[Hormonal and metabolic disorders as systemic factor for the formation of urinary calculi].

In patients suffering from urolithiasis, metabolic diagnostics often reveals abnormalities contributing to the formation of stones: hypocitraturia, hyper- and hypocalcemia, hypercalciuria, hypomagnesemia/hypomagnesuria, hyperoxalaturia, etc. Before surgery, complex biochemical examination of blood and 24-hourcollection urine in 82 patients with urolithiasis was performed. The analysis of the main laboratory parameters of carbohydrate, lipid, calcium and phosphorus and purine metabolism found the prevalence of violations of calcium and phosphorus metabolism in these patients. Dyslipidemia was diagnosed in 31 (37.8%) patients. There was a significant positive correlation between serum total cholesterol and serum total calcium (rs = 0.3315, P = 0.0103). Low serum calcium levels were associated with hyperoxalaturia (rs = -0.4270, P = 0.0295). There was a significant effect of natriuria on urinary excretion of oxalate (rs = 0.6107, P = 0.0001), Mg (rs = 0.4156, P = 0.0096) and K (rs = 0.5234, P = 0.00005). The study shows the role of magnesium in the prevention of recurrence and manifestation of urolithiasis. The combination of two or more types of hormonal and metabolic disorders increases the incidence of recurrent stones. Timely correction of hormonal-metabolic status allows to reduce the risk of stone formation, and hospitalization attributable to the complications associated.

[Pharmacotherapy for preventing calcium containing stone formation].

Many urinary tract stones consist of calcium, and has high relapse rate. Accordingly, it is very important to prevent calcium-containing stone formation. This paper describes about effects and mechanisms for Xanthine oxidase inhibitor, citrate formulation, magnesium formulation, thiazides, vitamin B(6), extract of Quercus salicina Blume and chorei-to (medical herb) . Recent new drugs and the elucidation of new metabolic pathways may lead to the development of prevention of urolithiasis.

Drug dosage protocol for calcium oxalate stone.

In earlier studies, we have confirmed that in most patients with calcium oxalate stone formation, a combination of allopurinol and pyridoxine is best suited for treatment and prevention of the stone forming process. The objective of this study is to identify the most effective directed medical treatment of urinary stones. The drug dose adjustment was based on clinical, radiological, biochemical, and microscopic parameters. 444 patients with proved calcium oxalate stone disease who were getting a combination of allopurinol and pyridoxine for a minimum period of 36 months were enrolled in this prospective study. The dosage schedule of these patients was recorded. Dosage adjustment was made depending upon the various clinical, biochemical, microscopic, and radiological changes during the study period. The dosage schedules were in six categories, namely very high dose chemotherapy (VHDC), i.e. allopurinol 600 mg/day and pyridoxine 240 mg/day, high-dose chemotherapy (HDC), i.e. allopurinol 300 mg/day and pyridoxine 120 mg/day, moderate dose prophylaxis (MDP), i.e. allopurinol 200 mg/day and pyridoxine 80 mg/day, low-dose prophylaxis (LDP), i.e. allopurinol 100 mg/day and pyridoxine 40 mg/day, and very low-dose prophylaxis (VLDP), i.e. allopurinol 50 mg/day and pyridoxine 20 mg/day and intermittent VLDP, wherein the VLDP was given on alternate months and still later at longer intervals. The temporary risk was assessed at each visit and dosage adjustment was made. The effect of the intervention was assessed during the next visit. All the patients involved in the study needed dose adjustment. The following schedules were initiated: VHDC (12) 3.5%, HDC (103) 23.2%, MDP (78) 17.57%, or LDP (251) 56.53%. Patients who defaulted for more than a month were excluded from the study. During each visit for follow up, all patients were advised change over of dose depending upon the clinical situation at the time of review. Patients on VHDC were advised reduction to lower doses systematically. On passage of stones, the dose was immediately reduced to LDP in all situations unless prevented by the presence of significant crystalluria or severe pain. All patients on MDP had reduction of dose to LDP subsequently. Patients started on LDP needed elevation in dose in 63 (16.8%) to HDC and 23 patients (12.87%) to MDP. Dose of 247 patients could be reduced to VLDP (55.63%) and later on to intermittent VLDP 85 (19.14%). 74 (16.7%) patients continued to be on LDP throughout the period of study. It is concluded that in managing the stone patient, the clinical, radiological, microscopic and biochemical parameters should be taken into consideration in deciding the reduction/increase in the dose of drugs. The principle of giving chemotherapy/chemoprophylaxis should be to administer the least number of drugs in the least dosage depending upon the requirement of the disease.

