Urinary Saturation Of Calcium Oxalate Research Articles

A patient with Primary Hyperoxaluria who developed excessive pericardial effusion despite intensive dialysis

Primary hyperoxaluria type 1 (PH type 1) is a hereditary disorder with excessive production of oxalate caused by deficient liver specific enzyme alanine-glyoxylate aminotransferase (AGT). Increased oxalate production leads to calcium oxalate deposition in different organs and tissues, such as kidney, heart, nervous system, skin, bone and bone marrow. Early diagnosis is essential to prevent complications. Family history, urine oxalate assesment, oxalaemia, determination of oxalate deposits in tissues and genetic analysis are beneficial for diagnosis. Treatment should be started at early stages of the disease in order to decrease urinary saturation of calcium oxalate. High fluid intake, urinary crystallisation inhibitors and pyridoxine may be used. In chronic kidney failure patients renal replacement therapies are necessary, early transplantation is mandatory. We present a 30 year old man with PH type 1 who admitted with severe pericardial effusion, despite the fact that he was maintained both peritoneal dialysis and frequent hemodialysis.

Animal Protein and the Risk of Kidney Stones: A Comparative Metabolic Study of Animal Protein Sources

We compared the effect of 3 animal protein sources on urinary stone risk. 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. 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). 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.

Comparison of Semi-Empirical and Computer Derived Methods for Estimating Urinary Saturation of Calcium Oxalate

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. 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. 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. 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.

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.

Biochemical and Stone-Risk Profiles With Topiramate Treatment

Topiramate is a novel neuromodulatory agent commonly prescribed for the treatment of seizure disorders and for migraine headache prophylaxis. Calcium phosphate kidney stones have been observed with topiramate treatment, but a comprehensive elucidation of stone-risk profile was not reported previously. This study explores the relationship between topiramate treatment and propensity for kidney stone formation. Thirty-two topiramate-treated subjects and 50 healthy volunteers participated in a cross-sectional study in which serum chemistry test and 24-hour urine collection results were evaluated for stone risk. Furthermore, a short-term longitudinal study was conducted in 7 patients to assess stone risk before and 3 months after topiramate treatment. Serum bicarbonate levels were lower with topiramate treatment. Urinary pH, urinary bicarbonate excretion, and fractional excretion of bicarbonate increased, whereas urinary citrate excretion was significantly lower (737 +/- 329 versus 278 +/- 226 mg/d; P < 0.001). Net acid excretion did not change. The relative saturation ratio for brushite increased with topiramate treatment (3.14 +/- 1.69 versus 1.27 +/- 1.26; P < 0.001) because of urinary alkalinization and decreased urinary citrate levels. Urinary saturation of undissociated uric acid decreased (41 +/- 52 versus 76 +/- 60 mg/d; P < 0.001). Treatment with topiramate causes systemic metabolic acidosis, markedly lower urinary citrate excretion, and increased urinary pH. These changes increase the propensity to form calcium phosphate stones.

Urinary Metabolic Evaluations in Normal and Stone Forming Children

Urinary stone disease is relatively rare in children and urinary metabolic evaluations have been the standard in our practice. We have previously reported a high rate of urinary metabolic abnormalities in stone forming children. We compared urinary chemistry values in normal and stone forming children. A prospective study was performed to assess urinary metabolic profiles in children with no history or a family history of urinary calculi. The 24-hour urine collections were performed and evaluated at an outside central laboratory. Urine chemistry studies were adjusted for creatinine. The data were compared to those on a historical cohort of calcium stone forming children. A total of 58 samples from normal children and 142 from stone forming children were evaluated. Mean age was 10 years in normal children and 12 years in stone forming children. of the normal and stone forming children 45% and 51%, respectively, were female. Supersaturation levels of calcium oxalate as well as calcium to creatinine levels were significantly higher in children with stones. No data confounding by age or sex was identified by stratification. There are significant differences in urinary metabolic evaluations between normal and stone forming children. This may allow more precise treatment to prevent recurrent stone episodes. We continue to perform metabolic evaluations in all children with documented urolithiasis.

