Urinary crystal formation and urothelial effects of pyroxasulfone administered to male rats.

Pyroxasulfone induced a low incidence of urinary bladder tumors in male rats in a 2-year bioassay at 1000 and 2000 ppm, with occasional urinary calculi. No increased incidence of tumors of any tissue occurred in female rats or in mice of either gender. We performed three short-term studies to evaluate early development of pyroxasulfone-induced urinary crystals and urothelial cytotoxicity with consequent regenerative proliferation. First, male rats were treated with dietary 50, 1000 or 2000 ppm pyroxasulfone for 1, 3 or 7 days. The urothelium was examined by light and scanning electron microscopy (LM, SEM) and bromodeoxyuridine labeling index (BrdU LI). In two other studies, male rats were treated with dietary 20 000 ppm pyroxasulfone for 1 week. Urine collected at various times of day was examined by SEM and energy dispersive spectroscopy (EDS) or by LM, SEM, EDS, and infrared spectroscopy (IFS). Urinary crystals were present at various time points. EDS and IFS showed some contained calcium; others contained organic matter. Cytotoxicity was detected by SEM as cellular swelling, craters, and necrosis and by LM as cellular hypertrophy. Increased cell proliferation was detected by LM (hyperplasia), SEM (piling up of round cells), and by increased BrdU LI. There was no evidence of increased apoptosis. These findings support a mode of action for pyroxasulfone-associated bladder tumors in male rats involving formation of urinary crystals leading to urothelial cytotoxicity and regenerative proliferation. This is a high dose phenomenon, therefore, pyroxasulfone is not likely to be carcinogenic to humans at exposure levels that do not cause crystals with subsequent calculi formation in the urinary tract.

Prevalence of twenty-four hour urine testing in Veterans with urinary stone disease.

OBJECTIVE: The American Urological Association guidelines recommend 24-hour urine testing in patients with urinary stone disease to decrease the risk of stone recurrence; however, national practice patterns for 24-hour urine testing are not well characterized. Our objective is to determine the prevalence of 24-hour urine testing in patients with urinary stone disease in the Veterans Health Administration and examine patient-specific and facility-level factors associated with 24-hour urine testing. Identifying variations in clinical practice can inform future quality improvement efforts in the management of urinary stone disease in integrated healthcare systems. MATERIALS AND METHODS: We accessed national Veterans Health Administration data through the Corporate Data Warehouse (CDW), hosted by the Veterans Affairs Informatics and Computing Infrastructure (VINCI), to identify patients with urinary stone disease. We defined stone formers as Veterans with one inpatient ICD-9 code for kidney or ureteral stones, two or more outpatient ICD-9 codes for kidney or ureteral stones, or one or more CPT codes for kidney or ureteral stone procedures from 2007 through 2013. We defined a 24-hour urine test as a 24-hour collection for calcium, oxalate, citrate or sulfate. We used multivariable regression to assess demographic, geographic, and selected clinical factors associated with 24-hour urine testing. RESULTS: We identified 130,489 Veterans with urinary stone disease; 19,288 (14.8%) underwent 24-hour urine testing. Patients who completed 24-hour urine testing were younger, had fewer comorbidities, and were more likely to be White. Utilization of 24-hour urine testing varied widely by geography and facility, the latter ranging from 1 to 40%. CONCLUSIONS: Fewer than one in six patients with urinary stone disease complete 24-hour urine testing in the Veterans Health Administration. In addition, utilization of 24-hour urine testing varies widely by facility identifying a target area for improvement in the care of patients with urinary stone disease. Future efforts to increase utilization of 24-hour urine testing and improve clinician awareness of targeted approaches to stone prevention may be warranted to reduce the morbidity and cost of urinary stone disease.

[Clinical value of Canephron N after surgical treatment of urinary stone disease].

