Identificación endoscópica de la composición de los cálculos urinarios: un estudio del Southeastern Group for Lithiasis Research (SEGUR 2)

Introduction and objectivesTo assess the surgeon's ability to evaluate the composition of the stone by observation of endoscopic images.Materials and methodsA series of 20 video clips of endoscopic treatments of urinary stones of which was also available the result of infrared spectroscopy was uploaded to a YouTube site accessible only to members of the South Eastern Group for Urolithiasis Research (SEGUR) who were asked to identify the composition of the stones.ResultsA total of 32 clinicians from 9 different countries participated in the study. The average number of correct detections of participants was 7.81 ± 2.68 (range 1-12). Overall accuracy was 39% (250 out of 640 predictions). Calcium oxalate dihydrate stones have been correctly detected in 69.8%, calcium oxalate monohydrate in 41.8%, uric acid in 33.3%, calcium oxalate/uric acid in 34.3% and cystine in 78.1%. Precision rates for struvite (15.6%), calcium phosphate (0%) and mixed calcium oxalate/calcium phosphate (9.3%) were quite low.ConclusionsObservation of the stone during the endoscopic procedure was not reliable to identify the composition of most stones although it gave some information allowing to identify with a good sensitivity calcium oxalate dihydrate and cystine stones. Nevertheless, photo or video reporting of the intact stone and its internal structure could should be encouraged to implement results of still mandatory post-operative stone analysis. Endourologists should improve their ability of visual identification of the different types of stones.     

Experimental technique simulating oxalocalcic renal stone generation

Summary A new technique simulating some of the conditions experienced by papillar and caliceal oxalocalcic stones during the early stages of their generation was developed. This technique enables the study of how conditions prevailing at calculogenesis, such as pH, composition of urine and presence of admixtures, influence the rate of formation and development, the crystalline texture and the composition of the concretion formed. Results achieved with this technique demonstrate that: (1) an appropriate substrate always gives rise to a crystalline concretion if it is in contact with supersaturated urine; (2) primary agglomeration plays a significant role in concretion development whereas secondary agglomeration is of minor importance; and (3) citrate and pyrophosphate exert a considerable influence on the shape and composition of particles constituting the concretion.     

Proteolysis and partial dissolution of calcium oxalate: a comparative, morphological study of urinary crystals from black and white subjects

Crystal adherence to the renal epithelium is widely regarded as a probable mechanism of stone formation. Intracrystalline proteins may provide access to the core of urinary crystals and thereby facilitate the dismantling of these crystals after their attachment to and phagocytosis by renal epithelial cells. The present study investigated the role of proteolysis and limited dissolution of urinary calcium oxalate (CaOx) crystals in South Africas white and black populations with a view to understanding the remarkably low stone incidence in the black population compared with the whites. CaOx crystals were precipitated from filtered urine or ultrafiltered urine dosed with an intracrystalline protein, urinary prothrombin fragment 1 (UPTF1), isolated from white and black subjects. The crystals were fractured and subjected to proteolysis and/or limited dissolution before examination using field emission scanning electron microscopy (FESEM). FESEM data showed that CaOx crystals from white and black subjects were eroded by treatment with proteases. Cathepsin D caused the most significant crystal erosion, and more noticeable degradation of CaOx monohydrate (COM) crystals compared to CaOx dihydrate (COD). Limited dissolution studies showed the unique ultrastructures and fragmentation processes of COM and COD crystals. COM crystals appeared to be more susceptible to degradation and dissolution than CODs. Since COMs are predominant in blacks, compared with COD crystals from whites, it is speculated that the lower stone rate amongst South African blacks might be attributed partly to their more efficient destruction of retained COM crystals.     

Calcium phosphate: an important crystal phase in patients with recurrent calcium stone formation?

Summary 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.     

