Spot urinary citrate-to-creatinine ratio is a marker for acid-base status in chronic kidney disease.

Due to multiple compensating mechanisms, the serum bicarbonate concentration is a relatively insensitive marker of acid-base status; especially in chronic kidney disease (CKD). This is a major drawback that impairs the ability to diagnose acid excess or monitor alkali therapy. We postulated that it is more logical to measure the compensatory defense mechanism(s) rather than the defended parameter, which remains normal if the compensation is successful. Therefore, a retrospective cross-sectional study was performed in 1733 stone formers along with a prospective cross-sectional study of 22 individuals with normal kidney function and 50 patients in different stages of CKD. While serum bicarbonate was flat and did not fall below the reference range until near CKD stage 5, citrate excretion (24-hour urinary citrate excretion rate; urinary citrate-to-creatinine ratio, in the retrospective analysis, and spot urinary citrate-to-creatinine ratio in the prospective study) progressively and significantly declined starting from CKD stage 2. Following an acute acid load in 25 participants with a wide range of estimated glomerular filtration rates, the urinary citrate-to-creatinine ratio inversely and significantly associated with acid accumulation, whereas serum bicarbonate did not. We compared changes in serum bicarbonate and urinary citrate-to-creatinine ratio in response to alkali therapy in patients with CKD stage 3 or 4 started on potassium citrate in our kidney stone database. With alkali therapy, there was no change in serum bicarbonate, but the urinary citrate-to-creatinine ratio rose consistently in all patients adherent to potassium citrate therapy. Thus, the urinary citrate-to-creatinine ratio (the defense mechanism) is a potential easily implementable, pragmatic, and a superior parameter to serum bicarbonate (the defended entity) to assess acid-base status, and monitor alkali therapy. Additional studies are needed before a clinical test can be devised.

Dietary effects on urinary physicochemistry in Navy bottlenose dolphins (Tursiops truncatus) for the prevention of ammonium urate kidney stones.

Bottlenose dolphins are susceptible to developing ammonium urate (NH4U) kidney stones. The current study was designed to test the hypothesis that diet influences the urinary physicochemistry risk factors associated with nephrolithiasis in dolphins. A comprehensive nutrient analysis was performed revealing that the baseline diet (BD) commonly fed to dolphins under professional care had a greater purine content and a more negative dietary cation-anion difference (DCAD) when compared with a model diet consumed by free-ranging dolphins. A modified diet (MD) was formulated to include free-ranging diet fish species and achieve a more positive DCAD. The BD had a more negative DCAD (-52 mEq/Mcal metabolizable energy) when compared with the MD (+51 mEq/Mcal ME), which more closely approximated the DCAD of the free-ranging model diet (+152 mEq/Mcal ME). Six dolphins (with stones) were fed the BD followed by the MD for a minimum of 4 wk. At the end of each feeding trial, a 6-h continuous urine collection was performed to compare urine parameters of dolphins fed the BD versus MD. Dolphins consuming the MD demonstrated a significant decrease in urinary ammonium, net acid excretion, saturation index of ammonium urate, and phosphorous, and a significant increase in urinary citrate and net gastrointestinal (GI) alkali absorption, as compared with urine parameters assessed when fed the BD. Increasing the proportion of free-ranging diet fish species and optimizing the DCAD positively influenced some of the risk factors believed to be associated with NH4U kidney stone development in bottlenose dolphins under professional care.

Increased production and reduced urinary buffering of acid in uric acid stone formers is ameliorated by pioglitazone.

