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Rationale & Objective: Most previous studies of the relationship between urinary factors and kidney stone risk have either assumed a linear effect of urinary parameters on kidney stone risk or implemented arbitrary thresholds suggesting biologically implausible "all-or-nothing" effects. In addition, little is known about the hierarchy of effects of urinary factors on kidney stone risk. This study evaluated the independent associations between urine chemistries and kidney stone formation and examined their magnitude and shape., Study Design: Prospective cohort study., Setting & Participants: We analyzed 9,045 24-hour urine collections from 6,217 participants of the Health Professionals Follow-Up Study and Nurses' Health Studies I and II., Exposure: Urine volume and pH, and concentrations of calcium, citrate, oxalate, potassium, magnesium, uric acid, phosphorus, and sodium., Outcome: Incident symptomatic kidney stones., Analytical Approach: Multivariable logistic regression analysis incorporating restricted cubic splines to explore potentially nonlinear relationships between urinary factors and the risk of forming a kidney stone. Optimal inflection point analysis was implemented for each factor, and dominance analysis was performed to establish the relative importance of each urinary factor., Results: Each urinary factor was significantly associated with stone formation except for urine pH. Higher urinary levels of calcium, oxalate, phosphorus, and sodium were associated with a higher risk of stone formation whereas higher urine volume, uric acid, citrate, potassium, and magnesium were associated with a lower risk. The relationships were substantially linear for urine calcium, uric acid, and sodium. By contrast, the magnitudes of the relationships were modestly attenuated at levels above the inflection points for urine oxalate, citrate, volume, phosphorus, potassium, and magnesium. Dominance analysis identified 3 categories of factors' relative importance: higher (calcium, volume, and citrate), intermediate (oxalate, potassium, and magnesium), and lower (uric acid, phosphorus, and sodium)., Limitations: Predominantly White participants, lack of information on stone composition., Conclusions: Urine chemistries have complex relationships and differential relative associations with the risk of kidney stone formation., Plain-Language Summary: Kidney stones are common and likely to recur. Certain urinary factors play a role in the development of stones, but their independent roles, relative importance, and shapes of association with stone formation are not well-characterized. We analyzed 24-hour urine collections from individuals with and without kidney stones. Stones were less likely in those with higher urine volume, citrate, potassium, magnesium, and uric acid and were more likely in those with higher calcium, oxalate, phosphorus, and sodium. The acidity of the urine was not related to stones. The urinary parameters showed different degrees of relative importance, with calcium, volume, and citrate being greatest. All parameters exhibited a linear or close-to-linear shape of association with stone formation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aims: Hypercalciuria is the most common identifiable risk factor predisposing to CaOx stone formation. Increased oral magnesium intake may lead to decreased CaOx stone formation by binding intestinal Ox leading to decreased absorption and/or binding urinary Ox to decrease urinary supersaturation. This study assessed the effect of oral magnesium on 24-h urine ion excretion, supersaturation, and kidney stone formation in a genetic hypercalciuric stone-forming (GHS) rat model of human idiopathic hypercalciuria., Methods: When fed the oxalate precursor, hydroxyproline, every GHS rat develops CaOx stones. The GHS rats, fed a normal calcium and phosphorus diet supplemented with hydroxyproline to induce CaOx, were divided into three groups of ten rats per group: control diet with 4.0 g/kg MgO, low MgO diet (0.5 g/kg), and high MgO diet (8 g/kg). At 6 weeks, 24-h urines were collected, and urine chemistry and supersaturation were determined. Stone formation was quantified., Results: The GHS rats fed the low and high Mg diets had a significant reduction and increase, respectively, in urinary Mg compared to those fed the control diet. Dietary Mg did not alter urine Ca excretion while the low Mg diet led to a significant fall in urinary Ox. Urine supersaturation with respect to CaOx was significantly increased with low Mg, whereas urine supersaturation was significantly decreased with high Mg. There was no effect of dietary Mg on stone formation within 6 weeks of treatment., Conclusion: Dietary magnesium decreases urine supersaturation but not CaOx stone formation in GHS rats., (© 2024 S. Karger AG, Basel.)

Introduction: Kidney stone formers can have higher oxalate and phosphate salt amounts in their urine than healthy people and we hypothesized that its acidification may be useful. The study aims to compare results of urine concentrations of calcium, magnesium, and inorganic phosphorus in the midstream portion of first voided morning urine samples without (FMU) and with post-collection acidification (FMUa) in kidney stone patients., Materials and Methods: This is a prospective single center study. A total of 138 kidney stone patients with spot urine samples were included in the study. Urine concentrations of calcium, magnesium and inorganic phosphorus were measured with and without post-collection acidification. Acidification was performed by adding 5 µL of 6 mol/L HCl to 1 mL of urine., Results: The median age (range) of all participants was 56 (18-87) years. The median paired differences between FMU and FMUa concentrations of calcium, magnesium, and inorganic phosphorus were: - 0.040 mmol/L, 0.035 mmol/L, and 0.060 mmol/L, respectively. They were statistically different: P < 0.001, P < 0.001, P = 0.004, respectively. These differences are not clinically significant because biological variations of these markers are much higher., Conclusions: No clinically significant differences in urinary calcium, magnesium, and inorganic phosphorus concentrations between FMU and FMUa in patients with kidney stones were found., Competing Interests: Potential conflict of interest None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Urinary stones tend to cluster in families. Of the known risk factors, evidence is strongest for heritability of urinary calcium excretion. Recent studies suggest that other stone risk factors may have heritable components including urinary pH, citrate and magnesium excretion, and circulating vitamin D concentration. Several risk factors assumed purely environmental may also have heritable components, including dietary intake and thirst. Thus, future studies may reveal that genetics plays an even stronger role in urinary stone pathogenesis than previously known.

Purpose: Magnesium plays numerous vital roles in human's body. It is known as a protective factor in stone formation by binding to oxalate in the intestinal and urinary system, and decreasing its absorption and crystallization, respectively. Due to controversies about the association between the 24-h urine magnesium and other urine metabolites in different studies, this study was designed to find a clear answer to this question., Methods: In this retrospective cross-sectional study, data from 24-h urinalysis of the calcium stone-forming (CSF) patients were assessed. The correlation between 24-h urine (24-U) magnesium to creatinine ratio (Mg/Cr) with other 24-U metabolites to creatinine ratio was assessed, using Spearman correlation test. The association between 24-U magnesium and 24-U oxalate was also studied in a multivariate logistic regression model., Results: Among 965 patients, the level of Mg/Cr showed a direct association with all other 24-U metabolite to Cr ratio (p-value < 0.001 for all analyses). The result of multivariate regression analysis showed that the higher quartile of 24-U oxalate (> 47 mg/24 h) increased the odds of 24-U magnesium more than 75 mg/24 h (data median) (OR 1.89, 95% CI 1.14-3.13) comparing with the lower quartile of 24-U oxalate (≤ 26 mg/24 h)., Conclusions: In a routine dietary habit, since rich sources of magnesium contain a high amount of oxalate at the same time, it is not surprising that magnesium level in 24-h urinalysis showed a direct association with 24-h urine oxalate.

