Diagnosis and prevention of uric acid stones

Uric acid stones occur in 10% of all kidney stones and are the second most-common cause of urinary stones after calcium oxalate and calcium phosphate calculi. The most important risk factor for uric acid crystallization and stone formation is a low urine pH (below 5.5) rather than an increased urinary uric acid excretion. Main causes of low urine pH are tubular disorders (including gout), chronic diarrhea or severe dehydration. Uric acid stone disease can be prevented and these are one of the few urinary tract stones that can be dissolved successfully. The treatment of uric acid stones consists not only of hydration (urine volume above 2000 ml daily), but mainly of urine alkalinization to pH values between 6.2 and 6.8. Urinary alkalization with potassium citrate or sodium bicarbonate is a highly effective treatment, resulting in dissolution of existing stones. Urinary uric acid excretion can be reduced by a low-purine diet. Potassium citrate is the treatment of choice for the prevention of recurrence of uric acid calculi. Allopurinol reduces the frequency of stone formation in hyperuricosuric patients with recurrent uric acid stones and/or gout.     

Physiology and biochemistry of uric acid

In humans, uric acid is the final breakdown product of unwanted purine nucleotides. Uric acid is the last stage in purine degradation, because humans lack the enzyme uricase which converts uric acid into allantoin. Uric acid has profound beneficial effects since it scavenges potential harmful radicals in our body. However, in conjunction with genetic or environmental factors, uric acid can cause significant health problems, leading to kidney stones when it builds up in the kidneys and to gout when crystals accumulate in the joints. The levels of uric acid in the blood must be tightly controlled to minimize these detrimental effects. Normally, the body eliminates enough uric acid in the kidney, and in part also through the intestines, to keep its concentration at a healthy level in the blood (approximately 300 microM). In patients with gout or kidney stone disease, however, the body either produces excessive amounts of uric acid or its ability to eliminate uric acid is disturbed in some way. In the kidney, uric acid is reabsorbed via the uric acid transporter URAT1. This transporter is the major mechanism for regulating blood uric acid levels and therefore may prove an interesting target for future drug development.     

Methylated purines in urinary stones

BACKGROUND: The aim of the study was to measure the content of methylated purines that appear as admixtures in uric acid stones. METHODS: We analyzed urinary calculi from 48 residents of Western Pomerania who underwent surgery at the urology ward in Szczecin. Stone samples were dissolved in 0.1 mol/L NaOH. Extracts were diluted in 50 mmol/L KH(2)PO(4) and analyzed by reversed-phase HPLC with ultraviolet detection and use of a gradient of methanol concentration and pH. RESULTS: Uric acid was the main component of 9 stones. All 9 showed admixtures of 9 other purine derivatives: endogenous purine breakdown products (xanthine, hypoxanthine, and 2,8-dihydroxyadenine) and exogenous methyl derivatives of uric acid and xanthine (1-, 3-, and 7-methyluric acid; 1,3-dimethyluric acid; and 3- and 7-methylxanthine). Amounts of these purine derivatives ranged from the limit of detection to 12 mg/g of stone weight and showed a strong positive correlation (Spearman rank correlation coefficients, 0.63-0.94) with the uric acid content of the samples. The main methylated purine in the stones was 1-methyluric acid. CONCLUSIONS: Urinary purines at concentrations below their saturation limits may coprecipitate in samples supersaturated with uric acid and appear as admixtures in urinary stones. The amount of each purine depends on its average urinary excretion, similarity to the chemical structure of uric acid, and concentration of the latter in the stone. These findings suggest that purines in stones represent a substitutional solid solution with uric acid as solvent. Methylxanthines, which are ubiquitous components of the diet, drugs, and uric acid calculi, may be involved in the pathogenesis of urolithiasis.     