Idiopathic uric acid nephrolithiasis is characterized by an overly acidic urine pH caused by the combination of increased acid production and inadequate buffering of urinary protons by ammonia. A large proportion of uric acid stone formers exhibit features of the metabolic syndrome. We previously demonstrated that thiazolidinediones improved the urinary biochemical profile in an animal model of the metabolic syndrome. In this proof-of-concept study, we examined whether the thiazolidinedione pioglitazone can also ameliorate the overly acidic urine in uric acid stone formers. Thirty-six adults with idiopathic uric acid nephrolithiasis were randomized to pioglitazone 30 mg/day or matching placebo for 24 weeks. At baseline and study end, participants underwent collection of blood and 24-hour urine in an inpatient research unit while consuming a fixed metabolic diet, followed by assessment of the ammoniagenic response to an acute oral acid load. Twenty-eight participants completed the study. Pioglitazone treatment improved features of the metabolic syndrome. Pioglitazone also reduced net acid excretion and increased urine pH (5.37 to 5.59), the proportion of net acid excreted as ammonium, and ammonium excretion in response to an acute acid load, whereas these parameters were unchanged with placebo. Treatment of patients with idiopathic uric acid nephrolithiasis with pioglitazone for 24 weeks led to a reduction in the acid load presented to the kidney and a more robust ammoniagenesis and ammonium excretion, resulting in significantly higher urine pH. Future studies should consider the impact of this targeted therapy on uric acid stone formation.

Impact of Potassium Citrate vs Citric Acid on Urinary Stone Risk in Calcium Phosphate Stone Formers.

PURPOSE: To our knowledge no medication has been shown to be effective for preventing recurrent calcium phosphate urinary stones. Potassium citrate may protect against calcium phosphate stones by enhancing urine citrate excretion and lowering urine calcium but it raises urine pH, which increases calcium phosphate saturation and may negate the beneficial effects. Citric acid can potentially raise urine citrate but not pH and, thus, it may be a useful countermeasure against calcium phosphate stones. We assessed whether these 2 agents could significantly alter urine composition and reduce calcium phosphate saturation. MATERIALS AND METHODS: In a crossover metabolic study 13 recurrent calcium phosphate stone formers without hypercalciuria were evaluated at the end of 3, 1-week study phases during which they consumed a fixed metabolic diet and received assigned study medications, including citric acid 30 mEq twice daily, potassium citrate 20 mEq twice daily or matching placebo. We collected 24-hour urine specimens to perform urine chemistry studies and calculate calcium phosphate saturation indexes. RESULTS: Urine parameters did not significantly differ between the citric acid and placebo phases. Potassium citrate significantly increased urine pH, potassium and citrate compared to citric acid and placebo (p <0.01) with a trend toward lower urine calcium (p = 0.062). Brushite saturation was increased by potassium citrate when calculated by the relative supersaturation ratio but not by the saturation index. CONCLUSIONS: Citric acid at a dose of 60 mEq per day did not significantly alter urine composition in calcium phosphate stone formers. The long-term impact of potassium citrate on calcium phosphate stone recurrence needs to be studied further.

Temporal Changes in Kidney Stone Composition and in Risk Factors Predisposing to Stone Formation.

PURPOSE: The prevalence of kidney stones has increased globally in recent decades. However, studies investigating the association between temporal changes in the risk of stone formation and stone types are scarce. We investigated temporal changes in stone composition, and demographic, serum and urinary parameters of kidney stone formers from 1980 to 2015. MATERIALS AND METHODS: We retrospectively analyzed the records of 1,516 patients diagnosed with either calcium or uric acid stones at an initial visit to a university kidney stone clinic from 1980 to 2015. RESULTS: From 1980 to 2015, the proportion of uric acid stones in all stone formers increased from 7% to 14%. While age and body mass index increased with time in both uric acid and calcium stone formers, uric acid stone formers were consistently older and had a higher body mass index and lower urinary pH than calcium stone formers. The proportion of females with stones has increased over time but the increase in female gender was more prominent among calcium stone formers. Urinary pH, phosphorus, oxalate and sodium increased with time in calcium stone formers but remained unchanged in uric acid stone formers. After accounting for various parameters of stone risk, the strongest clinical discriminant of uric acid vs calcium stones was urinary pH. Limitations of this study include the retrospective single center design and the available number of patients with stone analysis. CONCLUSIONS: From 1980 to 2015, the proportion of uric acid stones increased significantly. With time, there were proportionately more female calcium stone formers but not uric acid stone formers. Urinary pH is the most prominent factor distinguishing uric acid from calcium stones.

