Urinary oxalic acid excretion differs after oral loading of rats with various oxalate salts

BACKGROUND: To compare urinary oxalate excretion after the oral administration of oxalic acid, disodium oxalate, or calcium oxalate in rats. METHODS: Male Wistar rats were divided into four groups of six rats each and were intravenously hydrated with normal saline, and then were administered normal saline (control group), 10 mg of oxalic acid, equimolar disodium oxalate, or equimolar calcium oxalate via a gastrostomy. Urine specimens were collected just before administration and at hourly intervals up to 5 h afterwards. The urinary oxalate, calcium, magnesium and phosphorus levels were measured. RESULTS: Urinary oxalate excretion peaked at 1-2 h after administration of oxalic acid or equimolar disodium oxalate, while administration of calcium oxalate only caused a small increase of urinary oxalate excretion. Cumulative urinary oxalate excretion during 5 h was 1.69 +/- 0.10 mg (mean +/- SD; 17%), 1.43 +/- 0.13 mg (13%), and 0.22 +/- 0.03 mg (2%) after the administration of oxalic acid, disodium oxalate, and calcium oxalate, respectively. Urinary calcium excretion showed a decrease in the oxalic acid and disodium oxalate groups, while urinary magnesium or phosphorus excretion did not change significantly. CONCLUSION: The upper gastrointestinal tract seems to be the major site of oxalic acid absorption and only free oxalate is absorbed irrespective of whether it is the sodium salt or not. After binding to calcium in the gut, oxalic acid absorption seems to be inhibited in the presence of calcium and this means that calcium oxalate is poorly absorbed (at least in the upper gastrointestinal tract).     

Urinary pyrophosphate in patients with recurrent calcium urolithiasis and in healthy controls: a re-evaluation

The excretion of inorganic pyrophosphate was studied in daily, fasting and postprandial urine specimens of normocalciuric and hypercalciuric patients with recurrent renal calcium stone disease (40 men and 40 women), and healthy controls (20 men and 20 women). Both populations were subdivided into younger (20 to 40 years old) and older (more than 40 years old) individuals. In general, there was a tendency towards higher urinary pyrophosphate excretion with increasing age (both sexes and all groups studied), and lower excretion in women than in men. The urinary pyrophosphate excretion rate was unchanged in daily and fasting urine specimens of the younger male normocalciuric and idiopathic hypercalciuric stone patients, whereas in the daily and postprandial urine of younger women the median excretion rate was reduced (controls versus normocalciuric plus idiopathic hypercalciuric subjects, 3 versus 1 mumol., p less than 0.05). In contrast, in older men urinary pyrophosphate was reduced in daily specimens (controls versus normocalciuric plus idiopathic hypercalciuric subjects, 55 versus 33 mumol., p less than 0.05) but it was unchanged in fasting urine specimens. In older women no change was detectable in any of the 3 urine portions. Factorization of urinary pyrophosphate for the associated urinary creatinine did not alter these results substantially, and the presence of renal stones did not modify pyrophosphate excretion significantly. Urinary pyrophosphate was correlated significantly with urinary volume, citrate and phosphorus. We conclude that only subclassification of stone patients with respect to sex, age and type of calciuria, and consideration of additional urine portions besides the daily urine may help to uncover states of urinary pyrophosphate deficit. On the basis of the data, we recommend that clinically relevant studies on inhibitory effects of urinary pyrophosphate on the nucleation and growth of crystals and stones should be done preferentially in urine portions with a proved pyrophosphate deficit.     

The possible role of prostaglandin E2 in urinary stone formation

To investigate the role of prostaglandin E2 in urinary stone formation, urinary prostaglandin E2 was measured by radioimmunoassay in 28 men with recurrent idiopathic urolithiasis (14 normocalciuric and 14 hypercalciuric patients) and 6 healthy male volunteers. Urinary prostaglandin E2 levels were significantly higher (p less than 0.01) in the hypercalciuric group than in the normocalciuric and healthy control groups, and they showed a positive correlation with urinary calcium excretion. Urinary prostaglandin E2 and calcium excretions in the hypercalciuric and normocalciuric groups were suppressed significantly by indomethacin. Creatinine clearance was not reduced by indomethacin. The results suggest that renal prostaglandin E2 may participate in calcium stone formation by regulating the renal tubular handling 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.     

