Fragmentation of uric acid calculi with the holmium: YAG laser produces cyanide

BACKGROUND AND OBJECTIVES: To independently test previously reported findings of cyanide evolution under holmium:yttrium aluminum garnet (Ho:YAG) (holmium) lithotripsy of uric acid calculi, determine if this occurs with other forms of intracorporeal lithotripsy, and establish if this occurs due to a photothermal, photochemical, or photoacoustic reaction. STUDY DESIGN/MATERIALS AND METHODS: Human uric acid calculi were fragmented in vitro through exposure to holmium, ultrasound, and electrohydraulic (EHL) energy sources. The following parameters were varied: total laser energy, individual laser pulse energy, ultrasonic energies, and EHL energies. Uric acid powder was suspended in solution and exposed to holmium laser energy in vitro. Serum and irrigant samples from a human patient were collected following intrarenal holmium lithotripsy of a uric acid calculus. All samples were analyzed for hydrogen cyanide (HCN) content. RESULTS: Holmium lithotripsy of solid uric acid calculi produces cyanide. The yield is linearly dependent upon total laser energy delivered. Pulse energy does not affect cyanide yield. Photothermal mechanisms coupling laser energy to the solid crystal lattice are responsible for the production of cyanide. Ultrasound and EHL lithotripsy do not produce cyanide. A clinically insignificant level of cyanide was detected in the blood of a single patient following laser lithotripsy of a uric acid calculus. CONCLUSIONS: Our study confirms that cyanide is produced by a photothermal mechanism during holmium laser lithotripsy of uric acid calculi, and that the amount produced is clinically insignificant.     

Ammonium acid urate urolithiasis in Japan

AIM: Ammonium acid urate (AAU) calculi are a rare urolithiasis in developed countries but are endemic in developing countries. We assessed the features of AAU urolithiasis in Japanese patients. METHODS: We reviewed hospital charts of patients with urolithiasis who were treated with extracorporeal shock wave lithotripsy and endourological procedures at Sagamidai Hospital (Kanagawa, Japan) from January 1992 to December 2001. On the basis of the results of stone analysis with an infrared spectrophotometer, AAU stones were found. RESULTS: Of 8664 urolithiasis that we reviewed, 33 calculi (0.38%) from 29 patients contained AAU crystals. From crystallographic findings, we defined two types of AAU-containing stones: pure and mixed AAU urolithiasis. Pure AAU urolithiasis were seen in 13 stones from 10 patients and mixed AAU in 20 stones from 19 patients. We found significant differences between the groups: the pure AAU group predominantly consisted of young, thin women and the mixed group consisted of middle-aged men. Laboratory findings showed trends of low levels of serum protein, potassium, and urine pH in the pure AAU group. CONCLUSIONS: Because each type of AAU urolithiasis is associated with different patient characteristics and pathophysiological features, it is important to understand the type of AAU urolithiasis in patients with calculi.     

Urates in uric acid renal calculi

Objectives:   To investigate the presence of calcium urate, sodium, potassium and calcium in 'pure' uric acid calculi.
Methods:   Ten spontaneously passed uric acid urinary calculi have been examined by stereoscopic microscopy, infrared spectroscopy, scanning electron microscopy and energy dispersive X-Ray analysis.
Results:   The analysis of selected uric acid calculi revealed the presence of a near-pure calcium urate in two cases and of calcium enriched urate zones in all of the samples. Furthermore, in some cases complex urates containing sodium, potassium and calcium in different proportions appeared on the surface of the uric acid calculi studied, potassium being generally predominant. Ammonium urate was not detected.
Conclusions:   Most urinary uric acid calculi are not pure in composition. 'Complex urates', sodium, potassium and calcium were found together in various proportions in many areas of uric acid stones.     

