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.     

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.     

Reduced bone formation and relatively increased bone resorption in absorptive hypercalciuria

Absorptive hypercalciuria (AH), a common stone-forming condition characterized biochemically by intestinal hyperabsorption of calcium and hypercalciuria may be associated with bone loss. In AH type I (AH-1), hypercalciuria persists despite restriction in dietary calcium intake. We therefore hypothesized that the skeleton may contribute to the hypercalciuria in this subgroup of patients. Histomorphometric analysis of iliac crest biopsies were performed on nine stone-formers with AH-1 and on nine matched normal subjects. After stabilization on a stone-prevention diet, calcium homeostasis in the stone formers was then evaluated on inpatient constant metabolic diet before and after short-term blockade of bone resorption by alendronate (10 mg daily, 17 days total). Compared with controls, the stone-formers had lower indices of bone formation (osteoblast surface/bone surface 1.8+/-2.1 vs 3.0+/-1.5%, P=0.04; wall thickness 35.8+/-6.9 vs 47.2+/-7.6%, P=0.001) and relatively higher bone resorption (osteoclast surface/bone surface 0.4+/-0.2 vs 0.2+/-0.2%, P=0.05). In the stone-formers, a short-term course of alendronate treatment corrected fasting urinary calcium (0.14+/-0.06 to 0.06+/-0.04 mg Ca/mg Cr, P=0.001) and marginally reduced 24-h urinary calcium by 48 mg/day (P=0.06). Increased intestinal calcium absorption and hypercalciuria persisted, but estimated calcium balance improved (P=0.007). Our results suggest that the hypercalciuria of AH-1 originates primarily from intestinal hyperabsorption of calcium, but bone resorption in excess of bone formation may contribute.     

Metabolic risk factors in pediatric and adult calcium oxalate urinary stone formers: is there any difference?

OBJECTIVES: Urolithiasis in children is recognized with an increasing frequency, while exact etiological factors remain to be determined. The aim of this study is to compare the metabolic risk factors and saturation of urine in pediatric and adult calcium oxalate (Ca-Ox) stone formers. METHODS: A total of 33 pediatric (mean age: 6.8 +/- 3.1 years) and 120 adult patients (mean age: 39.7 +/- 5.7 years), with documented Ca-Ox urinary stone disease, underwent a comprehensive metabolic evaluation at our institution. Beside a broad serum analysis, concentrations of calcium, oxalate, magnesium, uric acid and citrate were measured in 24-hour collected urine. Saturation of urine was calculated by Marshall-Robertson's nomograms. RESULTS: Hypocitraturia, observed in 60.6%, and hypomagnesuria, detected in 39.4%, but not hypercalciuria, were the most common metabolic risk factors in the pediatric group. In adults, hypercalciuria still represented one of the major metabolic risk factors, detected in 44.1%, although hypocitraturia, observed in 45.8%, was the most prevalent metabolic risk factor, as it was in the pediatric group. Pediatric cases had significantly (p < 0.05) higher prevalence of hypocitraturia, hypomagnesuria and supersaturated urine when compared to adults. Metabolic abnormalities could be detected in a high percentage (82%) of primary and recurrent pediatric Ca-Ox stone formers, but not in primary adult stone formers. CONCLUSIONS: Metabolic risk factors significantly differ in pediatric and adult Ca-Ox stone formers. Hypocitraturia and hypomagnesuria seem to play a major role in stone formation, and metabolic abnormalities can be detected in a significant percentage of both primary and recurrent pediatric stone formers. Thus, a comprehensive metabolic evaluation is of utmost importance for all children with Ca-Ox stones.     