Gastrointestinal oxalic acid absorption in calcium-treated rats

We studied whether urinary oxalate excretion after an acute oral load of oxalic acid is influenced by concomitant administration of calcium in rats. Male Wistar rats weighing approximately 180 g were divided into six groups of five animals each. After inducing anesthesia, the animals were orally (via a gastrostomy) given 110 μmol of oxalic acid along with 0, 27.5, 55, 110, or 220 μmol of calcium (0, 27.5, 55, 110, or 220 μmol Ca group, respectively). Saline was given to the control group instead of oxalic acid. Urine specimens were collected before administration and then at hourly intervals up to 5 h afterward. Urinary oxalate and citrate levels were measured by capillary electrophoresis, while urinary calcium, magnesium, and phosphorus levels were measured by ICP spectrophotometry. Urinary oxalate excretion peaked at 1 h after administration and was higher in the 0, 27.5, and 55 μmol Ca groups than in the control group. The urinary recovery of oxalate in these groups was 10–15%, while the recovery rate was less than 3% in other groups. Urinary Ca excretion showed no significant changes, either over time or between groups. Free oxalic acid is absorbed more readily from the gastrointestinal tract than calcium oxalate, while simultaneous administration of calcium appears to block intestinal oxalic acid absorption in a dose-dependent manner.     

Urinary response to an oxalic acid load is influenced by the timing of calcium loading in rats

PURPOSE: Dietary intake of calcium or dairy products has been shown to decrease urinary oxalate excretion by limiting its intestinal absorption. However, not enough attention has been given to whether there is any benefit from altering the schedule of ingesting calcium and oxalate. Therefore, we investigated the effects of changes in the timing of calcium and oxalate loading on urinary oxalate excretion. MATERIALS AND METHODS: Male Wistar rats weighing 180 to 200 gm were fasted and randomized into several groups. They were then administered normal saline or oxalic acid with or without calcium or milk. Calcium or milk was given immediately, or 5, 10, 15 or 30 minutes before or after the oxalate load. All treatments were given via gastrostomy. Urine samples were collected by bladder puncture just before administration and at hourly intervals up to 5 hours afterward. Urinary oxalate was measured by capillary electrophoresis. RESULTS: Urinary oxalate increased after the administration of oxalate alone, while it decreased when oxalate was combined with calcium or milk. Urinary oxalate showed a smaller increment when calcium or milk was given before than after oxalate loading, and it was much smaller when calcium or milk was given immediately before oxalate. CONCLUSIONS: Prior calcium loading appears to have a positive influence on decreasing oxalic acid absorption from the intestinal tract. Therefore, calcium or dairy products should always be ingested before a meal rich in oxalate to prevent oxalate absorption and decrease urinary oxalate excretion.     

Urinary ionized calcium in urolithiasis. Effect of cranberry juice

Urinary ionized calcium was determined by a calcium activity electrode in 32 normal persons and in 54 patients with calcium-containing renal stones and without urinary tract infection. It was found to be 38 per cent higher in patients with calcium-containing renal stone in comparison to normal persons. However, this was not statistically significant. No consistant change in total or ionized calcium excretion was produced in normal volunteers by the administration of as much as 5 pints of cranberry juice. In patients with renal stones, the urinary ionized calcium was reduced during the cranberry juice ingestion by 50 per cent, which was statistically highly significant.     

Pattern of calcium metabolism in normo- and hypercalciuric patients with calcium urolithiasis in Saudi Arabia

Urinary calcium excretion was measured in 100 consecutive normocalcemic patients with calcium urolithiasis and 12 Saudi Arabian controls while the patients and the controls were eating their usual diet of unknown calcium content. Only 16 patients were hypercalciuric using the definition of twenty-four-hour urinary calcium of more than 300 mg for males and more than 250 mg for females, and one of these patients was subsequently found to have hyperparathyroidism. The twenty-four-hour urine calcium was less than 200 mg in 60 per cent of male patients and in all the male controls. Since the dietary intake of calcium during the twenty-four-hour urinary collection was unknown, a 1,000-mg calcium loading test was performed in an attempt to differentiate various patterns of abnormal calcium excretion. Of the twenty-four-hour normocalciuric patients 10 (18%) had "absorptive hypercalciuria" and 16 patients (29%) demonstrated a "renal hypercalciuria" pattern. Thirty-nine patients (57%) and all 12 controls had normocalciuria before and after calcium loading.     

