Role of osteopontin in diet-induced brown gallstone formation in rats / 中华医学杂志(英文版)

BACKGROUND@#Although osteopontin (OPN) is expressed in the liver and pigment gallstones of patients with hepatolithiasis, its role in pigment gallstone formation remains unclear. This study aimed to explore the function of OPN in pigment gallstone formation.@*METHODS@#Rats were fed a chow diet (CD) or lithogenic diet (LD) for 10 consecutive weeks; blocking tests were then performed using an OPN antibody (OPN-Ab). Incidence of gallstones and levels of several bile components, OPN, tumor necrosis factor alpha (TNF-α), and cholesterol 7 alpha-hydroxylase (CYP7A1) were analyzed. To determine TNF-α expression in hepatic macrophages and both CYP7A1 and bile acid (BA) expression in liver cells, recombinant rat OPN and recombinant rat TNF-α were used to treat rat hepatic macrophages and rat liver cells, respectively. Chi-square or Fisher exact tests were used to analyze qualitative data, Student t-test or one-way analysis of variance were used to analyze qualitative data.@*RESULTS@#Incidence of gallstones was higher in LD-fed rats than in CD-fed rats (80% vs. 10%, P < 0.05). BA content significantly decreased in bile (t = -36.08, P < 0.01) and liver tissue (t = -16.16, P < 0.01) of LD-fed rats. Both hepatic OPN protein expression (t = 9.78, P < 0.01) and TNF-α level (t = 8.83, P < 0.01) distinctly increased in the LD group; what's more, CYP7A1 mRNA and protein levels (t = -12.35, P < 0.01) were markedly down-regulated in the LD group. Following OPN-Ab pretreatment, gallstone formation decreased (85% vs. 25%, χ2 = 14.55, P < 0.01), liver TNF-α expression (F = 20.36, P < 0.01) was down-regulated in the LD group, and CYP7A1 expression (F = 17.51, P < 0.01) was up-regulated. Through CD44 and integrin receptors, OPN promoted TNF-α production in macrophage (F = 1041, P < 0.01), which suppressed CYP7A1 expression (F = 48.08, P < 0.01) and reduced liver BA synthesis (F = 119.4, P < 0.01).@*CONCLUSIONS@#We provide novel evidence of OPN involvement in pigmented gallstone pathogenesis in rats.

Ursodeoxycholic acid in the prevention of gallstones in patients subjected to Roux-en-Y gastric bypass

Abstract Purpose: To evaluate the contribution of ursodeoxycholic acid (UDCA) in the first 12 months after Roux-en-Y gastric bypass in the prevention of gallstone formation. Methods: A community-based clinical trial was conducted. A total of 137 patients were included in the study; 69 were treated with UDCA, starting 30 days after the surgery, at a dose of 150 mg twice daily (300 mg/day) over a period of 5 consecutive months (GROUP A), and 68 were control patients (GROUP B). The patients were followed-up, and ultrasonography was performed to determine the presence of gallstones at various times during follow-up. Demographic, anthropometric and comorbid indicators were obtained. The data were subjected to normality tests and evaluated using appropriate tests. Results: Patients did not differ in their baseline characteristics. Of the 69 patients who used UDCA, only one patient developed cholelithiasis (1%), whereas 18 controls (26%) formed gallstones (OR = 24.4, p <0.001). Also, other factors were found not to influence the formation of calculi, such as pre-operative or postoperative hepatic steatosis or diabetes (p = 0.759, 0.468, 0.956). Conclusion: The results demonstrated that patients who did not use UDCA showed a 24.4-fold greater probability of developing cholelithiasis.

Efecto de una dieta alta en grasas en el proceso de formación de cálculos biliares de colesterol / Effect of a high-fat diet on cholesterol gallstone formation