Dissolution of uric acid stones causing acute obstructing anuria in three consecutive infants

We report on 3 infants with obstructive anuria due to bilateral uric acid stones. In all patients the precipitating cause of acute obstructive renal failure was choking of bilateral ureteropelvic junction with numerous small uric acid stones without cause pelvicaliceal dilatation. While the chemical dissolution therapy succeeded in dissolving the stones in 2 patients, unilateral percutaneous nephrostomy application associated with alkalization achieved dissolution of obstructing stones in the remaining 1 patient.     

高血压及高血压前期血清尿酸水平的变化及临床意义

目的：探讨高血压及高血压前期血清尿酸水平变化及临床意义。方法选择某社区常住居民412例为研究对象。根据血压情况分为血压正常组、高血压前期组、高血压组。检测和比较3组的血清尿酸水平。结果血压正常组尿酸水平为（236.3±61.4）μmol/L,高血压前期组（292.7±73.6）mol/L,高血压组（336.2±113.7）mol/L,3组间比较 P ＜0.01。血清尿酸水平为228～280μmol/L、281～344μmol/L 和≥345μmol/L 组收缩压和舒张压水平显著高于血清尿酸为＜228μmol/L 组（P ＜0.05或＜0.01）。回顾分析显示尿酸水平≥228μmol/L 是高血压及高血压前期的危险因素。结论血清尿酸水平与高血压及高血压前期具有相关性。     

Urolithiasis in pediatric patients: a single center study of incidence, clinical presentation and outcome

PURPOSE: The incidence of kidney stones in adults has increased in the last 30 years. This retrospective, single site review was done to test the hypotheses that the incidence of urolithiasis in pediatric patients increased from 1994 to 2005, and that metabolic abnormalities were more common in patients with renal stones in the final 3 years of the study period. MATERIALS AND METHODS: Charts from 2 time periods were reviewed, 1994 to 1996 (period 1) and 2003 to 2005 (period 2). Clinical and laboratory data, including demographics, presenting complaints, laboratory assessment, treatment and outcome, were tabulated in patients with confirmed urolithiasis. RESULTS: The number of patients with urolithiasis increased from 7 in period 1 to 61 in period 2. When expressed as cases per 100 new patients the incidence increased 4.6 times (p = 0.014). Focusing on period 2, 28% of patients were younger than 10 years. While blood tests were generally normal, 76% of patients had at least 1 abnormality in the 24-hour urine collection. Hypocitraturia, which was the most common metabolic abnormality, was noted in 52% of patients. The small number of patients in period 1 precluded determination as to whether metabolic abnormalities were more common in period 2. Surgery and/or lithotripsy was required in 12 children. Stone disease recurred in 39% of the patients. CONCLUSIONS: The incidence of urolithiasis in the pediatric population increased nearly 5-fold at our institution during the last decade. We recommend that the primary diagnostic test be a 24-hour urine collection. The most common metabolic abnormality was hypocitraturia, followed by hypercalciuria. Recurrence of stones is common (approximately 40% rate) and followup is advised.     

男性不育精液中NO与UA含量的关系

目的探讨人精液中一氧化氮(NO)与尿酸(UA)含量的关系,及对精子质量的影响。方法参照WHO标准方法,进行精液常规分析,按精子密度、活动率不同分为(正常、＜20、20～40、＞40) 4个组。采用镀酮镉还原荧光法检测NO代谢产物硝酸盐(NO_3~-)。采用尿酶一过氧化物酶偶联法检测精液尿酸含量。结果70例不育组精液中尿酸含量和NO含量为(236．4±47．8)μmol/L、(78．7±1．6)μmol/L与正常生育组(398．6±52．3)μmol/L、(41．8±1．6)μmol/L呈显著性差异(P＜0．01)。将尿酸含量与NO含量进行相关性分析,两者呈显著性负相关(r=-0．96,P＜0．05)。不育各精子密度和活动率组精液尿酸含量随精子密度及活动率增加而上升,NO含量随之下降(P＜0．01)。结论精液尿酸含量测定可作为评价精子受活性氧损害的重要指标,证明尿酸对活性氧尤其在医学领域极为重视的NO损害精子具有保护性作用。     