BACKGROUND: The drug Canephron N is a combination of extracts of centaury, lovage and rosemary. Moderate antispasmoic, anti-inflammatory, antioxidant, diuretic and antimicrobial effects are of great interest for urological practice. The optimal combination of components that were made of herbal medicine allows to use their synergistic effect for prevention of recurrence of urinary stone disease. The experience of using the drug Canephron in clinical practice is of great interest. AIM: to clarify the clinical efficiency of Canephron N in patients with urinary stone disease after surgical treatment and to evaluate the changes in diuresis and calcium excretion. MATERIALS AND METHODS: The results of using the drug Canephron after surgical treatment of urinary stone disease are provided. The changes in diuresis and calcium excretion in 75 patients undergone surgical treatment of urinary stone disease were studied. Patients after ureteroscopy, percutaneous nephrolithotomy and extracorporeal shock-wave lithotripsy were prescribed treatment to prevent stone formation including herbal drug Canephron N. RESULTS: At baseline, there was negative correlation between 24-hours diuresis and calcium excretion in all groups. During follow-up, a positive correlation between 24-hours diuresis and calcium excretion was found in patients receiving Canephron N and other types of treatment. The average follow-up was 390 days. During this period, recurrence was noted in 1 patient receiving Canephron, 4 patients in patients who took other drugs and in 5 patients who didnt receive any treatment. CONCLUSION: Risk factors of stone formation persist after surgical treatment of urinary stone disease. This is reflected in a negative correlation between 24-hour diuresis and calcium excretion. During treatment, a positive correlation between diuresis and calcium excretion was noted in patients with urinary stone disease. The use of drugs that affect stone formation as well as herbal medicine Canephron N allow to obtain comparable ratio of diuresis and calcium excretion.

Comparison of metabolic changes for stone risks in 24-hour urine between non- and postmenopausal women.

BACKGROUND: To explore the differences of 24-hour urine compositions associated with urolithiasis between non- and postmenopausal females. METHODS: The 24-hour urine samples of female participants were collected from May 2013 to July 2014 along with national cross-sectional study of urolithiasis among adults aged ≥18 years in China. The exclusion criteria for the participants were: serum creatinine > 133µmol/L, with urinary tract infection, gout, hyperthyroidism, malignancy, had a history of cancer, kidney stones, enterectomy, had taken thiazide diuretics, allopurinol, vitamin supplement, potassium citrate or calcium supplements during the past two weeks. The compositions associated with urinary stone in 24-hour urine were measured and compared between non-and postmenopausal women. RESULTS: A total of 603 24-hour urine samples of female participants were analyzed. 354 women with a mean age of 52.5± 14.03 (range 19-84) years met the criteria, including 160 non-menopausal women and 194 postmenopausal women. Compared to the non-menopausal women, postmenopausal women had a lower secretion of citrate (p = 0.043), magnesium (p = 0.001) and creatinine (p = 0.001) in 24h urine. Multivariate linear regression analysis showed that the menopause status was associated with the changes in magnesium (p = 0.003) and creatinine (p = 0.002) secretion, whereas not with the changes in citrate (p = 0.402) secretion. CONCLUSIONS: Postmenopausal women have a significant lower secretion of magnesium in their 24-hour urine than non-menopausal ones. We suppose that might be associated with increased risk of urinary stone formation among postmenopausal women.

[Effects of a supplementation on sodium chloride or ammonium chloride on urolithic potential in the rabbit]. / Effekte einer Natriumchlorid- oder Ammoniumchloridsupplementierung auf das Harnsteinbildungspotenzial beim Kaninchen.

AIM: Reduction of urolithic potential by means of increased water intake and urine dilution through supplementation of sodium chloride (NaCl) or decrease of urine pH by supplementation of ammonium chloride (NH4Cl) in rabbits. MATERIALS AND METHODS: Sixteen female, 6-month-old dwarf rabbits received the following three feeding regimens in a random order: complete feed without supplements = control; complete feed + 10 g NaCl/kg feed = NaCl; complete feed + 2.5 g NH4Cl/kg feed = NH4Cl. The diets were fed ad libitum over a period of 27 days without roughage. Water was provided ad libitum by a drinker. A 14-day wash-out-period (hay feeding) was performed between the different diets. Blood, faeces, and urine were collected at the beginning of each feeding period, after 21-day adaptation to the respective diet, and after the 3-day collection period. The following parameters were analysed: water and food intake as well as acid-base balance and mineral content in blood, urine, and faeces. RESULTS: NaCl supplementation numerically increased the daily water intake from 40.5 ± 14.4 ml/kg body weight (BW) (control) up to 49.5 ± 14.3 ml/kg BW and significantly increased the daily urine volume from 16.9 ± 7.8 ml/kg BW (control group) to 21.1 ± 7.4 ml/kg BW. The specific gravity of urine samples from NaCl supplementation decreased from 1.060 ± 0.008 to 1.044 ± 0.008. NH4Cl supplementation did not induce significant changes in urine pH, blood acid-base parameters, or calcium retention. Relative supersaturations (RSS) for calcium oxalate and calcium phosphate showed no significant changes after treatment. RSS for struvite increased from 360 ± 735 (after hay feeding) to 3312 ± 6188 on control feeding, 2910 ± 4913 with NaCl supplementation, and 3022 ± 6635 with NH4Cl supplementation (p < 0.05). CONCLUSIONS: NaCl supplementation significantly increased the urine volume and decreased its specific gravity. Therefore, NaCl supplementation might be an additional dietary treatment to increase the elimination of urine crystals in rabbits. NH4Cl supplementation did not induce acidification of the urine.

