%, respectively). The number of CaOx crystals were decreased in presence of taraxasterol (p < .01), extract (p < .001), and PC (p < .001) in a dose-dependent manner. Presence of taraxasterol, extract, and PC decreased the number of CaC2O4 monohydrate, while increased CaC2O4 dihydrate crystals, significantly. Also, the diameter of CaC2O4 dihydrate crystals was decreased in presence of taraxasterol, extract and PC, significantly. CONCLUSIONS: This research indicated that taraxasterol and extract have anti-crystallization activities and effectiveness of the extract is more potent than taraxasterol. It could be because of another constituent in the extract with the synergistic effect.

Medical and dietary interventions for preventing recurrent urinary stones in children.

BACKGROUND: Nephrolithiasis, or urinary stone disease, in children causes significant morbidity, and is increasing in prevalence in the North American population. Therefore, medical and dietary interventions (MDI) for recurrent urinary stones in children are poised to gain increasing importance in the clinical armamentarium. OBJECTIVES: To assess the effects of medical and dietary interventions (MDI) for the prevention of idiopathic urinary stones in children aged from one to 18 years. SEARCH METHODS: We searched multiple databases using search terms relevant to this review, including studies identified from the Cochrane Central Register of Controlled Trials (CENTRAL, 2017, Issue 1), MEDLINE OvidSP (1946 to 14 February 2017), Embase OvidSP (1980 to 14 February 2017), International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Additionally, we handsearched renal-related journals and the proceedings of major renal conferences, and reviewed weekly current awareness alerts for selected renal journals. The date of the last search was 14 February 2017. There were no language restrictions. SELECTION CRITERIA: Randomized controlled trials of at least one year of MDI versus control for prevention of recurrent idiopathic (non-syndromic) nephrolithiasis in children. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. Titles and abstracts were identified by search criteria and then screened for relevance, and then data extraction and risk of bias assessment were carried out. We assessed the quality of evidence using GRADE. MAIN RESULTS: The search identified one study of 125 children (72 boys and 53 girls) with calcium-containing idiopathic nephrolithiasis and normal renal morphology following initial treatment with shockwave lithotripsy (SWL). Patients were randomized to oral potassium citrate 1 mEq/kg per day for 12 months versus no specific medication or preventive measure with results reported for a total of 96 patients (48 per group). This included children who were stone-free (n = 52) or had residual stone fragments (n = 44) following SWL. Primary outcomes:Medical therapy may lower rates of stone recurrence with a risk ratio (RR) of 0.19 (95% confidence interval (CI) 0.06 to 0.60; low quality evidence). This corresponds to 270 fewer stone recurrences per 1000 (133 fewer to 313 fewer) children. We downgraded the quality of evidence by two levels for very serious study limitations related to unclear allocation concealment (selection bias) and a high risk of performance, detection and attrition bias. While the data for adverse events were incomplete, they reported that six of 48 (12.5%) children receiving potassium citrate left the trial because of adverse effects. This corresponds to a RR of 13.0 (95% CI 0.75 to 224.53; very low quality evidence); an absolute effect size estimate could not be generated. We downgraded the quality of evidence for study limitations and imprecision.We found no information on retreatment rates. SECONDARY OUTCOMES: We found no evidence on serum electrolytes, 24-hour urine collection parameters or time to new stone formation.We were unable to perform any preplanned secondary analyses. AUTHORS' CONCLUSIONS: Oral potassium citrate supplementation may reduce recurrent calcium urinary stone formation in children following SWL; however, our confidence in this finding is limited. A substantial number of children stopped the medication due to adverse events. There is no trial evidence on retreatment rates. There is a critical need for additional well-designed trials in children with nephrolithiasis.

Calcium and vitamin D have a synergistic role in a rat model of kidney stone disease.

