Inhibitors Of Stone Formation Research Articles

Alendronate inhibits osteopontin expression enhanced by parathyroid hormone-related peptide (PTHrP) in the rat kidney.

It has been reported that osteopontin (OPN) plays an important role during urolithiasis as well as bone formation. Generation of stones in the urinary tract may be associated with osteoporosis and bisphosphonates are potent inhibitors of bone resorption, being used with effect in the management of bone disease. We therefore investigated the relationship between alendronate, a bisphosphonate derivative, and OPN expression in the kidney. Alendronate was administered to rats made hypercalcemic by treatment with parathyroid hormone-related peptide (PTHrP). The renal expression of OPN was then evaluated at both protein and mRNA levels. OPN expression was enhanced in the distal tubular cells of hypercalcemic rats and was decreased by alendronate. The observed inhibition of OPN expression suggests an ability of alendronate and other bisphosphonates to act as inhibitors of stone formation in the urinary tract.

Absence of Oxalobacter formigenes in cystic fibrosis patients: a risk factor for hyperoxaluria

Patients with cystic fibrosis have an increased risk of hyperoxaluria, and of subsequent nephrocalcinosis and calcium-oxalate urolithiasis. Oxalate homoeostasis is controlled, in part, by the intestinal bacterium, Oxalobacter formigenes. The loss of this bacterium from the gut flora is associated with an increased risk of hyperoxaluria and calcium-oxalate urolithiasis. We investigated whether the absence of O. formigenes and the presence of hyperoxaluria are correlated in cystic fibrosis (CF) patients. Stool specimens from 43 patients with CF aged 3-9 years and from 21 similarly aged healthy volunteers were examined for O. formigenes by culture and DNA analysis. At the same time, 24 h urine samples were collected and analysed for oxalate and other factors that promote or inhibit stone formation. 15 (71%) of 21 healthy volunteers but only seven (16%) of 43 CF patients were colonised with O. formigenes. Detection of O. formigenes in six of these seven patients required DNA-based identification, suggesting low numbers of colony-forming units, and the CF patient with normal numbers of O. formigenes was the only one of the 43 patients who had not been treated with antibiotics. All seven CF patients colonised with O. formigenes had normal urinary oxalate levels, but 19 (53%) of 36 patients not colonised with O. formigenes were hyperoxaluric, with the most severe hyperoxaluria occurring in young patients. Absence of O. formigenes from the intestinal tract of CF patients appears to lead to increased absorption of oxalate, thereby increasing the risk of hyperoxaluria and its complications (eg, nephrocalcinosis, urolithiasis). Prolonged widespread use of antibiotics, and alterations of the gastrointestinal tract that occur in CF, may induce a permanent decolonisation in CF patients.

Effect of endoscopic sphincterotomy on gall bladder bile lithogenicity and motility

Background—Endoscopic sphincterotomy has been shown to inhibit stone formation in the gall bladder of experimental animals.Aims—To investigate the alterations in bile composition and gall bladder motility after endoscopic sphincterotomy.Patients—A study...

Selective renal transplantation in primary hyperoxaluria type 1

Primary hyperoxaluria type I (PHI) is a cause of end-stage renal disease in young people. It is caused by deficient activity of hepatic peroxisomal alanine:glyoxylate aminotransferase (AGT), which results in hyperoxalemia and hyperoxaluria. The consequent urolithiasis and nephrocalcinosis result in renal impairment, with further reduction in oxalate excretion and eventual systemic oxalosis. Historically, renal transplantation has yielded very poor results in these patients because of recurrent oxalosis of the graft. Within the last 10 years, combined hepatorenal transplantation has been successfully applied, simultaneously correcting the metabolic lesion in the liver and replacing the damaged kidneys. It has, however, become apparent that medical therapy with vigorous hydration, inhibitors of stone formation and pyridoxine (AGT co-factor), may be successful at delaying, and occasionally in preventing, urolithiasis in some hyperoxaluric patients, particularly those whose hyperoxaluria is reduced by pyridoxine. This, together with intensive perioperative management and modem surgical methods of stone management such as lithotripsy, laser or ultrasound stone fragmentation, and peroutaneous nephrolithotomy, means that renal transplantation alone may be feasible in selected patients. We describe a patient with PHI with clinical and biochemical evidence of significant residual AGT activity who underwent a successful live-related renal transplantation with excellent renal function and no stone recurrence 1 year posttransplantation. The appropriate transplantation strategies for these complex patients are discussed and include isolated renal transplantation for those patients who are without significant systemic oxalosis and have evidence of residual AGT activity.

Dietary fat alters the distribution of cholesterol between vesicles and micelles in hamster bile.

