Effect of oral calcium loading on intact PTH and calcitriol in idiopathic renal calcium stone formers and healthy controls

The calciuric response after an oral calcium load (1000 mg elemental calcium together with a standard breakfast) was studied in 13 healthy male controls and 21 recurrent idiopathic renal calcium stone formers, 12 with hypercalciuria (UCa x V > 7.50 mmol/24 h) and nine with normocalciuria. In controls, serum 1,25(OH)2 vitamin D3 (calcitriol) remained unchanged 6 h after oral calcium load (50.6 +/- 5.1 versus 50.9 +/- 5.0 pg/ml), whereas it tended to increase in hypercalciuric (from 53.6 +/- 3.2 to 60.6 +/- 5.4 pg/ml, P = 0.182) and fell in normocalciuric stone formers (from 45.9 +/- 2.6 to 38.1 +/- 3.3 pg/ml, P = 0.011). The total amount of urinary calcium excreted after OCL was 2.50 +/- 0.20 mmol in controls, 2.27 +/- 0.27 mmol in normocalciuric and 3.62 +/- 0.32 mmol in hypercalciuric stone formers (P = 0.005 versus controls and normocalciuric stone formers respectively); it positively correlated with serum calcitriol 6 h after calcium load (r = 0.392, P = 0.024). Maximum increase in urinary calcium excretion rate, delta Ca-Emax, was inversely related to intact PTH levels in the first 4 h after calcium load, i.e. more pronounced PTH suppression predicted a steeper increase in urinary calcium excretion rate. Twenty-four-hour urine calcium excretion rate was inversely related to the ratio of delta calcitriol/deltaPTHmax after calcium load (r = -0.653, P = 0.0001), indicating that an abnormally up-regulated synthesis of calcitriol and consecutive relative PTH suppression induce hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)     

The tale of parathyroid function in idiopathic hypercalciuria

At the origin, idiopathic hypercalciuria has been described as a syndrome consisting of normocalcemia, low plasma phosphate levels and abnormally high urinary calcium excretion. The cause of this syndrome was subject to many investigations throughout the years. Two main pathophysiologic hypotheses have been proposed: a) primary intestinal hyperabsorption of calcium, leading to depression of parathyroid hormone (PTH) secretion ("absorptive" hypercalciuria); and b) primary renal tubular leak of calcium which stimulates PTH secretion (secondary hyperparathyroidism). Most of the published studies indicate that intestinal hyperabsorption of calcium with subsequent relative hypoparathyroidism is the primary event causing idiopathic hypercalciuria, and that this occurs as a consequence of increased production of 1,25(OH)2-vitamin D3 (calcitriol). Fasting hypercalciuria, originally taken as evidence for a "renal leak" of calcium, appears to be, at least in part, the consequence of relative hypoparathyroidism.     

Calciotropic hormones and nephrolithiasis

In recurrent calcium stone formers interfering factors or changes in receptor sensitivity may alter the interrelationships among calcium-regulating hormones, and hormonal behavior often does not fit with the theoretical assumptions. The vitamin D system appears to have the most important metabolic and clinical effects. Abnormal up-regulation of the synthesis of calcitriol and the consequent parathyroid hormone (PTH) suppression can induce hypercalciuria. Consequently, the hypocalciuric effect of thiazide would be caused by an enhanced response to PTH and by a reduction in 1,25(OH)2-vit D. A negative role of vitamin D on the skeleton has been observed in the presence of a negative calcium balance. Moreover, vitamin D also plays a role in urine oxalate excretion. PTH seems not to be directly stimulated in hypercalciuria and recurrent calcium nephrolithiasis, and patients with hyperparathyroidism and recurrent calcium nephrolithiasis show a similar degree of bone demineralization, irrespective of the presence of absence of the so-called 'primary hyperparathyroidism.' Calcitonin plays a contributory role in the pathogenesis of recurrent calcium nephrolithiasis that seems to be strictly related to dietary calcium intake. A higher sensitivity of thyroid C cells, particularly in absorptive hypercalciuric patients, could be related to the pathogenesis of hypercalciuria and contribute to its persistence.     

