Is calcium oxalate nucleation in postprandial urine of males with idiopathic recurrent calcium urolithiasis related to calcium phosphate nucleation and the intensity of stone formation? Studies allowing insight into a possible role of urinary free citrate and protein

2004 ◽  
Vol 42 (3) ◽  
Author(s):  
Paul O. Schwille ◽  
Angelika Schmiedl ◽  
Mahimaidos Manoharan
Keyword(s):  
Clinical Trial ◽  
Calcium Phosphate ◽  
Calcium Oxalate ◽  
Stone Formation ◽  
Urine Volume ◽  
Control Group ◽  
Urine Calcium ◽  
Element Analysis ◽  
Protein Ratio ◽  
Whole Urine

AbstractIn idiopathic recurrent urolithiasis (IRCU) calcium oxalate and calcium phosphate are components of stones. It is not sufficiently known whether in urine the nucleation (liquid-solid transition) of each salt requires a different environment, if so which environment, and whether there is an impact on stone formation. Nucleation was induced by in vitro addition of oxalate or calcium to post-test meal load whole urine of male stone patients (n=48), showing normal daily and baseline fasting oxaluria. The maximally tolerated (until visible precipitates occur) concentration of oxalate (T-Ox) or calcium (T-Ca) was determined; additionally evaluated were other variables in urine, including total, complexed and free citrate (F-Cit), protein (albumin, non-albumin protein) and the clinical intensity (synonymous metabolic activity; MA) of IRCU. In the first of three trials the accumulation of substances in stone-forming urine was verified (trial-V); in the second (clinical trial 1) two strata of T-Ox (Low, High) were compared; in the third (clinical trial 2) IRCU patients (n=27) and a control group (n=13) were included to clarify whether in stone-forming urine the first crystal formed was calcium oxalate or calcium phosphate, and to identify the state of F-Cit. T-Ox was studied at the original pH (average<6.0), T-Ca at prefixed pH 6.0; the precipitates were subjected to electron microscopy and element analysis. Trial-V: Among the urinary substances accumulating at the indicated pHs were calcium, oxalate and phosphate, and the crystal-urine ratios were compatible with the nucleation of calcium oxalate, calcium-poor and calcium-rich calcium phosphate; citrate, protein and potassium also accumulated. Clinical trial 1: the two strata exhibited an inverse change of T-Ox and T-Ca, the ratio T-Ox/T-Ca and MA. The initial (before induction of Ox or Ca excess) supersaturation of calcium oxalate and brushite were unchanged, with the difference of proteinuria being borderline. Several correlations were significant (p≤0.05): urine pH with citrate and volume, protein with volume and MA, T-Ox with T-Ca and MA. Clinical trial 2: in patients with reduced urine volume and moderate urine calcium excess, the first precipitate appeared to be calcium oxalate, followed by amorphous calcium phosphate. Conversely, when the calcium excess was extreme, calcium-rich hydroxyapatite developed, followed by calcium oxalate; F-Cit, not total and complexed citrate, was decreased in IRCU vs. male controls; F-Cit rose pH-dependently, and the ratio F-Cit at original pH vs. F-Cit at pH 6.0 correlated inversely with the nucleation index T-Ox/T-Ca; MA correlated inversely with the ratio F-Cit at pH 6.0, respectively, original pH, but directly with the urinary albumin/non-albumin protein ratio. In summary 1) to study calcium oxalate and calcium phosphate nucleation in whole urine of IRCU patients is feasible; 2) at this crystallization stage the two substances, dominant in calcium stones, appear intimately linked, 3) in stone-forming urine, calcium phosphate may be ubiquitously present, likely as particles <0.22 μm; 4) together with co-precipitation of calcium oxalate and calcium phosphate, low F-Cit and alteration of proteinuria may act in concert and accelerate stones.

Renal calcinosis and stone formation in mice lacking osteopontin, Tamm-Horsfall protein, or both

2007 ◽  
Vol 293 (6) ◽  
pp. F1935-F1943 ◽  
Author(s):  
Lan Mo ◽  
Lucy Liaw ◽  
Andrew P. Evan ◽  
Andre J. Sommer ◽  
John C. Lieske ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Calcium Oxalate ◽  
Stone Formation ◽  
Calcium Oxalate Monohydrate ◽  
Wild Type ◽  
Mineral Salts ◽  
Calcium Oxalate Crystallization ◽  
Whole Urine ◽  
Normal Urine

