肾结石大鼠钠/二羧基转运蛋白1的表达及枸橼酸钾防治机制的研究

目的 研究肾组织钠／二羧基转运蛋白1（SDCT1）与低枸橼酸尿的关系以及枸橼酸钾的干预作用，探讨肾结石发病的分子机制和防治措施。方法 雄性Wistar大鼠分为对照组、肾结石组及枸橼酸钾干预组。血、尿枸橼酸和草酸采用酶法测定，Northern blot检测大鼠肾组织SDCT1mRNA水平的改变，免疫组织化学观察SDCT1在肾组织的分布及表达变化。结果 与对照组比较，肾结石组第3天尿草酸水平显著升高，枸橼酸水平显著降低，同时肾组织SDCT1mRNA及其蛋白水平上调。第7天SDCT1mRNA及其表达产物增加更为显著，同时尿枸橼酸水平进一步降低，尿钙排泄显著增加，87.5%大鼠有中－大量的草酸钙结石形成。第14天上述改变更为明显，结石形成率达100％。枸橼酸钾干预组各时间点尿草酸水平与肾结石组差异无显著性意义，但尿枸橼酸水平显著高于肾结石组及对照组，肾组织SDCT1mRNA及蛋白表达显著低于肾结石组，与对照组差异无显著性意义；结石形成率显著低于肾结石组；肾小管扩张、炎细胞浸润等病变也明显减轻。结论 肾组织SDCT1表达上调可能是低枸橼酸尿的重要原因，与肾结石的形成有密切关系。枸橼酸钾可下调肾结石大鼠肾组织SDCT1的表达，对肾结石的形成具有明显的干预作用。     

草酸钙结石形成的代谢性变化的研究

目的分析顺德勒流地区草酸钙结石患者的血生化及尿液代谢变化,探讨草酸钙结石形成的代谢性因素,为临床提供诊治的依据。方法对确诊为草酸钙结石的患者进行病例对照研究,并进行尿pH值、24h尿定量分析及血生化检测。结果 （1）85例草酸钙结石患者中出现低尿量者71例,高钠尿症38例,高钙尿症53例,高尿酸尿症15例,低枸橼酸尿症74例,高草酸尿症42例,高磷尿症3例,高pH值尿28例,而28例高pH值尿患者合并低枸橼酸尿症者25例;（2）草酸钙组与对照组的24h尿定量分析结果显示,草酸钙结石组尿量、尿枸橼酸均显著低于对照组（均P〈0.005）,而尿pH值、尿钠、尿钙及尿草酸明显高于对照组（均P〈0.005）,其他指标无显著统计学差异;（3）草酸钙组与对照组血生化指标比较,血钙、血钠浓度明显高于对照组,其他指标无统计学差异（均P〈0.005）。结论低尿量、低枸橼酸尿症、高钠尿症、高钙尿症、高草酸尿症、高血钙及高血钠是顺德勒流地区草酸钙结石形成的重要代谢因素。     

离子色谱法同时测定24小时尿草酸和枸橼酸的应用价值

目的 评价离子色谱法同时测定24 h尿草酸、枸橼酸在实验室和临床应用中的价值.方法 收集24 h尿液用浓盐酸酸化和稀释处理,0.2 μm有机系微孔滤膜过滤注入离子色谱仪,同时检测24 h尿草酸、枸橼酸浓度.结果 离子色谱法对尿草酸、尿枸橼酸的最小检测限均为0.04mg/ml,标准曲线相关系数r分别为0.99992、0.99989,批内相对标准偏差RSD分别为1.50%、0.79%,尿样回收率分别为96.9%、92.3%,此法与草酸变色酸比色法及枸橼酸比色法显著相关(P＞0.05).结论 离子色谱法简单、快速、准确,适于实验室及临床24 h尿草酸、枸橼酸检验分析.     

口服枸橼酸钾镁预防复发性草酸钙结石的效果

口服枸橼酸钾镁预防复发性草酸钙结石的效果［ＥｔｉｎｇｅｒＢ，ｅｔａｌ．ＪＵｒｏｌ，１９９７，１５８∶２０６９］新近的研究表明，口服枸橼酸钾镁１周，能够使尿液枸橼酸水平提高６１％，尿镁水平提高４３％，尿ｐＨ值提高０．６个单位，尿草酸钙浓度降低３１％，对...     