Prevention of recurrent nephrolithiasis

The first episode of nephrolithiasis provides an opportunity to advise patients about measures for preventing future stones. Low fluid intake and excessive intake of protein, salt and oxalate are important modifiable risk factors for kidney stones. Calcium restriction is not useful and may potentiate osteoporosis. Diseases such as hyperparathyroidism, sarcoidosis and renal tubular acidosis should be considered in patients with nephrolithiasis. A 24-hour urine collection with measurement of the important analytes is usually reserved for use in patients with recurrent stone formation. In these patients, the major urinary risk factors include hypercalciuria, hyperoxaluria, hypocitraturia and hyperuricosuria. Effective preventive and treatment measures include thiazide therapy to lower the urinary calcium level, citrate supplementation to increase the urinary citrate level and, sometimes, allopurinol therapy to lower uric acid excretion. Uric acid stones are most often treated with citrate supplementation. Data now support the cost-effectiveness of evaluation and treatment of patients with recurrent stones.     

Is idiopathic recurrent calcium urolithiasis in males a cellular disease? Laboratory findings in plasma, urine and erythrocytes, emphasizing the absence and presence of stones, oxidative and mineral metabolism: an observational study.

BACKGROUND: The site of origin of idiopathic recurrent calcium urolithiasis (IRCU)--a disorder characterized by stones composed of calcium oxalate (CaOx) and/or calcium phosphate (CaPi)--is uncertain, because in urine such risk factors for stones as disturbed Ox, Ca and Pi are not regularly observed. AIMS: To evaluate whether imbalance of antioxidants and oxidants might be present in IRCU patients that is then followed by abnormal urine, plasma and intracellular mineral homeostasis, and stones. METHODS: Males were investigated in the laboratory under standardized conditions, and three trials were organized. Trial 1 was cross-sectional, comparing IRCU patients with (n = 111) and without stones in situ (n = 126), focussing on abnormalities of oxypurines and minerals in urine and plasma, and metabolic activity (MA) of the disease. Trial 2 was partly controlled (n = 14 healthy subjects; n = 53 IRCU patients), comparing the plasma levels of total antioxidant status (TAS) and uric acid, the major antioxidant in humans, using the subsets Low (n = 26) and High (n = 27) TAS among IRCU patients in terms of plasma levels of uric acid, ascorbic acid, albumin, alpha-tocopherol and minerals, urinary minerals, CaOx and CaPi (hydroxyapatite) supersaturation. Trial 3, comprising stone-free IRCU patients (n = 8) and healthy controls (n = 8), compared minerals and mineral ratios in plasma and red blood cells (RBCs). Established analytical methodologies were used throughout. RESULTS: In trial 1, uricemia, hypoxanthinuria and proteinuria were elevated, fractional urinary clearance (FE) of uric acid was decreased in stone-bearing patients, and MA correlated positively with uricemia and urinary total protein excretion. In trial 2, TAS was significantly decreased in IRCU patients vs. healthy controls; low TAS coincided with low plasma uric acid and albumin, unchanged ascorbic acid, alpha-tocopherol and parathyroid hormone, but increased FE-uric acid and Pi excretion; the latter correlated negatively with TAS. In trial 3, plasma minerals were significantly decreased in IRCU patients vs. controls, and Ca/Pi, (Ca/Pi)/Mg and (Ca/Pi)/Na molar ratios increased; the latter ratio was also increased in RBCs, and correlated highly positively with the same ratio in plasma. CONCLUSIONS: In IRCU 1) renal stones in situ in combination with high fasting uricemia, high hypoxanthinuria and protein-uria, and high MA suggest that a systemic metabolic anomaly underlies stone formation; 2) antioxidant deficit is frequent, unrelated to the presence or absence of stones but apparently related to poor renal uric acid recycling, low uricemia and albuminemia, exaggerated urinary Pi excretion, and low MA; 3) the combination of low plasma TAS, disordered Ca/Pi and other mineral ratios in urine, plasma and RBCs, but unchanged urinary Ca salt supersaturation is compatible with the view that CaPi solid and Ca microlith formation start inside oxidatively damaged cells.     