Although often supersaturated with mineral salts such as calcium phosphate and calcium oxalate, normal urine possesses an innate ability to keep them from forming harmful crystals. This inhibitory activity has been attributed to the presence of urinary macromolecules, although controversies abound regarding their role, or lack thereof, in preventing renal mineralization. Here, we show that 10% of the mice lacking osteopontin (OPN) and 14.3% of the mice lacking Tamm-Horsfall protein (THP) spontaneously form interstitial deposits of calcium phosphate within the renal papillae, events never seen in wild-type mice. Lack of both proteins causes renal crystallization in 39.3% of the double-null mice. Urinalysis revealed elevated concentrations of urine phosphorus and brushite (calcium phosphate) supersaturation in THP-null and OPN/THP-double null mice, suggesting that impaired phosphorus handling may be linked to interstitial papillary calcinosis in THP- but not in OPN-null mice. In contrast, experimentally induced hyperoxaluria provokes widespread intratubular calcium oxalate crystallization and stone formation in OPN/THP-double null mice, while completely sparing the wild-type controls. Whole urine from OPN-, THP-, or double-null mice all possessed a dramatically reduced ability to inhibit the adhesion of calcium oxalate monohydrate crystals to renal epithelial cells. These data establish OPN and THP as powerful and functionally synergistic inhibitors of calcium phosphate and calcium oxalate crystallization in vivo and suggest that defects in either molecule may contribute to renal calcinosis and stone formation, an exceedingly common condition that afflicts up to 12% males and 5% females.

Nephrolithiasis

2018 ◽  
Author(s):  
José Luiz Nishiura ◽  
Ita Pfeferman Heilberg
Keyword(s):  
Uric Acid ◽  
Calcium Oxalate ◽  
Dietary Habits ◽  
Stone Formation ◽  
Urine Volume ◽  
First Episode ◽  
Dietary Advice ◽  
Dietary Recommendations ◽  
Genetic Traits ◽  
Oxalate Precipitation

Nephrolithiasis is a highly prevalent condition, but its incidence varies depending on race, gender, and geographic location. Approximately half of patients form at least one recurrent stone within 10 years of the first episode. Renal stones are usually composed of calcium salts (calcium oxalate monohydrate or dihydrate, calcium phosphate), uric acid, or, less frequently, cystine and struvite (magnesium, ammonium, and phosphate). Calcium oxalate stones, the most commonly encountered ones, may result from urinary calcium oxalate precipitation on the Randall plaque, which is a hydroxyapatite deposit in the interstitium of the kidney medulla. Uric acid nephrolithiasis, which is common among patients with metabolic syndrome or diabetes mellitus, is caused by an excessively acidic urinary pH as a renal manifestation of insulin resistance. The medical evaluation of the kidney stone patient must be focused on identifying anatomic abnormalities of the urinary tract, associated systemic diseases, use of lithogenic drugs or supplements, and, mostly, urinary risk factors such as low urine volume, hypercalciuria, hyperuricosuria, hypocitraturia, hyperoxaluria, and abnormalities in urine pH that can be affected by dietary habits, environmental factors, and genetic traits. Metabolic evaluation requires a urinalysis, stone analysis (if available), serum chemistry, and urinary parameters, preferably obtained by two nonconsecutive 24-hour urine collections under a random diet. Targeted medication and dietary advice are effective to reduce the risk of recurrence. Clinical, radiologic, and laboratory follow-ups are needed to prevent stone growth and new stone formation, to assess treatment adherence or effectiveness to dietary recommendations, and to allow adjustment of pharmacologic treatment. This review contains 5 highly rendered figure, 3 tables, and 105 references.

Nephrolithiasis

2017 ◽  
Author(s):  
José Luiz Nishiura ◽  
Ita Pfeferman Heilberg
Keyword(s):  
Uric Acid ◽  
Calcium Oxalate ◽  
Dietary Habits ◽  
Stone Formation ◽  
Urine Volume ◽  
First Episode ◽  
Dietary Advice ◽  
Dietary Recommendations ◽  
Genetic Traits ◽  
Oxalate Precipitation

