Prevent Stone Formation Research Articles

Idiopathic hypercalciuria

Hypercalcuria is the most common metabolic disorder found in patients with nephrolithiasis. As the prevalence of kidney stones rises in industrialized nations, understanding the pathogenesis and treatment of hypercalciuria becomes increasingly important. Idiopathic hypercalciuria (IH), defined as an excess urine calcium excretion without an apparent underlying etiology, is the most frequent cause of hypercalciuria and will be the focus of this paper. Calcium homeostasis is tightly controlled and slight disturbances in transport at the level of the intestine, bone, and/or kidney can lead to excessive urine calcium excretion and promote stone formation. IH is a systemic disorder with dysregulation of calcium transport at a combination of these calcium regulatory sites. The goal of treatment is to prevent stone formation and relies on a combination of dietary and pharmaceutical interventions. Dietary management includes increasing fluid intake, salt restriction, animal protein restriction, and maintaining a normal calcium intake. Thiazide diuretics have proven effective in preventing calcium stone formation by reducing the urinary excretion of calcium. It is important to note that while decreasing urinary calcium excretion is important the clinician should focus primarily on reducing the supersaturation of calcium oxalate as this determines the true tendency for stone formation.

Prevention of stone formation and bone loss in absorptive hypercalciuria by combined dietary and pharmacological interventions.

We determined whether dietary restriction of calcium and oxalate, combined with thiazide and potassium citrate treatment, would prevent stone formation and avert bone loss in 18 men and 10 women with type I absorptive hypercalciuria. Patients were treated with thiazide (20) or indapamide (8) and potassium citrate (average dose 35 mEq. daily) for 1 to 11 years (mean 3.7) while maintained on low calcium oxalate diet. Serum and urinary chemistry studies and bone mineral density were measured at baseline and at the end of treatment. New stones formed were quantitated during 3 years before and during treatment. During treatment urinary calcium significantly decreased (346 +/- 85 to 248 +/- 79 mg. daily, p <0.001) but urinary oxalate did not change. Urinary pH and citrate significantly increased, and urinary saturation of calcium oxalate significantly decreased by 46%. Stone formation rate decreased significantly from 2.94 to 0.05 per year (p <0.001). L2-L4 bone mineral density increased significantly by 5.7% compared to normal peak value, and by 7.1% compared with normal age and gender matched value. Femoral neck bone mineral density also increased significantly. Dietary restriction of calcium and oxalate, combined with thiazide and potassium citrate, satisfactorily controlled hypercalciuria, prevented the secondary increase in urinary oxalate, reduced urinary saturation of calcium oxalate, virtually eliminated recurrent stone formation, and increased bone density of the spine and femoral neck. Thus, this dietary pharmacological program controlled stone formation as well as bone loss that often accompany type 1 absorptive hypercalciuria.

Épidémiologie actuelle de la lithiase rénale en France

Nephrolithiasis is a frequent disease that affects about 10% of people in western countries. The prevalence of calcium oxalate stones has been constantly increasing during the past fifty years in France as well as in other industrialized countries. Stone composition varies depending to gender and age of patients and also underlines the role of other risk factors and associated pathologies such as body mass index and diabetes mellitus. The decrease in struvite frequency in female patients is the result of a significantly improved diagnostic and treatment of urinary tract infections by urea-splitting bacteria. In contrast, the increasing occurrence of weddellite calculi in stone forming women aged more than 50 years could be the consequence of post-menopausal therapy. A high prevalence of uric acid was found in overweight and obese stone formers and in diabetic ones as well. Another important finding was the increased occurrence with time of calcium oxalate stones formed from papillary Randall's plaques, especially in young patients. Nutritional risk factors for stone disease are well known: they include excessive consumption of animal proteins, sodium chloride and rapidly absorbed glucides, and insufficient dietary intake of fruits and potassium-rich vegetables, which provide an alkaline load. As a consequence, an excessive production of hydrogen ions may induce several urinary disorders including low urine pH, high urine calcium and uric acid excretion and low urine citrate excretion. Excess in calorie intake, high chocolate consumption inducing hyperoxaluria and low water intake are other factors, which favour excessive urine concentration of solutes. Restoring the dietary balance is the first advice to prevent stone recurrence. However, the striking increase of some types of calculi, such as calcium oxalate stones developed from Randall's plaque, should alert to peculiar lithogenetic risk factors and suggests that specific advices should be given to prevent stone formation.