Effect of High and Low Calcium Diets on Stone Forming Risk During Liberal Oxalate Intake

Recent studies suggest that a high calcium diet protects against calcium oxalate stone formation. We compared the effect of high and low calcium diets on urinary saturation of calcium oxalate during liberal oxalate intake. A total of 10 healthy subjects (5 male, 5 female) participated in a 2-phase, randomized, crossover study comparing high (1,000 mg daily) and low (400 mg daily) calcium intake on a liberal oxalate diet (200 mg daily). During each phase subjects adhered to an instructed diet for 3 days followed by a controlled, metabolic diet for 4 days. Blood and 24-hour urine specimens collected on the last 2 days of each phase were analyzed for serum biochemistry studies and stone risk factors, respectively. Urinary calcium was higher (mean +/- SD 171 +/- 64 vs 124 +/- 49 mg daily, p = 0.002) and oxalate was lower (25 +/- 4.8 vs 27 +/- 4 mg daily, p = 0.02) on the high vs low calcium diet. Overall, the urinary relative saturation ratio of calcium oxalate was higher on the high compared with the low calcium diet (3.3 vs 2.5, p <0.0001) even after adjusting for confounding variables. In normal subjects urinary saturation of calcium oxalate was higher on a high calcium diet than a low calcium diet during liberal oxalate intake because the decrease in urinary oxalate did not overcome the effect of increased calcium. A high calcium diet during liberal oxalate intake may pose an increased risk of calcium oxalate stone formation.

Medical Management of Recurrent Idiopathic Nephrolithiasis

Abstract: This update reviews salient progress in pathophysiology, diagnosis, and medical management. In absorptive hypercalciuria, bone loss accompanies stone formation in some patients. Potential putative gene (soluble adenylyl cyclase) has been identified. The invariant feature in hypocitraturia is low intracellular pH that alters renal tubular metabolism and reabsorption of citrate. In gouty diathesis, uric acid stones develop from low urinary pH, probably resulting from impaired renal ammonia genesis of acquired insulin resistance. The protection against stone formation, conferred by citrus fruits, depends on the potassium content that determines the amount of alkali load delivered. Animal protein excess such as with the Atkins diet confers an acid load that increases urinary calcium and lowers citrate. Dietary calcium restriction lowers urinary calcium and saturation of calcium oxalate among patients with hypercalciuria, but not in those with normocalciuria. A simplified diagnostic evaluation and management may be used among patients with uncomplicated stone disease in an office setting. A 24-hour urine on a random diet should be collected for a full stone risk analysis. Among patients with hypercalciuria, dietary restriction of calcium and oxalate with indapamide (or thiazide) and potassium citrate is recommended. Among normocalciuric patients, liberal calcium intake and potassium citrate should be beneficial.

Prevention of stone formation and bone loss in absorptive hypercalciuria by combined dietary and pharmacological interventions.

We determined whether dietary restriction of calcium and oxalate, combined with thiazide and potassium citrate treatment, would prevent stone formation and avert bone loss in 18 men and 10 women with type I absorptive hypercalciuria. Patients were treated with thiazide (20) or indapamide (8) and potassium citrate (average dose 35 mEq. daily) for 1 to 11 years (mean 3.7) while maintained on low calcium oxalate diet. Serum and urinary chemistry studies and bone mineral density were measured at baseline and at the end of treatment. New stones formed were quantitated during 3 years before and during treatment. During treatment urinary calcium significantly decreased (346 +/- 85 to 248 +/- 79 mg. daily, p <0.001) but urinary oxalate did not change. Urinary pH and citrate significantly increased, and urinary saturation of calcium oxalate significantly decreased by 46%. Stone formation rate decreased significantly from 2.94 to 0.05 per year (p <0.001). L2-L4 bone mineral density increased significantly by 5.7% compared to normal peak value, and by 7.1% compared with normal age and gender matched value. Femoral neck bone mineral density also increased significantly. Dietary restriction of calcium and oxalate, combined with thiazide and potassium citrate, satisfactorily controlled hypercalciuria, prevented the secondary increase in urinary oxalate, reduced urinary saturation of calcium oxalate, virtually eliminated recurrent stone formation, and increased bone density of the spine and femoral neck. Thus, this dietary pharmacological program controlled stone formation as well as bone loss that often accompany type 1 absorptive hypercalciuria.

