Effect of Urate on Calcium Oxalate Crystallization in Human Urine: Evidence for a Promotory Role of Hyperuricosuria in Urolithiasis

1990 ◽  
Vol 79 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Phulwinder K. Grover ◽  
Rosemary L. Ryall ◽  
Villis R. Marshall

1. The effect of hyperuricosuria, simulated by increasing the concentration of dissolved urate, on the crystallization of calcium oxalate in human urine was examined. 2. Twenty urine samples were studied. Ten of these, designated type A, spontaneously precipitated calcium oxalate dihydrate crystals upon the addition of a solution of sodium urate solution which raised the median urate concentration from 3.1 to 7.0 mmol/l. 3. Adding dissolved urate to the remaining type B samples raised the median urate concentration from 2.2 to 6.2 mmol/l, but did not cause the precipitation of calcium oxalate. This was induced in these samples by the addition of a standard load of oxalate above an empirically determined metastable limit. 4. In the type B urine samples, the addition of urate decreased the median metastable limit from 125 to 66 μmol of oxalate, trebled the median volume of crystalline calcium oxalate deposited from 35 000 to 105 000 μm3/μl and significantly increased the overall size of the particles precipitated. Calcium oxalate monohydrate was exclusively precipitated, and the individual crystals deposited in the presence of urate were markedly smaller, more numerous, and more highly aggregated than those produced in its absence. 5. These results constitute the most convincing evidence yet obtained that hyperuricosuria may be a powerful promoter of calcium oxalate stone formation.

2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Bao-Song Gui ◽  
Rong Xie ◽  
Xiu-Qiong Yao ◽  
Mei-Ru Li ◽  
Jian-Ming Ouyang

The composition and morphology of nanocrystals in urines of healthy persons and lithogenic patients were comparatively investigated by means of X-ray diffraction (XRD) and transmission electron microscopy (TEM). It was shown that the main composition of urinary nanocrystals in healthy persons were calcium oxalate dihydrate (COD), uric acid, and ammonium magnesium phosphate (struvite). However, the main compositions of urinary nanocrystals in lithogenic patients were struvite,β-tricalcium phosphate, uric acid, COD, and calcium oxalate monohydrate (COM). According to the XRD data, the size of nanocrystals was calculated to be23∼72 nm in healthy urine and12∼118 nm in lithogenic urine by Scherer formula. TEM results showed that the nanocrystals in healthy urine were dispersive and uniform with a mean size of about 38 nm. In contrast, the nanocrystals in lithogenic urine were much aggregated with a mean size of about 55 nm. The results in this work indicated that the urinary stone formation may be prevented by diminishing the aggregation and the size differentiation of urinary nanocrystals by physical or chemical methods.


2001 ◽  
Vol 101 (2) ◽  
pp. 159-168 ◽  
Author(s):  
David E. FLEMING ◽  
Wilhelm VAN BRONSWIJK ◽  
Rosemary Lyons RYALL

To assess the binding of individual amino acids to the principal calcium minerals found in human kidney stones, the adsorption of 20 amino acids on to calcium oxalate monohydrate, CaHPO4.2H2O, Ca3(PO4)2 and Ca5(PO4)3OH crystals was determined over the physiological urinary pH range (pH 5–8) in aqueous solutions. All amino acids adsorbed most strongly at pH 5, and this decreased in all cases as the pH was increased. The amino acids which adsorbed most strongly were aspartic acid, glutamic acid and γ-carboxyglutamic acid, with the last displaying the strongest affinity. All amino acids bound more avidly to calcium oxalate monohydrate than to any of the phosphate minerals. Adsorption on to CaHPO4.2H2O was generally higher than for Ca3(PO4)2 and Ca5(PO4)3OH, for which all amino acids, with the exception of γ-carboxyglutamic acid, had only a weak affinity. The binding affinity of these acids is thought to be due to their zwitterions being able to adopt conformations in which two carboxyl groups, and possibly the amino group, can interact with the mineral surface without further rotation. The strong binding affinity of di-and tri-carboxylic acids for calcium stone minerals indicates that proteins rich in these amino acids are more likely to play a functional role in stone pathogenesis than those possessing only a few such residues. These findings, as well as the preferential adsorption of the amino acids for calcium oxalate monohydrate rather than calcium phosphate minerals, have ramifications for research aimed at discovering the true role of proteins in stone formation and for potential application in the design of synthetic peptides for use in stone therapy.