The Practical Value of Applying Chemical Biliary Duct Embolization to Chemical Hepatectomy for Treatment of Hepatolithiasis

The high recurrence rate of hepatolithiasis, together with the high operative risk of hepatectomy for specifically located stones, has not been effectively settled until now. Thus, the aim of this study was to investigate the feasibility and effectiveness of using chemical biliary duct embolization (CBDE) to achieve chemical hepatectomy in a rabbit model of hepatolithiasis. The animal model of hepatolithiasis was established using the methods of obstruction plus infection. Seven days later, the left hepatic ducts were embolized using phenol plus cyanoacrylate or absolute ethanol plus cyanoacrylate. Subsequently, the influence of CBDE on bile duct, liver, and stone formation was analyzed by histology, RT-PCR for procollagen, biochemistry, and enzymatic histochemistry for beta-glucuronidase (beta-G). CBDE resulted in the entire ablation of the diseased biliary duct mucosa and the complete occlusion of the diseased biliary duct lumen, thus effectively eradicating chronic proliferative cholangitis and preventing stone formation. More importantly, CBDE also resulted in the complete fibrosis and "self-cut" in the periphery of the embolized lobe, thus achieving chemical hepatectomy. Also of note, the embolized lobe exhibited a much lower level of endogenous beta-G than the nonembolized lobe, indicating an inhibitory effect of CBDE on beta-G. Besides, the mRNA level of procollagen I in the embolized bile duct wall of phenol embolization group was significantly higher than the ethanol embolization group. Chemical biliary duct embolization, especially using phenol plus cyanoacrylate, may prevent the recurrence of intrahepatic stone and concurrently achieve the effect of chemical hepatectomy.

Medical Treatment: Worthwhile and When?

The incidence of nephrolithiasis in industrialized countries is 0.5% to 1% annually. Stone formers subsequently face recurrence rates of 50% over 5 years. Annual costs in the United States for evaluation and treatment have been estimated at $1.83 billion USD [Clark JY, Thompson IM, Optenburg SA. Economic impact of urolithiasis in the United States. J Urol 1995;154:2020–2024]. Clearly the impact of urinary stone management poses an ever increasing medical, economic and social burden to modern society. The ability to detect 97% of underlying medical abnormalities in stone forming patients has stimulated discoveries of both selective and non-selective medical therapies to prevent stone recurrence. And yet there is no clear evidence in the literature that medical prophylaxis is cost effective. Various studies support the cost effectiveness of both proponents and adversaries of medical stone management. Nevertheless, there is clear evidence that medical therapy effectively prevents stone formation, especially when analyzing surrogate endpoints such as 24 urinary abnormalities, as well as primary endpoints such as stone formation. Therefore it makes intuitive sense to offer a search for underlying metabolic abnormalities in stone-forming patients and subsequently provide medical therapy, if the patient desires. Herein, we provide an overview in the medical evaluation and medical management of urinary stone disease.

Percutaneous removal of migratory intrabiliary surgical clips

To describe the technique of percutaneous removal of migratory intrabiliary surgical clips. Materials and methods: A 33-year-old male was admitted with recurrent cholangitis following choledochojejunostomy formation. Percutaneous transhepatic cholangiography demonstrated stricture at the hepaticojejunostomy and multiple intrabiliary surgical clips, two of which were mobile. Endoscopic retrograde cholangiopancreatography was not feasible due to the previous surgery. Balloon angioplasty of the choledochojejunostomy anastomosis was performed, followed by removal of the mobile surgical clips via a percutaneous tract. After dilatation of the tract, choledochoscopy, steerable catheters and angled tip catheters facilitated placement of a guidewire beyond the clips within a peripheral radicle. A Fogarty type balloon was then placed over the guidewire beyond the clip, enabling withdrawal of the balloon and clip into a sheath. Results: The two mobile migrated intrabiliary surgical clips were successfully removed using this technique. A 14F biliary Cope loop was placed across the choledochojejunostomy stricture for interim management, while the patient’s symptoms settled. Conclusion: Migratory intrabiliary surgical clips are important to detect to prevent stone formation or obstruction. Removal is usually via per oral endoscopy. We describe a percutaneous technique for the removal of such foreign bodies when an endoscopic approach fails or is not possible.

Modulators of urinary stone formation.