Comparison of urinary proteins in calcium stone formers and healthy individuals: a case-control study

OBJECTIVE: This study aimed at comparing the urinary protein levels in calcium stone formers with those of healthy individuals. PATIENTS AND METHODS: From January 2002 until June 2004, 100 calcium stone formers (mean age 38.6 +/- 10.3 years), who had at least two episodes of calcium stone formation, were compared with 100 healthy individuals (mean age 33.8 +/- 9.7 years). Their 24-hour urinary protein levels, using SDS-PAGE, were measured. RESULTS: The mean 24-hour urinary Tamm-Horsfall protein (THP) levels were 3.3 +/- 0.8 mg in the case group and 4.6 +/- 1.9 mg in the controls, and the difference was not statistically significant (p = 0.53). However, the THP levels in individuals with and without bacteriuria were significantly different (15.8 +/- 3.3 mg vs. 2.6 +/- 1.0 mg, p = 0.0001). The mean 24-hour urinary albumin concentrations were 163.31 +/- 15.1 mg in the case group and 74.26 +/- 4.6 mg in the controls. The mean 24-hour urinary transferrin levels were 8.09 +/- 2.7 mg in the case group and 0.40 +/- 0.3 mg in the controls. The differences were statistically significant for both albumin and transferrin (p < 0.0001 and p = 0.0063, respectively). There were no significant differences in any other mean urinary protein concentrations between cases and controls. CONCLUSIONS: The THP level in the urine of stone formers is not quantitatively different from that of healthy individuals, but it increases in association with bacteriuria. Albumin and transferrin may play a presumptive role in stone formation.     

Urine risk factors in children with calcium kidney stones and their siblings

Calcium nephrolithiasis in children is increasing in prevalence and tends to be recurrent. Although children have a lower incidence of nephrolithiasis than adults, its etiology in children is less well understood; hence, treatments targeted for adults may not be optimal in children. To better understand metabolic abnormalities in stone-forming children, we compared chemical measurements and the crystallization properties of 24-h urine collections from 129 stone formers matched to 105 non-stone-forming siblings and 183 normal, healthy children with no family history of stones, all aged 6 to 17 years. The principal risk factor for calcium stone formation was hypercalciuria. Stone formers have strikingly higher calcium excretion along with high supersaturation for calcium oxalate and calcium phosphate, and a reduced distance between the upper limit of metastability and supersaturation for calcium phosphate, indicating increased risk of calcium phosphate crystallization. Other differences in urine chemistry that exist between adult stone formers and normal individuals such as hyperoxaluria, hypocitraturia, abnormal urine pH, and low urine volume were not found in these children. Hence, hypercalciuria and a reduction in the gap between calcium phosphate upper limit of metastability and supersaturation are crucial determinants of stone risk. This highlights the importance of managing hypercalciuria in children with calcium stones.     

Metabolic risk factors in patients with ureteropelvic junction obstruction and renal calculi

PURPOSE: We performed a prospective study to determine the incidence and spectrum of metabolic abnormalities predisposing to stone formation in patients with ureteropelvic junction obstruction and renal calculi. MATERIALS AND METHODS: A total of 47 consecutive patients with congenital ureteropelvic junction obstruction underwent metabolic evaluation of stone risk factors. Of these patients 21 had associated stones (study group), while 26 did not (control group). Logistical regression, Wilcoxon rank sum and Fisher's exact tests were performed to determine whether there was a significant difference between these groups in regard to the presence of metabolic risk factors. RESULTS: Demographically and symptomatically the 2 groups were equivalent except that the study patients were older. The 24-hour urinary excretion of calcium was significantly higher in study than in the control patients (p = 0.007). While the incidence of hypercalciuria and hyperuricosuria was also higher in the study population, these differences were not significant (p = 0.08 and 0.07, respectively). CONCLUSIONS: Metabolic abnormalities predisposing to stone formation are present more frequently in patients with ureteropelvic junction obstruction who have associated stones compared to those who do not. As such, urinary stasis alone does not explain stone formation in these cases. Rather, the local physiological environment of urine likely has a predisposing role. In addition to restoring unobstructed urinary flow, consideration should be given to metabolic evaluation and prophylactic treatment for affected patients.     

Quantification of hypercalciuria with the urine calcium osmolality ratio in children