2021 ◽  
Vol 28 ◽  
Author(s):  
Priyadarshini ◽  
Abhishek Negi ◽  
Chetna Faujdar ◽  
Lokesh Nigam ◽  
Naidu Subbarao

Background: Human serum albumin (HSA) is one of the most abundant proteins in the blood plasma, urine as well as in the organic matrix of renal calculi. Macromolecules present in the urine modulate kidney stone formation either by stimulating or inhibiting crystallization process. Objective: In the present study, effect of HSA protein on the growth of calcium oxalate monohydrate crystal (COM) was investigated. Methods: Crystal growth assay was used to measure oxalate depletion in the crystal seeded solution in the presence of HSA. HSA concentrations exhibiting effect on crystal growth were selected for FTIR and XRD analysis. In silico docking was performed on seven different binding sites of HSA. Results: Albumin is playing dual role in growth of calcium oxalate crystallization. FTIR and XRD studies further revealed HSA exerted strain over crystal thus affecting its structure by interacting with amino acids of its pocket 1. Docking results indicate that out of 7 binding pocket in protein, calcium oxalate interacts with Arg-186 and Lys-190 amino acids of pocket 1. Conclusion: Our study confirms the role of HSA in calcium oxalate crystallization where acidic amino acids arginine and lysine are binding with COM crystals, revealing molecular interaction of macromolecule and crystal in urolithiasis.


2000 ◽  
Vol 278 (1) ◽  
pp. F130-F137 ◽  
Author(s):  
John C. Lieske ◽  
Erick Huang ◽  
F. Gary Toback

The binding and internalization of calcium oxalate monohydrate (COM) crystals by tubular epithelial cells may be a critical step leading to kidney stone formation. Exposure of MDCK cells to arachidonic acid (AA) for 3 days, but not oleic or linoleic acid, decreased COM crystal adhesion by 55%. Exogenous prostaglandin PGE1 or PGE2 decreased crystal binding 96% within 8 h, as did other agents that raise intracellular cAMP. Actinomycin D, cycloheximide, or tunicamycin each blocked the action of PGE2, suggesting that gene transcription, protein synthesis, and N-glycosylation were required. Blockade of crystal binding by AA was not prevented by the cyclooxygenase inhibitor flurbiprofen, and was mimicked by the nonmetabolizable AA analog eicosatetryanoic acid (ETYA), suggesting that generation of PGE from AA is not the pathway by which AA exerts its effect. These studies provide new evidence that binding of COM crystals to renal cells is regulated by physiological signals that could modify exposure of cell surface molecules to which the crystals bind. Intrarenal AA, PGs, and/or other agents that raise the intracellular concentration of cAMP may serve a protective function by preventing crystal adhesion along the nephron, thereby defending the kidney against crystal retention and stone formation.


1987 ◽  
Vol 42 (2) ◽  
pp. 89-93 ◽  
Author(s):  
Toshitsugu Oka ◽  
Toshiaki Yoshioka ◽  
Takuo Koide ◽  
Minato Takaha ◽  
Takao Sonoda

2012 ◽  
Vol 554-556 ◽  
pp. 1738-1741 ◽  
Author(s):  
Zhi Yue Xia ◽  
Yi Ming Ding ◽  
Jian Ming Ouyang

The differences between the urinary crystallites from patients with renal calculi and healthy subjects were compared using SEM, XRD, and nano-particle size analyzer, etc. These differences concern morphology, aggregation state, number, particle size, crystal phase and Zeta potential, etc. About 90% of the crystallites had the particle sizes less than 20 μm, the Zeta potential was -(113) mV, and the composition included a large proportion of calcium oxalate dihydrate (COD) crystals. By comparison, the urinary crystallites from patients with renal calculi had sharp edges and corners and exhibited significant aggregation. There were more crystallites with the size greater than 20 μm in comparison with those in healthy subjects, their Zeta potential was -(73) mV, and calcium oxalate existed mainly in the form of calcium oxalate monohydrate (COM) crystals. The above differences increased the aggregation trend of the crystallites in lithogenic urine and caused the probability of renal calculi formation to increase.