Background: It is known that some nutrients play an important role in the development of cholelithiasis. Cholesterol is carried by micelles and vesicles in the bile. During the first stage of gallstone formation, cholesterol crystals derive from thermodynamically unstable vesicles. Aim: To determine the effect of a high fat diet on blood lipids and bile composition, and its implication in the formation of gallstones. Material and Methods: Two groups of 15 BALB/c mice each, coming from the same litter, were treated with a control or with a high-fat diet (64% fat and 0.14% cholesterol). After two months, the animals were sacrificed, blood and bile samples were obtained. Serum glucose and the corresponding lipid profiles were measured. In bile samples, cholesterol and phospholipid levels were analyzed, and cholesterol transporters (vesicles and micelles) were separated by gel filtration chromatography. Results: Treated animals showed an 87% increase in serum total cholesterol (p < 0.01), a 97% increase in HDL-cholesterol (p < 0.05) and a 140% increase in LDL-cholesterol (p < 0.05). No changes in serum triglycerides or glucose were observed. In bile, a 13% increase in biliary cholesterol (p < 0.05) was observed but no change in biliary phospholipids. Also, an increase in biliary vesicular transporters and an increase of cholesterol/phospholipid ratio in vesicular transporters were observed. Conclusions: A high fat diet may contribute to the formation of gallstones in our experimental model.

A New Paradigm in Gallstones Diseases and Marked Elevation of Transaminases: An Observational Study

ABSTRACT Background. In clinical practice, it is assumed that a severe rise in transaminases is caused by ischemic, viral or toxic hepatitis. Nevertheless, cases of biliary obstruction have increasingly been associated with significant hypertransaminemia. With this study, we sought to determine the true etiology of marked rise in transaminases levels, in the context of an emergency department. Material and methods. We retrospectively identified all patients admitted to the emergency unit at Centro Hospitalar e Universitário de Coimbra between 1st January 2010 and 31st December 2010, displaying an increase of at least one of the transaminases by more than 15 times. All patient records were analyzed in order to determine the cause of hypertransaminemia. Results. We analyzed 273 patients - 146 males, mean age 65.1 ± 19.4 years. The most frequently etiology found for marked hypertransaminemia was pancreaticobiliary acute disease (n = 142;39.4%), mostly lithiasic (n = 113;79.6%), followed by malignancy (n = 74;20.6%), ischemic hepatitis (n = 61;17.0%), acute primary hepatocellular disease (n = 50;13.9%) and muscle damage (n = 23;6.4%). We were not able to determine a diagnosis for 10 cases. There were 27 cases of recurrence in the lithiasic pancreaticobiliary pathology group. Recurrence was more frequent in the group of patients who had not been submitted to early cholecystectomy after the first episode of biliary obstruction (p = 0.014). The etiology of hypertransaminemia varied according to age, cholestasis and glutamic-pyruvic transaminase values. Conclusion. Pancreaticobiliary lithiasis is the main cause of marked hypertransaminemia. Hence, it must be considered when dealing with such situations. Not performing cholecystectomy early on, after the first episode of biliary obstruction, may lead to recurrence.

A Case of Hereditary Spherocytosis Coexisting with Gilbert's Syndrome / 대한소화기학회지

We recently encountered a case of hereditary spherocytosis coexisting with Gilbert's syndrome. Patient was initially diagnosed with Gilbert's syndrome and observed, but other findings suggestive of concurrent hemolysis, such as splenomegaly and gallstones were noted during the follow-up period. Therefore, further evaluations, including a peripheral blood smear, osmotic fragility test, autohemolysis test, and red blood cell membrane protein test were performed, and coexisting hereditary spherocytosis was diagnosed. Genotyping of the conjugation enzyme uridine diphosphate-glucuronosyltransferase was used to confirm Gilbert's syndrome. Because of the high prevalence rates and similar symptoms of these 2 diseases, hereditary spherocytosis can be masked in patients with Gilbert's syndrome. In review of a case and other article, the possibility of the coexistence of these 2 diseases should be considered, especially in patients with unconjugated hyperbilirubinemia who also have splenomegaly and gallstones.

Temporary Placement of Fully Covered Self-expandable Metal Stents in Benign Biliary Strictures / 대한소화기학회지