枸橼酸钾防治泌尿系结石

枸橼酸钾防治泌尿系结石已在临床应用多年并已取得较好效果 ,枸橼酸钾可为低枸橼酸尿引起的泌尿系含钙结石和尿酸结石提供代谢及生理化学性纠正并抑制新结石形成。1　低枸橼酸尿正常人尿枸橼酸下限为 32 0 mg/d,低于此值为低枸橼酸尿。泌尿系结石患者中低枸橼酸尿的发生率为 1     

瘦猪肉餐对草酸钙结石患者尿生化的影响

目的研究瘦猪肉餐对一水草酸钙（calciumoxalate monohydrate,COM）与二水草酸钙（calciumoxalate dehydrate,COD）结石患者尿生化的影响,探讨草酸钙结石形成的机制。方法正常人、COM与COD结石患者各6例,共18例同予以煮瘦猪肉350g食用,收集实验日晨5-7时2h尿为样本,餐后各留3次2h尿标本,测定尿pH值和尿晶体成分浓度;采用SPSS软件对检测结果进行方差分析。结果三组受试者瘦猪肉餐后尿钙、尿酸和尿草酸排泄逐渐增加,而尿量、尿pH值和尿枸橼酸降低;瘦肉餐前后比较,COM与COD结石患者尿pH值、尿枸橼酸、尿钙和尿草酸有显著性差异（P〈0.05）,尿酸排泄有极显著性差异（P〈0.01）;对照组,尿钙、尿酸排泄均有显著性差异（P〈0.05,P〈0.01）。结论大量饮食猪瘦肉可导致尿pH值和尿晶体成分变化,可能是尿结石形成的重要原因之一。     

人肾脏尿酸盐转运的分子机制研究进展

90％以上的原发性高尿酸血症是因肾脏对尿酸盐的排泄减少所致。肾脏对尿酸盐的排泄主要包括肾小球的滤过、近曲肾小管的重吸收和主动分泌。近年来研究发现，有4个尿酸盐转运蛋白参与了近曲肾小管对尿酸盐的重吸收和主动分泌，目前这4种转运蛋白已相继在肾脏克隆成功，他们分别位于肾小管的顶膜和基底膜，本文对上述尿酸盐转运蛋白的基因结构和蛋白功能作一综述。     

导尿管留置时间对肾结石术后患者尿枸橼酸浓度的影响

目的探讨肾结石术后患者导尿管不同留置时间对尿液中结石抑制物枸橼酸浓度的影响．为肾结石术后患者导尿管最佳留置时间提供依据。方法对42例肾结石手术留置导尿管患者采用分光光度计比色法测定其术前1d及术后第3、5、7、10天的24h尿枸橼酸浓度。结果导尿管留置不同时间患者尿枸橼酸浓度比较,差异有统计学意义（P〈0．01）;术前1d及术后第10天24h尿枸橼酸浓度与术后第3、5、7天比较,差异有统计学意义（P〈0．05,P〈0．01）。结论肾结石术后患者导尿管留置时间不宜超过10d,否则有可能致尿枸橼酸浓度降低,利于尿石形成,使结石复发。     

泌尿系结石儿童患者24h尿液成石危险因素分析

目的:分析泌尿系结石儿童患者24h尿液成石危险因素的特点。方法:回顾性分析广州医科大学附属第一医院泌尿外科2004年1月至2013年12月泌尿系结石儿童患者(年龄0~18周岁)的24h尿液成石危险因素分析结果,包括尿量,尿钙,尿镁,尿钠,尿尿酸,尿磷,尿胱氨酸,尿草酸和尿枸橼酸等因素。结果:24h尿液成石危险因素分析结果显示,80名泌尿系结石儿童患者中仅2.5%未合并尿液代谢异常,其中97.5%有低枸橼酸尿症,50.0%有高钠尿症,48.7%有胱氨酸尿症,18.8%有高钙尿症,12.5%少尿,11.3%有低镁尿症,5.0%有高草酸尿症,1.3%有高尿酸尿症。此外,女性患儿的尿量明显多于男性患儿[(73.2±58.5)ml/kg vs.(51.3±45.3)ml/kg,P0.05],年长患儿(9~18岁)的尿钠及尿草酸排泄量高于年幼患儿(0~9岁)[尿钠:(5.24±3.25)mmol/kg vs.(3.32±2.23)mmol/kg;尿草酸:(0.014±0.016)mmol/kg vs.(0.008±0.007)mmol/kg],差异均有统计学意义(P0.05)。结论:泌尿系结石儿童患者24h尿液成石危险因素存在明显异常,其中低枸橼酸尿症是最常见的尿液代谢异常,而胱氨酸尿症的高发病率需要进一步重视。     

导尿管留置时间对肾结石术后患者尿枸橼酸浓度的影响

目的探讨肾结石术后患者导尿管不同留置时间对尿液中结石抑制物枸橼酸浓度的影响,为肾结石术后患者导尿管最佳留置时间提供依据。方法对42例肾结石手术留置导尿管患者采用分光光度计比色法测定其术前1d及术后第3、5、7、10天的24h尿枸橼酸浓度。结果导尿管留置不同时间患者尿枸橼酸浓度比较,差异有统计学意义(P0.01);术前1d及术后第10天24h尿枸橼酸浓度与术后第3、5、7天比较,差异有统计学意义(P0.05,P0.01)。结论肾结石术后患者导尿管留置时间不宜超过10d,否则有可能致尿枸橼酸浓度降低,利于尿石形成,使结石复发。     

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.     

