Chemical factors important to calcium nephrolithiasis: evidence for impaired hydroxycarboxylic acid absorption causing hyperoxaluria.

1987 ◽  
Vol 33 (2) ◽  
pp. 243-247 ◽  
Author(s):  
D M Cowley ◽  
B C McWhinney ◽  
J M Brown ◽  
A H Chalmers
Keyword(s):  
Stone Formation ◽  
Urine Volume ◽  
Normal Subjects ◽  
Concurrent Administration ◽  
Calcium Stone ◽  
Hydroxycarboxylic Acids ◽  
Stone Formers ◽  
Daily Excretion ◽  
Chemical Factors ◽  
Urinary Oxalate Excretion

Abstract An investigation of variables important to calcium stone formation in urine indicated significantly increased daily excretion of calcium and oxalate and decreased excretion of ascorbate and citrate by recurrent calcium stone formers. In addition, urine volume, sodium, mucopolysaccharide, and protein were also significantly increased. We compared the uptake of citrate and ascorbate from the gut into the blood in normal controls and stone formers. These studies indicated significantly depressed absorption of both these hydroxycarboxylic acids in recurrent calcium stone formers. We also found that concurrent administration of citrate inhibited ascorbate absorption and increased urinary oxalate excretion after an ascorbate load in normal subjects and stone formers. These findings suggest a mechanism that explains hyperoxaluria in stone patients on the basis of a malabsorption of citrate, ascorbate, and possibly other hydroxycarboxylic acids.

Seasonal Variations in the Composition of Urine in Relation to Calcium Stone-Formation

1975 ◽  
Vol 49 (6) ◽  
pp. 597-602 ◽  
Author(s):  
W. G. Robertson ◽  
M. Peacock ◽  
R. W. Marshall ◽  
R. Speed ◽  
B. E. C. Nordin
Keyword(s):  
Seasonal Variation ◽  
Calcium Oxalate ◽  
Seasonal Variations ◽  
Stone Formation ◽  
Urine Volume ◽  
Cross Sectional ◽  
Seasonal Incidence ◽  
Calcium Stone ◽  
Stone Formers ◽  
Significant Seasonal Variation

1. A retrospective cross-sectional study was carried out on data derived from single 24 h urine collections from 246 male idiopathic calcium stone-formers. 2. The daily urine volume and pH and the excretions of calcium, oxalate, phosphate, creatinine and magnesium were related to the time of year when the urine was collected, and the saturation of urine with calcium oxalate and octocalcium phosphate calculated for each month. 3. There were significant seasonal variations in the urinary excretion of calcium and oxalate, each showing a maximum during the summer months and a minimum in the winter. There was no significant seasonal variation in urinary pH, volume, creatinine, phosphate or magnesium. 4. There was a significant increase in the saturation of urine with calcium oxalate and a trend towards higher saturation levels of octo-calcium phosphate in the summer. These changes were dependent only on the seasonal variation in urinary calcium and oxalate and not on urine volume. 5. A retrospective study of the seasonal incidence of stone episodes among these 246 stone-formers showed that the rate of stone passage per month was 50% higher in the summer than in the winter. There was no significant seasonal variation in the incidence of stones removed surgically.

scholarly journals The Variability and Dietary Dependence of Urinary Oxalate Excretion in Recurrent Calcium Stone Formers

1987 ◽  
Vol 24 (4) ◽  
pp. 385-390 ◽  
Author(s):  
J M Brown ◽  
G Stratmann ◽  
D M Cowley ◽  
B M Mottram ◽  
A H Chalmers
Keyword(s):  
Calcium Intake ◽  
Normal Subjects ◽  
Urinary Calcium ◽  
Stone Disease ◽  
Calcium Excretion ◽  
Urinary Oxalate ◽  
Calcium Stone ◽  
Oxalate Excretion ◽  
Stone Formers ◽  
Urinary Oxalate Excretion

Twenty-two recurrent calcium stone formers had 24-h urinary oxalate excretions on their home diets which were significantly greater than those of 30 normal subjects (0·48±0·23 mmol/d; mean±SD compared with 0·31±0·11; P<0·01). The stone formers also demonstrated marked day to day variability in oxalate excretion indicating that a single normal urinary oxalate measurement did not exclude significant hyperoxaluria at other times. On a hospital diet containing 1000 mg calcium per day, urinary oxalate excretion fell significantly from 0·48±0·23 mmol/d to 0·32±0·12; P<0·01. As the urinary calcium excretion in and out of hospital was similar, it seems unlikely that low calcium intake at home was responsible for the hyperoxaluria. All patients had recurrent symptomatic stone disease and had been advised to avoid foods rich in oxalate. Whilst poor compliance is a possible explanation for the variability in oxalate excretion, we believe it is more likely that there is an inadvertent intake of oxalogenic precursors in their diet. As normal subjects do not demonstrate hyperoxaluria on similar home diets, stone formers may have a metabolic defect in the handling of these precursors.