Urine contains compounds that modulate the nucleation, growth and aggregation of crystals as well as their attachment to renal epithelial cells. These compounds may function to protect the kidneys against: 1, the possibility of crystallization in tubular fluid and urine, which are generally metastable with respect to calcium salts, 2, crystal retention within the kidneys thereby preventing stone formation and 3, possibly against plaque formation at the nephron basement membrane. Since oxalate is the most common stone type, the effect of various modulators on calcium oxalate (CaOx) crystallization has been examined in greater details. Most of the inhibitory activity resides in macromolecules such as glycoproteins and glycosaminoglycans while nucleation promotion activity is most likely sustained by membrane lipids. Nephrocalcin, Tamm-Horsfall protein, osteopontin, urinary prothrombin fragment 1, and bikunin are the most studied inhibitory proteins while chondroitin sulfate (CS), heparan sulfate (HS) and hyaluronic acid (HA) are the best studied glycosaminoglycans. Crystallization modulating macromolecules discussed here are also prominent in cell injury, inflammation and recovery. Renal epithelial cells on exposure to oxalate and CaOx crystals produce some of the inflammatory molecules such as monocyte chemoattractant protein-1 (MCP-1) with no apparent role in crystal formation. In addition, macrophages surround the CaOx crystals present in the renal interstitium. These observations indicate a close relationship between inflammation and nephrolithiasis.

Prevention of Stone Formation and Bone Loss In Absorptive Hypercalciuria by Combined Dietary and Pharmacological Interventions

Prevention of Stone Formation and Bone Loss In Absorptive Hypercalciuria by Combined Dietary and Pharmacological Interventions

Prevention of Stone Formation and Bone Loss In Absorptive Hypercalciuria by Combined Dietary and Pharmacological Interventions

Prevention of Stone Formation and Bone Loss In Absorptive Hypercalciuria by Combined Dietary and Pharmacological Interventions

Prevention of Spinal Bone Loss by Potassium Citrate in Cases of Calcium Urolithiasis

We determine if potassium citrate treatment stabilizes spinal bone density among patients with recurrent calcium oxalate nephrolithiasis. We studied a group of 16 men and 5 women with stones taking potassium citrate from 11 to 120 months. They represented all patients from the Stone Clinic who took potassium citrate alone for at least 11 months. L2-L4 bone mineral density data before and after potassium citrate treatment were retrieved retrospectively and analyzed. In the combined group L2-L4 bone mineral density increased significantly by 3.1% over mean duration of 44 months. Z score, corrected for age matched normal values, increased significantly by 3.8%. Urinary pH, citrate and potassium increased significantly during treatment but urinary calcium did not change. Potassium citrate, a commonly used drug for the prevention of recurrent nephrolithiasis, may avert age dependent bone loss. Spinal bone density increased in most patients when it normally decreases.

Protein-X, Pancreatic Stone-, Pancreatic thread-, reg-protein, P19, lithostathine, and now what? Characterization, structural analysis and putative function(s) of the major non-enzymatic protein of pancreatic secretions.

Reg protein was first found in pancreatic stones. It was named Pancreatic Stone Protein and later renamed lithostathine, as it was assumed to prevent stone formation. The 144 amino acid protein is O-glycosylated on Thr-5. The glycan chain is variable in length and in charge. Lithostathine 3-D organization is of the C-lectin type, even though it is unlikely to have any functional calcium-binding site. The Arg11-Ile12 bond is readily cleaved by trypsin; the resulting C-terminal polypeptide precipitates at physiological pH and tends to form fibrils. The protein was more recently found in the regenerating endocrine pancreas and it was named Reg (for regenerating) protein. Numerous proteins related to Reg have been identified successively in several mammalian species. They constitute the Reg superfamily. Reg genes show the same organization and are located in the same chromosome region. These genes are therefore likely to derive from a common ancestor gene by duplication. In the course of evolution, they may have diverged in tissue-related expression and function. In the endocrine pancreas, Reg protein stimulates islet beta-cell growth and reduces experimental diabetes via the activation of a high affinity receptor. The role of the protein produced by the exocrine pancreas, however, is controversial. Not only is Reg/lithostathine unlikely to be a physiologically relevant pancreatic stone inhibitor, but it may contribute to stone formation. We suggest that it might help prevent the harmful activation of protease precursors in the pancreatic juice. The protein provides a useful model for examining the conformational changes associated with globular to fibril transformation.

Impact of citrate therapy on the circadian rhythm of urinary magnesium ammonium phosphate saturation in normal individuals.