Calcium oxalate stone and gout.

Gout is well known to be produced by increased uric acid level in blood. The objective of this paper is to assess the relationship between gout and calcium oxalate stone formation in the humans. 48 patients with combination of gout and calcium oxalate stone problem were included. The biochemical values of this group were compared with 38 randomly selected uric acid stone patients with gout, 43 stone patients with gout alone, 100 calcium oxalate stone patients without gout and 30 controls, making a total of 259 patients. Various biochemical parameters, namely serum calcium, phosphorus and uric acid and 24-h urine calcium, phosphorus, uric acid, oxalate, citrate and magnesium were analysed. ANOVA and Duncan's multiple-range tests were performed to assess statistical significance of the variations. The promoters of stone formation, namely serum calcium (P < 0.05), phosphorus (P < 0.05) and uric acid (P < 0.05) and urine calcium (P < 0.05), uric acid (P < 0.05) and oxalate (P < 0.05) were significantly variable in the different groups. The inhibitor citrate (P < 0.05) was also significantly variable. Multiple-range test showed that the promoters, namely serum calcium (P < 0.05) and urine uric acid (P < 0.05) were in a significantly higher range in the gouty patients, gouty uric acid stone patients and gouty calcium oxalate stone patients compared to the non-gouty patients and controls. Urine oxalate (P < 0.0001) was in the highest range in the gouty calcium oxalate or gouty uric acid stones patients. The inhibitor urine citrate (P < 0.001) was significantly lower in the gouty, gouty uric acid and gouty calcium oxalate patients. Serum uric acid was highest in the non-stone gouty patients, followed by the gouty uric acid stone formers and gouty calcium oxalate stone patients. The high values of promoters, namely uric acid and calcium in the gouty stone patients indicate the tendency for urinary stone formation in the gouty stone patients. There is probably a correlation between gout and calcium oxalate urinary stone. We presume this mechanism is achieved through the uric acid metabolism. The findings point to the summation effect of metabolic changes in development of stone disease.

Effect of dietary changes on urinary oxalate excretion and calcium oxalate supersaturation in patients with hyperoxaluric stone formation.

OBJECTIVES: To test the hypothesis that patients with hyperoxaluria, who modified their dietary calcium intake, would reduce their urinary oxalate excretion without raising their urinary calcium excretion. Diet is a major factor in idiopathic calcium oxalate urolithiasis, yet controversy exists regarding the ideal clinical recommendations. Approximately 20% of patients with calcium oxalate stone formation have hyperoxaluria (> or = 45 mg oxalate/d). Calcium supplements to bind dietary oxalate have been suggested, but clinical evidence of this therapy is lacking. METHODS: Of 144 adult patients with stone formation seen by a registered dietitian from September 2006 to September 2007, 26 (18%) had hyperoxaluria on > or = 1 24-hour urinalyses. Of those with > or = 2 complete 24-hour collections and whose hyperoxaluria was observed before their last visit with the registered dietitian, 22 patients were identified. The patients were retrospectively separated into 2 groups according to whether they had been advised dietary changes alone (diet group, n = 10) or calcium citrate with meals, in addition to the dietary changes (supplement group, n = 12). The mean follow-up time was 317 and 266 days for the diet and supplement groups, respectively. Statistical comparisons within and between groups were made for urinary risk factors. RESULTS: Urinary oxalate excretion decreased from 56 to 43 mg/d and from 60 to 46 mg/d in the diet and supplement groups, respectively (P = .003 and P = .038, respectively). Calcium oxalate supersaturation decreased from 3.48 to 1.83 and from 2.37 to 1.52 in the diet and supplement groups, respectively (P = .043 and P = .002, respectively). Urinary calcium excretion did not change in either group. CONCLUSIONS: Gastrointestinal binding of oxalate by calcium is an effective clinical strategy for hyperoxaluria, whether mediated by calcium citrate with meals or by inclusion of calcium-containing foods with meals.