Pathophysiological and physicochemical basis of ammonium urate stone formation in dolphins.

PURPOSE: Nephrolithiasis is increasingly reported in bottle-nosed dolphins. All cases to date have been ammonium urate nephrolithiasis. MATERIALS AND METHODS: A case-control study was performed in dolphins with and without evidence of nephrolithiasis to identify biomarkers and risk factors associated with stone formation in a managed population. Dolphins were sampled in fasting and postprandial states to study the effect of dietary factors on serum and urinary biochemistry. Urine was continuously collected for 6 hours via catheter and divided into 3, 2-hour collections with a bolus fish meal given after completing the first collection. Blood was sampled at the beginning of the fasting period and the end of the postprandial period. RESULTS: There were no significant differences in serum and urine chemistry or acid-base profiles between dolphins with vs without stones at baseline or postprandially. This suggests that cases and controls represent a continuum of stone risk. On analysis combining cases and controls in a single cohort we noted significant postprandial increases in urinary uric acid, sulfate and net acid excretion accompanied by increased urinary ammonium excretion and a commensurate increase in urine pH. The supersaturation index of ammonium urate increased more than twofold postprandially. CONCLUSIONS: These findings suggest that dolphins are susceptible to ammonium urate nephrolithiasis at least in part because a high dietary load of acid and purines results in a transient but marked increase in the urinary supersaturation of the sparingly soluble ammonium urate salt.

Animal protein and the risk of kidney stones: a comparative metabolic study of animal protein sources.

PURPOSE: We compared the effect of 3 animal protein sources on urinary stone risk. MATERIALS AND METHODS: A total of 15 healthy subjects completed a 3-phase randomized, crossover metabolic study. During each 1-week phase subjects consumed a standard metabolic diet containing beef, chicken or fish. Serum chemistry and 24-hour urine samples collected at the end of each phase were compared using mixed model repeated measures analysis. RESULTS: Serum and urinary uric acid were increased for each phase. Beef was associated with lower serum uric acid than chicken or fish (6.5 vs 7.0 and 7.3 mg/dl, respectively, each p <0.05). Fish was associated with higher urinary uric acid than beef or chicken (741 vs 638 and 641 mg per day, p = 0.003 and 0.04, respectively). No significant difference among phases was noted in urinary pH, sulfate, calcium, citrate, oxalate or sodium. Mean saturation index for calcium oxalate was highest for beef (2.48), although the difference attained significance only compared to chicken (1.67, p = 0.02) but not to fish (1.79, p = 0.08). CONCLUSIONS: Consuming animal protein is associated with increased serum and urine uric acid in healthy individuals. The higher purine content of fish compared to beef or chicken is reflected in higher 24-hour urinary uric acid. However, as reflected in the saturation index, the stone forming propensity is marginally higher for beef compared to fish or chicken. Stone formers should be advised to limit the intake of all animal proteins, including fish.

Androgen Deprivation Therapy Differentially Impacts Bone and Muscle in the Short Term in Physically Active Men With Prostate Cancer.