BACKGROUND/AIMS: Benign biliary strictures (BBSs) have been endoscopically managed with plastic stent placement. However, data regarding fully covered self-expandable metal stents (FCSEMSs) in BBS patients remain scarce in Korea. METHODS: Forty-one patients (21 men, 65.9%) with BBSs underwent FCSEMS placement between February 2007 and July 2010 in Asan Medical Center. Efficacy and safety were evaluated retrospectively. Patients were considered to have resolution if they showed evidence of stricture resolution on cholangiography and if an inflated retrieval balloon easily passed through the strictures at FCSEMS removal. RESULTS: The mean FCSEMS placement time was 3.2 (1.9-6.2) months. Patients were followed for a mean of 10.2 (1.0-32.0) months after FCSEMS removal. The BBS resolution rate was confirmed in 38 of 41 (92.7%) patients who underwent FCSEMS removal. After FCSEMS removal, 6 of 38 (15.8%) patients experienced symptomatic recurrent stricture and repeat stenting was performed. When a breakdown by etiology of stricture was performed, 14 of 15 (93.3%) patients with chronic pancreatitis, 17 of 19 (89.5%) with gall stone-related disease, 4 of 4 (100%) with surgical procedures, and 2 of 2 (100%) with BBSs of other etiology had resolution at FCSEMS removal. Complications related to stent therapy occurred in 12 (29%) patients, including post-ERCP pancreatitis (n=4), proximal migration (n=3), distal migration (n=3), and occlusion (n=2). CONCLUSIONS: Temporary FCSEMS placement in BBS patients offers a potential alternative to plastic stenting. However, because of the significant complications and modest resolution rates, the potential benefits and risks should be evaluated in further investigations.

Correlation between the chemical components of gallstones and sera of stone formers

Major elements involved in the formation of human gallstones are cholesterol, bile pigment and calcium. These substances are normally found in the blood. This study was aimed to find out the frequency of different type of gallstones and correlation between the components of gallstones and sera of stone formers. Fifty gallstones and blood samples were collected and analyzed from patients admitted for cholecystectomy to Rizgary Teaching Hospital, Erbil, Iraq, from July 2008 to December 2008. In 50 gallstone, 27[54%] were cholesterol stones, 20[40%] mixed and 3[6%] pigment stones. Female to male ratio was 8:1 and the predominant age of stone formers was 31-60 years. There was significantly negative correlation between serum cholesterol and that of cholesterol and pigment gall stones [r=- 0.730 and -0.999]. There was significant positive correlation between serum bilirubin and pigment gallstones [r=0.812]. Inorganic phosphate in serum was moderately correlated to that in cholesterol and mixed gallstones [r=0.377 and 0.178] with significant negative correlation in case of pigment stones [r=-0.845]. Moderate positive and negative correlation was found for calcium in case of three stones [r=0.202, r=-0.213 and -0.210]. In Erbil the occurrence of cholesterol gallstones is high as compared to mixed and pigment gallstones. Our results indicated low, moderate and high positive or negative correlation between the chemical constituents of gallstones and sera of stone formers suggesting the different aetiology of the cholesterol, mixed and pigment stones

Quantitative Analysis of Gallstones in Libyan Patients

Gallstone disease is one of the major surgical problems in the Libyan population; it is probably related to diet; especially excessive consumption of meat. The study was conducted to determine the composition of gallstones and their possible etiology in a Libyan population. The chemical composition of gallstones from 41 patients (six males and 35 females) was analyzed. The stones were classified into cholesterol; pigment; and mixed stones (MS). Cholesterol stones (CS) showed a significantly higher cholesterol content than pigment stones (PS) (p=0.0085) though not significantly higher than MS. Their phospholipid content and inorganic phosphates were higher than in the other types of stones and oxalate content was significantly elevated in comparison with MS (p=0.0471). In MS; the cholesterol; bile acids; and bilirubin were intermediate between cholesterol and PS; whereas triglycerides were significantly more than PS (p=0.0004). Bilirubin (0.0001) and bile acids (p=0.0009) were significantly higher than CS (p=0.0001). However; they contained the lowest amounts of sodium; potassium; magnesium; and oxalate. In PS; bilirubin (p=0.0001) was significantly higher than both groups. Bile acid content was significantly higher than CS (p=0.0001) but not significantly more than MS. They showed the highest values of calcium; sodium; potassium; magnesium; and chlorides compared to the other types of stones. High levels of cholesterol in stones and dyslipidemia associated with mixed as well as cholesterol gallstones suggest an etiological association and efforts to reduce dietary fat among the Libyan population may lead to decreased cholesterol and mixed gallstones