Can lemon juice be an alternative to potassium citrate in the treatment of urinary calcium stones in patients with hypocitraturia? A prospective randomized study.

To investigate that lemon juice could be an alternative to potassium citrate in the treatment of urinary calcium stones in patients with hypocitraturia, 30 patients with hypocitraturic urinary calcium stones were enrolled into study. The patients were divided into three groups equally. Exactly 60 mEq/day fresh lemon juice ( approximately 85 cc/day) and potassium citrate (60 mEq/day) were given to the patients of first and second group, respectively. Dietary recommendations were made for the third group. Blood and 24-h urine tests were performed before treatment and repeated 3 months later. The differences between demographic datas of groups were not significant. There was no significant difference between values of blood tests performed before and after treatment in all groups. Statistically significant differences were found between pre- and post-treatment urine values in each group. Although there was no significant difference between pre-treatment citrate levels of the groups. A significant difference was found between post-treatment citrate levels of the groups. There was 2.5-, 3.5- and 0.8-fold increase in urinary citrate level of lemon juice, potassium citrate and dietary recommendation groups, respectively. Urinary calcium level was decreased only in lemon juice and potassium citrate groups after treatment. While there was no significant difference between pre- and post-treatment urinary oxalate levels in all groups, a significant decrease in urinary uric acid levels was determined in all groups. We suggest that lemon juice can be an alternative in the treatment of urinary calcium stones in patients with hypocitraturia. Additionally, dietary recommendations can increase effectiveness of the treatment.

Enteric oxalate secretion is not directly mediated by the human CFTR chloride channel.

The secretion of the oxalate anion by intestinal epithelia is a functionally significant component of oxalate homeostasis and hence a relevant factor in the etiology and management of calcium oxalate urolithiasis. To test the hypothesis that human cystic fibrosis transmembrane conductance regulator (hCFTR) can directly mediate the efflux of the oxalate anion, we compared cAMP-stimulated 36Cl-, 14C-oxalate, and 35SO(4)2- efflux from Xenopus oocytes expressing hCFTR with water-injected control oocytes. hCFTR-expressing oocytes exhibited a large, reversible cAMP-dependent increase in whole cell conductance measured using a two-electrode voltage clamp and a 13-fold increase in rate of cAMP-stimulated 36Cl- efflux. In contrast, the rate constants of oxalate and sulfate efflux were low and unaffected by cAMP in either control or hCFTR-expressing oocytes. We conclude that the human CFTR gene product does not directly mediate oxalate efflux in secretory epithelia and hence is not directly involved in oxalate homeostasis in humans.

A traditional Chinese herbal antilithic formula, Wulingsan, effectively prevents the renal deposition of calcium oxalate crystal in ethylene glycol-fed rats.

