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

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.

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.

Quantitative Composition of Kidney Stones

1961 ◽  
Vol 7 (5) ◽  
pp. 546-551 ◽  
Author(s):  
Reid H Leonard
Keyword(s):  
Calcium Phosphate ◽  
Calcium Oxalate ◽  
Kidney Stones ◽  
Kidney Stone ◽  
Phosphate Group ◽  
Quantitative Composition

Abstract The kidney stone season for the Pensacola, Fla., area is shown to extend from May through November. No differences in composition of stones in and out of season could be found. Classification of the calculi into five groups delineates the calcium oxalate and phosphate group as the typical stone. Calcium oxalate is more prominent than calcium phosphate, especially in sizes less than 10 mg.

Urolithiasis, Kidney Transplantation, and Pregnancy and Kidney Disease

2012 ◽  
Author(s):  
Stephen B. Erickson ◽  
Hatem Amer ◽  
Timothy S. Larson
Keyword(s):  
Kidney Stones ◽  
End Stage Renal Disease ◽  
Stone Formation ◽  
Renal Tubules ◽  
Anatomical Changes ◽  
Renal Enlargement ◽  
Ureteral Peristalsis ◽  
Total Body ◽  
Stage Renal Disease ◽  
End Stage

It was previously assumed that all kidney stones crystallized as urine passed through the renal tubules and were retained by means of crystal-tubular cell interactions. Recently uroscopy with papillary biopsies has shown 2 different pathways for stone formation, both mediated by calcium phosphate crystals. Kidney transplant has become the preferred treatment for patients with end-stage renal disease. Those benefiting from transplant included patients who would be deemed "high risk," such as those with diabetes mellitus and those older than 70 years. Anatomical changes associated with pregnancy are renal enlargement and dilatation of the calyces, renal pelvis, and ureters. Physiologic changes include a 30% to 50% increase in glomerular filtration rate and renal blood flow; a mean decrease of 0.5 mg/dL in the creatinine level and a mean decrease of 18 mg/dL in the serum urea nitrogen level; intermittent glycosuria independent of plasma glucose; proteinuria; aminoaciduria; increased uric acid excretion; increased total body water, with osmostat resetting; 50% increase in plasma volume and cardiac output; and increased ureteral peristalsis.

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.

scholarly journals Body size and risk of kidney stones.

1998 ◽  
Vol 9 (9) ◽  
pp. 1645-1652
Author(s):  
G C Curhan ◽  
W C Willett ◽  
E B Rimm ◽  
F E Speizer ◽  
M J Stampfer
Keyword(s):  
Body Mass Index ◽  
Body Size ◽  
Calcium Oxalate ◽  
Body Mass ◽  
Kidney Stones ◽  
Stone Formation ◽  
Stone Disease ◽  
Kidney Stone Formation ◽  
Risk Of Stone Formation

A variety of factors influence the formation of calcium oxalate kidney stones, including gender, diet, and urinary excretion of calcium, oxalate, and uric acid. Several of these factors may be related to body size. Because men on average have a larger body size and a threefold higher lifetime risk of stone formation than women, body size may be an important risk factor for calcium oxalate stone formation. The association between body size (height, weight, and body mass index) and the risk of kidney stone formation was studied in two large cohorts: the Nurses' Health Study (NHS; n = 89,376 women) and the Health Professionals Follow-up Study (HPFS; n = 51,529 men). Information on body size, kidney stone formation, and other exposures of interest was obtained by mailed questionnaires. A total of 1078 incident cases of kidney stones in NHS during 14 yr of follow-up and a total of 956 cases in HPFS during 8 yr of follow-up were confirmed. In both cohorts, the prevalence of a stone disease history and the incidence of stone disease were directly associated with weight and body mass index. However, the magnitude of the associations was consistently greater among women. Specifically, the age-adjusted prevalence odds ratio for women with body mass index > or = 32 kg/m2 compared with 21 to 22.9 kg/m2 was 1.76 (95% confidence interval, 1.50 to 2.07), but 1.38 (95% confidence interval, 1.16 to 1.65) for the same comparison in men. For incident stone formation, the multivariate relative risks for the similar comparisons were 1.89 (1.51 to 2.36) for women and 1.19 (0.83 to 1.70) in men. Height was inversely associated with the prevalence of stone disease but was not associated with incident stone formation. These results suggest that body size is associated with the risk of stone formation and that the magnitude of risk varies by gender. Additional studies are necessary to determine whether a reduction in body weight decreases the risk of stone formation, particularly in women.

scholarly journals Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with disrupted type IIa sodium-phosphate cotransporter

2008 ◽  
Vol 294 (5) ◽  
pp. F1109-F1115 ◽  
Author(s):  
Saeed R. Khan ◽  
Patricia A. Glenton
Keyword(s):  
Animal Model ◽  
Calcium Oxalate ◽  
Kidney Stones ◽  
Sodium Phosphate ◽  
Renal Tubules ◽  
Male Mice ◽  
Calcium Oxalate Crystal ◽  
Crystal Deposition ◽  
Caox Crystal ◽  
Local Supersaturation