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., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Kidney stone disease is characterized by a relatively high rate of recurrence. In our study we analyzed the association between relative supersaturation and the risk of stone recurrence. Additionally, we examined the association between the risk of recurrence and changes in relative supersaturation and urinary composition after 1 week of medical treatment., Materials and Methods: We performed a post hoc analysis of data from a previously published randomized controlled trial comparing the effect of 2 diets in 120 men with recurrent calcium oxalate stones and hypercalciuria. Baseline and followup 24-hour urine parameters were used to calculate the relative supersaturation of calcium oxalate, calcium phosphate and uric acid using the EQUIL2, JESS and LithoRisk computer programs. Cox models were used to calculate the estimated association between each baseline relative supersaturation, and 1-week changes and the risk of recurrence during followup., Results: During a 5-year followup 35 patients (34%) experienced recurrence. A reduction in calcium oxalate relative supersaturation at 1 week was significantly associated with a lower risk of recurrence using the EQUIL2 calculation (for every 10% reduction from baseline HR 0.92, 95% CI 0.86-1.00, p = 0.044). However, there was no association for relative supersaturation calculated by other methods or for the relative supersaturation of other salts. Changes in the 24-hour urine excretion of citrate, potassium and magnesium were significantly associated with a risk of recurrence., Conclusions: In recurrent stone formers with hypercalciuria baseline values and changes in the relative supersaturation of calcium oxalate may be associated with the risk of recurrence. Changes in urinary citrate, potassium and magnesium following dietary intervention may also be predictive., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Intermittent fasting and curtailing water intake for extended periods were likely common in Paleolithic times. Today it occurs for religious and dietary reasons. This restriction in intake should cause a decrease in the urine flow rate while raising the concentration of certain substances in urine to the point of precipitation. In this study we measured the risk of CaHPO 4 precipitation following 18 hours of food and water deprivation., Materials and Methods: Urine samples were periodically collected from 15 healthy subjects who fasted and abstained from drinking any liquid for 18 hours. The urine constituents Ca 2+ , HPO 4 2- and pH involved in CaHPO 4 formation were measured at various times throughout the fasting day. A comparison was made with control data, which consisted of diurnal urine collections taken throughout a separate nonfasting day prior to the fasting day., Results: The mean ± SEM urine flow rate decreased significantly from 0.93 ± 0.1 ml per minute in the control group to 0.37 ± 0.05 ml per minute in the fasting group (p <0.05). Mean Na + and Ca 2+ excretion rates decreased significantly from 127 ± 12 to 54 ± 13 μmol per minute and from 3.2 ± 0.4 to 0.80 ± 0.21, respectively. Mean urinary Na + and Ca 2+ concentrations also decreased from 161 ± 11.6 to 122 ± 16.0 mmol/l and from 3.7 ± 0.5 to 2.0 ± 0.55, respectively. Urinary pH and the concentration of phosphate, citrate and magnesium were not significantly affected., Conclusions: Although the steady decrease in the urine flow rate was statistically significant during 18 hours of food and water deprivation, there was no evidence that the calculated risk of CaHPO 4 precipitation in the healthy subjects had increased., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Phyllanthus niruri (P.niruri) or stone breaker is a plant commonly used to reduce stone risk, however, clinical studies on this issue are lacking., Objective: To prospectively evaluate the effect of P. niruri on the urinary metabolic parameters of patients with urinary lithiasis., Materials and Methods: We studied 56 patients with kidney stones <10mm. Clinical, metabolic, and ultrasonography assessment was conducted before (baseline) the use of P. niruri infusion for 12-weeks (P. niruri) and after a 12-week (wash out) Statistical analysis included ANOVA for repeated measures and Tukey's/McNemar´s test for categorical variables. Significance was set at 5%., Results: Mean age was 44±9.2 and BMI was 27.2±4.4kg/m2. Thirty-six patients (64%) were women. There were no significant changes in all periods for anthropometric and several serum measurements, including total blood count, creatinine, uric acid, sodium, potassium, calcium, urine volume and pH; a significant increase in urinary potassium from 50.5±20.4 to 56.2±21.8 mg/24-hour (p=0.017); magnesium/creatinine ratio 58±22.5 to 69.1±28.6mg/ gCr24-hour (p=0.013) and potassium/creatinine ratio 39.3±15.1 to 51.3±34.7mg/gCr24- hour (p=0.008) from baseline to wash out. The kidney stones decreased from 3.2±2 to 2.0±2per patient (p<0.001). In hyperoxaluria patients, urinary oxalate reduced from 59.0±11.7 to 28.8±16.0mg/24-hour (p=0.0002), and in hyperuricosuria there was a decrease in urinary uric acid from 0.77±0.22 to 0.54±0.07mg/24-hour (p=0.0057)., Conclusions: P.niruri intake is safe and does not cause significant adverse effects on serum metabolic parameters. It increases urinary excretion of magnesium and potassium caused a significant decrease in urinary oxalate and uric acid in patients with hyperoxaluria and hyperuricosuria. The consumption of P.niruri contributed to the elimination of urinary calculi., Competing Interests: Conflict of interest: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Objective: This study evaluated the role of body mass index (BMI) and dietary potential renal acid load (PRAL) with urinary saturation for calcium oxalate (US-CaOx), calcium phosphate (US-CaP) and uric acid (US-UA) in renal stone formers., Materials and Methods: A retrospective analysis was conducted of laboratory data collected on 442 renal stone-forming patients. Demographic information, BMI and 24 h urinary samples were collected from patients on their regular diets. PRAL was calculated as the Load of Acid to Kidney Evaluation (LAKE) score through a short questionnaire., Results: Urinary risk factors, but also inhibitors of calcium stone formation such as magnesium, tended to increase in relation to BMI (p = .000). Urinary pH (p = .002) and ammonium/sulfate ratio (p = .000) were negatively related to BMI. This resulted in a positive correlation between BMI and US-UA (p = .000), whereas US-CaOx and US-CaP were not influenced by BMI. LAKE score was positively correlated with US-CaOx (p = .022) and US-CaP (p = .000) as a consequence of the inverse relationship between LAKE score and citrate (p = .000). Multiple linear regression analysis identified BMI (p = .009) and male gender (p = .002) as independent predictors of US-UA, and LAKE score (p = .004) and age (p = .001) as independent predictors of US-CaP., Conclusions: BMI, which depends on excessive intake of energy from food, is not related to an increased biochemical risk of calcium stone formation, which is more dependent on the renal acid load of the diet. In contrast, obesity is associated with an increased risk of uric acid stone formation due to insulin resistance, impaired ammoniagenesis and low urinary pH.

It is a fact that recurrence of urinary stones is a common medical problem. One of the key factors used in determining the risk of urinary stone-formation is the urine relative saturation in the major constituents of lithiasis. Nomograms were developed in the 1970's to estimate the relative saturation of urine. We present here easy-to-use mathematical equations derived from these nomograms. These equations can be integrated directly in the LIS of any laboratories, and can be used as a tool in the treatment and prevention of recurrent stone-formation., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of demographics including age and sex on excretion of 4 key urinary factors (calcium [Ca], magnesium [Mg], oxalate and uric acid [UA]) related to kidney stone risk., Methods: Twenty-four-hour urine samples were collected from non-Hispanic white sibships in Rochester, MN. Height, weight, blood pressure, serum creatinine, and cystatin C were measured. Diet was assessed using the Viocare food frequency questionnaire. Effects of demographics and dietary elements on urinary excretions were evaluated in univariate, multivariate, and interaction models that included age, sex, and body mass index (BMI)., Results: Samples were available from 709 individuals. In multivariate models, sex was a significant predictor of all 4 urinary factors, age was significant for all but UA excretion, and serum creatinine was significant only for Ca and Mg excretion (P <.05). BMI or weight positively correlated with Mg, oxalate, and UA excretion (P <.05). Use of a thiazide diuretic (lower) and dietary protein (higher) were associated with Ca excretion, whereas dietary Ca was associated with higher Mg excretion. Urinary UA excretion increased with animal protein intake and cystatin C estimated glomerular filtration rate (eGFR) and was lower with concurrent loop diuretic use. Significant interaction effects on urinary UA excretion were observed for loop diuretic use and sex, eGFR and sex, age and animal protein intake, and BMI and eGFR (P <.05)., Conclusion: Age and sex influence excretion of key urinary factors related to kidney stone risk and should be taken into account when evaluating kidney stone patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Idiopathic hypercalciuria (IH) is a common familial trait among patients with calcium nephrolithiasis. Previously, we have demonstrated that hypercalciuria is primarily due to reduced renal proximal and distal tubule calcium reabsorption. Here, using measurements of the clearances of sodium, calcium, and endogenous lithium taken from the General Clinical Research Center, we test the hypothesis that patterns of segmental nephron tubule calcium reabsorption differ between the sexes in IH and normal subjects. When the sexes are compared, we reconfirm the reduced proximal and distal calcium reabsorption. In IH women, distal nephron calcium reabsorption is decreased compared to normal women. In IH men, proximal tubule calcium reabsorption falls significantly, with a more modest reduction in distal calcium reabsorption compared to normal men. Additionally, we demonstrate that male IH patients have lower systolic blood pressures than normal males. We conclude that women and men differ in the way they produce the hypercalciuria of IH, with females reducing distal reabsorption and males primarily reducing proximal tubule function., (Copyright © 2015 the American Physiological Society.)