Effect of dietary modification on urinary stone risk factors

AbstractEffect of dietary modification on urinary stone risk factors. BackgroundThis 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. MethodsA 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). ResultsUrinary 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. ConclusionSecondary 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.

RESULTS OF A PROSPECTIVE TRIAL TO COMPARE NORMAL URINE SUPERSATURATION IN CHILDREN AND ADULTS

Urinary stone disease is relatively rare in children but is often due to metabolic abnormalities. Urinary supersaturation (SS) indices have been suggested as more precise predictors of stone recurrence. We previously reported urinary metabolic evaluations in stone-forming children using adult references. We now assess normal SS values in children. A prospective trial was performed to assess urinary metabolic profiles in children with no personal or family history of urinary calculi. The 24-hour urine collections were performed and evaluated at an outside central laboratory. Urine chemistries were adjusted for urine creatinine. Urine pH and SS for calcium oxalate, calcium phosphate and uric acid were also assessed. The data were compared to a cohort of normal adults. A total of 168 samples from 168 adults (58% males) and 51 samples from 30 children (59% males) were evaluated. The mean age of the children was 8.8 years (range 5 to 18). Calcium oxalate SS was similar between children and adults, and urine pH was the major cause of differences seen in the calcium phosphate and uric acid SS indices. Children had a much higher excretion of calcium, oxalate and citrate when adjusted for creatinine. There are significant differences in the normal ranges of urine chemistries in children and adults. An understanding of normal supersaturation values may allow metabolic abnormalities in stone-forming children to be more precisely diagnosed and treated.

EFFECT OF CRANBERRY JUICE CONSUMPTION ON URINARY STONE RISK FACTORS

We evaluated the effect of cranberry juice on urinary stone risk factors. A total of 12 normal subjects and 12 calcium oxalate stone formers underwent 2, 7-day phases of study in random order while on a controlled metabolic diet. Subjects ingested 1 l of cranberry juice (CBJ) daily in 1 phase and 1 l of deionized water in the other phase. On the last 2 days of each phase 2, 24-hour urine collections and blood samples were obtained for stone risk factors and serum chemistries. No significant differences were found between normal subjects and stone formers in response to CBJ and, therefore, the groups were combined. CBJ significantly increased urinary calcium (from 154 to 177 mg per day, p =0.0008) and urinary oxalate (from 26.4 to 29.2 mg per day, p =0.04), thereby increasing urinary saturation of calcium oxalate by 18%. Urinary citrate was unchanged and urinary magnesium increased slightly. Urinary pH decreased (from 5.97 to 5.67, p =0.0005), and urinary ammonium, titratable acidity and net acid excretion increased during CBJ ingestion. Urinary uric acid decreased (from 544 to 442 mg per day, p <0.0001) as did serum uric acid. Thus, the urinary saturation of brushite and monosodium urate was reduced by CBJ but the amount of undissociated uric acid increased. CBJ exerts a mixed effect on urinary stone forming propensity. It reduces urinary pH likely by providing an acid load and decreases urinary uric acid perhaps by retarding urate synthesis. Overall CBJ increases the risk of calcium oxalate and uric acid stone formation but decreases the risk of brushite stones.

PHYSICOCHEMICAL METABOLIC CHARACTERISTICS FOR CALCIUM OXALATE STONE FORMATION IN PATIENTS WITH GOUTY DIATHESIS

We determined why calcium oxalate stones instead of uric acid stones form in some patients with gouty diathesis. 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. 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). 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.