Androgen deprivation therapy (ADT) is a cornerstone of advanced prostate cancer (PCa) therapy. Its use is associated with a loss of bone mineral density (BMD) and a greater risk of falls and osteoporotic fractures. In this prospective cohort study, we examined the impact of ADT on muscle and bone strength in men initiating ADT for PCa. Participants were evaluated at three time points: immediately before (week 0), and 6 and 24 weeks after ADT initiation. Study measures included fasting blood levels (for markers of muscle and bone metabolic activity), MRI and QCT imaging (for muscle fat content, and bone density and architecture), and validated clinical tests of muscle strength and gait. Sixteen men completed all study visits. At baseline and throughout the study, participants exercised a median of four times/week, but still experienced weight gain (+2.0 kg at week 24 versus week 0, p = 0.004). Biochemically, all men sustained dramatic early and persistent reductions in sex hormones post-ADT, along with a progressive and significant increase in serum C-telopeptide of type I collagen (CTX, +84% at week 24 versus week 0). There was a trend for rise in serum sclerostin (p = 0.09) and interleukin 6 (IL-6) (p = 0.08), but no significant change in serum myostatin (p = 0.99). Volumetric BMD by QCT declined significantly at the femoral neck (-3.7% at week 24 versus week 0), particularly at the trabecular compartment. On MRI, there were no significant changes in thigh muscle fat fraction. On physical testing, men developed weaker grip strength, but experienced no worsening in lower extremity and lumbar spine muscle strength, or on functional tests of gait. In conclusion, in physically active men, ADT for 24 weeks results in a significant increase in bone resorption and reduction in BMD, but nonsignificant changes in thigh muscle quality (on imaging) or strength and gait (on functional testing). © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Comparison of semi-empirical and computer derived methods for estimating urinary saturation of calcium oxalate.

PURPOSE: Estimating calcium oxalate saturation in human urine is critical for nephrolithiasis clinical research and practice. The Joint Expert Speciation System (Mayhem Unit Trust and Council for Scientific and Industrial Research, Pretoria, South Africa) computer program has questioned the validity of the widely used EQUIL 2 program in estimating calcium oxalate urinary saturation. To attempt resolution the computer model based supersaturation index (by the Joint Expert Speciation System) and the relative saturation ratio (by EQUIL 2) were compared with the experimentally derived activity product ratio, that is the ratio of activity products before and after incubating urine with synthetic calcium oxalate. MATERIALS AND METHODS: To determine the experimental conditions required to attain calcium oxalate steady state solubility the filtrate concentration product of calcium and oxalate was determined after incubating 8 urine samples with 2 to 15 mg/ml calcium oxalate for various intervals. In 20 urine samples the activity product ratio of calcium oxalate was compared with the relative saturation ratio and the supersaturation index. RESULTS: Steady state solubility occurred after incubating 15 mg calcium oxalate per ml urine for 72 hours. The mean +/- SD supersaturation index of 4.92 +/- 2.57 in the original urine samples closely approximated the activity product ratio of 5.08 +/- 3.10 but the relative saturation ratio of 7.47 +/- 3.89 was significantly higher than the activity product ratio. The supersaturation index was recalculated after omitting soluble complexes recognized by the Joint Expert Speciation System but not by EQUIL 2, including Ca(2)H(2)(PO(4))(2) and (CaCitPO(4))(4-). The corrected supersaturation index was compared with the relative saturation ratio. After correction the supersaturation index increased to 7.28 +/- 3.81, which was not significantly different from the relative saturation ratio. CONCLUSIONS: The Joint Expert Speciation System is more accurate than EQUIL 2 to estimate calcium oxalate saturation, probably by accounting for Ca(2)H(2)(PO(4))(2), (CaCitPO(4))(4-), and other minor complexes of calcium and oxalate.

Comparison of semi-empirical and computer derived methods for estimating urinary saturation of brushite.