Idiopathic hypercalciuria: association with isolated hematuria and risk for urolithiasis in children. The Southwest Pediatric Nephrology Study Group

A prospective multicenter study was designed to determine the frequency and prognostic importance of hypercalciuria in children with hematuria. Urinary calcium excretion was examined in 215 patients with unexplained isolated hematuria (no proteinuria, urolithiasis, infection or systemic disorder). Hypercalciuria (urinary calcium excretion greater than 4 mg/kg/day) was identified in 76 patients (35%). Compared to patients with normal urinary calcium excretion, children with hematuria and hypercalciuria were characterized by male preponderance, white race, family history of urolithiasis, gross hematuria and calcium oxalate crystals. Renal biopsies were performed in 10 patients with urinary calcium excretion 0.4 to 2.5 mg/kg/day; three had IgA glomerulonephritis, three had glomerular basement membrane thinning, one had proliferative glomerulonephritis and three were normal. Renal biopsies in three patients with hypercalciuria showed focal segmental glomerulosclerosis, hereditary nephritis or no abnormalities. Oral calcium loading tests showed renal hypercalciuria in 26 patients, absorptive hypercalciuria in 15 patients and were not diagnostic in 35 patients. Serum parathyroid hormone, bicarbonate and phosphorus and urinary cyclic adenosine monophosphate concentrations were similar in the three groups of hypercalciuric patients. Urinary calcium excretion after one week of dietary calcium restriction was higher (5.8 mg/kg/day) in renal hypercalciuria than in other hypercalciuric patients (3.4 mg/kg/day), P less than 0.01. One to four years follow-up was available for 184 patients. Eight of 60 hypercalciuric patients developed urolithiasis or renal colic compared to 2 of 124 patients with normal urinary calcium excretion (P less than 0.001). Hypercalciuria is commonly associated with isolated hematuria and represents a risk factor for future urolithiasis in children with hematuria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calcium phosphate supersaturation regulates stone formation in genetic hypercalciuric stone-forming rats

BACKGROUND: Hypercalciuria is the most common metabolic abnormality observed in patients with nephrolithiasis. Hypercalciuria raises urine supersaturation with respect to the solid phases of calcium oxalate and calcium phosphate, leading to an enhanced probability for nucleation and growth of crystals into clinically significant stones. However, there is little direct proof that supersaturation itself regulates stone formation. Through successive inbreeding of the most hypercalciuric progeny of hypercalciuric Sprague-Dawley rats, we have established a strain of rats, each of which excrete abnormally large amounts of urinary calcium and each of which forms calcium phosphate kidney stones. We used these hypercalciuric (GHS) rats to test the hypothesis that an isolated reduction in urine supersaturation, achieved by decreasing urine phosphorus excretion, would decrease stone formation in these rats. METHODS: Thirty 44th-generation female GHS rats were randomly divided into three groups. Ten rats received a high-phosphorus diet (0.565% phosphorus), 10 a medium-phosphorus diet (0.395% phosphorus), and 10 a low-phosphorus diet (0.225% phosphorus) for a total of 18 weeks. The lowered dietary phosphorus would be expected to result in a decrease in urine phosphorus excretion and a decrease in urinary supersaturation with respect to the calcium phosphate solid phase. Every two weeks, 24-hour urine collections were obtained. All relevant ions were measured, and supersaturation with respect to calcium oxalate and calcium hydrogen phosphate were determined. At the conclusion of the experiment, each rat was killed, and the kidneys, ureters, and bladder were dissected en block and x-rayed to determine whether any stones formed. A decrease in stone formation with a reduction in urinary supersaturation would support the hypothesis that supersaturation alone can regulate stone formation. RESULTS: Decreasing the dietary phosphorus intake led to a progressive decrease in urine phosphorus excretion and an increase in urine calcium excretion, the latter presumably caused by decreased intestinal calcium phosphate binding and increased calcium absorption. With decreasing dietary phosphorus intake, there was a progressive decrease in saturation with respect to the calcium phosphate solid phase. Fifteen of the 20 kidneys from the 10 rats fed the high-phosphorus diet had radiographic evidence of kidney stone formation, whereas no kidneys from the rats fed either the medium- or low-phosphorus diet developed kidney stones. CONCLUSIONS: A decrease in urine phosphorus excretion not only led to a decrease in urine supersaturation with respect to the calcium phosphate solid phase but to an elimination of renal stone formation. The results of this study support the hypothesis that variation in supersaturation alone can regulate renal stone formation. Whether a reduction of dietary phosphorus will alter stone formation in humans with calcium phosphate nephrolithiasis remains to be determined.     

