Abstract
Background. There are contradictory reports about the prevalence of cholelithiasis in chronic kidney disease (CKD). The pathogenesis of gallstones is associated with the lithogenic changes of bile composition, increased tendency to nucleation, and decreased gallbladder motility. The studies related to these factors can predict the development of cholelithiasis. The aim of this study was to evaluate the ultrasonic gallbladder function in CKD and to compare it in predialysis (PreD), hemodialysis (HD), and continuous ambulatory peritoneal dialysis (CAPD) patients. Methods. Age, gender, and body mass index matched 49 CKD patients (14 PreD, 19 HD, 16 CAPD), and 17 control individuals were included in the study. Diabetic and cirrhotic patients were not included. Ultrasonic gallbladder volume was evaluated in pre- and postprandial period, and ejection fraction was calculated. We also measured several biochemical parameters (cholesterol, triglyceride, blood urea nitrogen (BUN), creatinine, calcium, Phosphorus, parathormone, albumin, total protein) in blood. Results. Preprandial gallbladder volume in PreD, HD, CAPD, and control groups were 26.7 ± 13.6, 20.8 ± 10.4, 23.2 ± 14.7, and 26.4 ± 14.8 mL, respectively (p > 0.05). Ejection fractions were 54.1 ± 22.9%, 54.9 ± 23.9%, 48.6 ± 15.9%, and 51.8 ± 19.2% in PreD, HD, CAPD, and control groups, respectively (p > 0.05). Serum triglyceride was higher in PreD patients than control group (207 ± 144 vs. 110 ± 48 mg/dL) (p < 0.05). Serum BUN, Cre, P, and PTH levels were higher in CKD groups than the control group, whereas serum total protein and albumin levels were higher in the control group (p < 0.05). Serum Ca was lower in PreD and HD patients than in the controls (p < 0.05). Conclusions. In conclusion, CKD and renal replacement therapy (HD and CAPD) do not affect gallbladder functions, but more studies are needed to evaluate prevalence of gallstones, gallbladder motility, and the composition of bile in CKD.
Introduction
Gallstones have important morbidity (cholecystitis, cholangitis, pancreatitis) and sometimes cause mortality in patients. Epidemiologic studies have reported a prevalence of 10% in Western countries.Citation[1] In Turkey, it is about the same percentage as in the Western world.Citation[2] The most important factors in the pathogenesis of gallstones are the lithogenic changes of bile composition, increased tendency to nucleation, and impaired gallbladder motility. The percentage of gallstones in some diseases like liver failure, inflammatory bowel disease, and hemolytic anemia is higher than the normal population.Citation[3&4] Some studies reported higher percentage of gallstones in chronic kidney disease (CKD),Citation[5&6] whereas the others reported no difference with normal population.Citation[7-11] One of the most important factors in the formation of gallstones is the gallbladder function that was assessed in this study. Autonomic nervous system, which malfunctions in uremia, innervates the gallbladder. Dysfunction in neural innervation and nutritional problems in CKD may cause increased stone formation by the stasis of gallbladder.Citation[12&13] The aim of this study was to evaluate the ultrasonic gallbladder function in CKD and to compare it in predialysis (PreD), hemodialysis (HD), and continuous ambulatory peritoneal dialysis (CAPD) patients. To the best of our knowledge, this is the first study that evaluates and compares gallbladder motility in these patients separately.
Materials and Methods
Patients and Controls
A total of 49 CKD patients and 17 control individuals (gender and age matched) who had no diabetes mellitus and liver disease that might affect gallbladder functions were included in the study. The patients and controls who had symptoms or findings attributed to biliary diseases and who used drugs that might affect gallbladder functions were excluded. CKD patients were followed by our nephrology department, whereas the controls were the hospital staff without any known disease. CKD patients consisted of PreD (n = 14), HD (n = 19), and CAPD (n = 16) patients. All preD patients were grade 5 according to the CKD classification.Citation[14] The etiologies of CKD were chronic glomerulonephritis (n = 20), hypertensive glomerulosclerosis (n = 5), urolithiasis (n = 3), polycystic renal disease (n = 2), amyloidosis (n = 1), and unknown (n = 18). We recorded the duration of disease and dialysis, and calculated body mass index (BMI). CKD patients (PreD, HD, CAPD) and controls did not differ in age, gender, and BMI. Disease duration was similar in PreD, HD, and CAPD. There was no difference in the dialysis duration in HD and CAPD patients (). Blood chemistry (fasting glucose, cholesterol, triglyceride, blood urea nitrogen [BUN], creatinine [Cre], calcium, phosphorus [P], total protein, albumin, and parathormone [PTH]) were assessed in CKD patients and controls just before the study.
Table 1. Demographic and clinical features of study groups
Ultrasonic Gallbladder Function
All subjects fasted for 12 h, and each individual was examined in either the supine or decubitus position. Ultrasonographic (US) examinations were performed with a 3.5-MHz convex transducer (Toshiba Sonolayer model, SSA-270, Toehigi, Japan). The gallbladder volume evaluations were done by the same radiologist. The maximum length, width, and height of the gallbladder were measured in fasted individuals and 30 min after a standard meal consisting of 100 g chocolate (55.9% carbohydrate, 33.1% lipid, 7.6% protein). Gallbladder volume (mL) was calculated using ellipsoid method.Citation[15] Fasting gallbladder volume was designated as fasting volume (FV), whereas the volume achieved 30 min after the meal was considered the residual volume (RV). Gallbladder ejection fraction (EF) was calculated by the following formula; EF = (FV − RV)/FV × 100.