Pathophysiology,diagnosis and conservative therapy of non-calcium kidney calculi

While calcium oxalate and calcium phosphate make up at least 80% of all kidney stones, infection-induced and uric acid stones occur in 10% and 8%, respectively. Although any type of stone may become infected, the term "infection stones" means that stone formation exclusively depends on urease-producing bacteria. The splitting of urea leads to a rise in urinary pH which may induce crystallization of struvite (magnesium-ammonium-phosphate), the major constituent of infection stones, or carbonate apatite. Struvite stones account for the majority of staghorn calculi. They can grow quite large and may fill the entire collecting system. Patients with struvite stones may present with acute flank pain or remain completely asymptomatic. The cure of infection stones requires complete removal of the stone material. For uric acid crystallization and stone formation, low urine pH (below 5.5) is a more important risk factor than increased urinary uric acid excretion. Main causes of low urine pH are tubular disorders (including gout), chronic diarrheal states or severe dehydration. Accordingly, the treatment of uric acid stones consists not only of hydration (urine volume above 2000 ml per day), but mainly of urine alkalinization to pH values between 6.2 and 6.8. Urinary uric acid excretion can be reduced by a low-purine diet as well as--in case of recurrent uric acid stones and/or gout--by allopurinol. Cystinuria is a rare hereditary gene disorders with impaired tubular reabsorption of cystine. Stone formation occurs as a consequence of cystine's relatively low solubility at urine pH levels below 8. Only symptomatic diet and drug treatments are currently available, with urine dilution and urine alkalinization being the most efficient ones. Cystine stones respond poorly to shockwave lithotripsy, so that invasive procedures may regularly be necessary. 2,8-dihydroxy-adenine stones occur as a consequence of an enzyme deficiency that involves purine metabolism. These resulting stones are not visible by fluoroscopy and are therefore often misinterpreted as uric acid stones. Low-purine diet and allopurinol reduce the frequency of stone formation.     

Identification of myeloperoxidase, alpha-defensin and calgranulin in calcium oxalate renal stones

BACKGROUND: In order to understand the mechanism of stone genesis, it is essential to determine the characteristics of macromolecules constituting the urinary stones. We characterized proteins from the inner core and outer matrix of calcium oxalate (CaOx) renal stones. METHODS: Inner core and outer matrix of CaOx renal stones were separated and proteins were extracted with a buffer containing SDS and beta-mercaptoethanol. Proteins were analyzed and purified by SDS-PAGE and RP-HPLC respectively. The protein bands from gel and protein fractions were sequenced by MALDI TOF mass spectrometry. ELISA, western and slot blot immunoassays were performed to confirm the identity of the proteins in stones and urine of the stone formers. The potential of the identified protein as an effective promoter or inhibitor was assessed by observing their effects on CaOx crystallization using aggregometer. RESULTS: The inner core extract predominantly exhibited protein species in the molecular weight range of 12-14 kDa. However, a 66 kDa band, identified as osteopontin was also detected in the inner core along with outer matrix and in the urine of stone formers and non stone formers. Purification of low molecular weight proteins was carried out by reversed phase HPLC. Tandem mass spectrometry analysis identified them as myeloperoxidase chain A (MPO-A), alpha-defensin, and calgranulin. ELISA, western blot and slot-blot immuno-assays further confirmed their presence restricted to the inner core and not in the outer matrix. Turbidity assays showed that low molecular weight renal stone proteins promoted the aggregation of CaOx crystals. CONCLUSIONS: Persistent hyperoxaluria leads to tubular epithelial injury, resulting in the release of these anti-inflammatory proteins. These proteins could have been first adsorbed on CaOx crystals thereby become a part of nucleation process leading to inner matrix formation.     