Prevention of uric acid stone formation by sodium bicarbonate in an ileostomy patient —A case report

A 38 year old female underwent a proctocolectomy and ileostomy for ulcerative colitis in February, 1974. For 8 year post-operatively, she excreted innumerable renal stones, mainly composed of uric acid. Her urine was highly acidic and hyperuricosuric with a low concentration of sodium. Sodium bicarbonate 4 gm/day, t.i.d., was started in October 1985, after which her renal stone excretion completely ceased (up until March, 1987), except for one incidence of stone excretion when she discontinued therapy for a week. During the sodium bicarbonate therapy, her urinary pH and Na concentration were elevated. Furthermore, sodium bicarbonate significantly elevated the urinary pH and Na concentration of other ileostomy patients. Thus, sodium bicarbonate could be used for the possible prophylaxis of uric acid formation in selected ileostomy patients.     

过表达人SLC2A9基因的慢病毒载体对HK-2细胞尿酸转运功能的影响

目的构建含人SLC2A9基因的过表达慢病毒载体,探讨其对人肾脏近曲小管上皮细胞株HK-2尿酸转运功能的影响。方法 PCR反应扩增目的基因后连入慢病毒表达载体中构建重组载体pLEX-SLC2A9,使用PCR及测序的方法对其进行鉴定,并与辅助包装质粒共感染293T细胞。慢病毒颗粒感染HK-2细胞后,用PCR和Western blot检测SLC2A9基因的过表达效率,并检测SLC2A9过表达对其尿酸转运功能的影响。结果 PCR及测序结果表明重组慢病毒载体pLEX-SLC2A9的插入序列完全正确,重组慢病毒载体感染HK-2细胞后,细胞内的mRNA及蛋白水平增高,并且可以增强HK-2细胞对尿酸的转运。结论过表达SLC2A9基因后能显著增强HK-2细胞对尿酸的转运。     

白细胞精子症患者精液中一氧化氮和UA含量的关系分析

目的探讨白细胞精子症不育者精液中白细胞(WBC)密度、一氧化氮(NO)和尿酸(UA)之间的关系。方法依据WHO诊断标准,选择白细胞精子症不育者40例,非白细胞精子症不育者35例,生育者30例,采用过氧化物酶染色法进行精液WBC密度计数；采用镀铜镉还原荧光法检测NO代谢产物硝酸盐(NO_3)；UA含量测定采用尿酸酶。过氧化物酶偶联法。结果白细胞精子症组精液NO含量为(106．95±4．13)μmol/L、WBC为(1．985±0．696)×10~9/L,而UA含量(166．9±68．1)μmol/L,生育组NO含量(41．31±3．67)μmol/L、WBC为(0．038±0．024)×10~9/L和UA含量为(398．6±52．3)μmol/L。NO和WBC显著高于对照组,UA显著低于对照组(P＜0．01),UA与NO及WBC均呈显著性负相关(r=-0．795,P＜0．01：r=-0．857,P＜0．01)。结论白细胞精子症患者精液NO产生增多致UA含量下降,使精子中毒受损。提示临床在治疗时应加用抗氧化药物,可提高疗效。     