The type of dietary fat strongly affects the incidence of gallstones in the hamster model of cholesterol cholelithiasis. The present study was designed to determine whether dietary fats could affect gallstone formation by altering the microstructure (vesicular/micellar ratio) of cholesterol in bile. Golden Syrian hamsters from Sasco (Omaha, NE) or Charles River (Wilmington, MA) were fed nutritionally adequate semipurified diets to which were added: (i) 4.0% butterfat without added cholesterol; (ii) 1.2% palmitic acid plus 0.3% cholesterol; or (iii) 4.0% safflower oil plus 0.3% cholesterol. Gallstone incidence and the percentage of cholesterol in vesicles and micelles were determined after two- or six-week feeding periods. Three out of ten Sasco hamsters fed the 1.2% palmitic acid diet for two weeks had cholesterol stones, while none of the eight Charles River animals had stones. In the Sasco hamsters, a significant proportion of the biliary cholesterol was found in void volume vesicles (28.8%) and small vesicles (17.1%); Charles River hamsters had negligible proportions (1.1%) of cholesterol in void volume vesicles and 15.4% in small vesicles. Cholesterol gallstones were most abundant in Sasco hamsters fed 1.2% palmitic acid for six weeks (nine out of ten animals); the mean cholesterol saturation index of the bile was 1.27. A significant proportion of the biliary cholesterol was eluted in the void volume vesicles (21.4%) and in small vesicles (15.0%). Five of the eight identically treated Charles River hamsters had cholesterol stones; the cholesterol saturation index averaged 1.36, and the biliary cholesterol was present in void volume vesicles (31.3%) and small vesicles (14.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

8 Nephrolithiasis in pregnancy

Although the anatomical and physiological changes of normal pregnancy may predispose to kidney stone formation, it remains an uncommon occurrence. Correct diagnosis is often difficult. Ultrasonography has become the primary radiological diagnostic tool, with a limited excretory urogram only necessary in complicated cases. Nephrolithiasis during pregnancy occurs more frequently during the later stages of gestation, in multiparas, and without a difference in laterality. Conservative management with bed rest, hydration and analgesia can result in spontaneous passage of most stones in gravidas. Past experience of several groups suggests that cystoscopy and/or surgery can usually be done safely when absolutely necessary. Pre-existing stone disease can increase the incidence of maternal urinary tract infections by 10-20%. The most common obstetric complications of stones during gestation is premature labour induced by renal colic. Most drugs normally used to treat stone disease are contraindicated in gestation. Known inhibitors of stone formation are present in gestation and may partially explain why the incidence of stones is not increased in this hypercalciuric state.

Evaluation of Antiurolithiatic Activity ofTribulus Terrestris

AbstractTribulus Terrestris (Fruit) Has Been Used Widely In The Ayurvedic System Of Medicine For The Treatment Of Various Urinary Disorders Including Urolithiasis. In Order To Evaluate The Therapeutic Claims Made For This Plant In Traditional Medicine, The Ethanol Extract Of T. Terrestris (Fruit) Was Tested For Activity Against Artificially Induced Urolithiasis In Albino Rats. The Extract Was Administered At Daily Oral Doses Of 25, 50 and 100 Mg/Kg For 4 Months. It Exhibited Dose-Dependent Antiurolithiatic Activity and Almost Completely Inhibited Stone Formation. Other Biochemical Parameters In Urine and Serum, and The Histopathology Of Urinary Bladder, Which Were Altered During The Process Of Stone Formation, Were Also Normalized By The Plant Extract In A Dose-Dependent Manner. These Observations Thus Substantiate The Traditional Claim. Further Detailed Study Is In Progress To Isolate The Active Principle(S) and To Establish Their Mode(S) Of Action.

Increases in Urinary Inhibitor Activity and Excretion of an Inhibitor of Crystalluria in Pregnancy: A Defense Against the Hypercalciuria of Normal Gestation

Supplemental dietary calcium (2 gm/day) is recommended by some to prevent preeclampsia and premature labor. There are theoretical concerns, however, that such an approach may precipitate renal stone formation, since most gravidas are hypercalciuric, and their urine is supersaturated with calcium oxalate and phosphate salts. The present serial study of 8 healthy normotensive women at 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36+ weeks of pregnancy, and 12 weeks postpartum, was designed to assess the effects of gestation on urinary factors which inhibit stone formation. By gestational weeks 4 and 8, 24 hour creatinine clearances and calcium excretion, respectively, increased significantly, the former peaking by week 12, while the latter continued to rise and was 2.5-fold greater near term. Urinary inhibitor activity (14C oxalic acid incorporation into seed crystals) also increased significantly (27% near midpregnancy, remaining elevated till delivery). There was a striking increment of the glycoprotein cryst...

The effect of calcium and magnesium ions on urinary urokinase and sialidase activity.

The effect of a promoter (calcium) and an inhibitor (magnesium) of urolithiasis was spectrophotometrically studied on urokinase (0.45 IU) and sialidase (5 mM). Although these mineral did not affect the sialidase activity, total inhibition of urokinase activity was observed with either 0.05 M calcium chloride or 0.1 M magnesium chloride. This observation might explain why calcium and magnesium respectively function as a promoter and an inhibitor of stone formation.