Statistical Analysis
The data were analyzed by using SPSS 12.0 for windows (SPSS 12.0, Release 12.02, License Code 361835). Results are given as means ± SD. Differences were regarded as significant at p value < 0.05. Comparisons of FV, RV, and EFs were performed by analysis of variance and Bonferroni tests. Biochemical parameters showed skewed data. Kruskall-Wallis and Mann-Whitney U tests were used for analysis of biochemical data.
Results
Fasting versus residual gallbladder volumes were 26.7 ± 13.6 versus 12.3 ± 10.6, 20.8 ± 10.4 versus 9.8 ± 9.2, 23.2 ± 14.7 versus 11.8 ± 7.2, and 26.4 ± 14.8 versus 13.0 ± 9.1 mL in PreD, HD, CAPD, and control groups, respectively. Ejection fractions were 54.1 ± 22.9%, 54.9 ± 23.9%, 48.6 ± 15.9%, and 51.8 ± 19.2% in PreD, HD, CAPD, and control groups, respectively. Fasting and residual gallbladder volumes and ejection fractions did not differ in all groups including controls (). The evaluation of biochemical parameters revealed no significant difference in cholesterol and glucose levels between groups. TG levels were higher in PD patients than the controls (p < 0.05). Serum Ca level was lower in PD patients than the controls (p < 0.05), whereas no significant difference was found between the other groups (p > 0.05). BUN, Cre, P, and PTH were higher in PreD, HD, CAPD patients than the controls (p < 0.05). BUN was lower in CAPD than the PreD or HD patients (p < 0.05). PTH was higher in CAPD than PreD or HD patients (p < 0.05). Total protein and albumin were higher in control group than PreD, HD, or CAPD groups (p < 0.05) (). There was no correlation between biochemical parameters and gallbladder functions in groups.
Table 2. Gallbladder functions in study groups
Table 3. Biochemical findings in study groups
Discussion
Composition of bile (cholesterol, bile acids, and phospholipids), nucleation of crystals, and impaired gallbladder function are important factors in the pathogenesis of gallstones.Citation[16&17] Age, gender, hereditary factors, obesity, diet, drugs, and liver disease affect the saturation of bile. The impairment of gallbladder functions such as emptying, absorption, and secretion predispose to stone formation. The relationship between gallbladder emptying and the increased incidence of gallstones in parenteral nutrition and pregnant women showed the role of gallbladder stasis in the formation of gallstones.Citation[18] Reduced gallbladder motility is associated with sludge formation in parenteral nutrition, decreased food intake, or sympathic nerve supply interrupted patients.Citation[19] Sludge and debris that might initiate stone formation are cleared by emptying of gallbladder.
Cirrhosis, diabetes mellitus, ileal resection, colectomy, gastrectomy, cholesterol-lowering diets, parenteral nutrition, and drugs such as cholestyramine, clofibrate, and octreotide are associated with increased frequency of gallstones.Citation[20-24] The prevalence of gallstones in patients with CKD changes between 3.85% to 27.8%. Some studies reported high prevalence,Citation[5&6] whereas the others reported no differenceCitation[7&8], Citation[10],Citation[11], Citation[25] compared with control group. Gallstone prevalence was higher in the studies that showed no statistical differenceCitation[7&8], Citation[10]. Some abnormalities related to CKD that may predispose to gallstones are 1) autonomic nervous system innervates the gallbladder and uremia causes autonomic nervous system dysfunction, and 2) nutritional problems.
Mareckova et al.Citation[26] examined bile composition in CKD and found that the lithogenicity of bile had increased. The patients on HD were found to have increased bile cholesterol and an increased saturation index of bile. These changes were further enhanced by the effect of a low-protein diet. There was a decrease in primary and an increase in secondary bile acids in the bile, which is important in the pathogenesis of gallstones.
We investigated gallbladder motility, which is one of the most important factors that may affect the formation of gallstone in CKD. There were no significant differences in FV, RV, and EF between CKD and control groups. Results similar to ours have been observed in previous studiesCitation[7],Citation[27]. In both studies, gallbladder motility was matched between HD patients and controls. In our study, we evaluated gallbladder motility among PreD and CAPD patients, in addition to HD patients. We found no difference between these groups and the control group. To the best of our knowledge, this is the first study that evaluates and compares gallbladder motility in PreD, HD, and CAPD patients. In addition, our study did not demonstrate increased frequency of gallstones in PreD, HD, and CAPD patients compared with control group. Autonomic nervous system dysfunction is present in CKD. The absence of significant motility disorder of gallbladder in our study may reflect the role of other neuronal and hormonal mechanisms on the gallbladder.Citation[28-31]
In conclusion, CKD and renal replacement therapy (HD and CAPD) do not affect gallbladder functions, but more studies are needed to evaluate prevalence of gallstones, gallbladder motility, and the composition of bile in CKD.
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