Nephrolithiasis is a highly prevalent condition, but its incidence varies depending on race, gender, and geographic location. Approximately half of patients form at least one recurrent stone within 10 years of the first episode. Renal stones are usually composed of calcium salts (calcium oxalate monohydrate or dihydrate, calcium phosphate), uric acid, or, less frequently, cystine and struvite (magnesium, ammonium, and phosphate). Calcium oxalate stones, the most commonly encountered ones, may result from urinary calcium oxalate precipitation on the Randall plaque, which is a hydroxyapatite deposit in the interstitium of the kidney medulla. Uric acid nephrolithiasis, which is common among patients with metabolic syndrome or diabetes mellitus, is caused by an excessively acidic urinary pH as a renal manifestation of insulin resistance. The medical evaluation of the kidney stone patient must be focused on identifying anatomic abnormalities of the urinary tract, associated systemic diseases, use of lithogenic drugs or supplements, and, mostly, urinary risk factors such as low urine volume, hypercalciuria, hyperuricosuria, hypocitraturia, hyperoxaluria, and abnormalities in urine pH that can be affected by dietary habits, environmental factors, and genetic traits. Metabolic evaluation requires a urinalysis, stone analysis (if available), serum chemistry, and urinary parameters, preferably obtained by two nonconsecutive 24-hour urine collections under a random diet. Targeted medication and dietary advice are effective to reduce the risk of recurrence. Clinical, radiologic, and laboratory follow-ups are needed to prevent stone growth and new stone formation, to assess treatment adherence or effectiveness to dietary recommendations, and to allow adjustment of pharmacologic treatment. This review contains 5 highly rendered figure, 3 tables, and 105 references.

scholarly journals Sensitivity and specificity of 24-hour urine chemistry levels for detecting elevated calcium oxalate and calcium phosphate supersaturation

2013 ◽  
Vol 2 (2) ◽  
pp. 117 ◽  
Author(s):  
M. Adrian Rossi ◽  
Eric A. Singer ◽  
Dragan J. Golijanin ◽  
Rebeca D. Monk ◽  
Erdal Erturk ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Calcium Oxalate ◽  
Sensitivity And Specificity ◽  
Retrospective Review ◽  
Gold Standard ◽  
Urine Analysis ◽  
Stone Formation ◽  
Urine Collection ◽  
Total Calcium ◽  
Men And Women

Objectives: The gold standard for determining likelihood of calcium oxalate(CaOx) and calcium phosphate (CaPhos) stone formation in urine is supersaturationof CaOx and CaPhos. Our objective was to investigate whether traditionalmeasurement of total calcium, oxalate and phosphate in a 24-hour urinecollection is sufficiently sensitive and specific for detecting elevated supersaturationto preclude the more expensive supersaturation test.Methods: We performed a retrospective review of 150 consecutive patients withnephrolithiasis who underwent measurement of CaOx supersaturation (CaOxSS)and CaPhos supersaturation (CaPhosSS), as well as total calcium, oxalate andphosphate in a 24-hour urine collection. We used various cut-off values to determinesensitivity and specificity of 24-hour urine measurements for detectingelevated CaOxSS and CaPhosSS.Results: In men and women, the sensitivity of 24-hour calcium for detectingelevated CaOxSS was 71% and 79%, respectively; for oxalate, sensitivity was59% and 36%, respectively. In men and women, the sensitivity of 24-hour calciumfor detecting elevated CaPhosSS was 74% and 88%, respectively; for phosphate,sensitivity was 57% and 8%, respectively. In men and women, the specificityof 24-hour calcium for detecting elevated CaOxSS was 55% and 48%,respectively; it was 60% for detecting elevated CaPhosSS in both men andwomen.Conclusion: Traditional 24-hour urine analysis is sensitive, but not specific, fordetecting elevated CaOxSS and CaPhosSS. Most patients with abnormal 24-hour urine analysis have normal supersaturation, and treatment decisions basedon traditional urine analysis would lead to overtreatment in these patients.

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.

scholarly journals Anti-urolithiatic Activity of Sambong (Blumea balsamifera) Extract in Ethylene Glycol-induced Urolithiatic Wistar Rats (Rattus norvegicus)

2020 ◽  
Vol 54 (1) ◽  
Author(s):  
Althea Samantha C. Agdamag ◽  
Larielyn Hope C. Aggabao ◽  
Mary Sheena C. Agudo ◽  
Francis Louis M. Alcachupas ◽  
Jeremiah Carlo V. Alejo ◽  
...  
Keyword(s):  
Treatment Group ◽  
Ethylene Glycol ◽  
Calcium Oxalate ◽  
Stone Formation ◽  
Positive Control ◽  
Control Group ◽  
Control Group Design ◽  
Calcium Oxalate Stone ◽  
Kidney Homogenate ◽  
Calcium Oxalate Stones

Objective. The study aimed to determine if Blumea balsamifera inhibits calcium oxalate stone formation in the kidneys through determination of the number of calcium oxalate stones in the renal cortex and the percent mass of calcium oxalate. Methods. Post-test only control group design was used using five treatment groups with placebo as the negative control, potassium citrate as the positive control, and 50%, 100%, and 200% sambong treatment. Urolithiasis was induced through ethylene glycol and ammonium chloride. Each treatment group was administered its corresponding treatment solution once daily for twenty-one days. Histopathologic examination and kidney homogenate analysis were done to determine the degree of deposition of calcium oxalate stones in renal tissues and the oxalate content, respectively. Statistical analyses were performed using one-way ANOVA and post hoc Gabriel's Pairwise Comparisons Test. Results. The 100% sambong treatment group showed the least mean number of stones while the positive control and 50% sambong treatment group exhibited the highest anti-urolithiatic activity in terms of oxalate content of the kidney homogenate. Conclusion. It can be concluded from the study that Blumea balsamifera inhibits calcium oxalate stone formation in the kidneys with the 100% and 50% sambong treatment most effective in decreasing number of stones and oxalate content of the kidney homogenate, respectively.