Ceftriaxone induced biliary pseudolithiasis in children: report of 14 cases

Biliary pseudolithiasis has been reported in patients who received ceftriaxone therapy. In this study we evaluated children with ceftriaxone associated pseudolithiasis that was discovered incidentally in US examination. The study includes 14 children with gallstones in Ultrasound without biliary symptoms with recent ceftriaxone administration. All of them were treated for suspected or definite bacterial infection with ceftriaxone 50-100mg/kg/day divided into 2 equal intravenous doses under conditions of adequate hydration. There were no other known underlying diseases for gallstone. Fourteen patients [11 boys and 3 girls] with mean age of 4.5 years [range: 2 months to 14 years] were studied. Following cessation of treatment with ceftriaxone, a complete resolution of the lithiasis was seen in most of followed cases. All patients were free from biliary symptoms [Right upper quadrant pain, Cholestasis] during observation. Consultations with surgeon or subspecialist due to reported "gallstone in the Ultrasound" were performed in about two-thirds of patients. Development of pseudolithiasis after ceftriaxone administration is not uncommon and should be known by pediatricians and radiologists in order to avoid unnecessary surgery or additional consultations

Insulin Resistance is Associated with Gallstones Even in Non-obese, Non-diabetic Korean Men

It remains unclear as to whether insulin resistance alone or in the presence of wellknown risk factors, such as diabetes or obesity, is associated with gallstones in men. The aim of this study was to determine whether insulin resistance is associated independently with gallstone disease in non-diabetic men, regardless of obesity. Study subjects were 19,503 Korean men, aged 30-69 yr, with fasting blood glucose level 75 percentile) in subjects with gallstones was significantly higher than in those without, and this association remained even after the obesity stratification was applied. In multiple logistic regression analyses, only age and HOMA proved to be independent predictors of gallstones. Insulin resistance was positively associated with gallstones in non-diabetic Korean men, and this occurred regardless of obesity. Gallstones appear to be a marker for insulin resistance, even in non-diabetic, nonobese men.

Prevalence and risk factors of gallstone disease in a high altitude Saudi population

To study the prevalence of gallstone disease and related risk factors in a Saudi Arabian population a cross-sectional community-based study was made of 291 people from Abha district, Asir region. A structured interview collected background data and all participants had upper abdominal ultrasonography to detect gallstones. The overall prevalence of gallstone disease was 11.7%. Using logistic regression multivariate analysis, the following were significant risk factors for gallstone disease: female sex, family history of gallstone disease and past history of pancreatitis. Age, education, blood pressure, smoking, coffee intake, overweight, diabetes mellitus, number of pregnancies and use of oral contraceptives were not significant risk factors. Discriminant analysis of symptoms showed that only right hypochondrium pain was significantly associated with gallstone disease

A Common Bile Duct Stone formed by Suture Material after Open Cholecystectomy

The use of non-absorbable suture materials for cystic duct ligation after cholecystectomy can expose patients to the risk of recurrent stone formation in the common bile duct (CBD). However, in Korea suture materials have rarely been found to act as a nidus for common bile duct calculus formation. Recently, we experienced a case in which suture material, that had migrated from a previous cholecystectomy site into the CBD, probably served as a nidus for common bile duct stone formation. The stone was confirmed by endoscopic retrograde cholangiopancreatography (ERCP) and removed successfully using a basket. The authors report a case of surgical suture migration and discuss its subsequent role as a stone forming nucleus within the CBD in a patient who underwent open cholecystectomy; and include a review of the literature.

Spontaneous cholecystocutaneous fistula: a rare complication of gallbladder disease / Fistula colecistocutânea espontânea: uma rara complicação da colecistopatia crônica calculosa

CONTEXT: Spontaneous cholecystocutaneous abscess or fistula is an extremely uncommon complication secondary to cholecystitis. Over the past 50 years fewer than 20 cases of spontaneous cholecystocutaneous fistulas have been described in the medical literature. We here report a case of subcutaneous gallstone as a rare clinical presentation of the already uncommon cholecystocutaneous fistula. CASE REPORT: An 81-year-old man presented with a large subcutaneous abscess in the right subcostal area with surrounding cellulitis and crepitus. An abdominal computed tomography scan showed two subcutaneous gallstones and communication between the abscess and the gallbladder. Cholecystectomy was performed and the abdominal wall abscess was drained externally. This case report demonstrates that maintaining a high degree of suspicion of this rare entity is helpful in achieving correct preoperative diagnosis, and that computed tomography scan should be performed in all cases of unexplained abdominal wall suppuration or cellulitis.