We investigated the effects of a traditional Chinese herbal formula, Wulingsan (WLS), on renal stone prevention using an ethylene glycol-induced nephrocalcinosis rat model. Forty-one male Sprague-Dawley (SD) rats were divided into four groups. Group 1 (n=8) was the normal control; group 2 (n=11) served as the placebo group, and received a gastric gavage of starch and 0.75% ethylene glycol (EG) as a stone inducer; group 3 received EG and a low dose of WLS (375 mg/kg); and group 4 received EG and a high dose of WLS (1,125 mg/kg). Baseline and final 24 h urine samples were collected individually; biochemical data of urine and serum were also obtained at the beginning and at the end of the experiment. After 4 weeks, animals were killed and kidneys were harvested. The kidney specimens were examined by polarized light microscopy and the crystal deposits were evaluated by a semi-quantitative scoring method using computer software (ImageScoring). The results revealed that the rats of placebo group gained the least significant body weight; in contrast, the rats of WLS-fed groups could effectively reverse it. The placebo group exhibited lower levels of free calcium (p=0.059) and significantly lower serum phosphorus (p=0.015) in urine than WLS-fed rats. Histological findings of kidneys revealed tubular destruction, damage and inflammatory reactions in the EG-water rats. The crystal deposit scores dropped significantly in the WLS groups, from 1.40 to 0.46 in the low-dose group and from 1.40 to 0.45 in the high-dose group. Overall, WLS effectively inhibited the deposition of calcium oxalate (CaOx) crystal and lowered the incidence of stones in rats (p=0.035). In conclusion, WLS significantly reduced the severity of calcium oxalate crystal deposits in rat kidneys, indicating that Wulingsan may be an effective antilithic herbal formula.

Prevention of stone disease.

In recent years stone disease has become more widespread in developed countries. At present the prevalence is 5.2 and 15% of men and 6% of women are affected. The increase is linked to changes in lifestyle, eating patterns and obesity which has become very common. The 'metabolic syndrome' includes all the diseases, e.g. hypertension, lipid imbalances, type 2 diabetes mellitus, gout and cardiovascular disease, which are concomitant in the majority of stone formers. Dietary patterns, besides leading to stone formation, also determine stone chemistry. With a diet that is rich in oxalates, calcium oxalate will constitute 75% of stones, struvite 10-20%, uric acid 5-6% and cystine 1%. As approximately 50% of patients with stones suffer recurrences, metabolic and/or pharmacological prophylaxis is recommended.

Metabolic assessment in patients with urinary lithiasis.

INTRODUCTION: Metabolic investigation in patients with urinary lithiasis is very important for preventing recurrence of disease. The objective of this work was to diagnose and to determine the prevalence of metabolic disorders, to assess the quality of the water consumed and volume of diuresis as potential risk factors for this pathology. PATIENTS AND METHODS: We studied 182 patients older than 12 years. We included patients with history and/or imaging tests confirming at least 2 stones, with creatinine clearance > or = 60 mL/min and negative urine culture. The protocol consisted in the collection of 2, 24-hour urine samples, for dosing Ca, P, uric acid, Na, K, Mg, Ox and Ci, glycemia and serum levels of Ca, P, Uric acid, Na, K, Cl, Mg, U and Cr, urinary pH and urinary acidification test. RESULTS: 158 patients fulfilled the inclusion criteria. Among these, 151 (95.5%) presented metabolic changes, with 94 (62.2%) presenting isolated metabolic change and 57 (37.8%) had mixed changes. The main disorders detected were hypercalciuria (74%), hypocitraturia (37.3%), hyperoxaluria (24.1%), hypomagnesuria (21%), hyperuricosuria (20.2%), primary hyperparathyroidism (1.8%), secondary hyperparathyroidism (0.6%) and renal tubular acidosis (0.6). CONCLUSION: Metabolic change was diagnosed in 95.5% of patients. These results warrant the metabolic study and follow-up in patients with recurrent lithiasis in order to decrease the recurrence rate through specific treatments, modification in alimentary and behavioral habits.