scholarly journals Chlorthalidone Is Superior to Potassium Citrate in Reducing Calcium Phosphate Stones and Increasing Bone Quality in Hypercalciuric Stone-Forming Rats

2019 ◽  
Vol 30 (7) ◽  
pp. 1163-1173 ◽  
Author(s):  
Nancy S. Krieger ◽  
John R. Asplin ◽  
Ignacio Granja ◽  
Felix M. Ramos ◽  
Courtney Flotteron ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Potassium Chloride ◽  
Bone Quality ◽  
Stone Formation ◽  
Potassium Citrate ◽  
Idiopathic Hypercalciuria ◽  
Mineral Density ◽  
Urine Calcium ◽  
Fixed Amount ◽  
Normal Calcium

BackgroundThe pathophysiology of genetic hypercalciuric stone-forming rats parallels that of human idiopathic hypercalciuria. In this model, all animals form calcium phosphate stones. We previously found that chlorthalidone, but not potassium citrate, decreased stone formation in these rats.MethodsTo test whether chlorthalidone and potassium citrate combined would reduce calcium phosphate stone formation more than either medication alone, four groups of rats were fed a fixed amount of a normal calcium and phosphorus diet, supplemented with potassium chloride (as control), potassium citrate, chlorthalidone (with potassium chloride to equalize potassium intake), or potassium citrate plus chlorthalidone. We measured urine every 6 weeks and assessed stone formation and bone quality at 18 weeks.ResultsPotassium citrate reduced urine calcium compared with controls, chlorthalidone reduced it further, and potassium citrate plus chlorthalidone reduced it even more. Chlorthalidone increased urine citrate and potassium citrate increased it even more; the combination did not increase it further. Potassium citrate, alone or with chlorthalidone, increased urine calcium phosphate supersaturation, but chlorthalidone did not. All control rats formed stones. Potassium citrate did not alter stone formation. No stones formed with chlorthalidone, and rats given potassium citrate plus chlorthalidone had some stones but fewer than controls. Rats given chlorthalidone with or without potassium citrate had higher bone mineral density and better mechanical properties than controls, whereas those given potassium citrate did not.ConclusionsIn genetic hypercalciuric stone-forming rats, chlorthalidone is superior to potassium citrate alone or combined with chlorthalidone in reducing calcium phosphate stone formation and improving bone quality.

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.

Evaluation of Antiurolithiatic Activity of Lawsonia inermis Linn. in Rats

2017 ◽  
Vol 10 (3) ◽  
pp. 3728-3735
Author(s):  
Kruti M Patel ◽  
Samir K Shah
Keyword(s):  
Uric Acid ◽  
Calcium Phosphate ◽  
Urine Volume ◽  
Control Group ◽  
Lawsonia Inermis ◽  
Urea Nitrogen ◽  
Standard Drug ◽  
Kidney Homogenate ◽  
Group I ◽  
Model Control

This study was conducted to evaluate the potential antiurolithiatic effects of Lawsonia Inermis Linn. in rat models. Animals were divided into seven groups and urolithiasis was induced by ethylene glycol (0.75% v/v) in drinking water to all groups (Groups II-VII) except normal control (Group I) for 28 days. Methanolic extracts of Lawsonia inermis (MELI) bark (300 & 500 mg/kg, p.o.) were administered once daily, from 15th day to 28th day as curative regimen and from 1st day to 28th day as preventive regimen. Cystone (750 mg/kg, p.o.) was used as a standard drug for comparison. After 28 days, various biochemical parameters like urine volume, pH were measured. Calcium, phosphate and oxalate were measured in urine and kidney homogenate. Serum creatinine, uric acid and urea nitrogen were estimated. Histopathology of kidney was investigated. Treatment with the MELI extract significantly (p<0.05) restored all elevated parameters including calcium, phosphate and oxalate in urine and kidney homogenate; creatinine, uric acid and urea nitrogen in serum when compared to model control group. The histopathological study of the kidney also supported the above results. It was concluded that methanolic extract of bark of Lawsonia inermis Linn. has significant antiurolithiatic effect in experimental rats.   

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