维生素D受体基因多态性与草酸钙尿结石的关系

目的　探讨维生素D受体 (VDR)等位基因多态性与草酸钙尿结石之间的关系。　方法　非高钙尿结石患者 15 0例 ,高钙尿结石患者 36例 ,正常对照 90例。采用聚合酶链反应 (PCR)和限制性酶切法研究VDR的Taq1、Apa1、Fok1等位基因多态性与草酸钙尿结石之间的关系。　结果　两个结石组分别与对照组比较 ,VDR的Fok1启动子等位基因多态性分布差异有显著性意义 (P <0 .0 5 )。ff型等位基因 (Fok1等位基因有 2个酶切位点的纯合子出现 2个月条带 )人群中对照组、非高钙尿结石组及高钙尿结石组 2 4h尿钙含量分别为 (0 .0 5 1± 0 .0 0 4 )、(0 .0 74± 0 .0 0 4 )和 (0 .135± 0 .0 11)mmol/kg,FF型人群 3组分别为 (0 .0 31± 0 .0 0 3)、(0 .0 32± 0 .0 0 3)和 (0 .10 8± 0 .0 14 )mmol/kg,差异有显著性意义 (P <0 .0 5 )。Apa1、Taq1的基因多态性分布在各组之间差异无显著性意义 (P >0 .0 5 )。　结论　VDR的启动子Fok1基因多态性可作为鉴别草酸钙尿结石病因的基因标记物 ,ff型等位基因可作为含钙结石危险因素的标志 ,草酸钙尿结石与VDR基因内含子 8(Apa1)及外显子 9(Taq1)多态性无关。     

Study of a rat model for calcium oxalate crystal formation without severe renal damage in selected conditions

BACKGROUND: Although nephrotoxic in high doses, ethylene glycol (EG) has been used with ammonium chloride (NH(4)Cl) or vitamin D(3) to study calcium oxalate stone formation in rat models. In the present study we used EG alone or with NH(4)Cl to study hyperoxaluria, crystaluria, and crystal attachment to renal epithelial cells in rats with minimal renal damage. METHODS: Six-week-old male Sprague-Dawley (SD) rats were given food and special drinking water. In experiment 1 the drinking water contained 1.0% NH(4)Cl plus four different concentrations of EG (0.8%, 0.4%, 0.2%, 0.1%). In experiment 2 the drinking water contained EG alone (0.8%, 0.4%, 0.2%, 0.1%). Urine was collected for 24 h before the rats were sacrificed. In experiment 1 the rats were sacrificed 5-13 days after starting the special water. In experiment 2 the rats were sacrificed 7-21 days after starting the special water. Bladder urine was also obtained. Blood and urine were tested for calcium, phosphorus, and creatinine. In addition, urine was tested for pH, oxalate and N-acetyl-beta-D glucosaminidase (NAG). Kidney sections were stained with hematoxylin-eosin, von Kossa and Pizzolato stain. Crystal morphology was determined using polarizing microscopy, and composition was determined using high-resolution X-ray powder diffraction. RESULTS: Experiment 1: Aggravation of renal function, an increase in urinary oxalate and NAG excretion, and crystals observed in the kidneys all correlated with EG concentration and length of drinking time. In bladder urine, calcium oxalate monohydrate (COM) crystals exceeded calcium oxalate dihydrate (COD) crystals. Experiment 2: Renal function remained unchanged. Oxalate excretion increased and NAG increased slightly. Crystals occurred only in the papillary tip region. Crystals in bladder urine were mostly COD. CONCLUSION: In the current rat model, calcium oxalate crystaluria could be induced without severe renal damage in selected cases. Either and/or both COM and COD might form and interact with kidney epithelium. We propose different experimental conditions to study the various phases of calcium oxalate stone formation in young male SD rats.     

Kinetics of Calcium Oxalate Crystal Growth in the Presence of Osteopontin Isoforms: An Analysis by Scanning Confocal Interference Microcopy

Proteins that inhibit the growth and aggregation of calcium oxalate crystals play important roles in the prevention of kidney stone disease. One such protein is osteopontin (OPN), which inhibits the formation of calcium oxalate monohydrate (COM) in a phosphorylation-dependent manner. To determine the role of phosphate groups in the inhibition of COM growth by OPN, we used scanning confocal interference microscopy to compare the effects of highly phosphorylated OPN from cow milk, less phosphorylated OPN from rat bone, and nonphosphorylated recombinant OPN. COM growth was measured in the principal crystallographic directions <001>, <010>, and <100>, representing lattice-ion addition to {121}, {010}, and {100} faces, respectively. While the shapes of growth curves were very consistent from crystal to crystal, absolute growth rates varied widely. To control for this, results were expressed as changes in the aspect ratios <010>/<001> and <100>/<001>. Compared to control, bone OPN increased <010>/<001> and had no effect on <100>/<001>; milk OPN had no effect on <010>/<001>and decreased <100>/<001>; recombinant OPN had no significant effect on either aspect ratio. These findings indicate that milk OPN interacts with COM crystal faces in order of preference {100} > {121} ≈ {010}, whereas bone OPN interacts in order of preference {100}≈{121} > {010}. As {100} is the most Ca²⁺-rich face of COM, while {010} is the least Ca²⁺-rich, it appears that the OPN-mediated inhibition of COM growth occurs through a nonspecific electrostatic interaction between Ca²⁺ ions of the crystal and phosphate groups of the protein.