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Hyperuricosuria and urolithiasis

Hyperuricosuria with or without hypercalciuria amounted to about 23% of the possible cause of urolithiasis in my clinical experience. Approximately three forth of urolithiasis caused by hyperuricosuria was calcium oxalate stones and the rest was uric acid stones. Uric acid is one of the composition of urinary stones itself, but it has an activity of calcium oxalate stone formation. The hypotheses why the uric acid induced calcium oxalate stones were introduced. The preventive effect of allopurinol on the recurrent calcium oxalate stone formers was proved in our previous study which may revealed the urinary uric acid promoted calcium oxalate stone formation or masked the inhibitory activity of urinary macromolecular inhibitors. On the basis of above statement, I emphasize the importance of the treatment of hyperuricosuria in preventing urinary stones.     

Salt intake, urinary sodium, and hypercalciuria

Several studies have reported that high sodium (Na) intake increases not only urinary Na but also urinary calcium (Ca), suggesting that high Na intake could be involved in the pathogenesis of hypercalciuria. No research data are available on the relationship of Na intake to the prevalence of hypercalciuria within the general population. Moreover, it is not clear if Na intake relates only to urinary Ca or also to other indices of Ca homeostasis, including intestinal Ca absorption. In the present paper, two distinct studies addressed these points using 24-hour urinary Na as an index of salt intake in individuals on their habitual unrestricted free diet. Study 1 analyzed the relationship between 24-hour urinary Na and hypercalciuria (24-hour urinary Ca > or = 7.5 mmol in men, > or = 6.25 mmol in women) in a population sample of 203 men and women, aged 20-59 years. Study 2 analyzed the relationship between 24-hour urinary Na and intestinal strontium (Sr) absorption, used as an index of intestinal Ca absorption, urinary (24-hour and fasting) and plasma Ca, and plasma parathyroid hormone in 36 healthy men and women, aged 18-65 years. Within the population sample (study 1), 24-hour urinary Na was directly and significantly correlated with prevalence of hypercalciuria when controlling for gender, age, weight, and urinary creatinine: the relationship was continuous and linear for urinary Na ranging between 40 and 200 mmol/24 h. In the 36 volunteers (study 2), 24-hour urinary Na was related to 24-hour and fasting urinary Ca (p < 0.001) but not to intestinal Sr absorption: the relationship between 24-hour urinary Na and urinary Ca (both 24 h and fasting) was also significant, controlling for other variables. The results indicate that in adults on their habitual diet, urinary Na, which reflects dietary salt intake, correlates with the prevalence of hypercalciuria independently of intestinal Ca absorption and mainly via renal mechanisms.     

Reduction of urinary stone recurrence by dietary counseling after SWL

To reduce the recurrence rate of or urolithiasis, dietary counseling was conducted for calcium-stone patients. Sixty-six patients received dietary counseling and were in principle instructed to use the Recommended Dietary Allowance for Japanese as their goal. Seventy-three patients did not undergo the counseling. Comparison of the dietary intake of the patients with the dietary requirements for Japanese revealed that protein intake, especially animal protein intake, was higher and calcium intake lower in the patients. As a result of the counseling, intakes of total protein, animal protein, fat, and carbohydrates were all reduced. Patients in the stone recurrence-free group excreted less oxalate than those in the recurrent one. The excretion of oxalate was then reduced and urine volume increased owing to the diet counseling program. The stone recurrence rate of the group participating in the diet counseling was lower than that of the group not taking part. The recurrence rate of the hyperoxaluric group was higher, with statistical significance, than that of the normooxaluric group among those not receiving the dietary counseling. With dietary counseling, the recurrence rate significantly decreased in the hyperoxaluric patients. Thus, the reduction in the rate of stone recurrence resulting from participation in the diet counseling program seemed to be attributable to the decrease in urinary oxalate excretion. Dietary counseling seems to be a useful measure to prevent urinary stone recurrence.     

