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

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.

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

AJP Renal Physiology ◽

10.1152/ajprenal.00383.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. F1935-F1943 ◽

Cited By ~ 70

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.

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Involvement of Cellular Membranes and their Lipids in Nucleation of Stone Forming Crystals

MRS Proceedings ◽

10.1557/proc-599-269 ◽

1999 ◽

Vol 599 ◽

Author(s):

S. R. Khan ◽

J. M. Fasano ◽

R. Backov ◽

D. R. Talham

Keyword(s):

Calcium Phosphate ◽

Calcium Oxalate ◽

Kidney Stones ◽

Membrane Lipids ◽

Stone Formation ◽

Rat Kidney ◽

Langmuir Monolayers ◽

Membrane Vesicles ◽

In Vivo Studies ◽

Renal Tubules

AbstractMore than 80% of human kidney stones consist of calcium oxalate and/or calcium phosphate. Human urine is generally metastable with respect to these salts and their nucleation is heterogeneous. Based on: 1. ultrastructural and immunohistochemical studies of stones in which cellular degradation products and lipids were commonly seen in association with calcific crystals and 2. in vivo studies of nephrolithiasis in rat models where calcium oxalate (CaOx) and calcium phosphate (CaP) crystals almost always formed and seen in association with cell membranes, we proposed that membranes and their lipids are involved in crystallization of these salts. To test our hypothesis we isolated organic matrix of kidney stones, its lipid contents and membrane vesicles from epithelial cells of rat kidney and incubated them in metastable solution of CaOx. Both membrane vesicles and matrix from the stones supported crystallization of CaOx and crystals formed in association with the membranes. Lipids of the stone matrix appeared better nucleators than whole matrix. Urine spends only minutes within the kidneys thus any nucleation which can lead to stone formation has to occur rapidly. In studies described here, we demonstrate that under specific circumstances relevant to conditions in the kidney, membrane vesicle- supported CaOx crystallization can occur within seconds, demonstrating the possibility of such events happening in the kidneys. We also studied CaOx monohydrate (COM) precipitation at Langmuir monolayers of dipalmitoylphosphatidylglecerol (DPPG), dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylserine (DPPS) showed precipitation to be heterogeneous and selective with a majority of crystals orienting with the 101 face of COM facing the monolayer. Our results show that membrane lipids can initiate nucleation of calcium oxalate crystals in solutions similar to those present in the kidneys. In addition these crystals form within the time urine spends inside the renal tubules demonstrating for the first time the likelihood of occurrence of such a phenomenon in the kidneys during stone formation.

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E145 Evaluation of a statistical model to predict the calcium phosphate mixed stone formation in pure calcium oxalate stone formers

European Urology Supplements ◽

10.1016/s1569-9056(13)61804-7 ◽

2013 ◽

Vol 12 (3) ◽

pp. 78-79

Author(s):

S. Oehlschläger ◽

V. Neumeister ◽

R. Herout ◽

J. Graff ◽

M.P. Wirth

Keyword(s):

Calcium Phosphate ◽

Statistical Model ◽

Calcium Oxalate ◽

Stone Formation ◽

Calcium Oxalate Stone ◽

Stone Formers

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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

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2004.052 ◽

2004 ◽

Vol 42 (3) ◽

Cited By ~ 10

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.

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Dual modulatory effects of diosmin on calcium oxalate kidney stone formation processes: Crystallization, growth, aggregation, crystal-cell adhesion, internalization into renal tubular cells, and invasion through extracellular matrix

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2021.111903 ◽

2021 ◽

Vol 141 ◽

pp. 111903

Author(s):

Supaporn Khamchun ◽

Sunisa Yoodee ◽

Visith Thongboonkerd

Keyword(s):

Extracellular Matrix ◽

Cell Adhesion ◽

Calcium Oxalate ◽

Kidney Stone ◽

Stone Formation ◽

Formation Processes ◽

Tubular Cells ◽

Renal Tubular Cells ◽

Renal Tubular ◽

Kidney Stone Formation

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Short-Term Tolvaptan Increases Water Intake and Effectively Decreases Urinary Calcium Oxalate, Calcium Phosphate and Uric Acid Supersaturations

The Journal of Urology ◽

10.1016/j.juro.2015.11.027 ◽

2016 ◽

Vol 195 (5) ◽

pp. 1476-1481 ◽

Cited By ~ 12

Author(s):

Wisit Cheungpasitporn ◽

Stephen B. Erickson ◽

Andrew D. Rule ◽

Felicity Enders ◽

John C. Lieske

Keyword(s):

Uric Acid ◽

Calcium Phosphate ◽

Calcium Oxalate ◽

Water Intake ◽

Urinary Calcium ◽

Short Term

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The Relation between the Concentration of Calcium Salts in the Urine and Renal Stone Composition in Patients with Calcium-Containing Renal Stones