Background and Objectives: Kidney stones and their risk factors aggregate in families, yet few studies have systematically estimated heritabilities and genetic correlations of the numerous urinary traits associated with risk of kidney stones., Design, Setting, Participants, & Measurements: Twenty-four-hour urine samples were collected from the Genetic Epidemiology Network of Arteriopathy cohort of families in Rochester, Minnesota, to measure urinary determinants of supersaturation. Diet was assessed using the Viocare food frequency questionnaire. Heritabilities and genetic correlations among the urinary traits were estimated using variance components methods., Results: Samples were available from 811 individuals (344 men, 467 women; mean age 66 ± 9 years). Age, sex, and weight were significantly correlated with the majority of urinary traits. Many urine excretions (calcium, magnesium, citrate excretion) had strong evidence for heritability (P<0.01) both before and after adjusting for the identified covariates. Among significantly heritable urinary traits, genetic factors explained 20%-36% of interindividual variation after adjustment for covariates. Urinary calcium excretion was significantly genetically correlated with urinary magnesium and with urinary citrate excretion (P<0.05). Although eGFR influenced many urinary traits, controlling for eGFR did not greatly affect estimated heritabilities., Conclusions: Evidence from this cohort suggests a strong heritable component to many urinary nephrolithiasis risk factors. Further study of genetic influences on urinary traits relevant for kidney stone pathogenesis is warranted.

Background: The objective of this study is to determine in a case series (four patients) how calcified deposits in renal papillae are associated with the development of calcium oxalate monohydrate (COM) papillary calculi., Methods: From the recently collected papillary calculi, we evaluated retrospectively patients, subjected to retrograde ureteroscopy, with COM papillary lithiasis., Results: The COM papillary calculi were found to result from subepithelial injury. Many of these lesions underwent calcification by hydroxyapatite (HAP), with calculus morphology and the amount of HAP in the concave zone dependent on the location of the calcified injury. Most of these HAP deposits grew, eroding the epithelium covering the renal papillae, coming into contact with urine and starting the development of COM calculi. Subepithelial HAP plaques may alter the epithelium covering the papillae, resulting in the deposit of COM crystals directly onto the epithelium. Tissue calcification depends on a pre-existing injury, the continuation of this process is due to modulators and/or crystallization inhibitors deficiency., Conclusions: Since calculus morphology and the amount of detected HAP are dependent on the location and widespread of calcified injury, all types of papillary COM calculi can be found in the same patient. All patients had subepithelial calcifications, with fewer papillary calculi, demonstrating that some subepithelial calcifications did not further evolve and were reabsorbed. A high number of subepithelial calcifications increases the likelihood that some will be transformed into COM papillary calculi.

Background: Homoscedasticity (constant variance over axes or among statistical factors) is an integral assumption of most statistical analyses. However, a number of empirical studies in model organisms and humans demonstrate significant differences in residual variance (that component of phenotype unexplained by known factors) or intra-individual variation among genotypes. Our work suggests that renal traits may be particularly susceptible to randomization by genetic and non-genetic factors, including endogenous variables like age and weight., Methods: We tested associations between age, weight and intra-individual variation in urinary calcium, citrate, chloride, creatinine, potassium, magnesium, sodium, ammonium, oxalate, phosphorus, sulfate, uric acid and urea nitrogen in 9,024 male and 6,758 female kidney stone patients. Coefficients of variation (CVs) were calculated for each individual for each solute from paired 24-hour urines. Analysis of CVs was corrected for inter-measurement collection variance in creatinine and urine volume. CVs for sodium and urea nitrogen were included to correct for dietary salt and protein., Results: Age was positively associated with individual CVs for calcium and negatively associated with CVs for potassium, ammonium and phosphorus (p(FDR) < 0.01). Weight was associated with CVs for creatinine, magnesium and uric acid, and negatively associated with CVs for calcium, potassium and oxalate (p(FDR) < 0.05)., Conclusion: Intra-individual variation changes over age and weight axes for numerous urinary solutes. Changing residual variance over age and weight could cause bias in the detection or estimation of genetic or environmental effects. New methodologies may need to account for such residual unpredictability, especially in diverse collections., (Copyright © 2013 S. Karger AG, Basel.)

Introduction: Even though dehydration could aggravate formation of urinary calculi, the effects of fluid and food restriction on calculus formation is not thoroughly defined. The purpose of this study is to evaluate the effects of fluid and food restriction in Ramadan fasting on urinary factors in kidney and urinary calculus formation., Materials and Methods: Fifty-seven men aged 30 to 55 years old, including 37 recurrent calcium calculus formers and 20 with no history of kidney calculi were evaluated for blood tests, ultrasonography investigations, urinalysis, urine culture, and also 24-hour urine collection test. Metabolites including calcium, oxalate, citrate, uric acid, magnesium, phosphate, potassium, sodium, and creatinine were measured before and during Ramadan fasting. The values of calculus-precipitating solutes as well as inhibitory factors were documented thoroughly., Results: Total excretion of calcium, phosphate, and magnesium in 24-hour urine and also urine volume during fasting were significantly lower than those in the nonfasting period. Urine concentration of calcium during fasting was significantly lower than nonfasting (P < .001). Urine concentrations of uric acid, citrate, phosphate, sodium, and potassium during fasting were significantly higher than nonfasting. Uric acid supersaturation was accentuated, and calcium phosphate supersaturation was decreased significantly during fasting. There was no significant increase in calcium oxalate supersaturation during the fasting period., Conclusions: Fasting during Ramadan has different effects on total excretion and concentrations of urinary precipitate and inhibitory factors contributing to calculus formation. We did not find enough evidence in favor of increased risks of calculus formation during Ramadan fasting.

The pathogenesis of calcium urolithiasis involves complex interactions of urinary promoters and inhibitors of crystallization. A variety of risk formulas have been established to approximate these interactions for clinical evaluation, and the aim of our study was to determine their usefulness as predictors of stone formation. The study cohort comprised 126 patients (63 boys and 63 girls) aged 6.7-18 years (mean age 14.1 +/- 2.9 years) with calcium urolithiasis (61 with chemically confirmed calcium oxalate stones and 65 children with a strong clinical suspicion of this type of urolithiasis). Of these, 36 children were classified as recurrent stone-formers, whereas the remaining 90 had experienced only one stone episode. The values obtained were compared to those of a control group of 60 age- and gender- matched healthy children. A number of crystallization risk indices were calculated from analytes obtained in 24-h urine: calcium/magnesium ratio (Ca/Mg), calcium/citrate ratio (Ca/Cit), (calcium x oxalate)/(magnesium x citrate) ratio (CaOx/MgCit), relative urinary CaOx supersaturation (RS(CaOx)), CaOx activity product index (AP(CaOx)), and standardized CaOx activity product index (AP(CaOx stand)). All indices, except for the AP(CaOx) index, were significantly higher in stone-formers than in the controls. The Ca/Mg, Ca/Cit, CaOx/MgCit, AP(CaOx), and AP(CaOx stand) indices were significantly higher in recurrent stone-formers than in first-episode ones. However, the determination of precise cutoffs between pathological and non-pathological values was problematic due to a considerable overlap of individual values. Based on our results, we conclude that calculation of the majority of risk indices may play a rather supplementary role in the evaluation of children with calcium urolithiasis.

Background and Objectives: Higher levels of urinary oxalate substantially increase the risk of calcium oxalate kidney stones. However, the determinants of urinary oxalate excretion are unclear. The objective was to examine the impact of dietary factors, age, body size, diabetes, and urinary factors on 24-h urinary oxalate., Design, Setting, Participants, and Measurements: We conducted a cross-sectional study of 3348 stone forming and non-stone-forming participants in the Health Professionals Follow-up Study (men), the Nurses' Health Study (older women), and the Nurses' Health Study II (younger women)., Results: Median urinary oxalate was 39 mg/d in men, 27 mg/d in older women, and 26 mg/d in younger women. Participants in the highest quartile of dietary oxalate excreted 1.7 mg/d more urinary oxalate than participants in the lowest quartile (P trend 0.001). The relation between dietary and urinary oxalate was similar in individuals with and without nephrolithiasis. Participants consuming 1000 mg/d or more of vitamin C excreted 6.8 mg/d more urinary oxalate than participants consuming <90 mg/d (P trend < 0.001). Body mass index, total fructose intake, and 24-h urinary potassium, magnesium, and phosphorus levels also were positively associated with urinary oxalate. Calcium intake and age were inversely associated with urinary oxalate. After adjustment for body size, participants with diabetes excreted 2.0 mg/d more urinary oxalate than those without diabetes (P < 0.01)., Conclusions: The impact of dietary oxalate on urinary oxalate appears to be small. Further investigation of factors influencing urinary oxalate may lead to new approaches to prevent calcium kidney stones.