1974 ◽  
Vol 47 (1) ◽  
pp. 13-22 ◽  
Author(s):  
W. G. Robertson ◽  
M. Peacock ◽  
R. W. Marshall ◽  
F. Knowles

1. The volume, size and type of calcium oxalate crystals excreted in the urine of a group of patients with recurrent ‘idiopathic’ stones were studied on a controlled basal diet, after an oral supplement of sodium oxalate and after oral administration of ethane-1-hydroxy-1,1-diphosphonate (EHDP) for 4 weeks. 2. Before administration of EHDP the stone-formers passed the large crystals and aggregates of calcium oxalate dihydrate characteristic of recurrent calcium oxalate stone-formers. For the same level of urine saturation and crystalluria EHDP caused a significant reduction in the proportion of large crystals and aggregates excreted. Studies by light-microscopy confirmed that EHDP caused a striking change in the size and habit of calcium oxalate crystals in some but not all of the urine samples examined. 3. The decrease in average crystal size during the administration of EHDP was attributed to the observed increase in the ability of urine to inhibit the growth and aggregation of calcium oxalate crystals as measured by a growth system in vitro. 4. The possible use of EHDP as a therapeutic agent in the treatment of calcium oxalate stone-formation is discussed.


2000 ◽  
Vol 15 (2) ◽  
pp. 94-100
Author(s):  
K. D. Rogers ◽  
M. W. Sperrin ◽  
E. J. MacLean

The principal aim of this study was to assess a new approach to the characterization of uroliths using synchrotron radiation. To achieve this, a detailed investigation of the crystalline nature of a human bladder urolith has been undertaken. Changes in the phase composition and crystalline mineral nature have been measured from the urolith core center to its outer surface. Data were collected using a microbeam, synchrotron probe, and image plate. Rietveld analysis has enabled us to determine that the unit cell dimensions of the majority phases (anhydrous uric acid and calcium oxalate monohydrate) are significantly greater in the core region but become progressively smaller from the outer to inner regions. The crystallites of both phases are also shown to possess significant radial orientation which varies through the urolith and reaches a maximum at a point of principal fracture. The analysis has also allowed us to study the change in average crystallite morphology; the crystallites of both phases are shown to decrease in size toward the outer parts of the urolith although this is in a nonuniform fashion. Evidence of calcium oxalate dihydrate was also found, but only within the outermost region of the urolith.


1981 ◽  
Vol 61 (4) ◽  
pp. 487-491 ◽  
Author(s):  
P. G. Werness ◽  
Jan H. Bergert ◽  
Karen E. Lee

1. The crystal growth inhibitory activity of mixtures of known inhibitors and of mixtures of known inhibitors with normal urine was determined in calcium oxalate monohydrate and hydroxyapatite seeded crystal growth systems. 2. The inhibitory activity of the mixtures was compared with the measured activity of the individual components of the mixtures. All mixtures had inhibitory activity equal to the sum of the activities of their components, with the exception of RNA/urine mixtures in the calcium oxalate monohydrate system. 3. RNA/urine mixtures had inhibitory activity toward calcium oxalate monohydrate crystal growth which was less than would be predicted from the activity of the RNA and of the urine which were added. This reduced inhibitory activity was shown to be due probably to hydrolysis of RNA by the ribonuclease activity normally present in urine. 4. The results of these experiments make it possible to determine quantitatively the contribution of various naturally occurring urinary crystal growth inhibitors to the total measured inhibition observed in urine.


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