Clinical studies on recurrence of urolithiasis. (2) Hypercalciuria and recurrence of urolithiasis

According to the dynamics of the urinary calcium excretion mechanism, we have classified the patients with urolithiasis into 4 groups, namely group I (normocalciuria; urinary calcium excretion of 270 mg/day or less for male patients and 210 mg/day or less for female patients), group II (absorptive hypercalciuria; hypercalciuric with urinary calcium excretion of 200 mg/day or less under the low calcium diet), group III (renal hypercalciuria; hypercalciuric with urinary calcium excretion exceeds 200 mg/day even under a low calcium diet), and group IV (hyperparathyroidism; hypercalciuric patients as in group III with high serum calcium). Of the 97 stone formers, 77 were classified into group I, 9 into group II, 8 into group III and 3 into group IV. Both under the restricted diet and under the ambulatory free diet, urinary calcium excretion of groups II, III and IV was significantly higher than that of the group I patients. It was noteworthy, however, that some of the patients in group I excreted much calcium without restriction of their diet. Although no difference in excretion of oxalate, magnesium and phosphate was observed between the 4 groups, the patients in groups II, and III excreted more uric acid into their urine than group I patients. As for stone recurrence rate, no difference was noted between group I and group II, III or IV. Based on these findings, we conclude that hypercalciuria has no significant role in the stone forming mechanism. However, lowering of urinary calcium and other stone forming constituents is mandatory in preventing stone recurrence until the mechanism of stone formation is elucidated more precisely.     

Pattern of urolithiasis in a general hospital a prospective study

Judging from the abundance of papers published in the medical journals there appears to be a global increase in the incidence of urolithiasis. Urinary excretion of various stone-forming salts in a 24-hour urine specimen is the mainstay of the metabolic workup done in stone-formers. According to the findings patients have been classified into neat categories depending on whether they were hypercalciuric, hyperuriocosuric, etc. As a group their excretion of calcium, oxalate, and urate was not different from the controls. However, they excreted significantly more phosphate and had lower 24-hour urine volumes than the controls.     

The determination of urinary oxalate by gas chromatography

A new quantitative determination method for urinary oxalate by gas chromatography has been established. This method consists of concentration of urine to dryness followed by methylation of the oxalic acid with 7 per cent hydrochloric acid-methanol, subsequent extraction with chloroform and gas chromatographic analysis. The advantages of the technique are smaller sample sizes (only 5 ml.), rapidity (within 2 to 3 hours) and accuracy (99.14 plus or minus 1.34 per cent recovery). In addition, the treatment of the sample is simple and no specialized equipment is required. Therefore, this method is recommended to clinicians for routine determination of oxalic acid in urine. Urinary oxalate content was analyzed with this method in 62 male patients with calcium oxalate stones. Urinary oxalate concentration and excretion in 33 patients with recurrent stones were significantly higher than in the 22 controls using Welch's test.     

Interdependence of urinary factors in calcareous bladder stone patients

Twenty-four-hour urinary excretion of calcium, oxalic acid, inorganic phosphorus, magnesium and citric acid was examined in fifty-nine stone formers with bladder stones. Hypercalciuria and hyperoxaluria were present in 18.6% and 44.1%, respectively, while 11.9% of patients had both abnormalities. Hypomagnesuria and hypocitraturia were present in 67.8% and 69.5%, respectively, while 45.7% had both of these abnormalities. Normal urine chemistry in respect of parameters studied was observed only in 1.7% of cases. In 15.2% one risk factor was present, while 83.1% had two or more risk factors. “Path” analysis of the urinary parameters directly related to calcium lithiasis showed that magnesium and oxalic acid have substantial influence on calcium excretion, whereas citric acid had none. The influence of phosphorus did not provide any consistent trend.     