Hypercalciuria is a major risk factor for kidney stones and hematuria in children. Calcium measurements in 24-h collected urine (mg/kg/d) is still essential for the hypercalciuria diagnose but collection of 24 hour urine is difficult especially in young children. A prospective study was conducted to compare calcium/osmolality (Uca/Uosm) ratio to calcium/creatinine (Uea/Ucr) and to correlate both ratios to 24-hour urine calcium excretion (mg/kg/d) and the value of Uca/Uosm ratio for diagnosis of hypercalciuria in children. Two hundred and fifteen patients aged between 3 to 15 years (median 8 years) were included in the study. Early morining second urine samples and 24-hour collected urine samples were analyzed. The 24-hour urinary calcium excretions were significantly correlated with Uca/Ucr and Uca/Uosm ratio (r =0.67, P<0.001 and r =0.61, P<0.001 respectively). The accepted hypercalciuria level of 24-hour urine calcium of 4 mg/kg/day coincides with Uca/Ucr ratio of 0.18 mg/mg (sensitivity 90.0%, specificity 84.4%) and with Uca/Uosm ratio of 0.14 mg/l/mOsm/kg (sensitivity 90%, specificity 81.0%) in the ROC curve analysis. Positive and negative predictive values were found 98.3% and 39.1% for Uca/Uosm ratio and respectively 43.9% and 98.4% for Uca/Ucr ratio. In conclusion Uca/Uosm ratio is a good marker of hypercalciuria as well as Uca/Ucr ratio and may be used for screening of hypercalciuria.     

The efficacy of dietary intervention on urinary risk factors for stone formation in recurrent calcium oxalate stone patients

PURPOSE: Nutrition is suggested to be the major environmental risk factor in idiopathic calcium oxalate stone disease. The study was designed to evaluate the effect of dietary intervention on urinary risk factors for recurrence in calcium oxalate stone formers. MATERIALS AND METHODS: A total of 76 men and 31 women with idiopathic calcium oxalate stone disease collected 24-hour urine on their habitual, self-selected diets and after 7 days on a balanced standardized diet according to the recommendations for calcium oxalate stone formers. RESULTS: On the usual diet, a urine volume of less than 2.0 l per 24 hours was present in 57.9%, hypercalciuria in 25.2%, hypomagnesuria in 18.7%, hyperoxaluria in 14.0%, hyperuricosuria in 41.3% and hypocitraturia in 57.0% of patients. The frequency of metabolic abnormalities and the risk of calcium oxalate stone formation decreased significantly on the ingestion of the balanced diet, due to the significant increase in urinary volume, pH and citrate excretion and the significant decrease in urinary calcium and uric acid excretion. No change occurred in urinary oxalate and magnesium excretion. CONCLUSIONS: The evaluation of urinary risk profiles of the patients on their usual dietary habits revealed a high risk for calcium oxalate stone formation. A low fluid intake and an increased intake of protein and alcohol were identified as the most important dietary risk factors. The shift to a nutritionally balanced diet according to the recommendations for calcium oxalate stone formers significantly reduced the stone forming potential.     

The risk of renal stone formation during and after long duration space flight

BACKGROUND: The formation of a renal stone during space flight may have serious negative effects on the health of the crewmember and the success of the mission. Urinary biochemical factors and the influence of dietary factors associated with renal stone development were assessed during long duration Mir Space Station missions. METHODS: Twenty-four-hour urine samples were collected prior to, during and following long duration space flight. The relative urinary supersaturation of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were determined. RESULTS: Changes in the urinary biochemistry of crewmembers during long duration spaceflight demonstrated increases in the supersaturation of the stone-forming salts. In-flight hypercalciuria was evident in a number of individual crewmembers and 24-hour dietary fluid intake and urine volume were significantly lower. During flight, there was a significant increase in brushite supersaturation. CONCLUSIONS: These data suggest acute effects of space flight and postflight changes in the urinary biochemistry favoring increased crystallization in the urine. The effects of dietary intake, especially fluid intake, may have a significant impact on the potential for renal stone formation. Efforts are now underway to assess the efficacy of a countermeasure to mitigate the increased risk.     

The urinary excretion and serum concentration of calcium, magnesium, sodium and phosphate in male patients with recurring renal stone formation.

Only about 20% of renal stone cases have an unquestionable cause such as hyperparathyroidism, renal tubular acidosis etc. explaining their stone formation. About 20-40% are believed to result from idiopathic hypercalciuria. The purpose of the present investigation was to study the renal excretion of calcium, magnesium, sodium and phosphate in 47 consecutive men with recurring renal stone formation without a demonstrable underlining metabolic disease and, for comparison, 43 normal men. The results are related to previous hypotheses on renal stone formation. No difference in urinary calcium (either concentration or excretion) per day is found between the two groups. Consequently the concept of idiopathic hypercalciuria is questioned. The Mg/Ca ratio in urine is found lower in the stone patients than in the controls, suggesting that the Mg/Ca ratio might be of importance in stone formation.     