Alendronate decreases urine calcium and supersaturation in genetic hypercalciuric rats

BACKGROUND: The mechanism of excess urine calcium excretion in human idiopathic hypercalciuria (IH) has not been determined but may be secondary to enhanced intestinal calcium absorption, decreased renal calcium reabsorption, and/or enhanced bone demineralization. We have developed a strain of genetic hypercalciuric stone-forming (GHS) rats as an animal model of human IH. When these GHS rats are placed on a low-calcium diet (LCD), urinary calcium (UCa) excretion exceeds dietary calcium intake, suggesting that bone may contribute to the excess UCa excretion. We used the GHS rats to test the hypothesis that bone contributes to the persistent IH when they are fed an LCD by determining if alendronate (Aln), which inhibits bone resorption, would decrease UCa excretion. METHODS: GHS rats (N = 16) and the parent strain (Ctl, N = 16) were fed 13 g/day of a normal (1.2%) calcium diet (NCD) for seven days and were then switched to a LCD (0. 02%) for seven days. Ctl and GHS rats in each group were then continued on LCD for an additional seven days, with or without injection of Aln (50 micrograms/kg/24 hrs). UCa excretion was measured daily during the last five days of each seven-day period. To determine the effects of Aln on urine supersaturation, the experiment was repeated. All relevant ions were measured, and supersaturation with respect to calcium oxalate and calcium hydrogen phosphate was determined at the end of each period. RESULTS: UCa was greater in GHS than in Ctl on NCD (7.4 +/- 0.5 mg/24 hrs vs. 1.2 +/- 0.1, GHS vs. Ctl, P < 0.01) and on LCD (3.9 +/- 0.2 mg/24 hrs vs. 0. 7 +/- 0.1, GHS vs. Ctl, P < 0.01). LCD provides 2.6 mg of calcium/24 hrs, indicating that GHS rats are excreting more calcium than they are consuming. On LCD, Aln caused a significant decrease in UCa in GHS rats and brought GHS UCa well below calcium intake. Aln caused a marked decrease in calcium oxalate and calcium hydrogen phosphate supersaturation. CONCLUSION: Thus, on a LCD, there is a significant contribution of bone calcium to the increased UCa in this model of IH. Aln is effective in decreasing both UCa and supersaturation. The Aln-induced decrease in urine supersaturation should be beneficial in preventing stone formation in humans, if these results, observed in a short-term study using the hypercalciuric stone-forming rat can be confirmed in longer term human studies.     

Studies on the mechanism of protein-induced hypercalciuria in older men and women

A human metabolic study was conducted to observe the effect of level of protein intake on urinary calcium, calcium absorption and calcium balance in older adults and to further study the mechanisms of protein-induced hypercalciuria. An increase in protein intake from about 47 to 112 g while maintaining calcium, magnesium and phosphorus intakes constant caused an increase in urinary calcium and a decrease in calcium retention. Glomerular filtration rate was increased and fractional renal tubular reabsorption was decreased by the increase in protein intake; total renal acid, ammonium and sulfate excretions more than doubled, whereas urinary sodium decreased by 38%. The changes in urinary calcium were positively correlated with the increase in total renal acid and sulfate excretion as well as with the decrease in fractional renal tubular reabsorption of calcium. Thus, the data indicate that protein-induced hypercalciuria is due to an increase in glomerular filtration rate and a decrease in fractional renal tubular reabsorption of calcium, the latter of which may be caused by the increased acid load on the renal tubular cells.     

Evidence of absorptive hypercalciuria in tuberculosis patients

In patients with granulomatous diseases, disturbances in calcium metabolism have been described. The aim of the study was to evaluate alterations in calcium metabolism in patients with tuberculosis. Forty patients with tuberculosis (TB) were studied in a baseline state (calcium intake 1000 mg/day). Fourteen of these patients were also studied after restrictive calcium diet (400 mg/calcium/day) and after a load of oral calcium of 1000 mg. In all the studies, calcium and phosphorus were measured in serum and urine, and parathyroid hormone (PTH) in plasma. In addition, serum 25OHD and 1,25(OH)2D (calcitriol) levels were measured in the baseline state and after the restrictive diet. In the baseline state, 25OHD levels were lower and urinary calcium higher in TB patients than in the control group. No patients had hypercalcemia, but hypercalciuria was present in 10 patients (25%). The patients with tuberculosis were divided according to the presence or absence of hypercalciuria. In both groups, the 25OHD levels were lower than in controls. Hypercalciuric patients had lower plasma parathyroid hormone levels and higher serum calcitriol levels than the control group and the TB patients without hypercalciuria. Urinary calcium excretion after a calcium load was higher in TB patients with hypercalciuria than in controls. A positive correlation was found between the calcitriol levels and postcalcium load urinary calcium excretion in patients with calcium hyperabsorption. These data indicate that absorptive hypercalciuria is frequently observed in patients with TB and is possible due to inappropriately high serum calcitriol levels.     