Clinical Science ◽

10.1042/cs0430433 ◽

1972 ◽

Vol 43 (3) ◽

pp. 433-441 ◽

Cited By ~ 30

Author(s):

R. W. Marshall ◽

M. Cochran ◽

W. G. Robertson ◽

A. Hodgkinson ◽

B. E. C. Nordin

Keyword(s):

Calcium Phosphate ◽

Calcium Oxalate ◽

Renal Stones ◽

Urine Ph ◽

Stone Composition ◽

Calcium Oxalate Stones ◽

Urine Oxalate ◽

The Difference ◽

Normal Urine ◽

Normal Men

1. Diurnal variations in urine calcium oxalate and calcium phosphate activity products were observed in normal men and patients with recurrent calcium oxalate or mixed oxalate—phosphate renal stones. 2. Maximum and minimum calcium oxalate products were higher in the patients than in the controls, the difference being most marked in the patients with calcium oxalate stones. 3. Maximum and minimum calcium phosphate products expressed as octocalcium phosphate [(Ca8H2(PO4)6], brushite or hydroxyapatite, were significantly higher than normal in the patients with mixed stones but not in the patients with calcium oxalate stones. 4. The raised calcium oxalate products in the patients were due mainly to increased concentrations of Ca2+ ions; these, in turn, were due mainly to an increased rate of excretion of calcium. Raised calcium phosphate products were due mainly to hypercalciuria, combined with abnormally high urine pH values. 5. Patients with recurrent calcium stones appear to fall into two types: (1) patients with calcium oxalate stones associated with hypercalciuria, a normal or raised urine oxalate and a normal urine pH; (2) patients with mixed oxalate—phosphate stones associated with hypercalciuria, a normal or raised urine oxalate and a raised urine pH. 6. The implications of these findings in regard to treatment are discussed.

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Molecular modulation of calcium oxalate crystallization

AJP Renal Physiology ◽

10.1152/ajprenal.00136.2006 ◽

2006 ◽

Vol 291 (6) ◽

pp. F1123-F1132 ◽

Cited By ~ 57

Author(s):

James J. De Yoreo ◽

S. Roger Qiu ◽

John R. Hoyer

Keyword(s):

Molecular Modeling ◽

Calcium Oxalate ◽

Stone Formation ◽

Energy Levels ◽

Critical Role ◽

Specific Interactions ◽

Crystal Surfaces ◽

Site Specific

Calcium oxalate monohydrate (COM) is the primary constituent of the majority of renal stones. Osteopontin (OPN), an aspartic acid-rich urinary protein, and citrate, a much smaller molecule, are potent inhibitors of COM crystallization at levels present in normal urine. Current concepts of the role of site-specific interactions in crystallization derived from studies of biomineralization are reviewed to provide a context for understanding modulation of COM growth at a molecular level. Results from in situ atomic force microscopy (AFM) analyses of the effects of citrate and OPN on growth verified the critical role of site-specific interactions between these growth modulators and individual steps on COM crystal surfaces. Molecular modeling investigations of interactions of citrate with steps and faces on COM crystal surfaces provided links between the stereochemistry of interaction and the binding energy levels that underlie mechanisms of growth modification and changes in overall crystal morphology. The combination of in situ AFM and molecular modeling provides new knowledge that will aid rationale design of therapeutic agents for inhibition of stone formation.

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Association between endometritis and urocystitis in culled sows

Acta Veterinaria Hungarica ◽

10.1556/avet.50.2002.4.4 ◽

2002 ◽

Vol 50 (4) ◽

pp. 413-423 ◽

Cited By ~ 5

Author(s):

I. Biksi ◽

N. Takács ◽

F. Vetési ◽

Keyword(s):

Sensitivity And Specificity ◽

Gold Standard ◽

Positive Association ◽

Urogenital Tract

Slaughterhouse sampling and examination of urogenital tracts of 499 sows and gilts culled for reproductive reasons from 21 Hungarian herds were performed over a 6-year period. The aim was to estimate the prevalence of different urogenital tract lesions, and to provide sensitivity and specificity estimates for macroscopic and bacteriological examinations in the diagnosis of urocystitis and endometritis. Furthermore, the association between endometritis and urocystitis was assessed. The prevalence of main lesions of the urogenital tract was similar to that reported in other studies. The 'sensitivity' of macroscopic and bacteriological methods was determined statistically by taking histopathology as the 'Gold Standard'. As a result, the 'sensitivity' of macroscopic methods for the diagnosis of endometritis and urocystitis was ≤ 18.1% and 47.9%, respectively, while the 'sensitivity' of bacteriology for the diagnosis of the same conditions was ≤ 31.8% and 63.0%, respectively. The presumed positive association between urocystitis and endometritis was confirmed; it was not confounded by parity. Animals affected by urocystitis had a 3.5 times higher odds to simultaneously have endometritis than animals without urocystitis.

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