Sulfate but not thiosulfate reduces calculated and measured urinary ionized calcium and supersaturation: implications for the treatment of calcium renal stones.

BACKGROUND: Urinary sulfate (SO4(2-)) and thiosulfate (S2O3(2-)) can potentially bind with calcium and decrease kidney stone risk. We modeled the effects of these species on the concentration of ionized calcium (iCa) and on supersaturation (SS) of calcium oxalate (CaOx) and calcium phosphate (CaP), and measured their in vitro effects on iCa and the upper limit of stability (ULM) of these salts. METHODS: Urine data from 4 different types of stone patients were obtained from the Mayo Nephrology Clinic (Model 1). A second data set was obtained from healthy controls and hypercalciuric stone formers in the literature who had been treated with sodium thiosulfate (STS) (Model 2). The Joint Expert Speciation System (JESS) was used to calculate iCa and SS. In Model 1, these parameters were calculated as a function of sulfate and thiosulfate concentrations. In Model 2, data from pre- and post STS urines were analyzed. ULM and iCa were determined in human urine as a function of sulfate and thiosulfate concentrations. RESULTS: Calculated iCa and SS values for all calcium salts decreased with increasing sulfate concentration. Thiosulfate had no effect on these parameters. In Model 2, calculated iCa and CaOx SS increased after STS treatment, but CaP SS decreased, perhaps due to a decrease in pH after STS treatment. In confirmatory in vitro experiments supplemental sulfate, but not thiosulfate, significantly increased the calcium needed to achieve the ULM of CaP and tended to increase the oxalate needed to reach the ULM of CaOx. Sulfate also significantly decreased iCa in human urine, while thiosulfate had no effect. CONCLUSION: Increasing urinary sulfate could theoretically reduce CaOx and CaP stone risk. Although STS may reduce CaP stone risk by decreasing urinary pH, it might also paradoxically increase iCa and CaOx SS. As such, STS may not be a viable treatment option for stone disease.

Enteric hyperoxaluria secondary to small bowel resection: use of computer simulation to characterize urinary risk factors for stone formation and assess potential treatment protocols.

BACKGROUND AND PURPOSE: We used computer modeling to investigate the influence of physicochemical stone risk factors on urinary supersaturation (SS) of calcium oxalate (CaOx) in patients with severe hyperoxaluria, relative hypocalciuria, hypocitraturia, and CaOx nephrolithiasis after extensive small bowel resection, usually performed for Crohn's disease. We also simulated different treatment strategies, including oral calcium supplements and citrate, in such patients. MATERIALS AND METHODS: A baseline urine model was derived by consolidating data acquired by ourselves with those from another patient cohort. Calcium and oxalate excretions in this model were altered to obtain an extreme case. For comparison, additional models were based on published urine data from normal subjects (N) and idiopathic CaOx stone formers (SF). The Joint Expert Speciation System was used to simulate different urine situations based on reported compositional values. RESULTS: [Ca(2+)][Ox(2-)] ionic concentration products and SS(CaOx) are substantially higher in enteric hyperoxaluric patients than in N and SF, despite their relatively lower calcium excretions. Molar Ca:Ox ratios are substantially lower in enteric hyperoxalurics than in N and SF. Oral calcium supplements can reduce SS(CaOx), but monitoring is required to avoid exceeding a safe dosing threshold. A simple calculation can alert the clinician that this threshold is being approached or even exceeded. Increasing urinary pH and citrate decreases SS(CaOx) but not to the same extent as decreasing Ox excretion. CONCLUSIONS: Calcium supplements can help reduce stone risk in patients with severe enteric hyperoxaluria, but initial efforts should be directed toward reducing urinary oxalate by reducing dietary oxalate. Citrate therapy that increases both urine pH and urinary citrate provides an additional therapeutic benefit.