Estimation of the concentration of urinary ionic calcium and its clinical role in urolithiasis

The concentration of urinary ionic calcium was estimated using an ion-selective electrode and ion analyzer for healthy controls and patients with calcium urolithiasis. The following results were obtained: 1) After calculating the ionic strength and calibrating the standard solutions of ionic calcium in each urine, the urinary ionic calcium was estimated using an ion-selective electrode and ion analyzer. The reproducibility and accuracy of the value of urinary ionic calcium were satisfactory. 2) There was a significant correlation between the concentration of urinary ionic calcium and the total calcium excretion. Although the percentage of ionic calcium did not show any correlations among the total calcium, oxalate and urinary pH, it had an inverse relation to urinary citrate and phosphate. 3) In calcium stone formers, the excretion of ionic calcium was higher than in healthy controls significantly. 4) In hypercalciuric calcium stone formers, the concentrations and excretions of total and ionic calcium were significantly higher than in normocalciuric calcium stone formers. However, the percentage of ionic calcium was not different. 5) When the patients were treated with citrate orally, the excretion of urinary citrate was increased, and the excretion of ionic calcium and the percentage for total calcium were decreased significantly. There were significant reductions of ionic calcium in the urine after oral administration of rice-bran. 6) The estimation of urinary ionic calcium might be important to evaluate the urinary risk in recurrent calcium stone, and to estimate the effects of the preventive treatments for its recurrence.     

Ascorbic acid in idiopathic recurrent calcium urolithiasis in humans – does it have an abettor role in oxalate, and calcium oxalate crystallization?

The role of ascorbic acid (ASC) in the pathophysiology of renal calcium stones is not clear. We evaluated ASC in blood and urine of fasting male patients with idiopathic calcium urolithiasis (ICU) and healthy volunteers. Using smaller subgroups, we also evaluated their response to exogenous ASC [either intravenous or oral ASC (5 mg/kg bodyweight)] administered together with an oxalate-free test meal. The influence of ASC on calcium oxalate crystallization, the morphology of crystals at urinary pH 5, 6 and 7, and the effect of increasing duration of urine incubation on urinary oxalate at these pHs, without and with addition of ASC, were studied too. In normo- and hypercalciuric ICU, blood and urinary ASC from fasting patients remained unchanged, but the slope of the regression line of urinary ASC versus urinary oxalate was steeper than in the controls; the plasma ASC half-life did not differ between controls, normo- and hypercalciuric ICU; the ASC-supplemented meal caused an increase in the integrated plasma oxalate in the normocalciuric subgroup versus controls. In normo- and hypercalciuric ICU urinary oxalate, the oxalate/glycolate ratio, and calcium oxalate supersaturation were increased, but urinary glycolate was unchanged. In the controls, oral ASC did not affect calcium oxalate crystallization, while in ICU, ASC inhibited crystal growth. In control urine calcium oxalate dihydrate and calcium oxalate monohydrate develops, while in ICU urine only the former crystal type develops. In vitro oxalate neoformation from ASC did not occur. It was concluded that (1) under normal conditions an abettor role of ASC for renal stones is not recognizable, (2) in ICU, urinary oxalate excess unrelated to degradation of exogenous ASC is exhibited, and that this is most likely unrelated to an initial increase in oxalate biosynthesis, and (3) ASC appears to modulate directly calcium oxalate crystallization in ICU, although the true mode of action is still not known. Received: 24 September 1999 / Accepted: 16 December 1999     

The role of hyperoxaluria in the formation of calcium oxalate urinary calculi, and its association with other biochemical measurements

