Mechanisms of hypercalciuria.
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Benzothiadiazines↗
Biomedical subjects
C Y Pak
Publications and source records attributed to C Y Pak.
Oral magnesium load test for the assessment of intestinal magnesium absorption. Application in control subjects, absorptive hypercalciuria, primary hyperparathyroidism, and hypoparathyroidism.
The intestinal absorption of magnesium (Mg) was estimated from the increment in urinary Mg following oral administration of 25 mmol of Mg. Fasting urinary Mg did not differ between the control group and patient groups (absorptive hypercalciuria, primary hyperparathyroidism, and hypoparathyroidism). As compared to the value in the control group, the increment in urinary Mg above the fasting value was not significantly different in absorptive hypercalciuria. However, it was significantly increased in primary hyperparathyroidism and significantly reduced in hypoparathyroidism. In control subjects, the increment in urinary Mg was much higher during a low than during a high calcium diet. The results suggest that 1,25-(OH)2-vitamin D stimulates Mg absorption, since Mg absorption was elevated in situations associated with stimulated 1,25-(OH)2-vitamin D synthesis (primary hyperparathyroidism and low calcium diet) and reduced in a condition characterized by low 1,25-(OH)2-vitamin D production (hypoparathyroidism). Moreover, the data indicate that 1,25-(OH)2-vitamin D may not be pathogenetically important in absorptive hypercalciuria, since Mg absorption was normal.
Adult↗
Metabolic evaluation of nephrolithiasis in patients with medullary sponge kidney.
Seventeen patients with documented medullary sponge kidney and nephrolithiasis underwent metabolic evaluation. These patients constituted 3.6% of our stone-forming population. Fifteen (88%) of 17 were hypercalciuric. The most common abnormality was absorptive hypercalciuria, occurring in 59%. Only three patients (18%) had renal hypercalciuria. None of the patients had primary hyperparathyroidism. Hyperuricosuria occurred together with hypercalciuria in five patients. In two patients, the precise cause of hypercalciuria could not be determined, and in another two patients, no metabolic abnormality could be detected. Thus, the patients with medullary sponge kidney and renal stones had the same spectrum of metabolic abnormalities as the overall population of stone formers. While these patients may theoretically have a greater anatomic propensity to form stones because of their anatomic abnormality, they should be evaluated and treated appropriately for any metabolic defect.
Adult↗
Long-term persistence of metabolic abnormalities in absorptive or renal hypercalciuria.
Seven patients with absorptive hypercalciuria and seven with renal hypercalciuria were re-evaluated 1.67-7.33 years after the original diagnosis. When treatment was temporarily stopped, all showed the same metabolic abnormalities as before: those with absorptive hypercalciuria continued to show increased intestinal absorption of calcium and normal or suppressed parathyroid function, and those with renal hypercalciuria had persistent "renal leak" of calcium and parathyroid stimulation. In view of the persistence of metabolic abnormalities, medical therapy should be regarded as a long-term commitment.
Adult↗
The effect of chronic insulin therapy on phosphate metabolism in diabetes mellitus.
Plasma and urine phosphate concentrations were improved in 21 patients with diabetes mellitus during "optimal" metabolic control as compared with "suboptimal" control. During the "suboptimal" control phase the daily insulin dosage averaged 38 +/- 22 (SD) U/day and the mean plasma glucose levels averaged 17.1 +/- 1.8 mmol/l, while during the "optimal" control phase the daily insulin dosage averaged 84 +/- 59 U/day and the mean plasma glucose level was 6.2 +/- 1.4 mmol/l. The institution of rigid diabetic control over 4-10 days significantly raised serum phosphorus from 1.12 +/- 0.16 to 1.26 +/- 0.19 mmol/l (p less than 0.001), and decreased urinary phosphorus excretion from 686 +/- 125 to 588 +/- 88 mg/day (p less than 0.001). These changes were associated with significant reductions in urinary calcium, urinary glucose, plasma immunoreactive glucagon and serum parathyroid hormone. This diminution in urinary phosphorus loss may have been due to diminished glycosuria but equally could have been influenced by a direct action of insulin on the renal tubule or suppression of glucagon and parathyroid hormone secretion. Under the conditions of this study, reduced urinary phosphorus may have been sufficient to cause a rise in serum phosphorus despite the known effects of insulin on the cellular influx of phosphorus.