Vitamin D supplementation in humans should be accompanied by calcium administration to avoid bone demineralization through vitamin D receptor signaling. Here we analyzed whether long-term exposure of rats to vitamin D supplementation, with or without a calcium-rich diet, would promote kidney stone formation. Four groups of rats received vitamin D alone (100,000 UI/kg/3 weeks), a calcium-enriched diet alone, both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Serum and urine parameters and crystalluria were monitored. Kidney stones were assessed by 3-dimensional micro-computed tomography, infrared spectroscopy, von Kossa/Yasue staining, and field emission scanning electron microscopy. Although serum calcium levels were similar in the 4 groups, rats receiving vitamin D had a progressive increase in urinary calcium excretion over time, especially those receiving both calcium and vitamin D. However, oral calcium supplementation alone did not increase urinary calcium excretion. At 6 months, rats exposed to both calcium and vitamin D, but not rats exposed to calcium or vitamin D alone, developed significant apatite kidney calcifications (mean volume, 0.121 mm(3)). Thus, coadministration of vitamin D and increased calcium intake had a synergistic role in tubular calcifications or kidney stone formation in this rat model. Hence, one should be cautious about the cumulative risk of kidney stone formation in humans when exposed to both vitamin D supplementation and high calcium intake.

Proteomic changes in response to crystal formation in Drosophila Malpighian tubules.

Kidney stone disease is a major health burden with a complex and poorly understood pathophysiology. Drosophila Malpighian tubules have been shown to resemble human renal tubules in their physiological function. Herein, we have used Drosophila as a model to study the proteomic response to crystal formation induced by dietary manipulation in Malpighian tubules. Wild-type male flies were reared in parallel groups on standard medium supplemented with lithogenic agents: control, Sodium Oxalate (NaOx) and Ethylene Glycol (EG). Malpighian tubules were dissected after 2 weeks to visualize crystals with polarized light microscopy. The parallel group was dissected for protein extraction. A new method of Gel Assisted Sample Preparation (GASP) was used for protein extraction. Differentially abundant proteins (p<0.05) were identified by label-free quantitative proteomic analysis in flies fed with NaOx and EG diet compared with control. Their molecular functions were further screened for transmembrane ion transporter, calcium or zinc ion binder. Among these, 11 candidate proteins were shortlisted in NaOx diet and 16 proteins in EG diet. We concluded that GASP is a proteomic sample preparation method that can be applied to individual Drosophila Malpighian tubules. Our results may further increase the understanding of the pathophysiology of human kidney stone disease.

The importance of potassium citrate and potassium bicarbonate in the treatment of uric acid renal stones.

Uric acid calculi can also be treated without surgery, with simple medical lytic therapy. After appropriate dietary adjustments and add of mineral water, the needed amount of alkali supplementation can increase pH values of the urine in order to dissolve the stones. Treatment should be prolonged to prevent stone recurrence. A case of bilateral renal uric acid stones that were successfully treated by alakalizing treatment was presented.

Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of Hypercalciuria.

Potassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. Thus, the effect of potassium citrate on urine calcium oxalate and calcium phosphate supersaturation and stone formation is complex and difficult to predict. To study the effects of potassium citrate on urine supersaturation and stone formation, we utilized 95th-generation inbred genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a normal calcium (1.2%) diet supplemented with potassium citrate or potassium chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18 weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate, phosphate, oxalate, and pH levels were higher and urine calcium level was lower in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate supersaturation were higher with potassium citrate; however, uric acid supersaturation was lower. Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation.

Calcium nephrolithiasis induced by topiramate.

Topiramate is an approved drug to treat seizures, but its indications have been extended to other diseases of the nervous system and as an adjuvant to chronic pain. We present four cases of topiramate-induced nephrolithiasis from 2006-2012 in women whose treatment was prescribed for pain control and as a mood stabilizer at doses of 250-300 mg/day. In two cases, the lithiasis was caused by calcium phosphate (patite) and in the other two cases by oxalate and calcium phosphate. The most common metabolic alteration was an alkaline pH, followed by hypocitraturia. The drug was discontinued in two patient; it was reduced in one and was maintained in the fourth. An increase in fluid and potassium citrate intake was prescribed. In patients starting treatment with topiramate, an adequate control and prevention of nephrolithiasis should be performed due to the risk of mixed tubular acidosis and hypocitraturia. to the risk of mixed tubular acidosis and hypocitraturia.