Uric acid: an abettor or protector in calcium oxalate urolithiasis? Biochemical study in stone formers

BACKGROUND: Free radical induced renal damage leads to crystal retention and formation of large stones. However, the scenario behind uric acid (UA) stone formation is still a mystery, as uric acid, a risk factor of stone formation, seems to be a potent antioxidant that can protect cells from damage by reactive oxygen species. This study was intended to evaluate the role of uric acid in stone formers by assessing the oxidative stress status of the stone patients. METHODS: Determination of urinary stone forming risk factors and oxidative stress factors like plasma lipid peroxidation, protein carbonyls of stone formers and histopathological changes and uric acid deposition in stone patients kidney biopsy were studied. RESULTS: Increased concentrations of urinary uric acid and oxalate in both uric acid as well as calcium oxalate stone formers were observed, whereas calcium is increased in calcium stone formers and not in the uric acid stone patients. Inhibitors such as citrate and glycosaminoglycans (GAGs) were found to be significantly decreased in all the stone patients. Histopathological studies confirmed the deposition of crystals in the damaged tubules and De Galantha staining authenticates that the damage is caused due to uric acid crystals. Increased oxidative stress is dictated by the concentrations of lipid peroxidation and protein carbonyls in stone formers. Moreover, increased activities of urinary marker enzymes substantiate the tubular damage. CONCLUSION: We speculated that uric acid acts as a calculi forming salt rather than an antioxidant and it has no role in preventing oxidative stress pertaining to urolithiasis.     

老年收缩期高血压患者血清尿酸水平及氯沙坦钾的治疗作用

目的探讨老年收缩期高血压(ISH)患者血清尿酸水平的变化及氯沙坦钾的治疗作用。方法85例老年ISH患者和51例健康老年人血清尿酸水平的差异及老年ISH药物治疗(氯沙坦钾44例,苯那普利41例)8周后两组血压及血清尿酸水平变化的差异。结果老年ISH组血清尿酸水平显著高于正常对照组(P＜0.01)。经药物治疗8周后,两组降压效果无显著性差异,而两组治疗后血清尿酸水平,具有显著性差异(P＜0.01)。结论老年ISH患者血清尿酸水平显著升高,氯沙坦钾治疗ISH疗效肯定,且能有效地降低血清尿酸水平。     

高尿酸血症高危人群检测结果分析

目的 了解高尿酸血症(HUA)在其高发人群的发病率,为相关疾病防治提供科学依据.方法 使用雅培C8000全自动生化分析仪,血清尿酸采用TBHBA(速率法)检测,按照国际、国内诊断标准进行分析.结果 2 945例高危人群中,HUA患者为1 193例,发病率为40.51%.HUA患者合并糖尿病、高血脂、肥胖、高血压、泌尿系统结石、心脑血管疾病等发病率分别为31.57%、46.94%、51.62%、42.39%、28.69%和20.78%.结论 高尿酸血症多见于代射综合征,及时纠正HUA,利于患者转归及减少并发症.     

Evaluation and characterization of the effects of ticagrelor on serum and urinary uric acid in healthy volunteers

During its development, ticagrelor, a drug designed to prevent thrombotic events in patients with acute coronary syndromes, was found to have an association with mild hyperuricemia. To investigate this effect further, we carried out a placebo-controlled, randomized, crossover study in 24 healthy male volunteers. The volunteers received ticagrelor (90 mg b.i.d. for 5 days), and serum uric acid and urinary uric acid excretion were assessed under strictly controlled conditions. After administration of ticagrelor, serum uric acid significantly increased (day 1: 4-6%; day 5: 4-10%) relative to placebo and rapidly returned to baseline after the last dose of the drug. Urinary uric acid excretion was significantly higher on day 1 (7%) and at 24-48 h after the morning dose on day 5 (17%) relative to placebo. Uric acid clearance was significantly higher 24-48 h after the morning dose on day 5 (11%). Uric acid fractional excretion was unaffected. Serum hypoxanthine and xanthine were elevated after multiple ticagrelor doses. No uric acid-related adverse events were seen. The study showed that ticagrelor-associated hyperuricemia is modest and reversible; serum uric acid elevation may have been caused by altered tubular secretion and/or increase in production.     