The evaluation of metabolic risk factor in children with renal stone disease is the basis of medical treatment aimed at preventing recurrent stone events and the growth of preexisting calculi. In this retrospective study, we evaluated the metabolic risk factors and clinical and family histories of 90 children with kidney stone disease who had been referred to our institution and subjected to clinical tests using a standardized protocol. The mean age of our pediatric patients was 10.7 years, and the male:female ratio was 1.14:1.0. Biochemical abnormalities were found in 84.4% of all cases. A single urine metabolic risk factor was present in 52.2% (n = 47) of the patients, and multiple risk factors were present in the remaining 31.1% (n = 28). Idiopathic hypercalciuria (alone or in combination) and hypocitraturia (alone or in combination) were the most frequent risk factors identified in 40 and 37.8% of these patients, respectively. Renal colic or unspecified abdominal pain were the most frequent forms of presentation (76.9%), with 97.5% of stones located in the upper urinary tract. In most patients, stone disease was confirmed by renal ultrasonography (77%). A positive family history in first-degree and second-degree relatives was found in 46.2 and 32.5% of the cases, respectively. We conclude that specific urine metabolic risk factors are found in most children with kidney stones and that hypocitraturia is as frequent as hypercalciuria. Very often there is a positive family history of renal stone disease in first- and second-degree relatives.

In order to compare the effects of several experimental renal calcium oxalate stones formation models in rats and to find a simple and convenient model with significant effect of calcium oxalate crystals deposition in the kidney, several rat models of renal calcium oxalate stones formation were induced by some crystal-inducing drugs (CID) including ethylene glycol (EG), ammonium chloride (AC), vitamin D(3)[1alpha(OH)VitD(3), alfacalcidol], calcium gluconate, ammonium oxalate, gentamicin sulfate, L-hydroxyproline. The rats were fed with drugs given singly or unitedly. At the end of experiment, 24-h urines were collected and the serum creatinine (Cr), blood urea nitrogen (BUN), the extents of calcium oxalate crystal deposition in the renal tissue, urinary calcium and oxalate excretion were measured. The serum Cr levels in the stone-forming groups were significantly higher than those in the control group except for the group EG+L-hydroxyproline, group calcium gluconate and group oxalate. Blood BUN concentration was significantly higher in rats fed with CID than that in control group except for group EG+L-hydroxyproline and group ammonium oxalate plus calcium gluconate. In the group of rats administered with EG plus Vitamin D(3), the deposition of calcium oxalate crystal in the renal tissue and urinary calcium excretion were significantly greater than other model groups. The effect of the model induced by EG plus AC was similar to that in the group induced by EG plus Vitamin D(3). EG plus Vitamin D(3) or EG plus AC could stably and significantly induced the rat model of renal calcium oxalate stones formation.

Background: Greater body mass index (BMI) is a risk factor for kidney stones. However, the relation between BMI and the urinary excretion of many lithogenic factors remains unclear., Methods: We studied urine pH, urine volume, and 24-hour urinary excretion of calcium, oxalate, citrate, uric acid, sodium, magnesium, potassium, phosphate, and creatinine in stone-forming and non-stone-forming participants in the Health Professionals Follow-Up Study (599 stone-forming and 404 non-stone-forming men), Nurses' Health Study (888 stone-forming and 398 non-stone-forming older women), and Nurses' Health Study II (689 stone-forming and 295 non-stone-forming younger women). Each cohort was divided into quintiles of BMI. Tests of linear trend were conducted by 1-way analysis of variance. Linear regression models were adjusted for age, history of stone disease, dietary intake, and urinary factors., Results: Participants with greater BMIs excreted more urinary oxalate (P for trend

Metabolic evaluation of stone-forming (SF) patients is based on the determination of calcium, oxalate, citrate, uric acid and other parameters in 24-h urine samples under a random diet. A reliable measurement of urinary oxalate requires the collection of urine in a receptacle containing acid preservative. However, urinary uric acid cannot be determined in the same sample under this condition. Therefore, we tested the hypothesis that the addition of preservatives (acid or alkali) after urine collection would not modify the results of those lithogenic parameters. Thirty-four healthy subjects (HS) were submitted to two non-consecutive collections of 24-h urine. The first sample was collected in a receptacle containing hydrochloric acid (HCl 6 N) and the second in a dry plastic container, with HCl being added as soon as the urine sample was received at the laboratory. Additionally, 34 HS and 34 SF patients collected a spot urine sample that was divided into four aliquots, one containing HCl, another containing sodium bicarbonate (NaHCO(3 )5 g/l), and two others in which these two preservative agents were added 24 h later. Urinary oxalate, calcium, magnesium, citrate, creatinine and uric acid were determined. Urinary parameters were also evaluated in the presence of calcium oxalate or uric acid crystals. Mean values of all urinary parameters obtained from previously acidified 24-h urine samples did not differ from those where acid was added after urine collection. The same was true for spot urine samples, with the exception of urinary citrate that presented a slight albeit significant change of 5.9% between samples in HS and 3.1% in SF. Uric acid was also not different between pre- and post-alkalinized spot urine samples. The presence of crystals did not alter these results. We concluded that post-delivery acidification or alkalinization of urine samples does not modify the measured levels of urinary oxalate, calcium, magnesium, creatinine and uric acid, and that the change on citrate was not relevant, hence allowing all parameters to be determined in a single urine sample, thus avoiding the inconvenience and cost of multiple 24-h urine sample collections.

The ethanolic extract of Asparagus racemosus Willd. was evaluated for its inhibitory potential on lithiasis (stone formation), induced by oral administration of 0.75% ethylene glycolated water to adult male albino Wistar rats for 28 days. The ionic chemistry of urine was altered by ethylene glycol, which elevated the urinary concentration of crucial ions viz. calcium, oxalate, and phosphate, thereby contributing to renal stone formation. The ethanolic extract, however, significantly (p < 0.05) reduced the elevated level of these ions in urine. Also, it elevated the urinary concentration of magnesium, which is considered as one of the inhibitors of crystallization. The high serum creatinine level observed in ethylene glycol-treated rats was also reduced, following treatment with the extract. The histopathological findings also showed signs of improvement after treatment with the extract. All these observations provided the basis for the conclusion that this plant extract inhibits stone formation induced by ethylene glycol treatment.

The aim of this study was to determine whether protein, administered alone or simultaneously with a hypercalcic diet, was able to aggravate calcium oxalate stone formation in rats. Thirty-two male Wistar rats were randomly divided into four groups of 8 rats each and assigned a calcium oxalate lithogenic diet added to their drinking water for 3 weeks. One group, used as reference, received a standard diet prepared in our laboratory. The second was assigned the same diet but supplemented with 7.5 g animal proteins/100 g diet. The third received a diet containing 500 mg calcium more than the standard group. The diet given to the last group was supplemented with calcium and protein at the same doses indicated previously. One day before the end of treatment, each animal was placed in a metabolic cage to collect 24-hour urine samples and determine urinary creatinine, urea, calcium, magnesium, phosphate, uric acid, citric acid and oxalate levels. Immediately thereafter, aortic blood was collected to determine the same parameters as in urine. The kidneys were also removed to determine calcium oxalate deposits. Our results showed an increased 24-hour urinary excretion of calcium, oxalate and uric acid and decreased urinary citric acid excretion only in groups that received protein supplementation. At the same time, calcium oxalate deposits were found significantly higher in hyperprotidic diets than reference or calcium-supplemented groups. According to these findings, glomerular filtration, fractional excretion of urea and reabsorption of water, calcium and magnesium were found significantly lower in hyperprotidic diets compared to other groups. These results demonstrate that proteins could seriously aggravate calcium oxalate stones and cause renal disturbances., (Copyright (c) 2005 S. Karger AG, Basel.)