Kidney stone disease and risk factors for coronary heart disease

BACKGROUND: We conducted a case-control study to examine the impact of coronal heart disease (CHD) risk factors on calcium oxalate (CaOX) stone formation. METHODS: Variables included body mass index (BMI), current alcohol use, smoking habit, hypertension, hypercholesterolemia, diabetes mellitus, and hyperuricemia. Data suf fi cient for analysis were obtained for 181 CaOX stone formers and 187 controls. RESULTS: Seven of 181 stone formers (3.9%) had a history of CHD compared with none of 187 control subjects (P = 0.007). In univariate logistic regression analysis, smoking habit (OR 4.41, 95% CI 2.85-6.84, P < 0.0001), hypertension (OR 4.24, 95% CI 2.61-6.91, P < 0.0001), hypercholesterolemia (OR 3.03, 95% CI 1.77-5.20, P < 0.0001) and BMI (OR 1.10, 95% CI 1.04-1.17, P = 0.007) reached statistical signi fi cance. In a multivariate logistic regression analysis, smoking habit (OR 4.29, 95% CI 2.68-6.86, P < 0.0001), hypertension (OR 3.57, 95% CI 2.11-6.07, P < 0.0001), and hypercholesterolemia (OR 2.74, 95% CI 1.51-5.00, P = 0.001) reached statistical signi fi cance, while BMI (OR 1.06, 95% CI 0.99-1.12, P = 0.09) did not. CONCLUSIONS: CaOX stone formers are signi fi cantly associated with several CHD risk factors, including smoking habit, hypertension, hypercholesterolemia, and obesity.     

Dietary fibre: the effectiveness of a high bran intake in reducing renal calcium excretion

Summary Fifteen healthy women were given a standardized calcium-rich diet (1800 mg calcium/day) with or without 36 g bran for 5 days. A similar study was also carried out with rice, soy and wheat bran. Urine samples were also collected 24 h. With all brans renal calcium excretion decreased and renal oxalic acid excretion increased. However, influence of rice bran was statistically significant. After 5 days of consuming 36 g rice bran/day 14 of 15 subject showed decreased calcium excretion, but increased oxalic acid excretion. Relative supersaturation with calcium oxalate, as a measure for the risk of calcium stone formation, increased after addition of all brans.     

Effect of potential renal acid load of foods on urinary citrate excretion in calcium renal stone formers

The aim of this study was to investigate the influence of the potential renal acid load (PRAL) of the diet on the urinary risk factors for renal stone formation. The present series comprises 187 consecutive renal calcium stone patients (114 males, 73 females) who were studied in our stone clinic. Each patient was subjected to an investigation including a 24-h dietary record and 24-h urine sample taken over the same period. Nutrients and calories were calculated by means of food composition tables using a computerized procedure. Daily PRAL was calculated considering the mineral and protein composition of foods, the mean intestinal absorption rate for each nutrient and the metabolism of sulfur-containing amino acids. Sodium, potassium, calcium, magnesium, phosphate, oxalate, urate, citrate, and creatinine levels were measured in the urine. The mean daily PRAL was higher in male than in female patients (24.1±24.0 vs 16.1±20.1 mEq/day, P=0.000). A significantly (P=0.01) negative correlation (R=−0.18) was found between daily PRAL and daily urinary citrate, but no correlation between PRAL and urinary calcium, oxalate, and urate was shown. Daily urinary calcium (R=0.186, P=0.011) and uric acid (R=0.157, P=0.033) were significantly related to the dietary intake of protein. Daily urinary citrate was significantly related to the intakes of copper (R=0.178, P=0.015), riboflavin (R=0.20, P=0.006), piridoxine (R=0.169, P=0.021) and biotin (R=0.196, P=0.007). The regression analysis by stepwise selection confirmed the significant negative correlation between PRAL and urinary citrate (P=0.002) and the significant positive correlation between riboflavin and urinary citrate (P=0.000). Urinary citrate excretion of renal stone formers (RSFs) is highly dependant from dietary acid load. The computation of the renal acid load is advisable to investigate the role of diet in the pathogenesis of calcium stone disease and it is also a useful tool to evaluate the lithogenic potential of the diet of the individual patient.     