高糖与高尿酸通过醛糖还原酶通路协同作用加重内皮细胞损伤

目的寻找高血糖与高尿酸血症协同加重内皮细胞损伤的共同作用靶点和分子机制,为糖尿病合并高尿酸血症患者心血管疾病的保护提供干预靶点。 方法用人脐静脉内皮细胞系(HUVEC-C)给予高糖(30 mmol/L,HG)、高尿酸(600 μmol/L,UA)和高糖(HG)＋高尿酸(UA)联合培养48 h。利用10 μmol/L阿司他丁阻断醛糖还原酶(AR)的活性。实时定量PCR检测内皮型一氧化氮合成酶(eNOS)和AR mRNA的表达;Western blot检测还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶2 (NOX2)、NOX4、eNOS和AR蛋白的表达;共聚焦显微镜检测细胞内ROS的活性;一氧化氮(NO)试剂盒检测NO活性。 结果与单独HG组和UA组相比,HG＋UA共培养组明显降低eNOS mRNA水平和蛋白表达,减少NO产生,增加内皮细胞胞内ROS活性;HG＋UA共培养明显上调AR mRNA水平和蛋白表达。应用AR抑制剂能够明显增加HG＋UA组内皮细胞eNOS mRNA水平和蛋白表达,增加内皮细胞NO的分泌水平。AR抑制剂能够明显下调HG＋UA组内皮细胞NOX4的蛋白表达,对NOX2无影响;降低细胞内ROS的含量。 结论高血糖和高尿酸协同作用通过激活醛糖还原酶途径下调内皮细胞eNOS的表达,增加ROS活性,减少NO的产生,加重内皮细胞功能障碍;而抑制醛糖还原酶,能够通过抑制NOX4表达,阻断这种协同损伤作用。     

骨密度与血糖、血脂及血尿酸水平相关性分析

目的分析骨密度和血糖、血脂及血尿酸水平的相关性。方法选择在本院体检的无基础疾病的健康人群,询问患者病史,测量身高、体重,计算体重指数。空腹采集肘静脉血,采用全自动生化分析仪检测:空腹血糖、总胆固醇、低密度脂蛋白胆固醇、血尿酸。测定骨密度(BMD),测定部位为:股骨颈(左侧)。结果血尿酸、血糖及低密度脂蛋白胆固醇水平在骨质疏松组高于骨量减少组及骨量正常组;血糖、血尿酸与骨密度T值呈相关关系(P值均0.05;相关系数分别为-0.35,-0.49),进一步的多元线性回归分析显示,血尿酸、空腹血糖均是影响骨密度的危险因素,且空腹血糖对骨密度的影响较大。结论空腹血糖、血尿酸升高是中老年人群骨密度下降的危险因素。     

Serum uric acid and cardiovascular risk: State of the art and perspectives

Hyperuricaemia is commonly found in subjects with cardiovascular disease, but its role as risk factor is very controversial. Although several studies reported serum uric acid as a marker of an underlying pathophysiological process, other studies hypothesis a potential causal link between serum uric acid and cardiovascular diseases. Some studies suggest that uric acid is biologically active and may have an atherogenesis role in development of cardiovascular diseases, although the mechanisms are not fully understood. Other studies have shown that uric acid can independently predict the development of some cardiovascular risk factors such as hypertension and metabolic syndrome, as well as myocardial infarction and stroke. The relations between serum uric acid and established cardiovascular risk factors are complex, and these latter could be considered as confounding factors. In this report, we review the inextricably link of serum uric acid to known cardiovascular risk factors, and we describe the possible mechanisms and potential causative role between serum uric acid and cardiovascular events in the general population, in subjects with cardiovascular risk factors and in those with pre-existing cardiovascular diseases. Limited information however is available concerning the impact of urate-lowering treatments on cardiovascular events, whereas only a positive therapeutic trial could give definite answers to the difficult problem of causality of uric acid in relation to cardiovascular risk. Thus, it is time to propose the design of a therapeutic trial, integrating cardiologists and rheumatologists, in order to further decrease cardiovascular risk.     