Pathogenesis of idiopathic calcium nephrolithiasis: update 1997

Idiopathic calcium nephrolithiasis (ICN) is a frequent disease in Western countries. The physicochemical theory of lithogenesis, which explains stone formation by the precipitation, growth, and crystalline aggregation of lithogenic salts in the urine, has contributed greatly to the understanding of the pathogenesis of calcium urolithiasis. However, several aspects are still unexplained; the co-existence of familial occurrence, primary tubular dysfunctions with ICN, and anomalies in the systemic handling of oxalate and calcium led to the development of a cellular hypothesis of ICN. A number of cellular defects in the handling of ions has been reported that involves both anion and cation transport. These anomalies are probably the expression of a still unknown cellular defect in idiopathic calcium stone formers. We suggested that an anomaly in the cell membrane composition might be responsible for the complex array of cell ion flux abnormalities observed in ICN. Recently, a disorder in the n-6 polyunsaturated fatty acid series has been described; it is characterized by a lower linoleic acid content and a higher arachidonic acid concentration in both plasma and erythrocyte membrane phospholipids of renal calcium stone patients. This anomaly could cause an increased activity of ion carriers; furthermore, it may lead to increased prostaglandin synthesis and to secondary phenomena at the kidney, skeletal, and intestinal level. As a consequence, critical conditions for lithogenesis in the kidney may ensue. The data suggest a common pathogenesis for hypercalciuria and hyperoxaluria. The systemic defect in the phospholipid arachidonic acid level may be both of dietary or genetic origin; experimental data suggest that the increase in delta-6 desaturase activity, the limiting enzyme in the metabolic pathway of polyunsaturated fatty acids, might be relevant to the pathogenesis of lipid abnormalities observed in nephrolithiasis and to the pathogenesis of ICN and its related problems (at the kidney, intestinal, and bone level).     

Effect of protein-induced calciuria on calcium metabolism and bone status in adult rats

45Ca-labeled adult male rats were fed diets high in protein to determine long-term effects on calcium metabolism and bone status. Factors influencing renal excretion of calcium were examined for their involvement in protein-induced hypercalciuria. Control rats were fed a 6% casein diet. Test diets contained 6% casein plus 24% protein as lactalbumin, beef, casein, soy, egg white or gelatin. All diets were equal in Mg, P, and Ca. Collections made during the 20-week feeding regimen indicated a transient but marked calciuria (greater than or equal to 200% of control) occurring at or prior to days 56-59 by rats fed the lactalbumin, egg white, gelatin (P less than or equal to 0.001) and 30% casein (P less than or equal 0.01) diets. Soy and beef diets were not calciuric. At days 56-59, rats fed lactalbumin, 30% casein, soy and egg white exhibited significantly depressed urinary specific activity of calcium (P less than or equal to 0.001), and all rats fed test diets produced higher fecal endogenous calcium, suggesting an increased absorption. No compositional differences indicative of bone resorption were present in the femur or mandibles of any rat fed test protein, dismissing bone as the source of calciuria. End-products of protein metabolism known to chelate calcium or compete with its renal reabsorption were significantly correlated with urinary calcium; these included sulfate, oxalate and sodium.     

Dietary calcium, dietary protein, and kidney stone formation

Kidney stone disease is common and is a major cause of morbidity involving the urinary tract. Rising incidence rates of calcium oxalate stone disease, the most common type of kidney stone, have focused attention on dietary habits and their potential role in the development of nephrolithiasis. Traditionally, calcium restriction had been recommended to reduce the likelihood of calcium stone formation, but recent evidence suggests that dietary calcium restriction may actually increase the risk. Observational and experimental data suggest that restriction of animal protein may lower the risk of stone formation, but a randomized trial did not confirm this finding. Dietary modification may play an important role in reducing the likelihood of stone recurrence. Notably, dietary calcium restriction should be avoided in patients who have had a calcium oxalate kidney stone.     