PURPOSE: The Equil 2 computer program has been questioned by the new Joint Expert Speciation System program (Mayhem Unit Trust and Council for Scientific and Industrial Research, Pretoria, South Africa) for estimating the urinary saturation of stone forming salts to gauge the propensity for stone formation. To attempt resolution the supersaturation index according to the Joint Expert Speciation System and the relative saturation ratio according to Equil 2 were compared with the semi-empirically derived concentration-to-product ratio. MATERIALS AND METHODS: Data were obtained from a recent article in The Journal of Urology(R), in which pH, calcium and citrate were varied over a wide range in 72 urine samples. We calculated the relative saturation ratio and the supersaturation index of brushite, and compared them with the available concentration-to-product ratio derived from the growth or dissolution of synthetic brushite. RESULTS: The mean concentration-to-product ratio did not differ from the supersaturation index but the concentration-to-product ratio and the supersaturation index were significantly lower than the relative saturation ratio (p <0.004). On the saturation value and urinary variable plot the relative saturation ratio could be readily distinguished from the concentration-to-product ratio because it was consistently and significantly higher. While the supersaturation index pattern was similar to the concentration-to-product ratio, the supersaturation index was slightly lower at high urinary pH and calcium, and slightly higher at lower urinary pH and calcium (p <0.001). When the Ca(2)H(2)(PO(4))(2) complex was deleted from the Joint Expert Speciation System, the corrected supersaturation index was not significantly different from the relative saturation ratio determined by Equil 2. CONCLUSIONS: The relative saturation ratio overestimates brushite saturation by about 80%. The supersaturation index yields a good approximation of brushite saturation at modest degrees of saturation but it overestimates saturation at low pH or calcium (low saturation) and underestimates it at high pH or calcium (high saturation).

New methods of assessing crystal growth and saturation of brushite in whole urine: effect of pH, calcium and citrate.

PURPOSE: Brushite crystallization might be important in stone formation and prevention. To explore this question new methods for the saturation and crystal growth of brushite were devised that are applicable to whole urine without any computer program. MATERIALS AND METHODS: The saturation value (concentration-to-product ratio) was determined by dividing the molar concentration product of Ca ([Ca]) and phosphate ([P]), that is [Ca] x [P], of original urine by the steady state solubility obtained after incubating with an excess of brushite (10 mg/ml) for 5 hours. Crystal growth was measured from the depletion of filtrate ([Ca] x [P]) 3 hours after seeding with brushite (0.25 mg/ml). To test the effect of pH, Ca and citrate the saturation value and crystal growth were determined in 24-hour urine samples from 4 normal volunteers and 2 stone formers, and modified artificially to produce 4 ranges of pH, Ca and citrate by adding acid, base, Ca or citrate. RESULTS: The saturation value and crystal growth of brushite increased with an increase in pH or the Ca concentration but they decreased when the citrate concentration increased. The saturation value correlated strongly with crystal growth. CONCLUSIONS: The new methods of brushite saturation value and crystal growth should help discern how abnormalities in urinary pH, Ca and citrate interact to influence the formation of Ca stones in cases of distal renal tubular acidosis and alkali therapy.

Predictive value of kidney stone composition in the detection of metabolic abnormalities.

PURPOSE: To determine if kidney stone composition can predict the underlying medical diagnosis, and vice versa. METHODS: We studied 1392 patients with kidney stones who underwent a complete ambulatory evaluation and who submitted one or more stones for analysis. We ascertained the associations between medical diagnosis and stone composition. RESULTS: The most common kidney stones were composed of calcium oxalate (n = 1041 patients [74.8%]), mixed calcium oxalate-calcium apatite (n = 485 [34.8%]), and calcium apatite alone (n = 146 [10.5%]). The most common medical diagnoses were hypocitraturia (n = 616 patients [44.3%]), absorptive hypercalciuria (n = 511 [36.7%]), and hyperuricosuria (n = 395 [28.4%]). Calcium apatite and mixed calcium oxalate-calcium apatite stones were associated with the diagnoses of renal tubular acidosis and primary hyperparathyroidism (odds ratios >/=2), but not with chronic diarrheal syndromes. As the phosphate content of the stone increased from calcium oxalate to mixed calcium oxalate-calcium apatite, and finally to calcium apatite, the percentage of patients with renal tubular acidosis increased from 5% (57/1041) to 39% (57/146), and those with primary hyperparathyroidism increased from 2% (26/1041) to 10% (14/146). Calcium oxalate stones were associated with chronic diarrheal syndromes, but not with renal tubular acidosis. Pure and mixed uric acid stones were strongly associated with a gouty diathesis, and vice versa. Chronic diarrheal syndromes and uric acid stones were associated with one another, and brushite stones were associated with renal tubular acidosis. As expected, there was a very strong association between infection stones and infection, and between cystine stones and cystinuria. CONCLUSION: Stone composition has some predictive value in diagnosing medical conditions, and vice versa, especially for noncalcareous stones.