Adolescent↗
Is selective therapy of recurrent nephrolithiasis possible?
We evaluated, in 128 patients with recurrent nephrolithiasis, the efficacy of special treatment programs for some of the common causes of nephrolithiasis, chosen on the basis of their ability to correct underlying physicochemical and physiologic derangements. Therapy included sodium cellulose phosphate for 18 patients with absorptive hypercalciuria, thiazide diuretics for 27 patients with absorptive hypercalciuria and for 10 with renal hypercalciuria, orthophosphate for eight patients with hypophosphatemic absorptive hypercalciuria, allopurinol for 21 patients with hyperuricosuric calcium oxalate nephrolithiasis, thiazide and allopurinol for 26 patients with absorptive hypercalciuria with hyperuricosuria, and high fluid intake and/or low calcium diet for 22 patients with normocalciuric nephrolithiasis. Patients in all seven groups had a significant reduction in stone formation during 1.70 to 3.37 years of treatment, as compared with the pretreatment period of three years. Remission was found in 70 to 91 percent of patients and reduced stone formation rate was encountered in 88 to 100 percent. Each treatment program produced a significant decline in stone formation rate from 1.90 to 2.28 stones per year to 0.09 to 0.55 stones per year. The actual number of stones formed during treatment was significantly lower than the number predicted from the pretreatment frequency of stone formation (less than 26 percent). The results provide evidence supporting a selective approach to therapy of nephrolithiasis.
Allopurinol↗
An apparent 1,25-dihydroxyvitamin D-independent stimulation of intestinal calcium absorption in patients with Paget disease of bone during a short-term diphosphonate therapy.
Six patients with Paget disease of bone were treated with a 6-mo course of disodium-ethane-1-hydroxy-1, 1-diphosphate (EHDP) at a dosage of 5 mg/kg/day (one patient) or 20 mg/kg/day (five patients). In addition to symptomatic and biochemical improvement which persisted 3 mo after discontinuance of therapy, EHDP resulted in a significant increase in intestinal calcium absorption that was not correlated with a change in serum 1 alpha, 25-(OH)2-vitamin D concentration. EHDP appears to stimulate intestinal calcium transport by either a vitamin D independent process or by an increased intestinal mucosal cell sensitivity to vitamin D.
Aged↗
Bioavailability of oxalate in foods.
The ability of 7 "oxalate-rich" foods to enhance urinary oxalate excretion was measured in 8 normal volunteers. The analyzed value for oxalate was high for spinach (1,236 mg.), moderate for chocolate (126 mg.) and tea (66 mg.), and for low vegetable juice, cranberry juice, pecans, and orange juice (2 to 26 mg.). The urinary oxalate increased by 29.3 mg. during eight hours after ingestion of spinach. However, it rose by less than 4.2 mg. from consumption of other food items. The bioavailable oxalate (per cent of total appearing in urine) was much less from food items of high or moderate oxalate content (spinach and chocolate) than from standard solutions of sodium oxalate (2.4 to 2.6 versus 6.5 to 7.3 per cent). Thus, only spinach among food items tested was capable of causing hyperoxaluria in normal subjects.
Adult↗
Familial absorptive hypercalciuria in a large kindred.
The occurrence of calcareous renal stones in 12 members of a family was consistent with an autosomal dominant mode of inheritance. All 6 members with stones who were evaluated were shown to have absorptive hypercalciuria. The mother of 2 members with stones did not suffer stones but had biochemical evidence of absorptive hypercalciuria (increased intestinal calcium absorption, hypercalciuria and normal parathyroid function). Nephrolithiasis was encountered only in the progeny of members who had stones of biochemical absorptive hypercalciuria. The results suggest that physiological feature(s) of absorptive hypercalciuria may be an expression of the genetic trait.
Adult↗
Jejunal and ileal adaptation to alterations in dietary calcium: changes in calcium and magnesium absorption and pathogenetic role of parathyroid hormone and 1,25-dihydroxyvitamin D.