The most common theories about the pathogenesis of idiopathic kidney stones consider precipitation of calcium phosphate (CaP) within the kidneys critical for the development of the disease. We decided to test the hypothesis that a CaP substrate can promote the deposition of calcium oxalate (CaOx) in the kidneys. Experimental hyperoxaluria was induced by feeding glyoxylate to male mice with knockout (KO) of NaPi IIa (Npt2a), a sodium-phosphate cotransporter. Npt2a KO mice are hypercalciuric and produce CaP deposits in their renal tubules. Experimental hyperoxaluria led to CaOx crystalluria in both the hypercalciuric KO mice and the normocalciuric control B6 mice. Only the KO mice produced CaOx crystal deposits in their kidneys, but the CaOx crystals deposited separately from the CaP deposits. Perhaps CaP deposits were not available for a CaOx overgrowth. These results also validate earlier animal model observations that showed that CaP substrate is not required for renal deposition of CaOx and that other factors, such as local supersaturation, may be involved. The absence of CaOx deposition in the B6 mice despite extreme hyperoxaluria also signifies the importance of both calcium and oxalate in the development of CaOx nephrolithiasis.

scholarly journals In-Vitro antiurolithiatic activity of aqueous extract Pavonia lasiopetala

2019 ◽  
Vol 9 (2) ◽  
pp. 102-104
Author(s):  
R. Ramprasad ◽  
Anil Nilsha ◽  
S. Shahul Hameed ◽  
Junuha M R Shifama ◽  
N. Venkateshan
Keyword(s):  
Calcium Phosphate ◽  
Calcium Oxalate ◽  
Aqueous Extract ◽  
Inhibitory Action ◽  
In Vivo Studies ◽  
Precipitation Method ◽  
Calcium Oxalate Crystals ◽  
Permeable Membrane ◽  
Oxalate Crystals

Background: Upto date, the scientific documentation regarding in-vitro antiurolithiatic activity of has been reported, although it has not reported for in-vitro antiurolithiatic activity up till now. Objective: To explore anti-urolithiatic activities of Pavonia lasiopetala leaves extract by utilizing different in-vitro models. Material and Methods: Aqueous extract of Pavonia lasiopetala fresh leaves was prepared and arranged in the different concentrations. Homogenous precipitation method was used to prepare artificial stones such as calcium oxalate and calcium phosphate and semi-permeable membrane of eggs was used as dissolution bags. Dissolution models were incubated in 72 hrs and after that, the entire content in dissolution bags was estimated spectrophotometrically. The inhibitory activity of Pavonia lasiopetala leaves extract on the nucleation of calcium oxalate crystals and the rate of aggregation in calcium oxalate crystals was determined by spectrophotometric assay. Results: In dissolution models, the extract of Pavonia lasiopetala has greater capability to dissolve calcium oxalate while Cystone standard has shown better demineralization for calcium phosphate rather than extract of Pavonia lasiopetala. Cystone exhibited strongly inhibitory action in the nucleation assay rather than aggregation assay. The extract of Pavonia lasiopetala exhibited inhibitory action in both of nucleation and aggregation assays to significant level.  Discussion: Correlation between in-vitro and in-vivo studies may be helpful to understand the molecular mechanism of litholysis process and to reveal phytochemicals of the extract responsible for dissolving or disintegrating renal calculi. Conclusion: Pavonia lasiopetala extract exhibited significant in-vitro anti-urolithiatic activity. Keywords: Pavonia lasiopetala, spectrophotometrically, in-vitro antiurolithiatic.

933: Calcium Oxalate/Calcium Phosphate Association in Kidney Stones

2007 ◽  
Vol 177 (4S) ◽  
pp. 309-309
Author(s):  
Saeed R. Khan ◽  
Karen B. Priola ◽  
Patricia A. Glenton
Keyword(s):  
Calcium Phosphate ◽  
Calcium Oxalate ◽  
Kidney Stones

scholarly journals An in vitro screening potential traditional medicinal plants for nephrolithiasis

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Majid Shirani ◽  
Davood Arjaki ◽  
Soleiman Kheiri ◽  
Elham Bijad ◽  
Sareh Mohammadi ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Calcium Oxalate ◽  
Kidney Stones ◽  
Phenolic Content ◽  
Colorimetric Method ◽  
Total Phenolic ◽  
Root Extracts ◽  
Traditional Medicinal Plants ◽  
Percutaneous Nephrolithotripsy

Abstract Background Today, the attention of researchers has been drawn to the use of medicinal plant for the treatment of kidney stones. The aim of this study was to investigate the effect of five plants used in traditional medicine on the dissolution of calcium oxalate and calcium phosphate stones. Then, the ability of more effective plants to dissolve stones collected from patients after Percutaneous Nephrolithotripsy was investigated. Methods The aerial part of plants were extracted by maceration method. The synthesized stones in laboratory were incubated with different concentrations of the extract. Next, the concentrations of calcium oxalate and calcium phosphate were measured by a calcium kit and BT 3000. The effect of the extract with the best activity on the stones collected from the patients was also studied. The composition of clinical stones was determined by colorimetric method. The total phenolic content (TPC) of the extracts was determined. Results The highest dissolution of calcium oxalate stones was observed by the G. struthium extract and the highest dissolution of calcium phosphate stones by the A. euchroma and A. officinalis root extracts. The dissolution percentage of clinical stones by the A. euchroma extract was significantly higher than other extract (P < 0.05). The highest TPC was observed in A. euchroma extract (P < 0.05). Conclusion The A. euchroma extract exhibited the greatest dissolution activity on laboratory calcium oxalate and calcium phosphate stones as well as clinical stones made of high amounts of calcium oxalate. Therefore, the extract can be effective in preventing and treating kidney stones.

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