Metabolic assessment in patients with urinary lithiasis

INTRODUCTION: Metabolic investigation in patients with urinary lithiasis is very important for preventing recurrence of disease. The objective of this work was to diagnose and to determine the prevalence of metabolic disorders, to assess the quality of the water consumed and volume of diuresis as potential risk factors for this pathology. PATIENTS AND METHODS: We studied 182 patients older than 12 years. We included patients with history and/or imaging tests confirming at least 2 stones, with creatinine clearance > 60 mL/min and negative urine culture. The protocol consisted in the collection of 2, 24-hour urine samples, for dosing Ca, P, uric acid, Na, K, Mg, Ox and Ci, glycemia and serum levels of Ca, P, Uric acid, Na, K, Cl, Mg, U and Cr, urinary pH and urinary acidification test. RESULTS: 158 patients fulfilled the inclusion criteria. Among these, 151 (95.5 percent) presented metabolic changes, with 94 (62.2 percent) presenting isolated metabolic change and 57 (37.8 percent) had mixed changes. The main disorders detected were hypercalciuria (74 percent), hypocitraturia (37.3 percent), hyperoxaluria (24.1 percent), hypomagnesuria (21 percent), hyperuricosuria (20.2 percent), primary hyperparathyroidism (1.8 percent) secondary hyperparathyroidism (0.6 percent) and renal tubular acidosis (0.6). CONCLUSION: Metabolic change was diagnosed in 95.5 percent of patients. These results warrant the metabolic study and follow-up in patients with recurrent lithiasis in order to decrease the recurrence rate through specific treatments, modification in alimentary and behavioral habits.

Calcium oxalate crystal localization and osteopontin immunostaining in genetic hypercalciuric stone-forming rats.

BACKGROUND: The inbred genetic hypercalciuric stone-forming (GHS) rats develop calcium phosphate (apatite) stones when fed a normal 1.2% calcium diet. The addition of 1% hydroxyproline to this diet does not alter the type of stone formed, while rats fed this diet with 3% hydroxyproline form mixed apatite and calcium oxalate stones and those with 5% hydroxyproline added form only calcium oxalate stones. The present study was designed to determine the localization of stone formation and if this solid phase resulted in pathologic changes to the kidneys. METHODS: GHS rats were fed 15 g of the standard diet or the diet supplemented with 1%, 3%, or 5% hydroxyproline for 18 weeks. A separate group of Sprague-Dawley rats (the parental strain of the GHS rats), fed the standard diet for a similar duration, served as an additional control. At 18 weeks, all kidneys were perfusion-fixed for structural analysis, detection of crystal deposits using the Yasue silver substitution method, and osteopontin immunostaining. RESULTS: There were no crystal deposits found in the kidneys of Sprague-Dawley rats. Crystal deposits were found in the kidneys of all GHS rats and this Yasue-stained material was detected only in the urinary space. No crystal deposits were noted within the cortical or medullary segments of the nephron and there was no evidence for tubular damage in any group. The only pathologic changes occurred in 3% and 5% hydroxyproline groups with the 5% group showing the most severe changes. In these rats, which form only calcium oxalate stones, focal sites along the urothelial lining of the papilla and fornix of the urinary space demonstrated a proliferative response characterized by increased density of urothelial cells that surrounded the crystal deposits. At the fornix, some crystals were lodged within the interstitium, deep to the proliferative urothelium. There was increased osteopontin immunostaining in the proliferating urothelium. CONCLUSION: Thus in the GHS rat, the initial stone formation occurred solely in the urinary space. Tubular damage was not observed with either apatite or calcium oxalate stones. The apatite stones do not appear to cause any pathological change while those rats forming calcium oxalate stones have a proliferative response of the urothelium, with increased osteopontin immunostaining, around the crystal deposits in the fornix.

Is magnesium a marker of disordered mineral metabolism in males with idiopathic recurrent calcium urolithiasis? Observations focussing on fasting magnesiuria and magnesiemia, protein and other substances in urine and plasma.