Relative effect of urinary calcium and oxalate on saturation of calcium oxalate Rapid Communication

The study compared the effect of urinary calcium with that of oxalate on urinary saturation [relative saturation ratio (RSR)] of calcium oxalate. A retrospective data analysis was conducted on urinary stone risk analysis from 667 patients with predominantly calcium oxalate stones. Urinary RSR of calcium oxalate was individually calculated using Equil 2. A "theoretical" curve of the relationship between urinary RSR of calcium oxalate and concentration of calcium or oxalate was obtained at two stability constants for calcium oxalate complex, while varying calcium or oxalate and using group mean values for urinary constituents. At the stability constant of 7.07 x 10(3), the increase in RSR of calcium oxalate was less marked with calcium than with oxalate. However, at the stability constant of 2.746 x 10(3) from the Equil 2 that is considered the "gold standard," calcium and oxalate were equally effective in increasing RSR of calcium oxalate. The above theoretical curves (relating RSR with calcium or oxalate) were closely approximated by the actual curves constructed with data from individual urine samples. Urinary saturation of calcium oxalate was equally dependent on urinary concentrations of calcium and oxalate (r= 0.75 unadjusted and 0.57 adjusted for variables, and P < 0.0001 for calcium; r= 0.73 unadjusted and 0.60 adjusted, P <0.0001 for oxalate). Among calcium oxalate stone-formers, urinary calcium is equally effective as urinary oxalate in increasing RSR of calcium oxalate.

STONE FORMING RISK OF CALCIUM CITRATE SUPPLEMENTATION IN HEALTHY POSTMENOPAUSAL WOMEN

We evaluated the effect of calcium citrate supplementation alone or in combination with potassium citrate on the stone forming propensity in healthy postmenopausal women. 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. 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. 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.

Effect of Ascorbic Acid Consumption On Urinary Stone Risk Factors

Ascorbic acid (AA) has been implicated as a risk factor for calcium oxalate stones due to its conversion to oxalate and potential acidifying properties. We evaluated the effect of AA consumption on urinary saturation of calcium oxalate (CaOx) and urinary pH. A total of 12 normal subjects (NS) and 12 CaOx stone formers (SF) underwent 2, 6-day phases of study while maintained on a controlled metabolic diet. In each phase subjects ingested 1 gm AA or an identical appearing placebo twice daily. On the last 2 days of each phase 2, 24-hour urine collections were analyzed for pH and stone risk factors, and blood specimens were submitted for serum chemistry studies. No difference in urinary pH was found between placebo and AA phases in NS (6.02 versus 6.02) and SF (6.0 versus 6.0). However, urinary oxalate was statistically significantly higher in the AA versus placebo phase for NS (34.7 versus 28.5 mg, p = 0.008) and SF (41.0 versus 30.5 mg, p <0.001). Likewise, the CaOx relative saturation ratio was significantly higher in the AA versus placebo phase for both groups. Ingestion of 2 gm AA daily results in no change in urinary pH but a moderate though statistically significant increase in urinary oxalate in NS (20%) and SF (33%). Stone formers respond no differently to AA than normal subjects. We recommend limiting AA use to less than 2 gm daily in CaOx stone formers.

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.

Etiological Role of Estrogen Status in Renal Stone Formation

Estrogen may protect against kidney stone formation since nephrolithiasis is more common in men than in women. Moreover, the incidence of stones rises after menopause in women. We examined the contribution of estrogen to kidney stone risk by comparing outpatient evaluations in the 2 genders, and in estrogen treated and untreated postmenopausal women. We reviewed the results of the initial evaluation of 1,454 adult calcium oxalate stone formers, including 1,050 men and 404 women. Of the postmenopausal women 39 and 50 were estrogen treated and untreated, respectively. Samples of urine and blood were collected 1 week after the imposition of a diet restricted moderately in sodium and calcium, and modestly in oxalate and animal protein. Compared with men the daily excretion of urinary calcium, oxalate and uric acid was lower in women. Women had lower saturations of calcium oxalate and brushite as well as lower excretion of undissociated uric acid. Compared with men urinary calcium was lower in women until age 50 years, when it equaled that of men. Citrate was equal in the genders until the age 60 years, when it tended to decrease in women. Compared with nontreated postmenopausal women those treated with estrogen had lower mean 24-hour calcium plus or minus SD (155 +/- 62 versus 193 +/- 90 mg. per day, p <0.02), mean 2-hour fasting urine calcium (0.08 +/- 0.05 versus 0.12 +/- 0.09 mg./mg. creatinine, p <0.01) and mean calcium oxalate saturation (5.07 +/- 2.27 versus 6.48 +/- 3.44, p <0.05). The lower risk of stone formation in women may be due to the lower urinary saturation of stone forming salts. Estrogen treatment may decrease the risk of stone recurrence in postmenopausal women by lowering urinary calcium and calcium oxalate saturation.