Exclusion mapping of major crystallization inhibitors in idiopathic calcium urolithiasis

PURPOSE: We determined whether genetic variation at 3 loci coding for putative crystallization inhibitors is linked to calcium urolithiasis. MATERIALS AND METHODS: We studied a cohort of 64 French-Canadian sibships including multiple recurrent calcium stone formers, comprising 154 independent pairs of siblings with at least 1 stone episode. Physical and meiotic mapping of the genes coding for osteopontin and uromodulin (Tamm-Horsfall protein) as well as the osteocalcin related gene (ORG or putative nephrocalcin) was performed and microsatellite markers were identified. We used nonparametric linkage analysis in the whole affected sib pair cohort as well as in affected pairs without hypercalciuria, that is concordant for 24-hour urine calcium excretion in the first quartile (mean plus or minus standard deviation 0.053 +/- 0.020 mmol./kg. or 3.4 +/- 1.3 mmol. daily), and in the first and second quartiles (mean 0.064 +/- 0.027 mmol./kg. or 4.9 +/- 2.1 mmol. daily, respectively). RESULTS: Lod scores were less than 0.3 for all 3 loci using these affection statuses. Further analysis enabled the exclusion of uromodulin at (relative risk or lambda = 3.9 and 2.5), osteopontin (lambda = 2.7 and 1.6) and ORG (lambda = 5.5 and 3.7) for affected sib pairs concordant for urine calcium excretion in the lowest and 2 lowest quartiles, respectively. CONCLUSIONS: Loci encoding 3 crystallization inhibitors are unlikely to be major genes involved in calcium stone formation in our population.     

Fructose consumption and the risk of kidney stones

Fructose consumption has markedly increased over the past decades. This intake may increase the urinary excretion of calcium, oxalate, uric acid, and other factors associated with kidney stone risk. We prospectively examined the relationship between fructose intake and incident kidney stones in the Nurses' Health Study I (NHS I) (93,730 older women), the Nurses' Health Study II (NHS II) (101,824 younger women), and the Health Professionals Follow-up Study (45,984 men). Food frequency questionnaires were used to assess free fructose and sucrose intake every 4 years. Total-fructose intake was calculated as free fructose plus half the intake of sucrose, and expressed as percentage of total energy. Cox proportional hazard regressions were adjusted for age, body mass index (BMI), thiazide use, caloric intake, and other dietary factors. We documented 4902 incident kidney stones during a combined 48 years of follow-up. The multivariate relative risks of kidney stones significantly increased for participants in the highest compared to the lowest quintile of total-fructose intake for all three study groups. Free-fructose intake was also associated with increased risk. Non-fructose carbohydrates were not associated with increased risk in any cohort. Our study suggests that fructose intake is independently associated with an increased risk of incident kidney stones.     

The stone clinic effect in patients with idiopathic calcium urolithiasis

The "stone clinic effect" refers to the effect of encouraging a high intake of fluid and avoiding dietary excesses on stone formation and growth in patients with urolithiasis. To determine the extent of this effect we reviewed the clinical courses of 108 patients with idiopathic calcium urolithiasis and indeterminant metabolic activity. There was no evidence of stone growth or new stone formation (metabolic inactivity) after a mean followup of 62.6 months in 63 of the 108 patients (58.3 per cent), including 12 of 17 (70.6 per cent) with hypercalciuria and 7 of 15 (46.7 per cent) with hyperuricosuria. Comparison of initial and followup 24-hour urine volumes demonstrated a significant increase in patients who were metabolically inactive at followup (p less than 0.0005), while no increase was detected in patients who were metabolically active at followup. We recommend that specific drug therapy should not be given to patients with idiopathic calcium urolithiasis until the stone clinic effect has been evaluated.     