CONTEXTO: A fístula e/ou o abscesso colecistocutâneo são complicações extremamente raras da colecistopatia crônica calculosa. Nos últimos 50 anos, menos de 20 casos de fistulas colecistocutâneas foram descritos na literatura médica. Nós descrevemos um caso de cálculos biliares no tecido subcutâneo como rara apresentação clínica de fístula biliar. RELATO DO CASO: Paciente de 81 anos deu entrada no serviço de emergência apresentando um grande abscesso na região de hipocôndrio direito. A tomografia computadorizada de abdome demonstrou a presença de dois cálculos no tecido celular subcutâneo e a comunicação da vesícula biliar com a parede abdominal. O paciente foi submetido a uma colecistectomia e drenagem externa do abscesso da parede abdominal. Este caso demonstra que um alto grau de suspeita desta rara complicação da colecistopatia crônica calculosa é fundamental para o correto diagnóstico pré-operatório, e a tomografia computadorizada deve ser realizada rotineiramente em todos os casos de abscessos de parede abdominal de origem indeterminada.

Diagnóstico ultra-sonográfico de íleo biliar: relato de caso e revisão da literatura / Sonographic diagnosis of gallstone ileus: a case repost and review of the literature

Íleo biliar é uma obstrução mecânica do trato gastrintestinal, decorrente da impactação de um ou mais cálculos na luz intestinal. É condição rara, responsável por 1% a 3% das obstruções intestinais não malignas e por aproximadamente 25% dos casos de oclusão que acometem pacientes acima de 65 anos. O diagnóstico por imagem é feito principalmente por meio de tomografia computadorizada de abdome. Apresentamos um caso de íleo biliar diagnosticado no pré-operatório por ultra-sonografia abdominal.

Gallstone ileus is an uncommon cause of mechanical intestinal obstruction caused by impaction of a gallstone that has migrated from the gallbladder toward the intestine. It constitutes 1%–3%of not malignant intestinal obstruction and the incidence of 25% in patients older than 65 years old. The image diagnosis is mainly made through computed tomography of abdomen. We present a case of gallstone ileus detected by ultrasound findings.

El papel de la leptina en el desarrollo de esteatosis hepática y litiasis biliar / Leptine participation in the development of liver steatosis and biliar lithiasis

La obesidad incrementa el riesgo para varios padecimientos gastro intestinales como litiasis biliar (LB), esteatosis hepática (EH) y este-atohepatitis no alcohólica. Recientemente observamos una relación entre colesterol HDL, índice de saturación de colesterol en la bilis y leptina en pacientes obesos en reducción de peso. De igual manera la leptina tiene un papel importante en el desarrollo de la EH y probablemente en los mecanismos inflamatorios. El objetivo de este trabajo fue investigar la relación entre la LB y la EH. Se estudiaron a sujetos de la Unidad de Diagnóstico Clínico que acudieron a la realización de una revisión clínica preventiva. Aquellos que presentaron LB o EH por ultrasonido fueron considerados como casos, se compararon con controles sanos. Se tomaron medidas antropométricas, índice de masa corporal (IMC) y concentraciones de leptina, insulina, lípidos séricos, y lipoproteínas por métodos convencionales. Se estudiaron 317 sujetos, quienes fueron divididos en cuatro grupos: LB (n = 100), EH (n = 84), LB + EH (n = 33) y control (n = 100). La edad del grupo control fue significativamente mayor (LB, 52.6 ± 11.6; EH, 49.8 ± 11.1; LB +EH, 51.6 ± 10,5; controles 57.1 ± 7.4), p< 0.05. ElIMC fue mayor en los grupos de EH (28.7 ± 2.8) y LB +EH (29.0 ± 3.8) que en los grupos de LB (27.4 ± 4.3) y control (27.0 ± 3.0), p< 0.05. El grupo de LB (13.7 ± 8.1) presentó las concentraciones más elevadas de leptina comparado con los otros grupos, P < 0.05. Mientras que las concentraciones de insulina fueron similares en los cuatro grupos de sujetos. Los resultados del presente estudio muestran que los sujetos con LB y EH presentan concentraciones elevadas de leptina, comparados con controles. Esto sugiere que la leptina juega un papel importante en la fisiopatología de la LB y EH.