[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.

Therapeutic effects of potassium sodium hydrogen citrate on melamine-induced urinary calculi in China.

BACKGROUND: In 2008, a sharp increase of the number of children diagnosed with urinary calculi was observed in China, 9433 children were diagnosed as having melamine-induced urinary calculi at outpatient clinic in Beijing Children's Hospital. This study examined the therapeutic efficacy of potassium sodium hydrogen citrate (PSHC) used to treat melamine-induced urinary stones in Chinese children who consumed melamine-containing infant formula. METHODS: Seventy-two infants and children (average age (18.2 +/- 7.7) months) who were diagnosed with urinary calculi were randomly divided into three treatment groups using the SAS Plan program. Group 1 was given a low dose (1 g/d) of PSHC, group 2 was given high dose of PSHC (2 g/d) and group 3 was given no PSHC (control group). The dose of drug was adjusted according to the baseline urinary pH. This study analyzed the influence of the dose of PSHC, the age of patients, stone size and position, and urinary pH on the level of efficacy of PSHC (cured, effectively treated or not cured). RESULTS: After 1 - 6 months of therapy, 19 patients from group 1, five patients from group 2 and six patients from group 3 were cured. Five patients from group 1, five patients from group 2 and four patients from group 3 were effectively treated. There were significant differences in therapeutic efficacy between the two treatment doses after 3 and 6 months as measured by the increase in the successful expulsion rate and time of melamine-induced urinary calculi. After 6 months the mean time of expulsion of urinary calculi in groups 1 and 2 was significantly shorter than in the control group. CONCLUSIONS: PSHC can significantly increase the successful expulsion rate and time of melamine-induced urinary calculi. The therapeutic efficacy is affected by PSHC dose, treatment duration, calculi position, and urinary pH. There is no relationship between the therapeutic efficacy and the stone size or patient age.

Female stone disease: the changing trend.

This paper has attempted to assess the changes noted in the trends in the incidence and biochemical pattern of female urolithiasis patients during the period 1971-2008. A prospective descriptive clinical study was done on 8,590 stone patients belonging to both sexes treated at the urinary stone clinic. The incidence of stone disease among the two sexes was plotted. The various metabolic parameters including 24-h urine volume, urine calcium, phosphorus, uric acid, oxalate, magnesium, creatinine and citrate, serum creatinine, calcium, phosphorus, uric acid and magnesium and calculated parameter calcium:magnesium ratio were studied. The possible causes for the change in incidence of stone disease in the female sex were elucidated. Of the patients studied, 12.7% (1,091) were females. There was a definite increase in the incidence of female urolithiasis over the past 37 years (P < 0.001). There were significant variations in urine biochemical parameters. There was a definite increase in the excretion of urinary calcium over the years (P < 0.001). The excretion rate of oxalate in urine of females also increased steadily over the years (P < 0.001). The magnesium in urine of females reduced over the years (P < 0.001). Urinary citric acid has however shown an increase over the years (P < 0.001). Urinary excretion of phosphorus (P < 0.001) and urinary uric acid (P < 0.001) showed a decreasing trend. There was a considerable increase in the percentage of females with high calcium:magnesium ratio over the years (P < 0.001). There was a definite decrease in female patients with hypercalcemia over the years. Serum phosphorus and magnesium also increased significantly with the passage of time. Serum uric acid did not vary significantly through the years. The decrease in the excretion rate of magnesium which is inhibitory to stone genesis, together with the increased excretion of calcium and oxalate may have contributed to the increasing incidence of stone disease in females. This might be due to changes in living standards and dietary habits.