A clinical study of urolithiasis in Shizuoka City Hospital--stone analysis and 24-hour urine calcium and uric acid levels

Stone analysis was performed for 216 urinary calculi which were obtained from 205 patients in our hospital from January, 1980 to June, 1984. The results revealed 161 calcium stones, 21 uric acid stones, 19 struvite stones, 2 cystine stones and 13 others. Sixty one of the 205 patients (male 44, female 17) and 19 controls (male 11, female 8) were investigated for 24-hour urine calcium and uric acid. Forty seven of the patients had calcium stones, 7 of the patients had uric acid stones and 7 of the patients had struvite stones. The mean 24-hour urine calcium level was 146.8 +/- 76.5 mg/day for the male controls and 139.1 +/- 69.9 mg/day for the female controls. The mean 24-hour urine uric acid level was 528.1 +/- 132.6 mg/day for the male controls and 362.0 +/- 135.2 mg/day for the female controls. The mean 24-hour urine calcium level for the male calcium-stone group was 214.6 +/- 96.8 mg/day, and it was significantly higher than that for the male controls (p less than 0.05). The 24-hour urine analysis revealed abnormalities in 17 urolithiasis patients (27.9%) including hypercalciuria in 11 patients (18.0%) and hyperuricosuria in 9 patients (14.1%).     

Adjustment for body mass index and calcitrophic hormone levels improves the diagnostic accuracy of the spot urine calcium-to-creatinine ratio

Summary  

Providers diagnose hypercalciuria using a 24-hour or random urine samples. We compared calcium measurements from paired 24-hour and morning urine samples; measurements correlated poorly. We developed a formula to correct random urine calcium levels. Corrected levels showed excellent agreement with 24-hour measurements. Until validation, providers should diagnose hypercalciuria using 24-hour tests.     

Urine calcium and volume predict coverage of renal papilla by Randall's plaque

BACKGROUND: Renal papillary plaques are common in calcium stone formers. We hypothesized that plaque should increase directly with urine calcium excretion, and inversely with urine volume. To test this, we measured papillary plaque areas in both idiopathic calcium oxalate stone formers and nonstone formers and examined 24-hour urine data to identify significant correlations. METHODS: Fourteen stone formers and four nonstone forming controls underwent papillary mapping with flexible nephroscopy. For each papillum, representative still images and moving pictures expert group (MPEG) movies were used to identify plaque extent and papillary borders. The mean fractional plaque coverage for each polar region (upper, inter, lower) and per papillum was calculated. The relationship of the plaque coverage data to urine measurements was assessed with general multivariate linear modeling. RESULTS: Mean polar fractional plaque coverage was higher in the calcium oxalate stone formers (7.4% vs. 0.5%, P= 0.012) as was mean fractional plaque per papillum (7.6% vs. 0.6%, P= 0.011). When correlating mean polar plaque coverage to urine data, urine volume and calcium excretion were the only measurements with independent relationships to plaque (P= 0.002, adjusted multiple R2= 0.521), with higher calcium and lower volume increasing coverage. The same relationships hold for mean plaque per papillum, except that urine pH also becomes an independent factor (P= 0.001, adjusted multiple R2= 0.606). CONCLUSION: Utilizing advanced digital video and endoscopic equipment, we have achieved the most accurate estimation of papillary plaque coverage to date. Our findings support the idea that urine volume and calcium are the main correlates of plaque coverage.     

Effects of low animal protein or high-fiber diets on urine composition in calcium nephrolithiasis

BACKGROUND: The purpose of this article is to evaluate the impact of low protein and high fiber intakes on risk factors of stone recurrence in idiopathic calcium stone formers (ICSFs). METHODS: Ninety-six ICSFs were randomly assigned a low animal protein diet (< 10% of total energy), a high-fiber diet (> 25 g/day), or a usual diet (control group); all patients were recommended to increase their fluid intake. Their daily urine compositions were analyzed at baseline and at four months. Compliance with dietary recommendations was checked by validated food frequency questionnaires. Compliance with total and animal protein intakes was assessed by 24-hour urea and sulfate outputs, respectively. The nutritional intervention (oral instructions, written leaflet, phoning) and food assessment were carried out by a research dietitian. RESULTS: At baseline, diets and the daily urine composition did not differ between the three groups. At four months, while diets differed significantly, the 24-hour output of calcium and oxalate did not differ significantly within and between groups after adjustment for potential confounders (age, sex, and personal and family history of calcium stones) and baseline values. However, as many as 12 out of 31 ICSFs (95% CI, 22 to 58%) assigned to a low animal protein diet achieved a reduction in the urine urea excretion rate of more than 50 mmol/day and also exhibited a significant decrease in urinary calcium excretion that averaged 1.8 mmol/day. A significant correlation between urea and calcium outputs was observed only among patients with hypercalciuria. CONCLUSIONS: These results show that only ICSFs who markedly decrease their animal protein intake, especially those with hypercalciuria, can expect to benefit from dietary recommendations.     