Urinary Excretion of Calcium and Creatinine in Relation to Age and Body Weight in Normal Subjects and Patients with Renal Calculus

1970 ◽  
Vol 38 (5) ◽  
pp. 601-612 ◽  
Author(s):  
L. Bulusu ◽  
A. Hodgkinson ◽  
B. E. C. Nordin ◽  
M. Peacock
Keyword(s):  
Body Weight ◽  
Urine Volume ◽  
Normal Subjects ◽  
Renal Calculus ◽  
Calcium Excretion ◽  
Creatinine Excretion ◽  
Stone Formers ◽  
Daily Excretion ◽  
The Mean ◽  
Eighth Decade

1. Variations with age in body weight, urine volume and calcium and creatinine excretion were determined in 246 normal subjects and 305 patients with calcium-containing renal stones. 2. Body weight, urine volume and creatinine excretion increased with age to a maximum in the third decade in both male and female controls and stone-formers. Thereafter body weight and urine volume did not change appreciably but creatinine excretion decreased. 3. In normal subjects the daily excretion of calcium and calcium concentration increased in the first two decades and remained relatively constant thereafter until the eighth decade when they decreased. The calcium/creatinine ratio was high in the first decade and fell during the second and third decades. Thereafter it remained relatively constant in men until the eighth decade when it fell. In women, however, there was a second rise in the fifth and sixth decades. The calcium/body weight ratio remained relatively constant with age until the eighth decade, when it fell. 4. Patients with renal calculus showed similar variations in calcium excretion with age. The mean values, however they were expressed, were higher than those in normal subjects of the same age and sex. 5. The daily excretion of calcium was higher in men than women, whether normal subjects or stone-formers. This difference was abolished when calcium excretion was related to body weight and reversed when excretion was related to creatinine. 6. Comparison of the present data with previous data from the same population indicated that the mean daily excretion of calcium by both normal subjects and patients with renal calculi has increased during the last decade. 7. The significance of these observations in relation to calcium homeostasis and renal calculus formation is discussed.

scholarly journals A test of the hypothesis that the collecting duct calcium-sensing receptor limits rise of urine calcium molarity in hypercalciuric calcium kidney stone formers

2009 ◽  
Vol 297 (4) ◽  
pp. F1017-F1023 ◽  
Author(s):  
Kristin J. Bergsland ◽  
Fredric L. Coe ◽  
Daniel L. Gillen ◽  
Elaine M. Worcester
Keyword(s):  
Water Conservation ◽  
Kidney Stone ◽  
Stone Formation ◽  
Collecting Duct ◽  
Urine Volume ◽  
Calcium Excretion ◽  
Calcium Sensing Receptor ◽  
Urine Calcium ◽  
Calcium Sensing ◽  
Stone Formers

The process of kidney stone formation depends on an imbalance between excretion of water and insoluble stone-forming salts, leading to high concentrations that supersaturate urine and inner medullary collecting duct (IMCD) fluid. For common calcium-containing stones, a critical mechanism that has been proposed for integrating water and calcium salt excretions is activation of the cell surface calcium-sensing receptor (CaSR) on the apical membranes of IMCD cells. High deliveries of calcium into the IMCD would be predicted to activate CaSR, leading to reduced membrane abundance of aquaporin-2, thereby limiting water conservation and protecting against stone formation. We have tested this hypothesis in 16 idiopathic hypercalciuric calcium stone formers and 14 matched normal men and women in the General Clinical Research Center. Subjects were fed identical diets; we collected 14 urine samples at 1-h intervals during a single study day, and one sample overnight. Hypercalciuria did not increase urine volume, so urine calcium molarity and supersaturation with respect to calcium oxalate and calcium phosphate rose proportionately to calcium excretion. Thus CaSR modulation of urine volume via IMCD CaSR activation does not appear to be an important mechanism of protection against stone formation. The overnight period, one of maximal water conservation, was a time of maximal stone risk and perhaps a target of specific clinical intervention.