Effects of citrate on the different phases of calcium oxalate crystallization

Urinary citrate appears to be an important factor in the crystallization process of calcium oxalate and calcium phosphate. The urinary excretion of citrate was found to be significantly lower in patients with calcium oxalate stone disease as compared with normal subjects, and about 30 per cent of the calcium stone formers can be considered as hypocitraturic. The lowest excretion of citrate was recorded in urine collected during the night. Citrate has significant effects on supersaturation with respect to both calcium oxalate and calcium phosphate, it also inhibits the growth of these crystals. In addition, citrate appears to be capable of inhibiting the aggregation of crystals composed of calcium oxalate, brushite, and hydroxyapatite. The heterogenous growth of calcium oxalate on calcium phosphate is also counteracted by citrate. As a consequence of the crucial role of citrate in these processes, stone prevention with alkaline citrate has become an attractive form of treatment in patients with recurrent stone formation. Single evening dose administration of sodium potassium citrate resulted in an of sodium potassium citrate resulted in an increased excretion of citrate, reduced levels of the calcium/citrate ratio as well as supersaturation with respect to calcium oxalate and a decreased rate of stone formation. However, conflicting results of stone preventive treatment with alkaline citrate have been reported by different groups, and long-term follow-up of patients treated in a randomized way is necessary to definitely assess the efficacy of alkaline citrate.     

Oxalate: its role in lithogenesis and composition of calcium oxalate lithiasis

A prospective study was conducted on 374 patients with urinary lithiasis, aiming to analyze the participation of oxalate in the lithogenesis and composition of the calcium oxalate calculi, alone or associated to other factors. METHODOLOGY: Metabolic urinary study of the patient and analysis of calculi with infrared spectrography and optical microscopy. RESULTS: 26.3% patients had hyperoxaluria and 77.5% of the calculi contain calcium oxalate; these are 167 cases of calcium oxalate, 110 of oxalate and calcium phosphate and 13 cases of mixed calcium oxalate and uric acid lithiasis. 43.4% patients with pure monohydrate calcium oxalate calculi have hypercalciuria, 22.6% hyperoxaluria and 19% hyperuricosuria. Dihydrated calcium oxalate calculi are related to high hypercalciuria in 65% cases and to significant hyperoxaluria in 35% cases. 45% patients present a single lithogenic factor, either hypercalciuria (49.6%), hyperoxaluria (20.6%), hyperuricosuria (13.74%), hypocitraturia (9%), urinary infection (1.5%), A.T.R. (2.25%) or acid oliguria (3%).     

Cytokine and cytotoxic pathways of NK cell rejection of class I-deficient bone marrow grafts: influence of mouse colony environment

OBJECTIVE: To identify biochemical and dietary factors which may play a role in the low incidence of stone formation in the black South African population. SUBJECTS AND METHODS: The study included 31 semiurbanized black and 29 urbanized white subjects. The protocol and modern laboratory techniques used to assess recurrent stone formers were followed. Urinary sodium, potassium, creatinine, calcium, phosphate and urate levels were measured, and urinary citrate, oxalate and cystine assessed. RESULTS: Black subjects ate a diet significantly higher in sodium (P < 0.04); there was no difference in serum levels but urinary sodium was significantly higher (P < 0.001) in black than in white subjects. Urinary potassium, calcium, citrate, phosphate and cystine were all significantly lower in black than in white subjects (P < 0.001 for the first four and P < 0.03 for cystine). CONCLUSION: Certain intrinsic factors in South African black subjects may account for their lower frequency of stone formation than in white subjects. Of these, the very low urinary calcium, decreased urinary cystine and different interactions between sodium and calcium/cystine are probably important.     

Health care report cards

PURPOSE: A decreased concentration of magnesium in the urine is a risk factor for renal calcium stone disease that may be caused by decreased enteral absorption of magnesium. We analyze the possible reciprocal influences of enteral absorption of calcium and magnesium in patients with renal stone disease. MATERIALS AND METHODS: We measured the fractional enteral absorption of 47calcium and 28magnesium in 11 patients with renal calcium stone disease, including 8 with and 3 without hypercalciuria. Two tests were performed using calcium and magnesium, respectively, followed by another test in which the enteral absorption of calcium and magnesium was measured after both cations were administered together. RESULTS: We noted no clear influence of either cation on the absorption of the other in the 3 patients without hypercalciuria. However, in the 8 hypercalciuric patients enteral calcium absorption decreased after the concurrent administration of magnesium and enteral magnesium absorption increased after the concurrent administration of calcium. Each effect was proportional to the other. CONCLUSIONS: The results of this study indicate that the oral supplementation of magnesium in patients with hyperabsorptive hypercalciuria and renal calcium stone disease is favorable because it decreases calcium absorption and increases magnesium absorption. Both factors may reduce risk factors for renal calcium stone formation.     