Frequency of renal phosphate leak among patients with calcium nephrolithiasis.

BACKGROUND: Nephrolithiasis is a frequent disorder affecting 10 to 15% of the population in Europe and the United States. More than 80% of renal stones are made of calcium oxalate and calcium phosphate. The main identified risks for calcium renal stone formation are hypercalciuria and urinary saturation. A urine phosphate (Pi) loss is often associated with hypercalciuria; furthermore, hyperphosphaturia increases urinary saturation. METHODS: To determine whether urinary phosphate loss is associated with calcium urolithiasis, we measured renal Pi threshold (TmPi) in 207 stone formers with normal parathyroid hormone (PTH) serum concentration and in 105 control subjects. RESULTS: The TmPi followed a normal distribution in both groups. The mean TmPi was significantly lower in stone formers versus controls (0.72 +/- 0.13 vs. 0.87 +/- 0.18 mmol/L, P < 0.0001) because of a shift to the left of the TmPi distribution curve in the stone former population, with no evidence for bimodal distribution. Five percent of the controls had a TmPi <0.63 versus 19% of the stone formers. Daily urinary calcium excretion was significantly higher in stone formers than in controls. Calcium excretion was also significantly higher in stone formers with TmPi <0.63 mmol/L compared with those with TmPi > or =0.63. Serum PTH and ionized calcium concentrations were not different in stone formers and in control subjects, whatever the TmPi value. CONCLUSIONS:: A low TmPi is more frequently encountered in stone formers with a normal PTH concentration than in control subjects and is associated with a high urinary Ca excretion. The hypophosphatemia induced by a renal phosphate leak may predispose the subject to calcium stone formation by increasing the serum calcitriol level, calcium excretion, and urinary saturation.     

A family-based study of metabolic phenotypes in calcium urolithiasis

BACKGROUND: A family history increases the risk of kidney stone passage independent of dietary risk factors. However, the metabolic basis for familial aggregation of urolithiasis is unknown. METHODS: We evaluated metabolic risk factors in families with at least two sibs with a history of calcium stones. Sibs underwent outpatient evaluations simultaneously, including 24-hour urine collection and oral calcium loading. Phenotypes were compared between affected and unaffected sibs from the same sibship. RESULTS: Eighty-three sibships comprising 388 sibs (212 affected sibs, 114 males and 98 females, and 176 unaffected sibs, 68 males and 108 females) from 71 families were analyzed. Daily urine calcium excretion was higher in affected compared with unaffected sibs (0.64 +/- 0.33 vs. 0.50 +/- 0.22 mmol Ca(2+)/mmol creatinine, respectively, P < 10(-5)). This corresponded to absolute values of 7.4 +/- 3.9 and 5.1 +/- 2.3 mmol Ca(2+)/day, respectively, for affected and unaffected males, and 5.4 +/- 2.6 and 4.2 +/- 1.9 mmol Ca(2+)/day, respectively, for affected and unaffected female sibs. When analyzed by tertile of onset age of stone passage, the differences in urine calcium were only significant in the first two tertiles (with onset age of stone passage <35 years). The fasting urine Ca(2+)/creatinine ratio was significantly higher in stone formers compared with control sibs (0.46 +/- 0.27 vs. 0.40 +/- 0.27, P = 0.04), as was the postcalcium load Ca(2+)/creatinine ratio (0.57 +/- 0.46 vs. 0.43 +/- 0.41, respectively, P = 0.02). Body mass index was marginally significantly higher in stone forming sibs (P = 0.04). Other urine phenotypes, including oxalate, phosphate, magnesium, citrate, urate, sodium, ammonium, and volume, were not associated with stone passage. CONCLUSION: Increased urine calcium excretion is the only phenotype associated with a kidney stone formation in these French-Canadian families.