The part played by hyperoxaluria in the formation of calcium oxalate urinary calculi was studied in 153 patients who had each been diagnosed as having calcium oxalate urinary calculi on one or more occasions. Seventy-seven of the patients excreted normal amounts of calcium (less than 6.2 mmol/d), and 76 had hypercalciuria (excretion greater than or equal to 6.2 mmol/d); each group was divided into a further two groups depending on whether the oxalate concentration was above or below 0.16 mmol/l. Pure calcium oxalate stones were more common in patients whose calcium excretion was normal, and mixed calcium oxalate and phosphate stones were more common among hypercalciuric patients. Urinary concentrations/day of magnesium, citrate, and phosphorus were significantly lower in the two groups in which the oxalate concentrations were below 0.16 mmol/l than in a normal control group, and magnesium and phosphorus were significantly lower in the two groups in which oxalate concentrations were less than 0.16 mmol/l than in the two in which they were above that value. The concentration of citrate was also lower, but not significantly so. In addition, the pH of the urine in patients with mixed stones was significantly higher in all groups than when the stones were composed of pure calcium oxalate.     

Nutrition and urinary calcium stone formation in northwestern India: a case control study

The nutrient intake of 69 stone formers (SFs) from three subsets of the local population (urban 22, rural tribal 22 and rural nontribal 25) and 69 age, sex, weight and socioeconomically matched control subjects (NSs) (urban 20, rural tribal 22 and rural nontribal 27) was studied. Simultaneously their timed 24-h urine samples collected over a similar period were analyzed. In general caloric and protein intake was low in all the groups but was strikingly low in the rural subjects. Intake of all nutrients was lowest in the tribal group. Although no difference was observed in diet between NSs and SFs in the same population subjects, SFs had higher urinary excretion of oxalic acid and calcium and lower excretion of citric acid and excreted more saturated urine. Notably magnesium intake was normal in both NSs and SFs, but mean excretion of magnesium was lower than normal in all the groups, suggesting its defective absorption. The influence of dietary intake of protein, carbohydrate, fat, fiber, calcium and oxalic acid on urinary excretion of calcium, oxalic acid, uric acid, inorganic phosphorus, magnesium and citric acid was examined using the chi-square test. No association was observed, thus suggesting that this low nutrient intake did not influence the lithogenic process. Thus, the overall observations suggest: (a) poor nutrition, (b) no effect of diet on urinary stone disease, (c) no difference in the nutrient intake between NSs and SFs and (d) a higher excretion of promoters and a lower excretion of inhibitors in SFs than in NSs.     

The Relation Between Bone and Stone Formation

Hypercalciuria is the most common metabolic abnormality found in patients with calcium-containing kidney stones. Patients with hypercalciuria often excrete more calcium than they absorb, indicating a net loss of total-body calcium. The source of this additional urinary calcium is almost certainly the skeleton, the largest repository of calcium in the body. Hypercalciuric stone formers exhibit decreased bone mineral density (BMD), which is correlated with the increase in urine calcium excretion. The decreased BMD also correlates with an increase in markers of bone turnover as well as increased fractures. In humans, it is difficult to determine the cause of the decreased BMD in hypercalciuric stone formers. To study the effect of hypercalciuria on bone, we utilized our genetic hypercalciuric stone-forming (GHS) rats, which were developed through successive inbreeding of the most hypercalciuric Sprague-Dawley rats. GHS rats excrete significantly more urinary calcium than similarly fed controls, and all the GHS rats form kidney stones while control rats do not. The hypercalciuria is due to a systemic dysregulation of calcium homeostasis, with increased intestinal calcium absorption, enhanced bone mineral resorption, and decreased renal tubule calcium reabsorption associated with an increase in vitamin D receptors in all these target tissues. We recently found that GHS rats fed an ample calcium diet have reduced BMD and that their bones are more fracture-prone, indicating an intrinsic disorder of bone not secondary to diet. Using this model, we should better understand the pathogenesis of hypercalciuria and stone formation in humans to ultimately improve the bone health of patients with kidney stones.     

Treatment of hypercalciuria found in urolithiasis patients

To reduce urinary calcium excretion, 50 mg of hydrochlorothiazide per day was given to 35 patients with hypercalciuria. Urinary calcium decreased significantly after 4 weeks of drug administration, but urinary magnesium did not change. Magnesium calcium ratio increased significantly. Although serious side effects were not seen, serum potassium decreased and serum uric acid increased significantly. From these results thiazide seems to be a useful and safe medicine to reduce urinary calcium excretion. The dose and method of administration require further examination because the patients have to take the drug for a long time.