Mg can theoretically play a role in renal calcium stone formation of IRCU patients, but the status of Mg is uncertain. The aim of this study was to investigate whether in IRCU variation of Mg in fasting urine and plasma is associated with altered urine Ca, Pi, oxalate, Ca/Pi ratio, supersaturation and other factors, the clinical severity of stone disease (metabolic activity; MA) included. This was a cross-sectional study (284 IRCU patients), comprising males with mean age in the fifth decade and unimpaired renal function. Patients had an unrestricted home diet, standardized laboratory procedures, including sample collection (daily and fasting urine, plasma), with classification of patients according to tertiles of fasting Mg-uria, keeping comparable age, the number of patients with renal stones present or absent, and normo- or idiopathic hypercalciuria. MA was scored. We found that the tertile I patients (= referent) exhibited sub-normal fasting Mg excretion (< 4 mg/2 h) and fractional excretion (< 3.5%), in daily urine the lowest Mg and oxalate, but highest Ca excretion rate; compared with tertile III, tertile I patients had significantly lower plasma total (not ultrafiltrable) Mg, blood bicarbonate and pH, and the lowest MA; fasting urinary excretion of Ca and citrate were also low, but urinary Pi, body weight, plasma glucose and insulin were increased. In tertile III not only was Mg-uria (excretion, FE) significantly elevated vs I, but so were urinary pH, excretion of sodium, Ca, potassium, protein (total and non-albumin) and citrate, FE sodium and Ca, the urinary molar ratios Ca/Pi and Mg/Potassium, hydroxyapatite supersaturation, bone resorption markers, and MA; in this environment urinary oxalate and Ca oxalate supersaturation were unchanged, plasma glucose, insulin and parathyroid hormone decreased. The tertile II patients, showing intermediate Mg excretion, also exhibited (vs. I) increase of FE Mg, urinary excretion and FE of sodium and Ca, excretion of protein, citrate and bone markers, the ratios Ca/Pi and Mg/Potassium, and MA. When urinary Ca/Pi was considered as the outcome of disordered metabolism, significant determinants (according to multiple regression analysis) were urinary Pi (negative), Ca and Mg/Potassium (positive); significant determinants of MA, the sum of stone-forming processes, were the urinary concentration of non-albumin protein, Mg/Potassium and sodium (all positive). Among IRCU patients 1) approx. one third is in need of Mg conservation by the kidney, associated with low plasma total Mg, modest metabolic acidosis, a trend towards overweight, high plasma insulin and glucose; 2) low Mg- or acidosis-induced increase of bone resorption may follow, attenuating glycemia and insulinemia but forcing the kidney to functional adaptation, manifesting as a rise of urinary sodium, Mg, Ca, Pi, Ca/Pi, pH and protein, together presumably aggravating MA; 3) larger controlled studies are justified, to decide whether Mg deficiency initiates renal Ca stones, and if urinary Mg loss exaggerates IRCU.

Supplementation of vitamin E and selenium prevents hyperoxaluria in experimental urolithic rats.

Renal injury is considered as one of the prerequisites for calcium oxalate retention. In order to determine the role of lipid peroxidation related effects for hyperoxaluria, we evaluated the alterations in lipid peroxidation, antioxidants and oxalate synthesizing enzymes in lithogenic rats with response to vitamin E + selenium treatment. In kidney of lithogenic rats, the level of lipid peroxidation and the activities of oxalate synthesizing enzymes were found to be increased whereas the levels/activities of non-enzymatic and enzymatic antioxidants were found to be decreased. The urinary excretion of both oxalate and calcium were significantly elevated. Supplementation of lithogenic rats with vitamin E + selenium decreased the levels of lipid peroxides and the activities of oxalate synthesizing enzymes like glycolic acid oxidase (GAO), lactate dehydrogenase (LDH), xanthine oxidase (XO) with a concomitant increase in the activities of enzymatic antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PDH) and increased levels of non-enzymatic antioxidants like ascorbic acid, alpha-tocopherol and reduced glutathione (GSH). The urinary excretion of oxalate and calcium were normalized. The antioxidants vitamin E + selenium thereby protected from hyperoxaluria.

Cystine transport activity of heterozygous rBAT mutants expressed in Xenopus oocytes.