Calcium oxalate stone formation risk - a case of disturbed relative concentrations of urinary components.

BACKGROUND: Although afflicted with stone formation, urolithiasis patients often present with normal renal excretions of lithogenic and inhibitory substances. In this study, crystal formation is not interpreted as the result of urinary excretions simply exceeding the static limits of normal ranges but rather as the consequence of relative combinations of such parameters which convert urine into becoming potentially lithogenic. Our model embraces different triplet combinations of fundamental urinary risk factors for calcium oxalate (CaOx) crystallization, to characterize different levels of urinary stone formation risk. METHODS: Urinalyses and BONN-Risk-Indices (BRI) were determined for CaOx patients under home conditions, after 1 week of hospitalization, and for healthy controls. The relative urinary concentrations and interdependences of, inter alia, free ionized Ca (Ca2+), bound Ca (Ca b), and oxalic acid (OA) were compared. RESULTS: Three levels of CaOx formation risk can be distinguished: (I): low stone formation risk with an increase in (Ca2+) and concomitant decrease in (Ca b), while (OA) remains almost constant, BRI increases simultaneously; (II) moderate risk at (Ca2+)/(Ca b) approximately 1; and (III) high risk with decrease in (Ca2+)/(Ca b) and simultaneous increase in (OA). CONCLUSIONS: The proposed approach of urinalysis interpretation allows complementary strategy of identification of patterns of disturbed urinary composites leading to calculus formation.

Urinary macromolecular inhibition of crystal adhesion to renal epithelial cells is impaired in male stone formers.

BACKGROUND: Retention of microcrystals that form in tubular fluid could be a critical event in kidney stone formation. This study was performed to determine if urinary macromolecules from stone-forming (SF) individuals have reduced ability to inhibit crystal adhesion to renal cells. METHODS: A first morning whole urine (WU) sample was obtained from 24 SF subjects (17 males and 7 females) and 24 age-, race-, and sex-matched controls (C). An aliquot of urine was centrifuged and an ultrafiltrate (UF) free of macromolecules >10 kD and 10x concentrate (U(conc)) were prepared. RESULTS: Supplementing UF with increasing amounts of U(conc) to return the macromolecule concentration to 0.25x, 0.5x, or 1x of baseline progressively decreased crystal binding to cells. This effect was blunted in the male SF group compared to controls (P < 0.05, SF vs. C, for UF plus 0.25x macromolecules). No difference was apparent in the female groups. In order to identify responsible macromolecule(s), calcium oxalate monohydrate (COM) crystals were coated with U(conc) and adherent proteins then released and probed by Western blot. Coated COM crystals from male controls contained 3.5-fold more Tamm-Horsfall protein (THP) than SF subjects (P < 0.01). COM crystal coating with other proteins did not consistently differ between the groups. COM crystal coating by urinary prothrombin fragment 1 (UPTF1, P < 0.05) and crystal adhesion inhibitor (CAI) (P= 0.09) correlated with decreased crystal binding to cells, whereas coating with osteopontin (OPN) correlated with increased adhesion tendency (P < 0.05). CONCLUSION: Urinary macromolecules >10 kD coat COM crystals and block their adhesion to renal cells. This capacity appears to be blunted in male but not female SF individuals. Multiple urinary proteins may play a role in renal cell-urinary crystal interactions, and THP appears to be one of the more important ones.

[Study of crystalluria in diabetic patients]. / Etude de la cristallurie des sujets diabétiques.