草酸和一水草酸钙结晶对人肾小管上皮细胞的影响

目的 观察草酸和一水草酸钙结晶对体外培养的人肾小管上皮细胞(HK-2)的毒性作用和蛋白表达的影响,探讨上皮细胞受损在肾结石形成过程中的可能作用.方法 体外培养正常人HK-2细胞至长满后,换成无血清培养基,加入草酸至不同终浓度,显微镜下观察结晶的形成及其对细胞的粘附.收集结晶以傅立叶红外光谱仪(FT-IR)分析其成分.CCK-8试剂盒检测1、2、5和10mmol/L草酸分别作用4、12和24 h后对HK-2细胞的毒性反应,Bradford法检测HK-2细胞表达总蛋白量的变化.结果草酸加入含Ca2+的DMEM培养基后,数分钟内显微镜F即可见结晶形成并粘附于细胞表面.FT-IR分析表明结晶成分为一水草酸钙.草酸和一水草酸钙对HK-2的毒性作用呈明显浓度依赖性,但在1～10 mmol/L草酸浓度下毒性作用不随时间延长而增加.1、2、5mmol/L草酸作用12 h和对照组HK-2表达蛋白量分别为(358±51)、(365±43)、(328±52)和(329±60)mg/L,P值均＞0.05,而10 mmol/L草酸作用12 h后,HK-2表达蛋白量为(264±76)mg/L,显著低于对照组(P＜0.05).结论 草酸和一水草酸钙可对正常人HK-2细胞产生毒性损伤,造成细胞表达蛋白的改变,可能在肾结石的形成中起重要作用.     

Isoelectric focusing of Tamm-Horsfall glycoproteins: a simple tool for recognizing recurrent calcium oxalate renal stone formers

Tamm-Horsfall glycoproteins (THPs) from healthy probands and a majority of recurrent calcium oxalate renal stone formers reveal different physicochemical properties when analyzed using isoelectric focusing (IEF). The pI values of THPs from healthy probands are approximately 3.5 while THPs from recurrent renal stone formers have pI values of between 4.5 and 6. The two groups of THPs exhibit completely different protein patterns. The differences in IEF analysis allow differentiation between THPs from healthy probands and recurrent calcium oxalate stone formers and may possibly be used as a simple diagnostic method for the recognition of recurrent calcium oxalate renal stone formers.     

The riddle of kidney stone disease: lessons from Africa

Urolithiasis has not been extensively researched in the African continent due to a general lack of facilities and resources. Consideration of the few published papers indicates that there are some regions where the occurrence of stones is extremely rare. South Africa is unique in two respects. Firstly, it has both stone-prone and stone-free population groups and secondly, it is an African country in which a fair amount of research has been conducted in this field. These studies have shown that routine urine parameters cannot explain stone rarity, but that structural differences of inhibitory urinary proteins appear to be important. Similarly, the studies have demonstrated that common dietary components cannot necessarily be correlated with urine composition, particularly oxaluria, nor can they necessarily explain stone rarity, but that the role of oxalate-degrading bacteria has the potential to offer explanatory insights. By investigating the factors influencing stone rarity, those affecting stone formation have been concomitantly scrutinized. As a result, it is suggested that a paradigm shift from a focus on pathology to one on physiology is needed in urolithiasis research in general.     

May enzyme activity in urine play a role in kidney stone formation?

Summary It has been found that calcium oxalate stone formers have low UGOT and UGPT activity compared to healthy individuals. The urine of 23 stone formers and 19 controls has been tested for combined UGOT and UGPT activity. The effect of L-aspartic acid, alanine and L-glutamic acid on calcium oxalate precipitation has been tested. Only L-glutamic acid exerted a significant retardation effect at physiological concentrations. As GPT and GOT convert alanine and aspartic acid respectively into glutamic acid, a possible mechanism of retardation of kidney stone formation involving enzyme steps via glutamic acid creation in situ is suggested.     