Controlling the crystal structure of succinic acid via microfluidic spray-drying

Many properties of materials, including their dissolution kinetics, hardness, and optical appearance, depend on their structure. Unfortunately, it is often difficult to control the structure of low molecular weight organic compounds that have a high propensity to crystallize if they are formulated from solutions wherein they have a high mobility. This limitation can be overcome by formulating these compounds within small airborne drops that rapidly dry, thereby limiting the time molecules have to arrange into the thermodynamically most stable phase. Such drops can be formed with a surface acoustic wave (SAW)-based spray-drier. In this paper, we demonstrate that the structure of a model low molecular weight compound relevant to applications in pharmacology and food, succinic acid, can be readily controlled with the supersaturation rate. Succinic acid particles preserve the metastable structure over at least 3 months if the initial succinic acid concentration is below 2% of its saturation concentration such that the supersaturation rate is high. We demonstrate that also the stability of the metastable phases against their transformation into the most stable phase increases with decreasing initial solute concentration and hence with increasing supersaturation rate of the spray-dried solution. These insights open up new opportunities to control the crystal structure and therefore properties of low molecular weight compounds that have a high propensity to crystallize.

A surface acoustic wave based microfluidic spray-drier is used to spray dry succinic acid, a model low molecular weight matrix substance. We demonstrate that the structure of succinic acid can be tuned with its formation time within drying drops.     

心力衰竭与血尿酸的关系探讨

目的　探讨尿酸与心力衰竭的关系。方法　选择健康对照组 30例 ,高血压病例 12 0例 (其中不伴靶器官损害组 4 4例 ,伴左室肥厚组 39例 ,伴心力衰竭组 37例 )。比较心功能不同程度受损时血尿酸的变化。结果　尿酸在心力衰竭组中明显升高 ,差异有显著意义 (P <0 0 1)。结论　心力衰竭患者尿酸升高     

双源 CT 在尿路结石成分分析中的临床研究

目的：探讨双源CT （DSCT）双能量技术应用于尿路结石成分分析中的临床价值。方法对75例尿路结石患者行DSCT双能量扫描及血清尿酸测定,对其结石成分进行分析,将结果与采用红外光谱法分析结石成分的结果作对比,计算DSCT在体分析尿酸盐结石及非尿酸盐结石的灵敏度与特异度。结果75例结石标本中尿酸盐结石25例,在140 kV能量下的CT值为（316.3±64.5）HU,在80 kV能量下的CT值为（336.4±55.7）HU;非尿酸盐结石为50例,在140 kV能量下的CT值为（680.7±334.1）HU,在80 kV能量状态下为（1005.2±221.3）HU。尿酸盐结石在2种能量状态下差值、比值分别为（20.1±8.1）、（1.06±0.02） HU;非尿酸盐结石在2种能量状态下差值、比值分别为（324.6±31.2）、（1.48±0.03）HU,尿酸盐结石差值、比值均明显低于非尿酸盐结石（均P＜0.05）。 DSCT能准确地区分尿酸盐结石和非尿酸盐结石,灵敏度及特异度分别为88.0%及98.0%。结论 DSCT能准确地区分尿酸盐结石和非尿酸盐结石。使用DSCT双能量技术在治疗前对尿路结石的成分进行初步分析,对了解结石成因、预防结石形成及指导治疗具有重要的意义。     

Uric acid estimation: a comparison of the manual uricase-UV and the phosphotungstate auto-analyzer methods.

1. Uric acid estimations by the uricase-UV and the autoanalyzer colorimetric procedures were compared. 2. At all levels of serum uric acid concentration measured, results with the uricase-UV method were significantly lower than those with the phosphotungstate method. 3. The data indicate that the critical uric acid level (measured by the autoanalyzer) at which allopurinol, uricosuric, and other agents are instituted should be decreased approximately 10 per cent when determinations are done by the uricase method.     