The effects of potassium and magnesium supplementation on urinary risk factors for renal stone disease were studied in 61 renal stone patients. The subjects were divided into four groups and supplemented for a period of one month with potassium chloride (KCl, Group 1), potassium sodium citrate (K Na citrate, Group 2), magnesium glycine (Mg glycine, Group 3) and potassium magnesium citrate (K Mg citrate, Group 4) with a daily dose of 42 mEq potassium, 21 mEq magnesium or sodium and 63 mEq citrate, accordingly. The results showed that serum potassium and magnesium of all four groups normalized after the supplementation. Though urinary potassium significantly increased in all three groups supplemented with elemental potassium containing solutions [i.e. KCl (p < 0.001), K Na citrate (p < 0.001) and K Mg citrate (p < 0.001)] only K Na citrate and K Mg citrate, caused a significant increase in urinary pH and citrate but decrease in calcium. Supplementation with Mg glycine in Group 3 although caused a significant increase in urinary magnesium, its effects on urinary pH, citrate and calcium, however, were similar to KCl, in that they caused a significant decrease in urinary pH without any change in urinary citrate or calcium. Supplementation with K Mg citrate in Group 4 seems to have given the best results, as far as lowering stone risk factors in that it caused an increase in urinary pH, potassium and citrate and decreased calcium excretions similar to K Na citrate in Group 2. In addition, K Mg citrate also caused the enrichment of urine with magnesium, another inhibitor of calcium-containing stones. Although the four supplements had no effect on urinary saturation of calcium oxalate salt, their effects on the saturations of brushite (CaHPO4 x 2H2O), octacalcium phosphate (Ca8H2 (PO4)6 x 5H2O) and uric acid were clearly associated with changes in urinary pH. Therefore, in Group 1 and 3, subjects having a decrease in urinary pH, also experienced a significant increase in uric acid saturation. Though the saturation of brushite and octacalcium phosphate in Group 2 and 4 and the sodium acid urate in Group 2 were significantly increased, these urinary risk factors could be overcome, however, by the concomitant increase in urinary citrate. The present results demonstrate that for those stone vulnerable subjects having a high risk of potassium and magnesium depletion, to obtain the best therapeutic results, they should be provided supplementations of both potassium and magnesium together and also in the forms that would result in the delivery of an alkali loading effect.

Objectives: To determine whether lipid peroxidation plays a role in patients with calcium oxalate kidney stones and to determine the correlation of lipid peroxidation with tubular damage and the major urinary risk factors. We also used the isoenzymes of glutathione S-transferase (GST) to examine which parts of the renal tubules were injured in patients with renal stones., Methods: This clinical study included two study groups. Group 1 included 32 normal volunteers, and group 2 included 32 patients with calcium oxalate kidney stones. A 24-hour urine sample was collected from each subject, and the levels of Ca, P, Mg, oxalate, citrate, N-acetyl-beta-glucosaminidase (NAG), beta-galactosidase (GAL), alphaGST, piGST, osteopontin (OPN), thiobarbituric acid-reactive substances (TBARS), and malondialdehyde (MDA) were examined., Results: Hyperoxaluria, hypocitraturia, and low urinary OPN were the major abnormalities found in the patients with stones. Elevated urinary alphaGST, NAG, and GAL were also noted in the patients with stones; however, urinary piGST showed no statistically significant difference compared with the controls. Urinary TBARS and MDA had statistically significant correlations with alphaGST, GAL, NAG, Ca, and oxalate, but had no correlation with piGST, citrate, OPN, Mg, and P. Urinary citrate had a negative, linear, and statistically significant correlation with alphaGST, GAL, and NAG., Conclusions: Lipid peroxidation correlated with hyperoxaluria and renal tubular damage, indicating that hyperoxaluria can induce tubular cell injury and that this injury may be due to the production of free radicals in patients with calcium oxalate stones. Renal tubular damage in patients with stones may be limited to the proximal tubules.

Objective: To study the effect of different extracts of Alisma orientalis on urinary calcium oxalate stone formation in rats and to identify the effective constituents., Method: Different extracts were administered through a stomach tube to rats of different groups with renal calcium oxalate stones induced by ethylene glycol (EG) and ammonium chloride (AC)., Result: In the rats administered with ethyl acetate elution of ethyl acetate extract, blood Cr, BUN, renal tissue calcium content, urinary calcium excretion and crystals deposition in renal tissue were significantly lower than those of the stone formation group., Conclusion: The ethyl acetate elution of ethyl acetate fraction extract of Alisma orientalis can significantly inhibit urinary calcium oxalate stone formation in rats and be the most effective constituent of Alisma orientalis.

Objectives: To determine the extent of transient changes of tubular function in idiopathic calcium-oxalate (CaOx) stone-bearing patients after extracorporeal shock wave lithotripsy (ESWL), calcium and oxalate excretion were measured before and after ESWL., Methods: In 22 patients with renal CaOx stones, the plasma values and urine excretion of creatinine, calcium, oxalate, magnesium, and citrate were measured before and on days 1 and 2 after ESWL under conditions of a standardized diet. Overnight urine collection for an 8-hour period was used to measure the urine excretion, and the values were extrapolated to a 24-hour period. For calculation of the urine ion activity, the AP(CaOx) index EQ(s) and the CaOx risk index were used., Results: After ESWL, hyperoxaluria was noted in 10 patients compared with 2 before ESWL. Hypercalciuria was seen in 11 patients after ESWL compared with 3 before. Combined hyperoxaluria and hypercalciuria was found in 7 patients after ESWL compared with 1 before. Both the oxalate/creatinine and calcium/creatinine ratios were significantly increased after ESWL. The AP(CaOx) index EQ(s) and the CaOx risk index were significantly increased after ESWL in patients with increased post-ESWL calcium and/or oxalate excretion., Conclusions: Increased calcium and/or oxalate excretion can be seen in patients with CaOx stones early after ESWL. This increased excretion of lithogenic substances represents an increased risk of fragment apposition after ESWL for the group with a significantly increased AP(CaOx) index EQ(s) and CaOx risk index. Therefore, prophylactic measures in patients at risk early after ESWL might be warranted to prevent possible recurrent stone formation.

Unlabelled: The aim of this study was to evaluate prospectively the influence of nutrition on certain factors which may inhibit or promote nephrocalcinosis in two groups of preterm infants, receiving total parenteral nutrition (TPN) and special preterm milk formula respectively, but not furosemide. A total of 37 preterm infants, 15 on TPN and 22 fed a special preterm formula were studied at the end of the 1st, 2nd and 3rd weeks of life, at which time serum and 8 h urine specimens were collected. High ratios of urinary calcium to urinary creatinine (UCa/cr), urinary oxalate to urinary creatinine (Uox/cr) and urinary calcium to urinary citrate (UCa/cit) indicates an increased risk for nephrocalcinosis while high urinary citrate to urinary creatinine (Ucit/cr) ratio indicates protection. Uox/cr increased significantly (P<0.05) in those infants fed preterm formula, from the end of 2nd week of life and was two-fold higher than in the TPN group of preterm infants (P<0.01). Ucit/cr was higher throughout the study period in the formula fed than in the TPN preterm infants. UCa/cit was five-fold higher (P<0.01) in the TPN group, by the end of the 3rd week. Urinary calcium and magnesium was similar in both groups during the study period. Two of the infants studied (5.4%), one from each group, developed nephrocalcinosis., Conclusion: In preterm neonates on total parenteral nutrition, urinary oxalate -to-creatinine ratio (a potent lithogenic factor) was lower and urinary citrate -to-creatinine ratio (a lithoprotective factor) also lower than in formula fed neonates. The type of feeding (total parenteral nutrition or special preterm milk formula) seems to affect urinary oxalate and citrate but not calcium and magnesium in non-furosemide treated preterm infants during the first 3 weeks of life.

The effect of citrus fruit juice ingestion on the risk of calcium oxalate stone formation is still debated. The present study was undertaken to investigate changes in urinary stone risk factors after administration of a soft drink containing grapefruit juice. Seven healthy subjects, with no history of kidney stones, were submitted to an acute oral load (20 ml/kg body weight over 60 min) of a soft drink containing grapefruit juice diluted (10%) in mineral water. After a 7-day wash-out period, each subject underwent an oral load with mineral water alone under the same conditions. Urine specimens were collected before (for 120 min) and after each oral fluid load (for 180 min). Urinary flow was significantly increased after both grapefruit juice (46+/-26 vs 186+/-109 ml/h, p = 0.01) and mineral water (42+/-16 vs 230+/-72 ml/h, p=0.001) compared to baseline. Compared to mineral water, grapefruit juice significantly (p=0.021) increased urinary excretion of citrate (25.8+/-9.3 vs 18.7+/-6.2 mg/h), calcium (6.7+/-4.3 vs 3.3+/-2.3 mg/h, p=0.015) and magnesium (2.9+/-1.5 vs 1.0+/-0.7 mg/h, p=0.003). Citrus fruit juices could represent a natural alternative to potassium citrate in the management of nephrolithiasis, because they could be better tolerated and cost-effective than pharmacological calcium treatment. However, in order to obtain a beneficial effect in the prevention of calcium renal stones a reduced sugar content is desirable to avoid the increase of urinary calcium due to the effect of sugar supplementation.