Alkaline citrate has been used widely in the prevention of stone formation. However, the risk of struvite stone during the alkalinizing therapy has not been adequately studied in terms of magnesium ammonium phosphate saturation. The circadian rhythm of the urinary saturation of magnesium ammonium phosphate was estimated by using the differential Gibbs' free energy values of magnesium ammonium phosphate before and during 5 days of treatment with sodium-potassium citrate (1 g t.i.d., 1 g q.i.d. or 3 g t.i.d.) in five healthy male volunteers. The magnesium ammonium phosphate saturation varied during the day, peaking far below the solubility product between 08.00 and 10.30 h and between 13.00 and 18.00 h. The mean peak levels were increased by each treatment regimen in comparison with the control day. The mean increase on day 1 was significant between 10.30 and 23.00 h with the 3 g t.i.d. regimen, but the mean saturation still remained below the solubility product throughout the day. The urinary magnesium ammonium phosphate saturation appeared hard to exceed the solubility product with a high dose of alkaline citrate.

The effect of takusha, a kampo medicine, on renal stone formation and osteopontin expression in a rat urolithiasis model.

Kampo medicine is a traditional Japanese therapeutic system which originated in China and was used to treat various diseases for hundreds of years. Kampo medicine had been also used for the cure and the prevention of urinary calculi for many years, but the effect and the mechanism of this use of kampo medicine are unclear. We examined the inhibitory effect of the kampo medicine takusha on the formation of calcium oxalate renal stones induced by ethylene glycol (EG) and vitamin D3 in rats. We also investigated the effect of takusha on osteopontin (OPN) expression, which we previously identified as an important stone matrix protein. The control group rats were non-treated; the stone group rats were administered EG and vitamin D3, and the takusha group was administered takusha in addition to EG and vitamin D3. The rate of renal stone formation was lower in the takusha group than in the stone group; thus, the OPN expression in the takusha group was smaller than in the stone group. Takusha was effective in preventing oxalate calculi formation and OPN expression in rats. These findings suggest that takusha prevents stone formation including not only calcium oxalate aggregation but also proliferation.

Nucleation of calcium oxalate crystals by albumin: Involvement in the prevention of stone formation

Urine is supersaturated in calcium oxalate, which means that it will contain calcium oxalate crystals that form spontaneously. Their size must be controlled to prevent retention in ducts and the eventual development of a lithiasis. This is achieved, in part, by specific inhibitors of crystal growth. We investigated whether promoters of crystal nucleation could also participate in that control, because for the same amount of salt that will precipitate from a supersaturated solution, increasing the number of crystals will decrease their average size and facilitate their elimination. Albumin was purified from commercial sources and from the urine of healthy subjects or idiopathic calcium stone formers. Its aggregation properties were characterized by biophysical and biochemical techniques. Albumin was then either attached to several supports or left free in solution and incubated in a metastable solution of calcium oxalate. Kinetics of calcium oxalate crystallization were determined by turbidimetry. The nature and efficiency of nucleation were measured by examining the type and number of neoformed crystals. Albumin, one of the most abundant proteins in urine, was a powerful nucleator of calcium oxalate crystals in vitro, with the polymers being more active than monomers. In addition, nucleation by albumin apparently led exclusively to the formation of calcium oxalate dihydrate crystals, whereas calcium oxalate monohydrate crystals were formed in the absence of albumin. An analysis of calcium oxalate crystals in urine showed that the dihydrate form was present in healthy subjects and stone formers, whereas the monohydrate, which is thermodynamically more stable and constitutes the core of most calcium oxalate stones, was present in stone formers only. Finally, urinary albumin purified from healthy subjects contained significantly more polymers and was a stronger promoter of calcium oxalate nucleation than albumin from idiopathic calcium stone formers. Promotion by albumin of calcium oxalate crystallization with specific formation of the dihydrate form might be protective, because with rapid nucleation of small crystals, the saturation levels fall; thus, larger crystal formation and aggregation with subsequent stone formation may be prevented. We believe that albumin may be an important factor of urine stability.

Intake of vitamins B6 and C and the risk of kidney stones in women.

Urinary oxalate is an important determinant of calcium oxalate kidney stone formation. High doses of vitamin B6 may decrease oxalate production, whereas vitamin C can be metabolized to oxalate. This study was conducted to examine the association between the intakes of vitamins B6 and C and risk of kidney stone formation in women. The relation between the intake of vitamins B6 and C and the risk of symptomatic kidney stones were prospectively studied in a cohort of 85,557 women with no history of kidney stones. Semiquantitative food-frequency questionnaires were used to assess vitamin consumption from both foods and supplements. A total of 1078 incident cases of kidney stones was documented during the 14-yr follow-up period. A high intake of vitamin B6 was inversely associated with risk of stone formation. After adjusting for other dietary factors, the relative risk of incident stone formation for women in the highest category of B6 intake (> or =40 mg/d) compared with the lowest category (<3 mg/d) was 0.66 (95% confidence interval, 0.44 to 0.98). In contrast, vitamin C intake was not associated with risk. The multivariate relative risk for women in the highest category of vitamin C intake (> or =1500 mg/d) compared with the lowest category (<250 mg/d) was 1.06 (95% confidence interval, 0.69 to 1.64). Large doses of vitamin B6 may reduce the risk of kidney stone formation in women. Routine restriction of vitamin C to prevent stone formation appears unwarranted.