Effect of estrogen treatment and vitamin D status on differing bioavailabilities of calcium carbonate and calcium citrate.

The authors hypothesized that estrogen treatment or vitamin D status may affect the bioavailability of two common calcium supplements differently. Using data derived from a recent trial in 25 postmenopausal women, the authors found that deltaAUC of serum calcium after subtraction of placebo was significantly higher after calcium citrate (median, 0.85; 25th to 75th percentile, 0.70 to 3.15) than after calcium carbonate (0.25; -0.58 to 1.00) in non-estrogen-treated patients. There was no difference in the bioavailability of calcium between the two calcium formulations in estrogen-treated patients. Bioavailability was also significantly higher with the citrate salt for the subgroups with lower serum 25-hydroxyvitamin D and higher serum 1,25-dihydroxyvitamin D concentrations. In summary, bioavailability of calcium from the calcium carbonate product was more dependent on estrogen treatment and vitamin D status than that of calcium citrate. This may explain the variable results of reported calcium supplementation studies.

Intestinal hyperabsorption of calcium and low bone turnover in hypercalciuric postmenopausal osteoporosis.

Hypercalciuria of intestinal origin has been linked with bone loss in calcium nephrolithiasis and idiopathic osteoporosis. This retrospective data analysis was performed to explore potential pathogenetic link between intestinal hyperabsorption of calcium and postmenopausal osteoporosis. Data were retrieved from postmenopausal women who were evaluated for osteoporosis or osteopenia at the Mineral Metabolism Clinic of UT Southwestern Medical Center. A total of 319 patients underwent the test of calciuric response to oral calcium load to obtain an indirect measure of intestinal calcium absorption. Serum and urinary biochemistry and L2-L4 bone mineral density (BMD) were compared between five quintiles of calciuric response. There was a statistically significant trend toward a rise in 24-h urinary calcium and a decrease in urinary deoxypyridinoline (DPD) and BMD, with increasing order of quintiles. The presentation of those in the 1st quintile was consistent with vitamin D insufficiency or deficiency, with impaired calcium absorption, secondary hyperparathyroidism, and stimulated bone turnover (high normal urinary DPD). In contrast, patients in the 5th quintile displayed a picture of absorptive hypercalciuria of stone disease, with intestinal hyperabsorption of calcium, high or high normal urinary calcium and suppressed bone turnover (low or low normal urinary DPD). Thus, the assessment of intestinal calcium absorption in a seemingly homogeneous group of postmenopausal women with osteoporosis or osteopenia revealed a spectrum of calciuric response whose extremes may represent two physiologically distinct subtypes that have important diagnostic and therapeutic implications.

Biochemical characterization of primary hyperparathyroidism with and without kidney stones.

The exact metabolic-physiological background for kidney stone formation in primary hyperparathyroidism (PHPT) is unclear. To obtain clarification, this retrospective data analysis was conducted in 131 patients with PHPT who had undergone a detailed ambulatory evaluation on a random diet since 1980. The baseline biochemical presentation of 78 patients with PHPT with stones was compared with that of 53 patients without stones. Compared to those without stones, the stone-forming patients had a more marked hypercalciuria (343 +/- 148 vs. 273 +/- 148 mg/day, P < 0.01). Urinary saturation of calcium oxalate and brushite was significantly higher in stone-formers. Serum PTH and fasting urinary calcium were similar between the two groups, but serum phosphorus was significantly lower in stone-formers. Serum calcitriol (available in some patients) showed a slightly higher mean value in stone-formers but the difference was not significant. The increment in urinary calcium after oral load of 1-g calcium was twofold higher among stone-formers. Radial shaft and L2-L4 bone mineral densities resided within the normal ranges. Stone-formers with PHPT display exaggerated urinary calcium excretion due to intestinal hyperabsorption of calcium, contributing to a greater enhancement of the saturation of stone-forming calcium salts.