酒石酸钾预防草酸钙肾结石形成的研究

体外实验证明酒石酸钾对一水草酸钙晶体的生长和聚集有抑制作用。动物实验发现酒石酸钾能够降低鼠肾组织中钙及草酸的沉积。２７例患者口服酒石酸钾期间，２４小时尿钙、磷和草酸明显下降，尿枸橼酸和尿ＰＨ显著上升，实验证明，酒石酸钾能够抑制草酸钙肾结石的形成，是一种有希望的防石药物。     

单味中药金钱草、石韦、车前子对肾结石模型大鼠的预防作用

目的：观察单味中药金钱草、石韦、车前子对肾结石的预防作用。方法：90只大鼠随机分为5组,采用1.25%乙二醇和1%氯化铵制备大鼠肾结石模型,用上述3种单味中药的免煎剂型分别给各实验组大鼠肾结石模型灌胃,对照组用枸橼酸钾,4周后观察尿和肾组织中草酸钙结晶的形成情况。结果：单味中药金钱草组、石韦组、车前子组大鼠肾内草酸钙结晶明显少于模型组,而与西药枸橼酸钾组相当。金钱草组、石韦组、车前子组大鼠尿中草酸钙结晶的排泄均明显多于模型组。结论：单味中药金钱草、石韦、车前子对预防大鼠肾结石的形成有确切效果,并与西药枸橼酸钾相当,其作用可能主要是通过增加尿中草酸钙结晶的排泄而达到的。     

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     

Use of genetic immunization to generate a high-level antibody against rat dicarboxylate transporter

Background  Rat dicarboxylate transporter (SDCT1), expressed in renal tubular epithelial cells, plays a key role in regulating blood and urinary citrate level by reabsorbing citrate from the lumen. Antibodies against this transporter are very important for investigating its expression and function. With the cytokine gene as a molecular adjuvant, genetic immunization-based antibody production offers several advantages compared with current methods. This study aimed, by genetic immunization, to produce a high-specificity antibody against SDCT1. Methods  We fused a high-antigenicity fragment of SDCT1 to the plasmid pBQAP-TT containing T-cell epitopes and flanking regions from tetanus toxin. Mice were immunized by gene-gun immunization with recombinant plasmid and two other adjuvant plasmids that express granulocyte/macrophage colony-stimulating factor and FMS-like tyrosine kinase 3 ligand, respectively. The titer of the antibody was detected by enzyme-linked immunosorbent assay (ELISA). Specificity of the antibody was identified with SDCT1 native protein in rat kidney by Western blot analysis and immunohistochemistry, and with SDCT1 protein expressed on Xenopus oocytes plasma membranes by immunofluorescence. Results  ELISA measurements showed that the antibody titer was 1:32,000. The native protein of SDCT1 in rat kidney can be recognized by this antibody with Western blot analysis and immunohistochemistry. Immunofluorescence showed that this antibody also recognized SDCT1 protein targeted to Xenopus oocytes plasma membranes into which SDCT1 full-length cRNA was injected. Conclusion  Generation of a high-specificity immunoglobulin G antibody against SDCT1 by genetic immunization has provided an important tool for the study of citrate transport. G. Xu and A. Liu contributed equally to this work.     

Citrate inhibits growth of residual fragments in an in vitro model of calcium oxalate renal stones

BACKGROUND: Alkaline citrate is thought to be helpful in reducing recurrences of calcium oxalate stones. The evidence for this is incomplete, there have been few good trials, all with their own limitations, and not all reported any significant benefit. In vitro studies are usually cited to support the clinical studies but these too have their drawbacks, in particular they relate to crystals and microscopic aggregates and not to actual stone growth. Here we test citrate in vitro using a model of macroscopic calcium oxalate stone enlargement. METHODS: Twelve calcium oxalate stones were grown at a time in a stone farm. Six were grown with 2 mmol/L citrate and six with 6 mmol/L citrate. Three protocols were tested; artificial urine, artificial urine with urinary macromolecules (UMM) from male controls and artificial urine with UMM from male stone formers. The stones were grown continuously for at least 24 days. RESULTS: In all three experiments the higher citrate concentration significantly reduced the growth rate of stones by more than 50% (P < 0.001). There was a small decrease in ionised calcium in the stone growth media (P < 0.001) and significant (P < 0.001) but small increase in pH (about 0.07 pH units). The inclusion of UMM also brought about a decrease in stone growth, particularly at 2 mmol/L citrate. CONCLUSION: Citrate inhibited stone growth in this laboratory model. This was true both in defined media and with addition of UMM. This adds to evidence justifying the use of alkaline citrate in calcium oxalate nephrolithiasis.     