Markers of bone turnover in patients with nephrolithiasis

A total of 19 patients with active nephrolithiasis, 14 patients with non-active nephrolithiasis and 17 healthy subjects were examined under standardized intake of calcium, phosphorus, purine and protein. In patients with both active and non-active renal stone disease the following abnormalities were found: elevated plasma levels of PTH and osteocalcin, increased activity of the bone isozyme of alkaline phosphatase, low plasma levels of phosphate and increased urinary excretion of calcium and oxalic acid. These abnormalities were more marked in patients with active than non-active nephrolithiasis. No correlation was found between plasma PTH levels and parameters of bone turnover as well as calciuria and oxaluria. Results presented in this paper suggest that (a) Smith's criteria of active renal stone disease are of minor pathogenetic and therapeutic value and (b) patients with active nephrolithiasis differ from non-active renal stone formers by more elevated oxaluria and markers of bone turnover and more marked abnormalities in calcium-phosphate metabolism related parameters.     

NGF induces transient but not sustained activation of ERK in PC12 mutant cells incapable of differentiating

Calcium urolithiasis is often associated with increased intestinal absorption and urine excretion of calcium, and has been suggested to result from increased vitamin D production. The role of the enzyme 1 alpha-hydroxylase, the rate-limiting step in active vitamin D production, was evaluated in 36 families, including 28 sibships with at least a pair of affected sibs, using qualitative and quantitative trait linkage analyses. Sibs with a verified calcium urolithiasis passage (n = 117) had higher 24-h calciuria (P = 0.03), oxaluria (P = 0.02), fasting and postcalcium loading urine calcium/creatinine (Ca/cr) ratios (P = 0.008 and P = 0.002, respectively), and serum 1,25(OH)2 vitamin D levels (P = 0.02) compared with nonstone-forming sibs (n = 120). Markers from a 9-centiMorgan interval encompassing the VDD1 locus on chromosome 12q13-14 (putative 1 alpha-hydroxylase) were analyzed in 28 sibships (146 sib pairs) of single and recurrent stone formers and in 14 sibships (65 sib pairs) with recurrent-only (> or = 3 episodes) stone-forming sibs. Two-point and multipoint analyses did not reveal excess in alleles shared among affected sibs at the VDD1 locus. Linkage of stone formation to the VDD1 locus could be excluded, respectively, with a lambda d of 2.0 (single and recurrent stone formers) and 3.25 (recurrent stone formers). Quantitative trait analyses revealed no evidence for linkage to 24-h calciuria and oxaluria, serum 1,25(OH)2 vitamin D levels, and Ca/cr ratios. This study shows absence of linkage of the putative 1 alpha-hydroxylase locus to calcium stone formation or to quantitative traits associated with idiopathic hypercalciuria. In addition, there is coaggregation of calciuric and oxaluric phenotypes with stone formation.     

Urinary calcium oxalate saturation in healthy infants and children

PURPOSE: A number of factors influence the development of renal calculi, the most essential of which is the supersaturation of urine with lithogenic substances. Calcium oxalate stones occur most frequently in adult and pediatric patients with urolithiasis. Therefore, we established normal age and sex related data for urinary calcium oxalate saturation in infancy and childhood to allow a more specific prediction of the risk of (recurrent) stone disease. MATERIALS AND METHODS: We collected 24-hour urine samples from 473 healthy infants and children without a history of renal stones. Urinary lithogenic and stone inhibitory substances were measured, and the urinary calcium oxalate saturation was calculated using a computer program. RESULTS: Mean urinary calcium oxalate saturation was always higher in boys than in girls, which was significant in infancy (5.22 versus 2.03, p < 0.05) and at ages 7 to 9 years (8.84 versus 5.47, p < 0.05). The saturation first increased (p < 0.05) until age 7 to 9 years in boys and girls, and remained at high levels at ages 10 to 12 years (7.03 versus 5.49, p < 0.05 compared to infancy). Calcium oxalate saturation then decreased until adolescence when values were comparable to those of infancy (5.29 versus 3.35). CONCLUSIONS: We recommend calculating urinary calcium oxalate saturation for diagnostic purposes as well as for therapy control. Normal age and sex related values must be considered.