Uptake of uric acid by separated renal tubules of the rabbit. I. Characteristics of transport.

A rapid filtration procedure was used to determine rates of uric acid uptake by a preparation of separated renal cortical tubules of the rabbit. The rate of uric acid uptake was temperature dependent and showed saturation kinetics with a K of 3.2 mM. The uptake was 50% lower when measured under nitrogen as compared with uptake under oxygen. The uptake rate increased with increasing sodium concentration and decreased with increasing potassium concentration. Uptake was stimulated by citrate, succinate and pyruvate, and inhibited by alpha-ketoglutarate. Parathyroid hormone and 10(-4) M adenosine 3':5'-monophosphate increased the uric acid uptake rate when preincubated with the tubules for 130 minutes before the addition of uric acid. Uric acid uptake in this preparation appears to occur by some form of carrier-mediated active transport.     

The hyperiricosuria as an indicator of derangement of biologic functions of endoecology and adaptation, biologic reactions of excretion, inflammation and arterial tension

During millions years in all animals allantoine (oxidized by uricase uric acid) was catabolite of purines and ascorbic acid was an acceptor of active forms of oxygen. The proximal tubules of nephron reabsorbed the trace amounts of uric acid Then during phylogenesis the primates had a mutation of ascorbic acid gen minus. Later on occurred a second spontaneous mutation and uricase gen minus and uric acid became catabolites of purines. In absence of ascorbic acid synthesis ions of urates became a major capturers of active forms of oxygen and all uric acid as before underwent the reabsorption. Later the carriers were formed which began in epithelium of proximal tubules to secrete all uric acid into urine. At every incident of "littering" of intercellular medium with endogenic flogogens (impairment of biologic function of endoecology) under compensatory development of biologic reaction of inflammation the need in inactivation of active forms of oxygen increases. Hence later on in phylogenesis one more stage was formed--post secretory reabsorption of uric acid In the biologic reaction of inflammation epithelium of proximal tubules initiates retentional hyperiricosuria. The general antioxidant activity of human blood plasma in 60% is presented by urates' ions. The excretion of uric acid includes 4 stages: filtration, full reabsorption, secretion and post secretory reabsorption. In phylogenesis these stages formed in sequence. The mild hyperiricosuria is most frequently considered as a non-specific indicator of activation of biologic reaction of inflammation. The productive hyperiricosuria develops more infrequently under surplus of meat food and cytolysis syndrome (intensification of cell loss in vivo). Under concentration of uric acid more than 400 mkmol/l part of urates circulates in intercellular medium in the form of crystals. The microcrystals of uric acid (biologic "litter") initiate the syndrome of systemic inflammatory response as an endogenic flogogen--initiator of inflammation. The uric acid in the form of ion-capturers of active forms of oxygen is involved into in the formation of syndrome of compensatory anti-inflammatory defense. It may be assumed that simultaneously with post-secretory reabsorption of ions of urates in proximal tubules of nephron occurs intensification of philogenetically late post-secretory reabsorption of ions of sodium and activation of of biologic reaction of hydrodynamic and hydraulic pressure in local pool of intravascular medium i.e. arterial tension. The uric acid simultaneously participates in realization of biologic function of endoecology and adaptation, biologic reactions of excretion, inflammation and arterial tension.     