Alendronate decreases urine calcium and supersaturation in genetic hypercalciuric rats

The mechanism of excess urine calcium excretion in human idiopathic hypercalciuria (IH) has not been determined but may be secondary to enhanced intestinal calcium absorption, decreased renal calcium reabsorption, and/or enhanced bone demineralization. We have developed a strain of genetic hypercalciuric stone-forming (GHS) rats as an animal model of human IH. When these GHS rats are placed on a low-calcium diet (LCD), urinary calcium (UCa) excretion exceeds dietary calcium intake, suggesting that bone may contribute to the excess UCa excretion. We used the GHS rats to test the hypothesis that bone contributes to the persistent IH when they are fed an LCD by determining if alendronate (Aln), which inhibits bone resorption, would decrease UCa excretion. GHS rats (N = 16) and the parent strain (Ctl, N = 16) were fed 13 g/day of a normal (1.2%) calcium diet (NCD) for seven days and were then switched to a LCD (0. 02%) for seven days. Ctl and GHS rats in each group were then continued on LCD for an additional seven days, with or without injection of Aln (50 micrograms/kg/24 hrs). UCa excretion was measured daily during the last five days of each seven-day period. To determine the effects of Aln on urine supersaturation, the experiment was repeated. All relevant ions were measured, and supersaturation with respect to calcium oxalate and calcium hydrogen phosphate was determined at the end of each period. UCa was greater in GHS than in Ctl on NCD (7.4 +/- 0.5 mg/24 hrs vs. 1.2 +/- 0.1, GHS vs. Ctl, P < 0.01) and on LCD (3.9 +/- 0.2 mg/24 hrs vs. 0. 7 +/- 0.1, GHS vs. Ctl, P < 0.01). LCD provides 2.6 mg of calcium/24 hrs, indicating that GHS rats are excreting more calcium than they are consuming. On LCD, Aln caused a significant decrease in UCa in GHS rats and brought GHS UCa well below calcium intake. Aln caused a marked decrease in calcium oxalate and calcium hydrogen phosphate supersaturation. Thus, on a LCD, there is a significant contribution of bone calcium to the increased UCa in this model of IH. Aln is effective in decreasing both UCa and supersaturation. The Aln-induced decrease in urine supersaturation should be beneficial in preventing stone formation in humans, if these results, observed in a short-term study using the hypercalciuric stone-forming rat can be confirmed in longer term human studies.

Calyceal microlithiasis in children: report on 196 cases.

Recognition of children at greatest risk for urolithiasis may allow early detection or prevention of stone formation. We report clinical data from 196 children aged 0.9-15.9 years in whom renal ultrasound examination revealed hyperechogenic spots in renal calyces less than 3 mm in diameter. We called this finding "calyceal microlithiasis" (CM). There was a history of urolithiasis in 70.4% of patients in at least one first- or second-degree relative. Presenting symptoms were recurrent abdominal pain, dysuria, and hematuria, occurring alone or in combination. Hematuria was the presenting symptom in 41% of patients and was the only urinary finding in more than one-third. Hypercalciuria was present in about one-third and hyperuricuria in one-fifth of the patients. Of 29 patients who were followed for at least 2 years, 9 developed calculi 4-7 mm in diameter. CM possibly represents the first step in calculus formation. The finding of CM might explain a number of symptoms and signs that are often mild and non-specific, thus reducing invasive diagnostic procedures.