Urinary Adenosine Cyclic 3′,5′-Monophosphate in Idiopathic Calcium Stone-Formers: Response to An Oral Calcium Load

1984 ◽  
Vol 66 (2) ◽  
pp. 193-199 ◽  
Author(s):  
V. R. Walker ◽  
R. A. L. Sutton
Keyword(s):  
Cyclic Amp ◽  
Excretion Rate ◽  
Normal Subjects ◽  
Oral Calcium ◽  
Calcium Stone ◽  
Stone Formers ◽  
Glomerular Filtrate ◽  
Calcium Load ◽  
Urinary Cyclic Amp ◽  
Lower Urinary

1. Idiopathic calcium stone-formers with hypercalciuria during fasting have significantly lower urinary cyclic AMP levels (nmol/dl of glomerular filtrate) than fasting normocalciuric stone-formers. 2. Female subjects, including both normal subjects and idiopathic calcium stone-formers, have higher urinary cyclic AMP levels than their male counterparts, and this difference is significant when urinary cyclic AMP is expressed in the units μmol/g of creatinine. Expressing urinary cyclic AMP in nmol/dl of glomerular filtrate reduces this difference but does not abolish it. Thus, in comparing urinary cyclic AMP levels in various subgroups of the calcium stone-formers and in normal subjects, both sex differences and the units of urinary cyclic AMP expression must be taken into consideration. 3. The magnitude of the change in urinary cyclic AMP in response to an oral calcium load appears to depend on the antecedent urinary cyclic AMP excretion rate, whereby those individuals (either normal subjects or calcium stone-formers) having the highest urinary cyclic AMP levels demonstrate the greatest fall in urinary cyclic AMP after a calcium load.

Evidence of Increased Oxalate Absorption in Patients with Calcium-Containing Renal Stones

1978 ◽  
Vol 54 (3) ◽  
pp. 291-294 ◽  
Author(s):  
A. Hodgkinson
Keyword(s):  
Daily Intake ◽  
Renal Stones ◽  
Normal Subjects ◽  
Molar Ratio ◽  
Oxalate Absorption ◽  
Stone Formers ◽  
The Mean ◽  
The Difference ◽  
Urinary Oxalate Excretion ◽  
And Control

1. The possible roles of the diet and of intestinal absorption in the increased excretion of oxalate by patients with renal calcium stones have been studied. 2. Dietary surveys showed that the mean daily intake of oxalic acid by stone-formers was not significantly different from that of non-stone-formers. 3. The mean urinary excretion of oxalate, expressed as an oxalate/creatinine molar ratio, was significantly reduced by fasting, the change being more marked in the stone-formers than in the normal subjects. Moreover, fasting abolished the difference in mean oxalate/creatinine ratios between stone-formers and control subjects. 4. These results are compatible with the hypothesis that the small increases in urinary oxalate excretion which occur in some idiopathic calcium oxalate stone-formers are due to increased absorption of oxalate from the intestine, which may be due to a reduction in intraluminal calcium concentration.

scholarly journals Evidence for net renal tubule oxalate secretion in patients with calcium kidney stones

2011 ◽  
Vol 300 (2) ◽  
pp. F311-F318 ◽  
Author(s):  
Kristin J. Bergsland ◽  
Anna L. Zisman ◽  
John R. Asplin ◽  
Elaine M. Worcester ◽  
Fredric L. Coe
Keyword(s):  
Fractional Excretion ◽  
Normal Subjects ◽  
Tubular Secretion ◽  
Idiopathic Hypercalciuria ◽  
Renal Handling ◽  
Stone Formers ◽  
Oxalate Secretion ◽  
Calcium Phosphorus ◽  
Urine Oxalate ◽  
Urinary Oxalate Excretion

Little is known about the renal handling of oxalate in patients with idiopathic hypercalciuria (IH). To explore the role of tubular oxalate handling in IH and to evaluate whether differences exist between IH and normal controls, we studied 19 IH subjects, 8 normal subjects, and 2 bariatric stone formers (BSF) during a 1-day General Clinical Research Center protocol utilizing a low-oxalate diet. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, oxalate, and calories. Plasma oxalate concentrations and oxalate-filtered loads were similar between patients (includes IH and BSF) and controls in both the fasting and fed states. Urinary oxalate excretion was significantly higher in patients vs. controls regardless of feeding state. Fractional excretion of oxalate (FEOx) was >1, suggesting tubular secretion of oxalate, in 6 of 19 IH and both BSF, compared with none of the controls ( P < 0.00001). Adjusted for water extraction along the nephron, urine oxalate rose more rapidly among patients than normal subjects with increases in plasma oxalate. Our findings identify tubular secretion of oxalate as a key mediator of hyperoxaluria in calcium stone formers, potentially as a means of maintaining plasma oxalate in a tight range.

scholarly journals The 1 alpha-hydroxylase locus is not linked to calcium stone formation or calciuric phenotypes in French-Canadian families.

1998 ◽  
Vol 9 (3) ◽  
pp. 425-432 ◽  
Author(s):  
P Scott ◽  
D Ouimet ◽  
Y Proulx ◽  
M L Trouvé ◽  
G Guay ◽  
...  
Keyword(s):  
Vitamin D ◽  
Quantitative Trait ◽  
Stone Formation ◽  
Calcium Stone ◽  
Stone Formers ◽  
Vitamin D Levels ◽  
Calcium Urolithiasis ◽  
Recurrent Stone ◽  
Recurrent Stone Formers ◽  
Sib Pairs

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.

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