The rBAT gene encodes a transport protein for cystine and dibasic amino acids. It is a candidate gene for type I cystinuria, a genetic disorder inherited as an autosomal-recessive trait. Recently, several mutations in rBAT from Japanese patients with cystinuria have been reported from our laboratory. Some of these patients were heterozygous, which appears to be inconsistent with the previous concept that mutations in rBAT are recessive. To investigate the function of heterozygous mutants, we introduced these mutations into rBAT gene and analyzed the transport activity of cystine associated with the mutants in Xenopus oocytes. Co-injection of the mutant T1037C (L346P) and the polymorphism G1854A (M6181) into Xenopus oocytes produced a transport activity of 67.9% of the wild type. Oocytes co-injected with T2017C (C673R) and wild type had a transport activity of 70.3% of the wild type. These findings indicate that the heterozygous mutants show decreased transport activity compared to wild-type rBAT. Further, some mutants in rBAT may show decreased cystine transport activity even in heterozygous condition, which may contribute to stone-forming cystinuria.

Effect of A. lanata leaf extract and Vediuppu chunnam on the urinary risk factors of calcium oxalate urolithiasis during experimental hyperoxaluria.

Urolithiasis is one of the third most common afflictions found in humans. The efficacy of the two Siddha drugs, Aerva lanata and Vediuppu chunnam as antilithic agents using a urolithic rat model were tested in this study. Hyperoxaluria was induced in rats using 0.75% ethylene glycol in drinking water. Aerva lanata(3.0 mg kg(-1)body weight) and Vediuppu chunnam (3.5 mg kg(-1)body weight) were given orally for 28 days. Urinary risk factors of urolithiasis were monitored at the end of 7th, 14th, 21st and 28th days. Urinary volume was increased in hyperoxaluric as well as drug-treated rats. Increased urinary excretion of calcium, oxalate, uric acid, phosphorus and protein in hyperoxaluric rats was brought down significantly by the administration of A. lanata or Vediuppu chunnam. Decreased magnesium excretion in hyperoxaluric rats was normalized by drug treatment. The drug increases the urine volume, thereby reducing the solubility product with respect to calcium oxalate and other crystallizing salts such as uric acid, which may induce epitaxial deposition of calcium oxalate. Drug alone treated rats did not show any adverse effects. Combination therapy was found to be more effective and this indigenous medicine can be used successfully as an antilithic agent.

Urinary calculi: bacteriological and chemical association.

We investigated the bacteriology of urinary calculi in relation to urinary tract infection, stone formation, chemical composition and antibiotic sensitivity. Fifty-two patients (37 males, 15 females) with urolithiasis were studied. Urine, serum and urinary calculi specimens were taken and serum biochemical tests to detect uric acid, calcium and phosphorus were performed. Urine analysis and culture were also performed. Of the 52 patients, 19 (37%) had associated urinary tract infection, with Escherichia coli and Proteus mirabilis being the most common causative microorganisms. The bacterial isolates from urine and those from calculi differed in their susceptibility to antimicrobial agents. We conclude that in over 50% of patients with urolithiasis, urine culture can detect the infecting organisms associated with stone formation and the organisms within urinary calculi.

Protective effect of triterpenes on calcium oxalate crystal-induced peroxidative changes in experimental urolithiasis.

Naturally occurring pentacyclic triterpenes of plant origin have been identified as possessing a wide range of pharmacological effects. Lupeol (Lupa-21,20(29) dien, 3beta-ol) has been found to be efficient in reducing the risk of stone formation in animals by way of preventing crystal-induced tissue damage and dilution of urinary stone-forming constituents. In the present study, two structurally related triterpenes, lupeol and betulin (Lupa-20(29)ene-3,28 diol) were assessed for their antilithiatic effect. Foreign body implantation method followed by supplementation of ammonium oxalate was adapted to induce stone formation in the bladder. This led to elevated lipid peroxidation and depleted antioxidant status in the renal tissues. Both the triterpenes were equally efficient in minimizing crystal-induced renal peroxidative changes measured in terms of malondialdehyde and subsequent tissue damage. The antioxidant status, comprising of the enzymatic and non-enzymatic components, was found to be significantly depleted in the kidney and bladder of stone-forming animals. Both lupeol and betulin were comparable in their ability to restore the thiol status and the antioxidant enzymes like superoxide dismutase, catalase and glutathione peroxidase. The mechanism by which the two compounds render protection against oxalate-induced toxic manifestations and free radical production may involve the inhibition of calcium oxalate crystal aggregation and enhancement of the body defence systems. 2000 Academic Press.