Physicochemical metabolic characteristics for calcium oxalate stone formation in patients with gouty diathesis.

PURPOSE: We determined why calcium oxalate stones instead of uric acid stones form in some patients with gouty diathesis. MATERIALS AND METHODS: Gouty diathesis was diagnosed from absence of secondary causes of uric acid stones or low urinary pH, and reduced fractional excretion of urate with discriminant score of the relationship between urinary pH and fractional excretion of urate less than 80. From the stone registry 163 patients with gouty diathesis were identified, including 62 with uric acid stones (GD + UA) and 101 patients with calcium oxalate stones (GD + Ca). Metabolic data and 24-hour urinary chemistry study were compared between the 2 groups. RESULTS: Compared with GD + UA, GD + Ca had significantly greater urinary calcium (196 +/- 96 mg per day vs 162 +/- 82 mg per day, p <0.05) and significantly lower urinary citrate (430 +/- 228 vs 519 +/- 288 mg per day, p <0.05), resulting in higher urinary saturation of calcium oxalate. Both groups had low urinary pH (less than 5.5) and high urinary undissociated uric acid (greater than 100 mg/dl). Urinary calcium post-oral calcium load was significantly higher in GD + Ca than in GD + UA (0.227 vs 0.168 mg/dl glomerular filtrate, p <0.001). CONCLUSIONS: Calcium oxalate stones may form in some patients with gouty diathesis due to increased urinary excretion of calcium and reduced excretion of citrate. Relative hypercalciuria in GD + Ca may be due to intestinal hyperabsorption of calcium.

Effect of dietary modification on urinary stone risk factors.

BACKGROUND: This study was undertaken to ascertain the effect of dietary modification on urinary stone risks, and to determine whether the response depends on the prevailing urinary calcium. METHODS: A retrospective data analysis was conducted from our stone registry involving 951 patients with calcareous stones undergoing ambulatory evaluation, whereby 24-hour urine samples were collected during random diet and after dietary modification composed of restriction of calcium, oxalate, sodium, and meat products. Samples were analyzed for stone risk factors. Urinary calcium was also obtained after overnight fast and following a 1 g-calcium load. Changes produced by dietary modification from the random diet were evaluated in 356 patients with moderate-severe hypercalciuria (>6.88 mmol/day, group I), 243 patients with mild hypercalciuria (5.00-6.88 mmol/day, group II), and 352 with normocalciuria (<5.00 mmol/day, group III). RESULTS: Urinary calcium postcalcium load and the percentage of patients with absorptive hypercalciuria type I were highest in group I, intermediate in group II, and lowest in group III. During dietary modification, urinary calcium declined by 29% in group I, 19% in group II, and 10% in group III. Urinary oxalate did not change. Urinary saturation of calcium oxalate declined by only 12% in group I, 6% in group II, and nonsignificantly in group III, owing to various physicochemical changes in urinary biochemistry, which attenuated the effect of the decline in urinary calcium. Urinary saturation of brushite declined in all 3 groups due to the fall in urinary calcium, phosphorus, and pH. This reduction was more marked in the hypercalciuric groups than in the normocalciuric group. Urinary saturation of monosodium urate also decreased from a decline in urinary sodium and uric acid. CONCLUSION: Secondary rise in urinary oxalate occurring from calcium restriction can be avoided by concurrent dietary oxalate restriction. Dietary modification (restriction of dietary calcium, oxalate, sodium, and meat products) is more useful in reducing urinary saturation of calcium oxalate among patients with hypercalciuria than among those with normocalciuria.