Objective: To correlate renal calculi and other clinical factors with urinary biochemical analytes in patients with inflammatory bowel disease, and to investigate the relative importance of hyperoxaluria (associated with fat malabsorption) or reduced stone inhibitors in the development of calculi in these patients., Patients, Subjects and Methods: Samples were obtained from 25 patients with Crohn's disease (CD), 15 with ulcerative colitis (UC) and 17 normal subjects (controls). Evidence for the presence of renal calculi was obtained from plain films, ultrasonography or intravenous urography. Urine oxalate and citrate were analysed using commercial enzymatic assays; magnesium was measured using atomic absorption and other analytes assayed using standard methods on automated analysers., Results: Renal calculi were found in two patients with CD and in none with UC. Hyperoxaluria was present in 36% of patients with CD but was absent in those with UC. Analysis of covariance showed an association between low urinary citrate/creatinine ratio and renal stones (P=0.02), and between a combined urinary citrate and magnesium deficit relative to calcium, as expressed in the CMC index ((citratexmagnesium)/calcium), and renal stones (P=0.017). Changes in urinary calcium, oxalate, urate, magnesium or the calcium oxalate index were not associated with the presence of stones. There was no independent relationship between any clinical factor and the presence of stones., Conclusion: Lower urinary concentrations of magnesium and citrate (stone inhibitors), relative to calcium (stone promoter; the CMC index) may be more important in lithogenesis in inflammatory bowel disease than is hyperoxaluria. In patients with a functioning colon, a low CMC index may predict likely stone-formers; this requires a prospective evaluation. Avoiding low urinary levels of magnesium and citrate may aid in preventing and treating renal calculi.

Enzymuria, principal fractions of phospholipids, crystal-inhibiting urine activity were measured in 120 patients with nephrolithiasis combined with cholelithiasis. The patients were divided into two groups: group 1-80 patients with symptoms of nephrolithiasis and latent cholelithiasis; group 2-40 patients with symptoms of cholelithiasis and latent nephrolithiasis. It is shown that hyperenzymuria/microproteinuria, high excretion of phospholipids and cholesterol with urine in patients with nephrolithiasis and its complications not only affect physico-chemical properties of urine promoting atypical salt crystallization with stone formation but also determine characteristics of phasic urine conditions. High urine concentration of phospholipid (acyl derivatives) degradation products and cholesterol in patients with combination of nephrolithiasis with cholelithiasis changes solubilizing and micello-forming ability of urine and can directly stimulate crystal formation and development of aseptic inflammation in renal parenchyma. Low total crystal-inhibiting urine activity, altered surface-free energy due to surface-active substances, high calcium ionization and low urine magnesium ionization are not only pathognomonic criteria of nephrolithiasis but also parameters reflecting high risk of oxalate-calcium formation in patients with nephrolithiasis combination with cholelithiasis.

Purpose: Cystic fibrosis is characterized by chronic pulmonary disease, insufficient pancreatic and digestive function, and abnormal sweat concentrations. Patients with cystic fibrosis also have an increased incidence of nephrolithiasis. We compared the results of metabolic evaluation in patients with cystic fibrosis with and without nephrolithiasis., Materials and Methods: A total of 496 patients were evaluated at our center, including 98 with a mean age of 25 years who had cystic fibrosis and complete metabolic evaluation available between 1996 and 2000. Of these patients 13 (13%) had a history of nephrolithiasis. The records were reviewed for clinical characteristics and all patients underwent metabolic evaluation, including serum electrolyte measurement and 24-hour urine collection. Statistical analysis was done to compare the stone versus nonstone groups., Results: The incidence of nephrolithiasis in our study was 3%. We identified 13 patients 16 to 41 years old (mean age 27) with nephrolithiasis, of whom 62% had had multiple episodes. Flank pain was the presenting symptom in 9 of the 13 cases (69%). Renal ultrasound and computerized tomography were the most common imaging modalities. In 9 cases stones were passed without intervention, extracorporeal shock wave lithotripsy was required in 2 and ureteroscopy with stone extraction was done in 2. Calcium oxalate was the dominant stone composition in the 9 patients in whom stone analysis was performed. Metabolic evaluation of the stone versus no stone groups showed elevated urinary oxalate (45.5 versus 42.5 mg./24 hours), relative calcium oxalate supersaturation (5.3 versus 7.2) and decreased urinary citrate in the 2 groups. There was a statistical difference in citrate excretion with lower levels in stone formers (102 versus 218 mg./24 hours, p = 0.0007)., Conclusions: Patients with cystic fibrosis have an increased incidence of nephrolithiasis and are at high risk for recurrence. Metabolic evaluation is indicated in all patients with cystic fibrosis and urolithiasis since most have hyperoxaluria, urinary calcium oxalate supersaturation and decreased urinary citrate. Correcting detected stone risk factors in these cases may decrease stone recurrence.

The prevalence of nephrolithiasis is considerably greater in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the general population. We evaluated anatomic and metabolic factors that may be associated with an increased prevalence of nephrolithiasis in patients with ADPKD. We compared anatomic parameters among ADPKD patients with or without nephrolithiasis as diagnosed by ultrasonography, whereas metabolic factors were determined by 24-hour urinary chemical analysis. Patients with ADPKD and nephrolithiasis had more renal cysts (P < 0.05) and a larger predominant renal cyst size (P < 0.005) than patients without nephrolithiasis. Concurrently, individual stone-forming kidneys had a greater cyst number (P < 0.05) and a significantly larger predominant cyst size (P < 0.01) compared with kidneys without stones. Patients with ADPKD and nephrolithiasis had a significantly lower creatinine clearance than those without nephrolithiasis (68.7 +/- 8.6 versus 94.8 +/- 5.4 mL/min, respectively; P < 0.05). Twenty-four-hour urinary analysis showed that patients with ADPKD and nephrolithiasis had significantly lower urinary volumes (P < 0. 05), and levels of urinary phosphate (P < 0.05), magnesium (P < 0. 005), and potassium (P < 0.05). Although not statistically significant, patients with ADPKD with stones tended to have lower levels of urinary citrate, and both groups showed a high percentage (range, 49% to 60%) of patients with hypocitraturia. Our data are consistent with the hypothesis that patients with ADPKD who develop nephrolithiasis do so because of increased intrarenal anatomic obstruction, as well as lower levels of such urinary inhibitors of stones as magnesium and citrate.