Coexistence of VATER association and recurrent urolithiasis: a case report

VATER association is diagnosed by the combined presence of at least three of the following features: vertebral anomalies, anal atresia, tracheo-esophageal fistula and/or esophageal atresia, radial ray anomalies, and renal anomalies (53%). Urolithiasis has not been reported in this syndrome. A 4-month old girl presented because of irritability, and the presence of stones in the diapers. Physical examination revealed anal atresia for which colostomy was performed in the newborn period. The diagnosis of VATER association was established by the additional findings of hemivertebrae, sacral dysgenesis, and horseshoe kidney which was partly non-functional. Urinary pH was repeatedly below 6. An excreted stone consisted of pure uric acid. Metabolic investigations detected no specific pathology in purine metabolism. Urolithiasis did not recur after reconstructive anal and anorecto-vaginoplasty, implying that it was a consequence of colostomy and/or of the underlying renal anomaly. We suggest that after colostomy patients with VATER association should be followed for possible urate stones, e.g. by regular screening of urinary pH. Received May 20, 1997; received in revised form August 6, 1997; accepted August 12, 1997     

问题奶粉致尿路结石形成机制初探及诊治建议

目的：问题奶粉中所含的三聚氰胺是引发婴幼儿泌尿系结石形成的主要有毒物质,但其导致结石形成的机制至今未明。目前已知,这种结石的成分主要是二水尿酸和尿酸铵,所以本文通过这两种成分的代谢过程来逆向推导这种特殊结石形成的过程,同时也提出一些相关的诊断和治疗上的建议。     

尿液成分对草酸钙结石的影响

目的 探讨尿液成分对草酸钙尿结石形成的影响。方珐 应用红外光谱仪对50份尿结石标本进行成分检测；对16例一水草酸钙（COM）与10例二水草酸钙（COD）尿结石患者的24h尿液进行生化检测，并比较两组生化指标。结果 87．5％的c0M结石患者和90％的c0D结石患者24h尿量减少；COM结石患者尿钙（4．94±2．11）mmol／24h，COD结石患者尿钙（9．43±3．78）mmol／24h；差异有统计学意义（P〈0．01）；COM结石患者尿磷（20．50±8．76）mmol／24h，COD结石患者尿磷（28．38±10．21）mmol／24h，差异有统计学意义（P〈0．05）；87．5％的COM结石患者尿枸橼酸低于正常水平。结论 COD结石患者尿钙、尿磷高于COM结石患者，表明COD结石的形成与高钙尿和高磷尿有关；COM结石的形成可能与低尿枸橼酸有关。     

Nephrolithiasis in children

A metabolic etiology is the most common cause for pediatric kidney stones. Appropriate evaluation of affected children should include assessment of stone type, if available, and assessment of predisposing factors in all cases. This review discusses the metabolic disorders that lead to nephrolithiasis with respect to the development of calcium, uric acid, struvite, and cystine stones. Environmental and hereditary factors are summarized to provide a guide in the evaluation of pediatric stone formers.     

Calcium oxalate crystal interaction with renal tubular epithelium,mechanism of crystal adhesion and its impact on stone development

The interaction between renal epithelial cells and calcium oxalate (CaOx) crystals and/or oxalate ions plays a critical role in the formation of urinary stones. Epithelial cells respond to hyperoxaluria and the presence of CaOx crystals in the kidneys by increased enzymuria and internalization of the crystals. Crystal cell interaction results in movement of crystals from the luminal to the basolateral side between the cells and the basement membrane. Once beneath the epithelium, crystals adhere to the basement membrane and become anchored inside the kidneys. Crystals anchored to basement membrane of the peripheral collecting duct aggregate with other crystals and move through an eroding epithelium to the papillary surface, furnishing an encrustation platform or a nidus for future development of a kidney stone. Thus interaction between renal epithelial cells and CaOx crystals and/or oxalate ions is an essential element in the development of urinary stone disease.     

Glycosaminoglycans,uric acid and calcium oxalate urolithiasis

Summary The interaction between calcium and glycosaminoglycans (GAGs) was studied using a calcium ion-selective electrode. The Ca-binding capacity of GAGs involved 16% of total calcium in the presence of chondroitin sulphate and 28% in the presence of pentosan polysulphate. The action of GAGs on the nucleation of uric acid and sodium urate was examined and inhibitory effects were observed. The action of uric acid as a heterogeneous nucleant of calcium oxalate was studied, and considerable promotion of the heterogeneous nucleation of calcium oxalate by uric acid was found, which could be inhibited by the action of GAGs. From these summarised in vitro results, we conclude that uric can constitute an important risk factor for calcium oxalate urolithiasis through heterogeneous nucleation and the GAGs can play an important role as preventive agents.