INTRODUCTION: The incidence of diabetes, particularly non-insulin-dependent diabetes, is on the increase in industrialized and developing countries. The prevalence of renal stones in the diabetic population was recently estimated to be 21%, i.e. more than twice the prevalence of stones in the general population. Other studies have emphasized the high frequency of uric acid stones in this particular population. The present study was designed to verify whether diabetic patients present a particular type of crystalluria predisposing them to a high frequency of uric acid stones than other types of stones, which could allow detection of this risk and the proposal of therapeutic measures to prevent these stones. MATERIAL AND METHOD: The first morning urine of 208 diabetic patients was examined by polarized light microscopy to detect and identify crystalluria. Patients were distributed into 3 age-groups: less than 40 years, 40 to 59.9 years and 60 years or more. The results are expressed as the predominant crystalline species. RESULTS: The overall frequency of crystalluria was 29.8%, i.e. about one half that observed in calcium stones. However, the crystallogenic profile was very unusual, as 61.3% of cases of crystalluria consisted of purine. Uric acid crystalluria was twice as frequent in women than in men (66% vs 33.3%, p < 0.05). The mean pH of the urine of diabetic subjects was 5.5, i.e. significantly more acidic than that of normal subjects or patients with calcium stones. pH was negatively correlated with the patient's age, decreasing from 5.54 in patients younger than 40 to 5.3 in patients over the age of 60 (p < 0.05). The mean pH of crystalluric urine was significantly more acidic than that of crystal-free urine (pH 5.2 +/- 0.46 vs 5.5 +/- 0.67, p < 0.01). CONCLUSION: Diabetic patients have an acidic urinary pH which tends to decrease with age, predisposing to uric acid crystalluria, which is particularly frequent in women. The high prevalence of uric acid crystalluria and the high proportion of uric acid stones reported in diabetic women suggest that women are at greater risk than men of developing uric acid stones in the context of diabetes. The study of crystalluria could be useful to detect this risk and to propose preventive measures. Complementary studies are necessary to identify factors accounting for the increased risk of uric acid stones in diabetic women and to verify whether good glycaemic control can reduce the crystallogenic risk.

Urolithiasis in adults. Clinical and biochemical aspects.

Urolithiasis is a multifactorial recurrent disease of world-wide distribution in rural, urban, industrial and non-industrial regions. Changes in urinary pH is a risk factor especially with hyperuricosuria, hypercalciuria or hyperoxaluria. With recurrence, hypercalcuria and higher urinary oxalate levels are more frequent. Hypercalciuria and hyperuricosuria showed correlation with family history of stones. The ionic relations between various stone forming salts in urine of patients are opposite to that in controls and are well represented in stone composition. Obesity is a risk factor in both genders. Over eating a diet rich in all nutrients was associated with hyperuricosuria while a diet high only in fat was associated with other urinary disturbances. High protein and fat intake are risk factors. High or low calcium diet was associated with urolithiasis and supplemental calcium is not a risk factor. Potassium and magnesium citrate are potent in inhibiting the growth of stone fragments after extracorporeal shock wave lithotripsy. Whether in patients or normal subjects, drinking hard water should be avoided; tap water or low calcium content water is preferable. Seasonal variations in temperature affected urinary volume, pH and relative saturation of uric acid. To prevent recurrence, patients should maintain high fluid intake achieving a urine volume of 2 liters per day.

Importance of magnesium in absorption and excretion of oxalate.

INTRODUCTION: Magnesium treatment for calcium oxalate urolithiasis is discussed controversially. The aim of this study was to investigate the influence of magnesium supplementation on the oxalate absorption. MATERIALS AND METHODS: The [13C2]oxalate absorption test was always performed three times in 6 healthy volunteers under standardized conditions, with one 10-mmol magnesium supplement together with the labeled oxalate and with two 10-mmol magnesium supplements given in 12-hour intervals. RESULTS: The mean intestinal oxalate absorption under standard conditions was 8.6 +/- 2.83%. The oxalate absorption with one 10-mmol magnesium supplement was 5.2 +/- 1.40% and with two supplements 5.5 +/- 1.62%. Both decreases were statistically significant relative to the standard test, however, not significantly different from each other. CONCLUSIONS: The results show that magnesium administration decreases the oxalate absorption, when magnesium is taken together with oxalate. However, magnesium administration does not decrease the oxalate absorption, when magnesium and oxalate intake differ by 12 h.

Stone forming risk of calcium citrate supplementation in healthy postmenopausal women.