Influence of Gender and Age on Calcium Oxalate Crystal Growth Inhibition by Urine from Relatives of Stone Forming Patients

We define the relationships between urine inhibition of calcium oxalate crystal growth and age, gender, urine chemistries and stone formation among relatives of calcium stone forming patients. We collected 24-hour urine samples from 366 first degree relatives of calcium stone formers. Calcium oxalate crystal growth inhibition was studied using a constant amount of dialyzed urine protein in a seeded crystallization system. Standard stone risk measurements were also performed on the urine, including supersaturation for calcium oxalate, calcium phosphate and uric acid. By multivariate analysis crystal growth inhibition is strongly inversely related to the amount of protein excreted per day, and the age of the subject. When corrected for protein excretion and age, urine proteins from nonstone forming male subjects inhibited crystal growth more strongly than those from corresponding female subjects. Among stone formers the sex difference was not present. Inhibition of calcium oxalate crystal growth is influenced by a complex combination of gender, age, stone formation and assay conditions. The effect of daily protein excretion is most likely a consequence of using a fixed amount of urine protein per assay. The influence of age is significant and unexplained, with the urine of young people (less than 20 years) demonstrating a vigorous ability to inhibit crystallization. In addition, the urine of nonstone forming male relatives appears to have a greater ability to inhibit crystallization than that of nonstone forming female relatives. Further use of this assay in clinical investigations must take age and gender into proper account.

Increased dietary oxalate does not increase urinary calcium oxalate saturation in hypercalciuric rats

Human calcium oxalate (CaOx) nephrolithiasis may occur if urine is supersaturated with respect to the solid-phase CaOx. In these patients, dietary oxalate is often restricted to reduce its absorption and subsequent excretion in an effort to lower supersaturation and to decrease stone formation. However, dietary oxalate also binds intestinal calcium which lowers calcium absorption and excretion. The effect of increasing dietary oxalate on urinary CaOx supersaturation is difficult to predict. To determine the effect of dietary oxalate intake on urinary supersaturation with respect to CaOx and brushite (CaHPO4), we fed 36th and 37th generation genetic hypercalciuric rats a normal Ca diet (1.2% Ca) alone or with sodium oxalate added at 0.5%, 1.0%, or 2.0% for a total of 18 weeks. We measured urinary ion excretion and calculated supersaturation with respect to the CaOx and CaHPO4 solid phases and determined the type of stones formed. Increasing dietary oxalate from 0% to 2.0% significantly increased urinary oxalate and decreased urinary calcium excretion, the latter presumably due to increased dietary oxalate-binding intestinal calcium. Increasing dietary oxalate from 0% to 2.0% decreased CaOx supersaturation due to the decrease in urinary calcium offsetting the increase in urinary oxalate and the decreased CaHPO4 supersaturation. Each rat in each group formed stones. Scanning electron microscopy revealed discrete stones and not nephrocalcinosis. X-ray and electron diffraction and x-ray microanalysis revealed that the stones were composed of calcium and phosphate; there were no CaOx stones. Thus, increasing dietary oxalate led to a decrease in CaOx and CaHPO4 supersaturation and did not alter the universal stone formation found in these rats, nor the type of stones formed. These results suggest the necessity for human studies aimed at determining the role, if any, of limiting oxalate intake to prevent recurrence of CaOx nephrolithiasis.