Increased production and reduced urinary buffering of acid in uric acid stone formers is ameliorated by pioglitazone

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Experimental determination of the kinetics of calcium-binding with chondroitin sulphate and the effects of uric acid on this process

Summary The calcium-binding kinetics of chondroitin sulphate C (CS) have been determined using equilibrium analysis including ⁴⁵Ca. There is a linear relationship between the extent of the Ca binding and the concentration of CS present. 1 mol CS disaccharide unit binds 0.757 mol Ca. Scatchard plots of the data have revealed a single constant of dissociation (K _D =1429). In the presence of urate ions, and dependent on the pH value, the ability of CS to bind Ca may be impaired by as much as 31%. These measurements have supported the theory that urate ions interact with the GAGs in urine.     

Impact of serum uric acid on renal function after bariatric surgery: a retrospective study

BackgroundDespite a known negative association between serum uric acid level (SUA) and renal function, this correlation in patients after bariatric surgery remains unknown.ObjectiveTo assess correlation between postoperative SUA and estimated glomerular filtration rate (eGFR) at 12 months after bariatric surgery.SettingA single tertiary referral center.MethodsA total of 252 patients (age = 40.5 ± 11.2; body mass index = 39.0 ± 5.5 kg/m²) undergoing bariatric surgery divided into 2 groups (i.e., normal renal function [90 ≤ eGFR < 125 mL/min/1.73 m², n = 176] versus renal function impairment [eGFR < 90 mL/min/1.73 m², n = 76]) were assessed for relationships between SUA and eGFR in both groups (primary endpoint) and associations of percentage weight loss with changes in SUA (△SUA) and eGFR (△eGFR) for all patients (secondary endpoint) at 12 months.ResultsOverall, prevalence of hyperuricemia was 40.4% and 22.2% (baseline and postoperative 12 mo, respectively). Reverse relationship was observed between SUA and eGFR (r = −.152, P = .007) for all patients with no association noted between baseline SUA and eGFR in each group as well as between SUA and eGFR at 12 months in the normal group (r = −.076, P = .437). The reverse relationship was found (r = −.417, P = .005) in renal function impairment group for whom SUA was identified as a predictor of eGFR at 12 months. There was no association of percentage weight loss with △SUA (r = .089, P = .601) and △eGFR (r = −.046, P = .785).ConclusionThe results demonstrated a negative relationship between postoperative SUA and renal function in patients with preexisting renal dysfunction undergoing bariatric surgery. Clinical significance of our findings warrants further investigation.     

Role of uric acid in different types of calcium oxalate renal calculi

AIM: The presence of uric acid in the beginning zone of different types of 'pure' calcium oxalate renal calculi was evaluated with the aim of establishing the degree of participation of uric acid crystals in the formation of such calculi. METHODS: The core or fragment of different types of 'pure' calcium oxalate renal calculi was detached, pulverized and uric acid extracted. Uric acid was determined using a high-performance liquid chromatography/mass spectrometry method. RESULTS: In calcium oxalate monohydrate (COM) papillary calculi with a core constituted by COM crystals and organic matter, 0.030+/-0.007% uric acid was found in the core. In COM papillary calculi with a core constituted by hydroxyapatite, 0.031+/-0.008% uric acid was found in the core. In COM unattached calculi (formed in renal cavities) with the core mainly formed by COM crystals and organic matter, 0.24+/-0.09% uric acid was found in the core. In COM unattached calculi with the core formed by uric acid identifiable by scanning electron microscopy (SEM) coupled to X-ray microanalysis, 20.8+/-7.8% uric acid was found in the core. In calcium oxalate dihydrate (COD) unattached calculi containing little amounts of organic matter, 0.012+/-0.004% uric acid was found. In COD unattached calculi containing little amounts of organic matter and hydroxyapatite, 0.0030+/-0.0004% of uric acid was found. CONCLUSIONS: From these results it can be deduced that uric acid can play an important role as inducer (heterogeneous nucleant) of COM unattached calculi with the core formed by uric acid identifiable by SEM coupled to X-ray microanalysis (these calculi constitute the 1.2% of all calculi) and in COM unattached calculi with the core mainly formed by COM crystals and organic matter (these calculi constitute the 10.8% of all calculi).