Previous balance studies have shown that fractional calcium absorption is increased by a low and reduced by a high calcium diet. The present studies were done to determine which segment of the small intestine is most sensitive to alterations in dietary calcium, and to see if dietary calcium intake has an effect on the intestinal absorption of another divalent cation, magnesium. Absorption was measured during constant perfusion of 30-cm segments of jejunum and ileum of normal subjects after 4 or 8 wk of a high (1,900 mg/d) or a low (20 mg/d) calcium diet. We found that calcium absorption rate was higher when subjects had been on a low than when they had been on a high calcium diet; the ileum responded more rapidly and more completely than the jejunum. Similar results were obtained with magnesium, but only the difference in the ileum was statistically significant. Sodium and xylose absorption were not influenced by dietary calcium intake. The serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D were higher on the low than on the high calcium diet. We conclude that the ileum is more sensitive than the jejunum to changes in dietary calcium intake, and that ileal adaptation probably plays a major role in protecting the body against a deficiency or excess of body calcium that otherwise would occur when dietary calcium is abnormally low or high. Calcium intake influences ileal magnesium absorption in a similar fashion; it is not known whether or not this serves a protective function. Our data are compatible with the concept that adaptation to dietary calcium intake is mediated by changes in the serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D.
Adaptation, Physiological↗
A lack of unique pathophysiologic background for nephrolithiasis of primary hyperparathyroidism.
The metabolic picture of 32 patients with surgically proven primary hyperparathyroidism presenting with renal stones was compared with that of 37 patients without stones. Between stone-forming and nonstone-forming groups, there was no significant difference in serum 1,25-dihydroxyvitamin D [6.82 +/- 2.62 vs. 6.22 +/- 2.33 ng/dl (mean +/- SD); P greater than 0.05], fractional (intestinal) calcium absorption (0.726 +/- 0.141 vs. 0.690 +/- 0.120), urinary calcium (299 +/- 139 vs. 284 +/- 144 mg/day), serum calcium, phosphorus, and parathyroid hormone, or bone density. Similarly, no differences were found between 29 patients presenting with stones alone and 9 presenting with bone disease alone with respect to the above measures. Moreover, urinary environment was typically supersaturated with respect to stone-forming salts regardless of the presence of stones. The results indicate that there is no unique pathophysiological background for the nephrolithiasis of primary hyperparathyroidism.
Blood Chemical Analysis↗
The spectrum and pathogenesis of hypercalciuria.
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Benzothiadiazines↗
Practical outpatient evaluation for recurrent nephrolithiasis.
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Calcium Oxalate↗
Utility and limitation of calciuric response to oral calcium load as a measure of intestinal calcium absorption: comparison with isotopic fractional calcium absorption.
The intestinal absorption of calcium (Ca), indirectly measured from the calciuric response to oral Ca load (1g), was compared to the more directly obtained isotopic fractional absorption, alpha (from the fecal recovery of orally administered 47Ca). In 17 normal subjects and 30 patients with absorptive hypercalciuria (AH), there was a significant (P less than 0.001) correlation of alpha with the Ca load responses, (r = 0.81). However, this correlation was not observed in patients with renal hypercalciuria (RH), and those with AH receiving thiazide or orthophosphate. In RH, 38 per cent of patients had elevated Ca load responses, despite normal values for alpha. The point correlating the calciuric response and alpha in these patients was below the 95 per cent confidence limit of the line correlating alpha and the load response. Thus, Ca load response often overestimated intestinal Ca absorption, because of the high basal (fasting) urinary Ca. Thiazide therapy in RH improved the correlation between the two tests of Ca absorption. However, thiazide therapy in AH produced normal Ca load responses despite persistently high alpha in 60 per cent of patients. Similarly, 50 per cent of patients with AH receiving orthophosphate had normal Ca load response, although alpha remained elevated. Thus, Ca load response underestimated Ca absorption when patients with AH took thiazide or orthophosphate, probably because these drugs augment renal tubular reabsorption of Ca. These data support the Ca load test as a valid indirect measure of intestinal Ca absorption in normal subjects and patients with AH, in whom fasting urinary Ca is not elevated. In conditions of renal Ca, leak or with various drugs known to alter renal Ca handling, there seen to be large deviations of Ca load response from alpha. Care should be exercised before reaching conclusions regarding the intestinal Ca absorption in these situations.