大黄对尿酸性肾病大鼠肾组织碱性成纤维细胞生长因子和环氧化酶-2的影响

目的：研究大黄对尿酸性肾病大鼠肾组织碱性成纤维细胞生长因子（bFGF）和环氧化酶-2（COX-2）的作用及探讨大黄治疗肾脏病的作用机制。方法：将32只SD雄性大鼠随机分为4组，即正常对照组、模型组、大黄组、别嘌呤醇组．用酵母和腺嘌呤合用造模，造模成功后正常对照组、模型组以生理盐水4mL灌胃，别嘌呤醇组以别嘌呤醇0．01g／（kg·d）加生理盐水制成dmL液体灌胃，大黄组以大黄0．5g／（kg·d）加生理盐水制成4mL混悬液灌胃，治疗2周后，检测各组大鼠血中尿素氮（BUN）、肌酐（Cr）、尿酸（UA），应用免疫组织化学技术检测大鼠肾组织bFGF和COX-2的表达情况。结果：与正常对照组比较，模型组血UA、BUN、Cr均明显升高（P〈0．01），COX．2、bFGF在肾组织表达明显增加（P〈0．01）；与用药前比较，用药后，大黄组和别嘌呤醇组大鼠血UA、BUN、Cr均明显降低（P〈0．05），大黄组血UA、BUN及Cr水平与别嘌呤醇组比较，差异无显著性（P〉0．05），而大黄组肾组织bFGF与COX-2表达明显低于别嘌呤醇组（P〈0．01）。结论：大黄能降低bFGF、COX-2在尿酸性肾病大鼠模型肾组织中的表达，从而减轻肾脏损害，保护肾功能。[著者文摘]     

64排CT对上尿路结石成分分析的临床意义

目的探讨64排CT对上尿路结石成分分析的临床意义.方法选择肾盂结石及输尿管结石患者136例,64排CT扫描,对结石测量最大径和CT值,并对结石用红外光谱自动分析仪作成分分析.结果136例患者中纯结石患者78例,草酸钙结石和羟磷灰石结石的CT值显著高于L-胱氨酸结石和尿酸结石的CT值（P〈0.01）,草酸钙结石、羟磷灰石结石之间CT值差异无统计学意义,L-胱氨酸结石虽略高于尿酸结石CT值,但差异也无统计学意义.羟磷灰石结石CT值/结石最大横径较草酸钙结石差异有统计学意义（P〈0.05）,L-胱氨酸结石CT值/结石最大横径较尿酸结石差异有统计学意义（P〈0.05）.结论采用64排CT对结石CT值进行测定并计算CT值/最大横面直径能更好的判断结石成分,对于指导选择治疗方法及用药方案有积极作用.     

Biliary lipid composition in patients with cholesterol and pigment gallstones and gallstone-free subjects: deoxycholic acid does not contribute to formation of cholesterol gallstones

BACKGROUND: Four main disturbances have been attributed to cholesterol gallstone disease: hypersecretion of cholesterol from the liver with cholesterol supersaturation in bile; disturbed motility with defective absorption and secretion by the gallbladder; increased crystallisation of cholesterol in the gallbladder bile; and slow intestinal transit with increased amount of deoxycholic acid in the bile acid pool. We aimed to evaluate the biliary lipid composition in a large series of gallstone patients, with emphasis on the amount of deoxycholic acid and with respect to number of stones, compared to gallstone free subjects. MATERIALS AND METHODS: Bile was sampled during operations through puncture of the gallbladder from 145 cholesterol gallstone patients, 23 patients with pigment stones and 87 gallstone free patients undergoing cholecystectomy. Biliary lipid composition, cholesterol saturation, bile acid composition, nucleation time and cholesterol crystals were analysed. RESULTS: The patients with cholesterol gallstones showed higher molar percentage of cholesterol, lower total biliary lipid concentration, higher cholesterol saturation, shorter nucleation time and higher proportion of crystals in bile than the other groups. The nucleation time was significantly shorter in multiple cholesterol gallstone patients, but this was not due to higher cholesterol saturation. Male cholesterol gallstone patients showed higher cholesterol levels, lower total biliary lipid concentration, and higher cholesterol saturation in bile than female patients. There was no difference in biliary content of deoxycholic acid, but significantly lower content of cholic acid in gallstone patients compared to gallstone free patients. CONCLUSIONS: We conclude that deoxycholic acid does not contribute to gallstone formation in cholesterol gallstone patients. The short nucleation time in patients with multiple cholesterol stones is not due to higher cholesterol saturation.