Effects of dietary calcium, magnesium and phosphorus on the formation of struvite stones in the urinary tract of rats

After feeding various diets we studied the effects of dietary calcium, magnesium and phosphorus on the formation of struvite stones in rats with urinary tract infections, and also studied the effects of the administration of vitamin D3 and aluminium gel on stone formation. A low-magnesium diet decreased urinary magnesium and prevented stone formation, but a medium-calcium diet did not significantly decrease stone weight. A high-calcium diet decreased urinary phosphorus and inhibited stone formation. A high-calcium and high-phosphorus diet decreased urinary excretion of magnesium and inhibited stone formation. Although the administration of vitamin D3 did not inhibit stone formation, aluminium gel decreased the urinary level of phosphorus and prevented stone formation. A marked decrease in urinary magnesium and/or phosphorus may prevent struvite stone formation in rats with urinary tract infections.

8 Nephrolithiasis and gestation

Although both anatomical and physiological changes in pregnancy may predispose to kidney stone formation, it still remains an uncommon occurrence. Correct diagnosis is often difficult. Ultrasound has become the primary diagnostic tool, and a limited study excretory urogram is only necessary for complicated cases. Nephrolithiasis during pregnancy occurs more frequently during the later stages of gestation in multiparas, and without a difference in laterality. Conservative management with bed rest, hydration and analgesia can result in spontaneous passage of the majority of stones in gravidas. Past experience indicates that cystoscopy and/or surgery can usually be done safely when absolutely necessary. Pre-existing stone disease can increase the incidence of maternal urinary tract infections by 10-20%. The most common obstetric complication of stones during gestation is the precipitation of premature labour by renal colic. Unfortunately, most drugs used to treat stone disease are contraindicated in gestation. Experimental evidence suggests that known inhibitors of stone formation are present in gestation, and may help to explain why the incidence of stones is not increased in this particularly hypercalciuric state.

Nephrolithiasis in pregnancy.

Despite anatomic and physiologic changes that predispose to stone formation, nephrolithiasis in pregnancy remains an uncommon occurrence. Stones occur more frequently in multiparas, during the later stages of gestation, and without a difference in laterality. Correct diagnosis can be confusing. Ultrasound has become a primary diagnostic tool and limited excretory urograms are only recommended for complicated cases. Conservative management can result in spontaneous passage of most stones. When necessary, cystoscopy or surgery can be done safely. Preexisting stone disease is associated with an increased incidence of urinary tract infections in pregnancy. Renal colic often precipitates premature labor. Most drugs used to treat stone disease are contraindicated in gestation. Increased quantities of known inhibitors of stone formation are present in gestation and may explain why the incidence of stones is not increased in this hypercalciuric state.

Methylene blue as an inhibitor of stone formation

Kinetics of growth and dissolution of calcium oxalate monohydrate were examined in the presence of small concentrations of methylene blue. The data presented show moderate retardation in growth and dissolution rates. It was also found that methylene blue decreased the decalcification rate of calcium oxalate renal calculi. The implications of these findings in the treatment of urolithiasis are discussed.

Physicochemical Principles and Clinical Results Concerning the Conservative Treatment of Kidney Stones

Physicochemical principles and clinical results concerning the conservative treatment of kidney stones are discussed. Litholytic agents, developed over the last decades, are able to dissolve a number of kidney stones either directly through a retrograde irrigation of the kidney cavities or indirectly by using suitable drugs which can be administered orally or intravenously. Both ways of administration have their advantages and problems. The relation of chemical, physical, bacteriological, anatomical and metabolic factors to stone formation, as well as to stone dissolution and/or stone prophylaxis (metaphylaxis), is demonstrated. In addition, attention is called to the four physical factors – (1) crystallizing propensity, (2) exceeding the saturation point of the urine, (3) urine pH, and (4) ‘salting out’ effect – and their influence on stone formation. Factors promoting or preventing crystallization are classified in a biological relation. According to this ‘relation, it is theoretically possible by selective elimination of substances promoting crystallization to achieve suitable conditions for dissolving uric acid, phosphate and L-cystine stones and also to inhibit stone formation (prophylaxis/metaphylaxis). The frequency of recurrent calcium oxalate calculi can be reduced by achieving ‘anti-salting out’ conditions in human urine. These ideas were proved experimentally and in a preliminary clinical study with a limited number of kidney-stone patients.

A New Hydrophilic Polymer as a Common Duct Replacement

A suitable artificial conduit to replace a diseased or damaged common duct segment is not currently available. In the experimental laboratory a variety of materials have failed when used either as permanent channels or as extractable prostheses.1Cicatricial stenosis, occluding stone formation, implant rejection, and functional obstruction have thrwarted attempts to develop a satisfactory bile duct substitute for clinical application. Previous experience with a biologically nonreactive, conductive hydrophilic polymer (Hydron) suggested its use for bridging defects in the extrahepatic biliary system. Since this material is capable of absorbing water-soluble ions to equilibrium, it appeared that a compatible bile plastic interface could be established to inhibit stone formation.2Molded, multisized, supple cylinders of the synthetic seemed to possess sufficient body to resist the stenosing effects of the scarring commonly encountered in the region of the porta hepatis. This report deals with the use of Hydron as a canine-common bile