Evaluation of the antiurolithiatic activity of the extract of Costus spiralis Roscoe in rats.

The antiurolithiatic activity of the water extract of Costus spiralis Roscoe was tested on formation of calculi on implants of calcium oxalate crystals or zinc disc in the urinary bladder of rats. The plant is a species from the family Zingiberaceae used in Brazilian folk medicine in urinary affections and for expelling urinary stones. Implantation of the foreign body in the urinary bladder of adult rats induced formation of urinary stones and hypertrophy of the smooth musculature. Oral treatment with the extract of Costus spiralis Roscoe (0.25 and 0.5 g/kg per day) after 4 weeks surgery reduced the growth of calculi, but it did not prevent hypertrophy of the organ smooth musculature. The contractile responses of isolated urinary bladder preparations to the muscarinic agonist bethanecol, in the presence and absence of the extract (0.3-3 mg/ml) or atropine (0.3-3 nM) did not differ among the experimental groups. The results indicate that the extract of Costus spiralis Roscoe is endowed with antiurolithiatic activity confirming thus folk information. The effect, however, was unrelated to increased diuresis or to a change of the muscarinic receptor affinity of the bladder smooth musculature to cholinergic ligands.

Magnesium, citrate, magnesium citrate and magnesium-alkali citrate as modulators of calcium oxalate crystallization in urine: observations in patients with recurrent idiopathic calcium urolithiasis.

The effects of magnesium (Mg) and citrate on the metastable limit of calcium oxalate (CaOx) solubility (synonym: tolerable oxalate TO) were examined in artificial urine and in postprandial urine of male patients with idiopathic calcium urolithiasis (ICU). In artificial urine increasing pH, Mg and citrate elevate TO, decrease CaOx supersaturation only marginally, but elevate considerably free citrate; the effect of Mg alone was small in comparison with citrate alone, and the effects of both substances appeared additive. In ICU patients, matched for sex, age and CaOx supersaturation to non-stone-forming controls, TO was decreased (mean values 0.33 vs. 0.52 mM/l in controls, P < 0.05). Additional significant (P < 0.05) differences were found between ICU and controls: the former exhibited increased CaOx crystal growth, decreased crystal agglomeration time, a more acidic urinary pH, increased concentrations of free calcium and free Mg, and decreased free oxalate and free citrate. After ingestion of a urine-acidifying test meal, or this meal supplemented with either neutral Mg citrate or Mg-alkali citrate, by three groups of male ICU patients, matched for age and CaOx supersaturation, only the last-named preparation evoked an increase in TO and a decrease in crystal diameter, while the normally occurring pH decline from fasting urine was virtually abolished, and the ratios urinary Mg/citrate and calcium/citrate tended towards low values. In contrast, Mg citrate increased crystal agglomeration time, while changes in the other parameters were only insignificant. The crystals formed in urine were CaOx di- and monohydrate (by electron microscopy), and energy dispersive X-ray analysis showed calcium peaks exclusively. However, chemical analysis of crystals verified the presence not only of oxalate and calcium, but also of Mg, phosphate, citrate, and urate; moreover, these crystal constituents seemed to be influenced by Mg citrate and Mg-alkali citrate in different ways. It was concluded that (1) Mg and citrate are effectors of TO in artificial and natural urine; (2) in ICU, low TO and other disturbed CaOx crystallization parameters appear related to the prevailing low urinary pH and low free citrate; (3) Mg-alkali citrate inhibits CaOx crystallization, probably via actions of the citrate, but not the Mg. Because of the eminent role of Mg in human health and ICU, further studies on crystallization after oral intake of Mg in the form of citrate are warranted.