The role of hyperoxaluria in the formation of calcium oxalate urinary calculi, and its association with other biochemical measurements

The part played by hyperoxaluria in the formation of calcium oxalate urinary calculi was studied in 153 patients who had each been diagnosed as having calcium oxalate urinary calculi on one or more occasions. Seventy-seven of the patients excreted normal amounts of calcium (less than 6.2 mmol/d), and 76 had hypercalciuria (excretion greater than or equal to 6.2 mmol/d); each group was divided into a further two groups depending on whether the oxalate concentration was above or below 0.16 mmol/l. Pure calcium oxalate stones were more common in patients whose calcium excretion was normal, and mixed calcium oxalate and phosphate stones were more common among hypercalciuric patients. Urinary concentrations/day of magnesium, citrate, and phosphorus were significantly lower in the two groups in which the oxalate concentrations were below 0.16 mmol/l than in a normal control group, and magnesium and phosphorus were significantly lower in the two groups in which oxalate concentrations were less than 0.16 mmol/l than in the two in which they were above that value. The concentration of citrate was also lower, but not significantly so. In addition, the pH of the urine in patients with mixed stones was significantly higher in all groups than when the stones were composed of pure calcium oxalate.     

Prevention of renal crystal deposition by an extract of <Emphasis Type="Italic">Ammi visnaga</Emphasis> L. and its constituents khellin and visnagin in hyperoxaluric rats

In Egypt, teas prepared from the fruits of Ammi visnaga L. (syn. “Khella”) are traditionally used by patients with urolithiasis. The aim of this study was to evaluate whether oral administration of an aqueous extract prepared from the fruits of A. visnaga as well as two major constituents khellin and visnagin could prevent crystal deposition in stone-forming rats. Hyperoxaluria was induced in male Sprague-Dawley rats by giving 0.75% ethylene glycol and 1% ammonium chloride via the drinking water. The Khella extract (KE; 125, 250 or 500 mg/kg) was orally administered for 14 days. The histopathological examination of the kidneys revealed that KE significantly reduced the incidence of calcium oxalate (CaOx) crystal deposition. In addition, KE significantly increased urinary excretion of citrate along with a decrease of oxalate excretion. Comparable to the extract, khellin and visnagin significantly reduced the incidence of CaOx deposition in the kidneys. However, both compounds did not affect urinary citrate or oxalate excretion indicating a mechanism of action that differs from that of the extract. For KE, a reasonably good correlation was observed between the incidence of crystal deposition, the increase in citrate excretion and urine pH suggesting a mechanisms that may interfere with citrate reabsorption. In conclusion, our data suggest that KE and its compounds, khellin and visnagin, may be beneficial in the management of kidney stone disease caused by hyperoxaluria but that it is likely that different mechanism of action are involved in mediating these effects.     

Stone forming risk of calcium citrate supplementation in healthy postmenopausal women

PURPOSE: We evaluated the effect of calcium citrate supplementation alone or in combination with potassium citrate on the stone forming propensity in healthy postmenopausal women. MATERIALS AND METHODS: A total of 18 postmenopausal women without stones underwent a randomized trial of 4 phases comprised of 2 weeks of treatment with placebo, calcium citrate (400 mg calcium twice daily), potassium citrate (20 mEq twice daily), and calcium citrate and potassium citrate (at same doses). During the last 2 days of each phase urine was collected in 24-hour pools for complete stone risk analysis. RESULTS: Compared to placebo, calcium citrate increased urinary calcium and citrate but decreased urinary oxalate and phosphate. Urinary saturation of calcium oxalate, brushite and undissociated uric acid did not change. Potassium citrate decreased urinary calcium, and increased urinary citrate and pH. It decreased urinary saturation of calcium oxalate and undissociated uric acid, and did not change the saturation of brushite. When calcium citrate was combined with potassium citrate, urinary calcium remained high, urinary citrate increased even further and urinary oxalate remained reduced from the calcium citrate alone, thereby marginally decreasing the urinary saturation of calcium oxalate. Urinary pH increased, decreasing urinary undissociated uric acid. The increase in pH increased the saturation of brushite despite the decrease in urinary phosphorus. CONCLUSIONS: Calcium citrate supplementation does not increase the risk of stone formation in healthy postmenopausal women. The co-administered potassium citrate may provide additional protection against formation of uric acid and calcium oxalate stones.