Administration, Oral↗
A cautious use of sodium cellulose phosphate in the management of calcium nephrolithiasis.
Oral sodium cellulose phosphate, an inhibitor of intestinal calcium absorption, may reduce urinary magnesium, increase urinary oxalate, and have a limited hypocalciuric action or cause negative calcium balance in the absence of increased calcium absorption or in the presence of renal calcium "leak". To overcome these potential complications, we have taken the following precautions: oral magnesium supplements were given, a moderate oxalate restriction was imposed, a modest dose of sodium cellulose phosphate was used (usually 10 g per day), and only patients with documented absorptive hypercalciuria were treated. During a cumulative treatment period of 42.8 years, 18 patients with recurrent calcium nephrolithiasis showed a sustained reduction in urinary calcium, without developing consistent or substantial reduction in urinary magnesium, hyperoxaluria, hyperparathyroidism, or reduced bone density, Urinary saturation (relative saturation ratio) of calcium oxalate and brushite typically decreased. Remission of stone disease was found in 78 per cent of patients. We conclude that sodium cellulose phosphate is a useful drug for absorptive hypercalciuria when used appropriately.
Calcium↗
A critical evaluation of treatment of calcium stones.
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Allopurinol↗
Tumoral calcinosis: evidence for concurrent defects in renal tubular phosphorus transport and in 1 alpha,25-dihydroxycholecalciferol synthesis.
A 50-year-old Latin American man with tumoral calcinosis presented with hyperphosphatemia (6.62 +/- 1.04 SD mg/dl), elevated renal threshold phosphorus concentration (TmP) (7.3 mg/GFR), and 1,25-dihydroxyvitamin D [1,25-(OH)2D] (69 pg/ml) hypercalciuria (239 mg/day), and a high fractional intestinal calcium (Ca) absorption (0.74). Sodium cellulose phosphate therapy (20 g/day) lowered urinary Ca, and partially reduced serum phosphorus (P) and TmP to 5.91 +/- 0.63 mg/dl and 6.2 mg/GFR, respectively. Serum 1,25-(OH)2D remained elevated at 58-64 pg/ml. Amphojel therapy (4 oz/day) decreased urinary P to 23 +/- 21 mg/day and lowered serum P to 5.75 +/- 0.36 mg/dl (P < 0.05). TmP increased to a value of 8.0 mg/GFR while serum 1,25-(OH)2D continued to remain elevated at 53 pg/ml. This case illustrates the probable operation of dual abnormalities in tumoral calcinosis represented by augmented renal conservation of P and an elevation in the circulating concentration of 1,25-(OH)2D.
Calcinosis↗
Propensity for spontaneous nucleation of calcium oxalate. Quantitative assessment by urinary FPR-APR discriminant score.
The stone-forming urinary environment may be conducive to spontaneous nucleation of calcium salts, since it is generally characterized by a reduced limit of metastability (FPR or minimum supersaturation required for initiation of spontaneous nucleation) and an increased saturation (APR) of calcium oxalate and brushite (CaHPO4.2H2O). A discriminant analysis of the relationship between FPR and APR yielded a FPR-APR discriminant score, which gave a quantitative measure of the propensity for spontaneous nucleation. Positive scores, indicative of the "likelihood" of spontaneous nucleation, were found in the majority of patients with hypercalciuria in whom stones formed. Negative scores, representative of the "unlikelihood" of nucleation, were found in the majority of control subjects. Treatment with thiazide or sodium cellulose phosphate significantly reduced the discriminant score for both calcium oxalate and brushite, a finding which suggested that the propensity for spontaneous nucleation of calcium salts was retarded. Allopurinol lowered the score for calcium oxalate but not for brushite. Moreover, the FPR-APR discriminant score for calcium oxalate was positively correlated with the stone formation rate. It is concluded that FPR-APR discriminant scores are useful in the identification of stone-forming potential in urine, and in the assessment of response to therapy.
Adolescent↗