Although calcium supplementation can cause hypercalciuria, the risk of nephrolithiasis has been shown to decrease rather than increase among subjects who had a higher calcium intake. Hypercalciuria is also a well-established side effect of calcitriol administration. However, the risk of nephrolithiasis is not well defined. The present study was undertaken to prospectively determine the effect of calcium with or without calcitriol on physicochemical risk factors associated with calcium oxalate nephrolithiasis in Thai postmenopausal women with osteoporosis. Subjects consisted of 53 Thai women more than 10 years postmenopausal who were randomly allocated to receive 750 mg of calcium carbonate supplement alone (n = 28) or 750 mg of calcium carbonate plus 0.5 microg calcitriol (n = 25) daily. Mean +/- SEM for age was 65.3+/-1.1 years, body weight 53.5+/-1.3 kg. Urine samples for biochemical assays were collected at baseline and 3 months after treatment. Supersaturation for calcium oxalate stone formation was assessed from the 24 h urine constituents by the Tiselius's index, AP(CaOx). Three months of calcium supplement alone resulted in a modest, but not significant, increase in urinary calcium (baseline, 2.90+/-0.43 mmol/day; after treatment 3.58+/-0.54 mmol/day) with no change in urinary oxalate, citrate or magnesium. In contrast, calcium together with calcitriol caused a significant increase in urinary calcium (baseline, 2.87+/-0.41 mmol/day; after treatment, 4.08+/-0.57 mmol/day; p < 0.05). No significant change in other urine constituents after treatment with calcium and calcitriol was detected. Therefore, AP(CaOx) did not significantly increase either after calcium alone (baseline, 1.17+/-0.39; after treatment, 1.36+/-0.28) or after calcium plus calcitriol (baseline, 1.09+/-0.17; after treatment, 1.09+/-0.19). However, after treatments, 12 subjects (23%)--6 receiving calcium supplement alone and 6 receiving calcium plus calcitriol supplement--had high AP(CaOx) values (greater than the upper limit of 95% Cl for AP(CaOx) derived from non-stone-forming Thai women). The post-treatment/baseline ratio was 3.21+/-0.74 for urinary calcium, 1.01+/-0.19 for urinary oxalate, and 2.23+/-0.42 (median 1.15) for AP(CaOx). The post-treatment/baseline ratio of calcium, but not for urinary oxalate, had a significant correlation with the post-treatment/baseline ratio of AP(CaOx). Our findings suggest that the alteration in the risk of calcium oxalate nephrolithiasis based on urinary composition is related to the alteration in urinary calcium. The risk of calcium oxalate nephrolithiasis does not increase significantly after calcium or combined calcium and calcitriol supplement in the majority of postmenopausal women with osteoporosis.

Background: The effects of female sex hormones on urinary stone formation are not known. This study was conducted to investigate the effects of these hormones on stone formation by using an ethylene glycol (EG) and vitamin D-induced rat urolithiasis model., Methods: Adult female Wistar rats were fed the same diet for four weeks and were then divided into four groups (N = 10 each). One group was administered 0.5 ml of olive oil three times per week for four weeks as a control. The other three groups were administered 0. 5 microg of vitamin D3 and 0.5 ml of 5% EG three times per week for four weeks. The rats in two of these three groups were oophorectomized, and the rats of the remaining group underwent a sham operation on the day before the start of the four-week treatment period. One of the two oophorectomized groups was then administered a supplementation of female sex hormones (0.1 mg of estrogen and 2.5 mg of progesterone 3 times per week for 4 weeks). On the first day of the fifth week of the experimental period, the degree of crystal deposition was determined histologically, and the calcium content in renal tissue was measured. We also investigated the level of osteopontin (OPN) mRNA in renal tissues by Northern blot analysis. OPN is a matrix protein thought to be a promoter of stone formation., Results: The urinary oxalate excretion, crystal deposition and calcium content in renal tissue and the expression of OPN-mRNA were greater in the oophorectomized rats compared with the controls, and the same parameters were inhibited by the female sex hormone supplementation., Conclusions: These results suggest that female sex hormones can inhibit renal crystal deposition in EG-treated rats by suppressing the urinary oxalate excretion and the expression of OPN.

Background: Cross-sectional studies have shown that nephrolithiasis is more frequently found in hypertensive patients than in normotensive subjects, but the pathogenic link between hypertension and stone disease is still not clear., Methods: Between 1984 and 1991, we studied the baseline stone risk profile, including supersaturation of lithogenic salts, in 132 patients with stable essential hypertension (diastolic blood pressure of more than 95 mm Hg) without stone disease and 135 normotensive subjects (diastolic blood pressure less than 85 mm Hg) without stone disease who were matched for age and sex (controls). Subsequently, both controls and hypertensives were followed up for at least five years to check on the eventual formation of kidney stones., Results: Baseline urine levels in hypertensive males were different from that of normotensive males with regards to calcium (263 vs. 199 mg/day), magnesium (100 vs. 85 mg/day), uric acid (707 vs. 586 mg/day), and oxalate (34.8 vs. 26.5 mg/day). Moreover, the urine of hypertensive males was more supersaturated for calcium oxalate (8.9 vs. 6.1) and calcium phosphate (1.39 vs. 0.74). Baseline urine levels in hypertensive females were different from that of normotensive females with regards to calcium (212 vs. 154 mg/day), phosphorus (696 vs. 614 mg/day), and oxalate (26.2 vs. 21.7 mg/day), and the urine of hypertensive females was more supersaturated for calcium oxalate (7.1 vs. 4.8). These urinary alterations were only partially dependent on the greater body mass index in hypertensive patients. During the follow-up, 19 out of 132 hypertensive patients and 4 out of 135 normotensive patients had stone episodes (14.3 vs. 2.9%, chi-square 11.07, P = 0.001; odds ratio 5.5, 95% CI, 1.82 to 16.66). Of the 19 stone-former hypertensive patients, 12 formed calcium calculi, 5 formed uric acid calculi, and 2 formed nondetermined calculi. Of the urinary factors for lithogenous risk, those with the greatest predictive value were supersaturation of calcium oxalate for calcium calculi and uric acid supersaturation for uric acid calculi., Conclusions: A significant percentage of hypertensive subjects has a greater risk of renal stone formation, especially when hypertension is associated with excessive body weight. Higher oxaluria and calciuria as well as supersaturation of calcium oxalate and uric acid appear to be the most important factors. Excessive weight and consumption of salt and animal proteins may also play an important role.

Background: 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., Methods: 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., Results: 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., Conclusion: 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.

Objectives: This study was undertaken to identify a South African mineral water containing relatively high concentrations of calcium and magnesium and to investigate its effect on urinary biochemical and physicochemical risk factors associated with calcium oxalate kidney stone formation., Design: The study followed a change-over design in which each subject followed a randomised sequence of three water-drinking protocols involving their normal diet, a calcium and magnesium-rich mineral water and a mineral water deficient in these elements., Setting: University of Cape Town., Subjects: 54 volunteers without any previous history of stone disease (27 men, 27 women) in the age group 21-35 years and 31 with a history of calcium oxalate kidney stones (24 men, 7 women) in the age group 25-45 years participated in the study., Outcome Measures: Both mineral waters favourably altered several risk factors. However, the effect of the calcium- and magnesium-rich water was shown to be significantly greater as it altered a larger number of these factors and induced several unique changes that were not achieved by the other water., Conclusions: The risk of calcium oxalate stone formation can be significantly reduced by consumption of mineral water which is rich in calcium and magnesium.

1. Dietary calcium restriction, an efficient practice in reducing urinary calcium excretion, has been reported to induce either an increase or no change in oxalate excretion, questioning its use in hypercalciuric stone-forming patients. In addition, calcium restriction has been previously demonstrated to induce other urinary changes which might influence the relative supersaturation of calcium oxalate. So the overall effect of calcium deprivation on the relative supersaturation of calcium oxalate is unpredictable. 2. The aim of the study was to evaluate the effect of dietary calcium restriction on the relative supersaturation of calcium oxalate in the urine of stone-forming patients utilizing a computer methodology which takes into account the main soluble complex species of oxalate. 3. We studied 34 stone-forming patients on both a free-choice diet, whose Ca and oxalate content (24 and 1.2 mmol respectively) was assessed by dietary inquiry, and after 30 days on a prescribed low-calcium and normal oxalate diet (11 and 1.1 mmol respectively). Under both conditions, the excretion of the main urinary parameters related to dietary composition, electrolytes, oxalate and daily citrate urinary excretion, were measured. The relative supersaturation of calcium oxalate was calculated by means of an iterative computer method which takes into account the main soluble complex species on which the solubility of calcium oxalate is dependent. In addition, intact parathyroid hormone and 1,25-dihydroxyvitamin D blood levels were also evaluated. In 13 of the patients intestinal calcium absorption was evaluated during both a free- and a low-calcium diet, utilizing kinetics methodology. 4. The low-calcium diet induced, together with an expected reduction of calcium excretion, a marked increase in oxalate urinary output. This finding was independent of the presence or otherwise of hypercalciuria and of the serum levels of parathyroid hormone and vitamin D. Intestinal calcium absorption was also stimulated by calcium deprivation and its levels were well correlated with oxalate excretion. Minor changes in magnesium and citrate excretion were also observed. The overall effect on the relative supersaturation of calcium oxalate consisted in a substantial increase in this parameter during the low-calcium diet. 5. In conclusion, our data reinforce the concept that dietary calcium restriction has potentially deleterious effects on lithogenesis, by increasing the relative supersaturation of calcium oxalate.