PURPOSE: We evaluated the effect of calcium citrate supplementation alone or in combination with potassium citrate on the stone forming propensity in healthy postmenopausal women. MATERIALS AND METHODS: A total of 18 postmenopausal women without stones underwent a randomized trial of 4 phases comprised of 2 weeks of treatment with placebo, calcium citrate (400 mg calcium twice daily), potassium citrate (20 mEq twice daily), and calcium citrate and potassium citrate (at same doses). During the last 2 days of each phase urine was collected in 24-hour pools for complete stone risk analysis. RESULTS: Compared to placebo, calcium citrate increased urinary calcium and citrate but decreased urinary oxalate and phosphate. Urinary saturation of calcium oxalate, brushite and undissociated uric acid did not change. Potassium citrate decreased urinary calcium, and increased urinary citrate and pH. It decreased urinary saturation of calcium oxalate and undissociated uric acid, and did not change the saturation of brushite. When calcium citrate was combined with potassium citrate, urinary calcium remained high, urinary citrate increased even further and urinary oxalate remained reduced from the calcium citrate alone, thereby marginally decreasing the urinary saturation of calcium oxalate. Urinary pH increased, decreasing urinary undissociated uric acid. The increase in pH increased the saturation of brushite despite the decrease in urinary phosphorus. CONCLUSIONS: Calcium citrate supplementation does not increase the risk of stone formation in healthy postmenopausal women. The co-administered potassium citrate may provide additional protection against formation of uric acid and calcium oxalate stones.

Phyllanthus niruri normalizes elevated urinary calcium levels in calcium stone forming (CSF) patients.

Phyllanthus niruri is a plant used for years in Brazil to treat urinary calculi. We prospectively evaluated the effect of P. niruri intake on 24 h urinary biochemical parameters in an attempt to assess its in vivo effect in calcium stone forming (CSF) patients. A total of 69 CSF patients (39 males and 30 females, 38+/-8 years old) were randomized to take either P. niruri ( n=33) (450 mg capsules, td) or placebo ( n=36) for 3 months. Blood calcium, uric acid, citrate, magnesium, oxalate, sodium and potassium were determined at baseline and at the end of the study. A subset analysis was made in patients classified according to the presence of metabolic abnormalities (hypercalciuria, hyperuricosuria, hyperoxaluria, hypocitraturia and hypomagnesiuria). Overall, there were no significant differences in the mean values of urinary parameters between the urine samples before and after P. niruri intake, except for a slight reduction in mean urinary magnesium after P. niruri, which was within the normal range. However, in the subset analysis, we observed that P. niruri induced a significant reduction in the mean urinary calcium in hypercalciuric patients (4.8+/-1.0 vs 3.4+/-1.1 mg/kg/24 h, P<0.05). In this short-term follow-up, no significant differences in calculi voiding and/or pain relief between the groups taking P. niruri or the placebo were detected. Our data suggest that P. niruri intake reduces urinary calcium based on the analysis of a subset of patients presenting with hypercalciuria. Larger trials including primary hypercalciuric stone formers should be performed in order to confirm these findings and to determine the possible clinical consequences of urinary calcium reduction during P. niruri administration.

Changes in urinary parameters after oral administration of potassium-sodium citrate and magnesium oxide to prevent urolithiasis.

OBJECTIVES: To examine urinary parameters among normal individuals and patients with calcium oxalate (CaOx) stones after oral administration of potassium-sodium citrate (KNa-Cit) and magnesium oxide (MgO). Urinary citrate and magnesium have been known as the inhibitors of CaOx stone formation. Supplementation with potassium-magnesium citrate prevents the recurrence of CaOx stones. METHODS: Twenty-five male volunteers aged 21 to 42 years without a history of urinary stones were given either KNa-Cit or MgO, or both. Fourteen patients with recurrent CaOx stones were also given both supplements, and 24-hour urine samples were collected to determine the urinary parameters. RESULTS: The administration of both KNa-Cit and MgO to the normal individuals increased the excretion of citrate, magnesium, and potassium by 70.0%, 44.2%, and 50.0%, respectively. These parameters increased less when KNa-Cit or MgO was administered individually. After administration of both supplements to the patients with stones, the citrate, magnesium, and potassium levels increased by 62.1%, 63.3%, and 25.3%, respectively, and oxalate decreased by 66.5%. In both normal individuals and patients, the ion activity product index of CaOx decreased significantly more after administration of the combination than with either compound alone or before administration. CONCLUSION: The combination of KNa-Cit and MgO is more effective than either supplement alone in inhibiting the crystallization of CaOx stones. The combination may improve the urinary parameters of patients with stones accompanied by hypocitraturia and/or hypomagnesuria.

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.