Obesity increases significantly the risk of developing several common gastrointestinal diseases such as gallstone disease (GD) and hepatic steatosis (HS). Elsewhere we have shown a relationship between HDL cholesterol, cholesterol saturation index, and leptin in obese patients loosing weight. Furthermore, leptin plays an important role facilitating HS and possibly in the associated inflammatory process. The aim of this study was to investigate the relationship between GD and HS. The sample was comprised by patients attending the unit for check up. Subjects with visible stones or HS by ultrasound (cases) were compared with healthy controls. Demographic and body mass index (BMI) were recorded. Plasma leptin, insulin and serum lipids and lipoproteins levels were measured by standard methods. A total of 317 subjects were included in this study. They were divided in four groups as follows: GD (n=100), HS (n=84), GD + HS (n=33) and controls (n=100). The control group was significantly older (GD, 52.6 ± 11.6; HS, 49.8 ±11.1; GD +HS, 51.6 ±10.5; 57.1 ± 7.4), p< 0.05. BMI was higher in the HS groups (28.7 ± 2.8) and GD +EH (29.0 ± 3.8) than in the GD (27.4 ± 4.3) and control (27.0 ± 3.1) group, p< 0.05. The GD group displayed the highest leptin levels (13.7 241 8.1), P < 0.05, whereas insulin levels were similar in all groups. Since GD and HS subjects have high plasma leptin levels compared with controls, our results suggest that leptin plays an important role in the pathophysiology of GD and HS.

Ultrasonographic evaluation of gallbladder volume in diabetics.

AIMS AND OBJECTIVE: Ultrasonographic determination of gallbladder volume in diabetics [both type I and type 2], it's comparison with a control group, and correlation of gallbladder volume in diabetics with parameters such as age, sex, body mass index, parity, hyperlipidaemia, and autonomic neuropathy. MATERIALS AND METHOD: Ninety one cases of diabetes mellitus and 40 healthy controls were recruited for the study. A detailed history and physical examination were recorded. Laboratory investigations done were--fasting and postprandial blood sugar, glycosylated haemoglobin, microalbuminuria, and serum lipid profile. Autonomic neuropathy was determined by using simple non-invasive bedside tests. Fasting gallbladder volume was measured by ultrasonography (calculated by ellipsoid formula). RESULTS: The mean fasting gallbladder volume was 18.20 +/- 2.54 ml in type I diabetics and 25.87 +/- 13.90 ml in type 2 diabetics, with a minimum value of 9.30 ml and maximum value of 88 ml. When type 2 diabetics were subgrouped according to the presence of autonomic neuropathy, higher gallbladder volumes were seen in patients with autonomic neuropathy. CONCLUSIONS: Cholecystomegaly, to a significant degree, was found in type 2 diabetics in the present study. It was significantly correlated with age, body mass index, and the severity of autonomic neuropathy. In male type 2 diabetics, gallbladder volume was significantly correlated with LDL cholesterol levels. In female type 2 diabetics, gallbladder volume was significantly correlated with waist-hip ratio. Gallbladder volume also had significant correlation with proliferative diabetic retinopathy, but not with glycaemic control, microalbuminuria, hypertension, or the duration of diabetes.

Incidence of Gallbladder Stones in Renal Transplant Recipients / 대한소화기학회지

BACKGROUND/AIMS: Gallbladder stone is one of the major cause of morbidity in adults. Renal transplantation has been found to increase the risk of gallbladder stone formation. The real incidence of gallbladder stones in renal transplant recipients is not exactly known. We performed this study to identify the risk factors for cholecystolithiasis. METHODS: We compared the prevalence of gallbladder stone in 222 renal transplantation patients with that in 222 age and sex matched controls. Patients who had chronic liver disease, renal disease, and diabetes were excluded from the control group. RESULTS: In our study, the incidence of gallbladder stones is 8.6% (19/222 patients) in renal transplantation patients, which was significantly higher than 3.60% (8/222 control) in the control group (p=0.029). In the most of our renal transplantation patients, cholecystolithiasis was asymptomatic. We did not find a difference in age, sex, duration after transplantation, causes of renal failure, resistance index between patients with and without gallbladder stones in renal transplantation patients. CONCLUSIONS: Our results suggest that the incidence of gallbladder stones is higher in renal transplant recipients than non-transplant population in Korea. Further studies will be needed to focus the factors contributing to the gallbladder stone formation after renal transplantation, especially in regard to immunosuppressive drugs.