Lithostathine, the Presumed Pancreatic Stone Inhibitor, Does Not Interact Specifically with Calcium Carbonate Crystals

Lithostathine (pancreatic stone protein, Reg protein) is, in addition to albumin, the major nonenzymatic protein of the pancreatic juice. It has been assumed to inhibit calcium carbonate precipitation and therefore to prevent stone formation in the pancreatic ducts. This function is, however, debatable. The assumption is based on the inhibition of in vitro crystal nucleation and growth by lithostathine. Considering that these phenomena occur only under certain critical conditions, we re-examined the question using a protein preparation where the purity and folding have been tested by mass spectroscopy and NMR in the absence of nonprotein contaminants. Under these conditions, we showed conclusively that lithostathine does not inhibit calcium carbonate nucleation and crystal growth. We demonstrated that previous findings on the alleged inhibition can be attributed to the uncontrolled presence of salts in the protein preparation used. Moreover, the affinity of lithostathine to calcite crystals, expressed as the half-life of bound iodinated protein in the presence of unlabeled competitor, was significantly lower than that of bovine serum albumin (8.8 and 11.2 h, respectively). Using glass microspheres instead of crystals did not significantly change the half-life of bound lithostathine (8.0 h). These findings are incompatible with the hypothesis of a specific interaction of lithostathine with calcium carbonate crystals. In conclusion, considering that components of pancreatic juice such as NaCl and phosphate ions are powerful inhibitors of calcium carbonate crystal growth, the mechanism of stone formation in pancreatic ducts must be reconsidered. The presence in normal pancreatic juice of small amounts of the 133-residue isoform of lithostathine (PSP-S1), which precipitates at physiological pH, should be noted, and the possibility should be considered that they form micro-precipitates that aggregate and are progressively calcified.

Cholecystokinin Increases Bile Acid Synthesis with Total Parenteral Nutrition but Does Not Prevent Stone Formation

Total parenteral nutrition (TPN) is associated with cholestasis and gallstones. Gallbladder stasis may be important in the development of gallstones, and cholecystokinin (CCK) to stimulate gallbadder contraction has been proposed as a treatment to prevent this complication. We studiedin vivobile acid synthesis and bile acid output in miniswine on TPN to test whether daily CCK improves bile acid output and normalizes bile acid profiles with TPN. Nine miniswine were nutritionally maintained with TPN for 4 weeks; four pigs received CCK (0.1 mg/kg) iv daily.In vivobile acid synthesis was measured with injection of 7α-tritiated cholesterol. An increase in tritiated water reflects the activity of 7α-hydroxylation, the rate-limiting step in bile acid synthesis. At the end of 4 weeks, bile was collected and bile acid output and bile salt profiles were determined. One of five animals on TPN developed gallstones while two of four receiving daily CCK developed stones.In vivobile acid synthesis decreased with TPN (controls, 63 ± 9 mg/24 hr versus TPN, 13 ± 4 mg/24 hr) and increased in TPN animals with CCK treatment (TPN-CCK, 105 ± 35 mg/24 hr). Bile acid profiles are changed with TPN with more secondary bile acids, this was not improved with CCK. CCK improved bile acid synthesis and bile acid output but failed to prevent gallstone formation or normalize bile salt profiles. In addition to promoting gallbladder contraction, CCK may have a stimulatory effect on bile acid synthesis. CCK alone did not prevent gallstone formation.

Hydrophilic bile acids: Prevention and dissolution experiments in two animal models of cholesterol cholelithiasis

The effects of beta-muricholic acid and hyocholic acid on cholesterol cholelithiasis were examined in two animal models. The following experiments were carried out: A) In a gallstone prevention study, prairie dogs were fed the lithogenic diet with or without 0.1% beta-muricholic or 0.1% hyocholic acid for eight weeks. B) In a second prevention study, hamsters were fed the lithogenic diet with or without 0.1% beta-muricholic acid or 0.1% hyocholic acid for six weeks. C) In a gallstone dissolution study, hamsters were fed the lithogenic diet for six weeks to induce stones; stone dissolution was examined during administration of a cholesterol-free purified diet with or without 0.1% beta-muricholic acid or 0.1% hyocholic acid. In the prevention study in prairie dogs (A), both bile acids failed to prevent stone formation, the cholesterol saturation index of bile was 0.89 in the lithogenic controls, remained unchanged with hyocholic acid and increased to 1.52 in the beta-muricholic acid group. In the prevention study in hamsters (B), beta-muricholic acid completely inhibited the cholesterol cholelithiasis (0% stone incidence); the cholesterol saturation index of bile was 1.78 (compared to lithogenic controls, 1.37). Hyocholic acid reduced stone incidence to 16% with a cholesterol saturation index of 0.98. In the dissolution study in hamsters (C), preexisting cholesterol gallstones were not dissolved by either hydrophilic bile acid after feeding these bile acids for an additional six weeks; at the end of the experiment, the cholesterol saturation indices were below unity.(ABSTRACT TRUNCATED AT 250 WORDS)