Reduction in normalized bone elasticity following long-term bisphosphonate treatment as measured by ultrasound critical angle reflectometry.

Using an improved version of ultrasound critical angle reflectometry, the bone quality of cortical and trabecular bone was assessed in vivo by measuring elastic moduli (normalized for bone density) at both principal axes, referred to as the minimum and maximum normalized elasticities. The measurements were made in 30 normal premenopausal women, 30 normal postmenopausal women, 22 untreated postmenopausal women with osteoporosis, 74 postmenopausal women with osteoporosis or osteopenia on bisphosphonate treatment, and 32 patients with renal transplantation (16 women and 16 men) taking steroids. Cortical elasticity was higher than trabecular elasticity; both declined slightly and non-significantly with age in normal women. Among untreated postmenopausal women with osteoporosis, cortical maximum normalized elasticity (E(cmax)) remained within 95% prediction intervals of normal women. Among patients on bisphosphonate, E(cmax) was low in the majority of patients. E(cmax) was significantly more depressed among those taking the drug > or =3 years than <3 years (22.1% below normal premenopausal women versus 17.2%, P =0.001), and among those with incident non-spinal fractures than without (75.9 vs. 81.5%, P =0.008). E(cmax) was independent of bone mineral density at the calcaneus. Most patients with renal transplantation had low E(cmax), with a mean 20.8% below the normal premenopausal mean. Qualitatively similar findings were found with cortical minimum elasticity and with trabecular minimum and maximum elasticities. Thus, the material bone quality of cortical and trabecular bone may be impaired following bisphosphonate treatment, as in renal transplantation on steroids.

Biochemical distinction between hyperuricosuric calcium urolithiasis and gouty diathesis.

OBJECTIVES: To determine whether the biochemical presentation and urinary physicochemical environment of patients with hyperuricosuria presenting with calcium stones (hyperuricosuric calcium urolithiasis [HUCU]) differs from those of patients with gouty diathesis (GD) or idiopathic uric acid urolithiasis. METHODS: A total of 122 patients with HUCU and 68 patients with GD were identified from our "stone registry" of patients who underwent a full ambulatory evaluation. All patients with HUCU had urinary uric acid greater than 800 mg/day in men and greater than 750 mg/day in women and presented with calcium stones. Those with GD had pure uric acid stones or mixed uric acid-calcium stones and did not have secondary causes of uric acid urolithiasis. Data derived from the fasting serum and 24-hour urine samples collected on a random diet and on a diet restricted in calcium, sodium, and oxalate were compared between the two groups. RESULTS: Compared with patients with HUCU, those with GD had significantly higher serum uric acid and lower urinary uric acid and pH levels (mean value 5.38 and 5.35 on random and restricted diets versus 6.09 and 6.14, respectively). The fractional excretion of urate and the discriminant score of the relationship between urinary pH and the fractional excretion of urate were significantly lower in those with GD than in those with HUCU. Patients with HUCU displayed a greater urinary saturation of sodium urate and calcium oxalate compared with those with GD, and those with GD had a higher urinary content of undissociated uric acid and lower urinary saturation of brushite (calcium phosphate). CONCLUSIONS: Patients with HUCU presented with normal urinary pH and hyperuricosuria, accompanied sometimes by hypercalciuria, which produced increased urinary saturation of sodium urate and calcium oxalate. In contrast, those with GD had a low fractional excretion of urate (that contributed to hyperuricemia) and low urinary pH (that led to increased amount of undissociated uric acid). The varying biochemical and physicochemical presentations of the two conditions can be ascribed to overindulgence with purine-rich foods in those with HUCU and underlying primary gout in those with GD.

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.