This study presents the results of a 10-year metaphylaxis of 19 former struvite stone formers, each having had 2-3 stone operations. In these patients, urine was acidified with L-methionine (Acimethin) using a dose of three to six tablets 500 mg/day. Every three months, 11 laboratory parameters were checked in 24-hour urine. 6 parameters were determined in serum. In addition, urine samples were tested for infection. Statistical analysis of analytical data, which was supported by computer graphs, provided the results for the urinary parameters. They were described by geometric means and 95% confidence intervals using ANOVA (analysis of variance). During therapy, the mean pH values decreased significantly from 7.5 to 5.5. Signific-ant increases were found in the excretion of citrate, magnesium, potassium, and uric acid. An increase was also found for calcium, which, however, could not be confirmed to be statistically significant (p = 0.08). In serum, changes of parameters could only be registered for calcium and phosphate. However, at all times, total serum concentrations stayed within their normal limits. Three patients suffered occasional infections (16%), only two of them formed recurrent stones (10%). In assessing the efficacy of L-methionine therapy, the drop in urinary pH to acidic values was the most relevant factor for metaphylaxis.

Early morning urinary concentrations of 10 elements which had demonstrated a "week-end effect" in a previous study, were subjected to a normalization procedure thereby allowing a re-assessment of their potential role in urolithiasis. After transformation of each concentration to a weighted proportion of the total concentration on each day, only Cu and P values were significantly different for kidney stone formers and healthy controls on all three days indicating that these elements may play a role in the pathogenesis of renal calculi. The results obtained in this study demonstrate that a more meaningful picture of the possible differences in the urinary concentrations of stone formers and normal controls might emerge if "proportional" rather than "raw" concentrations are compared.

A preliminary diagnosis of the disease responsible for the stones is essential to allow appropriate medical treatment of renal stones. In this paper, the authors describe their diagnostic and treatment protocol based on computer-assisted urinary metabolic analysis. 413 subjects, divided into four groups, were prospectively evaluated to calculate their specificity, sensitivity, reproducibility and efficacy and to demonstrate the usefulness of this protocol.

Evaluations of 1,270 patients with recurrent nephrolithiasis in an outpatient setting were analyzed for the purpose of updating the classification of nephrolithiasis. All but 4% had abnormal urinary biochemistry that placed them into one or more of 20 etiologic categories. A single diagnosis was documented in 41.3% of patients. The remaining 58.7% had more than one diagnosis. Hypercalciuric calcium (Ca) nephrolithiasis, encountered in 60.9% of patients, comprised six variants--absorptive hypercalciuria Type I and II, renal hypercalciuria, primary hyperparathyroidism, and unclassified hypercalciuria (renal phosphate leak and fasting hypercalciuria). Hyperuricosuria Ca nephrolithiasis (HUCN) and gouty diathesis (GD) accounted for 35.8% and 10.0% of patients, respectively. Distinguishing features were hyperuricosuria and normal urinary pH in HUCN, and normal urinary uric acid and low urinary pH (< 5.5) in GD. Hyperoxaluric Ca nephrolithiasis, occurring in 8.1% of patients, was subdivided into enteric, primary, and dietary variants. Hypocitraturic Ca nephrolithiasis affected 28% of patients in its idiopathic variant. Many of these patients' problems were probably dietary in origin, while some could have had incomplete renal tubular acidosis. Hypocitraturia due to renal tubular acidosis or chronic diarrheal syndrome affected only 3.3% of patients. Hypomagnesiuric Ca nephrolithiasis, infection stones, and cystinuria were uncommon, accounting for 6.8%, 5.9%, and 0.9% of patients, respectively. The acquired problem of low urine volume (< 1 L/d) was found in 15.3% of patients. The remaining 3.5% of patients were difficult to classify despite the presence of abnormal urinary biochemistry.

Factors influencing the growth of renal calculi were examined. In order to calculate the volume of stone on X-ray film, stones obtained from open operation or spontaneous passage were measured long (a) and short (b) diameter, and equation to obtain stone volume was assumed. Stone volume = 0.43 (pi ab (a + b))/12 + 0.04 was the mostly related to the volume measured by water volume, when size was less than 2 cm in diameter. Using the equation, factors influencing the growth of renal calculi of 136 kidney, which were followed over 6 months, were studied with monovariate analysis. Of the 136 kidneys, 36 have calcium oxalete stones, 54 have mixed stones with calcium oxalate and calcium phosphate, 3 have mixed stones with calcium oxalate and uric acid, and other 43 have stones with unknown composition. Uric acid stones, cystine stones and infectious stones were excluded in the study. Growth of stone was greater in male than in female. Pelvic stones grew rapidly than renal caliceal stones. The patients were divided into two groups by growth rate; non growing (< 10%/year), and growing group (> 10%/year), respectively. Excretion of urinary calcium was high in the growing group. Urinary magnesium/calcium was low in the growing group. When divided into two groups by growth volume; non growing (< 0.005 cm3/year), and growing group (> 0.005 cm3/year), respectively, excretion of urinary calcium was high in the growing group and urinary magnesium/calcium was low in the growing group.(ABSTRACT TRUNCATED AT 250 WORDS)

A scheme for the chemical microanalysis of renal stone fragments recovered from urine voided immediately after lithotripsy has been developed and evaluated. The analytical procedure includes assay of calcium, magnesium, phosphate, oxalate and urate and has been applied to 78 such urine samples. Problems relating to co-existing crystalluria and blood and urine contaminants have been recognised and overcome. However, significant loss of all stone components due to fragment dissolution in urine prior to recovery was found to occur and was investigated. The distribution of stone components found in these analyses was similar to that seen in previous surveys of intact stones.

Two sets of animal experiments using guinea pigs were planned to evaluate the effect of ascorbic acid supplementation on the lithogenic process. In the first set of experiments, 10, 40, and 60 mg doses of ascorbic acid/100g body weight/day were given for 105 days. Neither of the ascorbic acid doses given induced crystalluria, calcification or stone formation, thereby confirming our previous findings that ascorbic acid in the doses used by clinicians does not cause urolith formation. In the second set of experiments, ascorbic acid was supplemented in hypercalciuric (induced by calcium carbonate feeding) and hyperoxaluric (induced by sodium oxalate feeding) animals for 45 days. The results indicated that it exacerbated the calcification process in renal and bladder tissue.

The effect of the calcium antagonist verapamil on urinary calcium and oxalate excretion was examined and compared with that of trichlormethiazide to evaluate whether verapamil is useful in the prevention of calcium oxalate renal stones. Twenty-four-hour urine of 16 renal stone formers was measured at the outpatient clinic before and after administration of 120 mg/day verapamil for a mean duration of 2.7 months (range, 2 weeks to 6 months). The 24-hour urine was analyzed for creatinine, calcium, oxalic acid, magnesium and citric acid and the results compared with those in 20 renal stone formers who were administered trichlormethiazide. Verapamil was found to significantly reduce the urinary oxalate excretion of the 5 hyperoxaluric (> or = 50 mg/day) patients but no significant effect on urinary calcium, magnesium or citric acid was observed. Conversely, trichlormethiazide significantly decreased urinary calcium excretion in the hypercalciuric (> or = 250 mg/day) patients. Calcium oxalate risk index of hypercalciuric and hyperoxaluric patients was significantly reduced after the administration of verapamil. These findings suggest that verapamil is effective in reducing urinary oxalate excretion in the hyperoxaluric patients.

The effect of sodium pentosan polysulphate (SPP) was investigated in calcium oxalate stone forming rats with respect to the urinary excretion of certain risk factors and enzymes. Calcium oxalate stones were induced by feeding 3% w/w sodium glycollate to the rats. Urinary calcium, oxalate, phosphorus and uric acid levels were increased in stone formers. In contrast magnesium excretion was low in this group. SPP treatment lowered oxalate and calcium levels in both controls and experimental animals. Magnesium levels were increased moderately. Increased excretion of urinary enzymes--LDH, alkaline phosphatase, gamma-GT and beta glucuronidase--in calculogenic rats indicates membranuria and damage to proximal tubules during stone formation. Decreased pyrophosphatase activity was observed in glycollate fed rats. SPP treatment decreased the excretion of the above enzymes in the treated groups. Stone formers exhibited decreased LAP and fibrinolytic (urokinase) activities. SPP being associated with fibrinolytic properties, increased the activities of the above two enzymes to that of control levels in calculogenic rats.