Nephrocalcin Isolated from Human Kidney Stones is a Defective Calcium-Oxalate-Monohydrate Crystal-Aggregation Inhibitor

Urolithiasis ◽  
1989 ◽  
pp. 137-139 ◽  
Author(s):  
B. Hess ◽  
Y. Nakagawa ◽  
F. L. Coe
The Analyst ◽  
2022 ◽  
Author(s):  
Iris H.Valido ◽  
Victor Fuentes-Cebrian ◽  
Roberto Boada ◽  
Oriol Vallcorba ◽  
Montserrat Resina-Gallego ◽  
...  

Nephrolithiasis is a multifactor disease that produces nephrolites in the kidney. Calcium oxalate hydrates (dihydrated, COD, or monohydrated, COM) stones are the most common ones with more than sixty percent...


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.


Crystals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 954
Author(s):  
Silvija Šafranko ◽  
Sara Goman ◽  
Dominik Goman ◽  
Stela Jokić ◽  
Ida Delač Marion ◽  
...  

The search for an efficient drug or inhibitor in the formation process of kidney stones has been a promising research topic towards reducing the risks of the formation of disease. However, several challenges have been faced in investigating the most common constituents of kidney stones, calcium oxalate and its hydrate forms (COM, COD and COT). This study focuses on the preparation and structural characterization (TG, XRD, FTIR, SEM) of calcium oxalate hydrates in the presence of gallic acid (GA) and by varying operating parameters such as temperature (25 °C, 36.5 °C and 48 °C), pH (5.6, 6.5 and 7.5) and amount of added GA (ranging from 100 mg to 1000 mg). Response surface methodology was applied in order to evaluate the effects of operating parameters in the formation of COM and COD, and for the process optimization towards maximizing their content in samples. The results indicated that GA inhibited the formation of COM (0–100%) and promoted the formation of COD (0 ≤ 99%), while a medium pH and the amount of added GA showed a significant effect in the process of COD formation. In order to investigate the interactions established in the formation process and the possible adsorption between GA and the formed crystals, electrochemical measurements were performed.


2021 ◽  
Vol 18 (5) ◽  
pp. 1077-1081
Author(s):  
Haijie Xie ◽  
Rui Yang ◽  
Yong Xu ◽  
Chunyu Liu

Purpose: To explore the effect of total flavone of Desmodium styracifolium (TFDS) on calcium oxalate monohydrate (COM)-triggered IL-2Rβ expression in human kidney proximal tubular epithelial cells. Methods: Human kidney proximal tubular epithelial cell line HK-2 was treated with COM, TFDS or both. The expression of IL-2Rβ was evaluated by quantitative polymerase chain reaction (qPCR) or flow cytometry. The responsiveness of HK-2 cells to IL-2 was determined by enzyme-linked immunosorbent assay (ELISA), qPCR and western blot. The signaling mechanism underlying the effect of TFDS was studied using western blot and qPCR. The clinical relevance of IL-2Rβ to renal inflammation was investigated by re-analyzing a Gene Expression Omnibus (GEO) dataset. Results: Total flavones of Desmodium styracifolium (TFDS) antagonize COM-triggered IL-2Rβ expression in HK-2 cells, thus reducing the responsiveness of HK-2 cells to IL-2 stimulation. Mechanistically, TFDS dampens IL-2Rβ expression by preventing the activation of STAT3. The level of IL-2Rβ is positively correlated with the inflammatory status of the kidney. Conclusions: The total flavones of Desmodium styracifolium (TFDS) prevent the upregulation of IL2Rβ in renal epithelial cells upon COM stimulation in a STAT3-dependent manner.


1989 ◽  
Vol 257 (1) ◽  
pp. F99-F106 ◽  
Author(s):  
B. Hess ◽  
Y. Nakagawa ◽  
F. L. Coe

Normal urine inhibits both the growth and the aggregation of calcium oxalate monohydrate (COM) crystals but the molecules that inhibit aggregation are not well defined. We have developed a spectrophotometric assay method to measure the aggregation of COM crystals in vitro under conditions that avoid simultaneous crystal growth. At pH 7.2 and 90 mM NaCl, Tamm-Horsfall glycoprotein (THP) and nephrocalcin (NC), a major urinary inhibitor of COM crystal growth, inhibit COM crystal aggregation at concentrations as low as 2 X 10(-9) and 1 X 10(-8) M, respectively. When increasing NaCl to 270 mM or lowering pH to 5.7, inhibition by both glycoproteins, but more markedly by THP, is decreased. Urinary NC from calcium oxalate renal stone formers (SF NC) and NC isolated from calcium oxalate renal stones (stone NC) both inhibit COM crystal aggregation 10-fold less than NC from normal urine. Citrate is ineffective even at millimolar concentrations. Thus THP and NC are two major inhibitors of COM crystal aggregation in normal urine; SF NC and stone NC are defective aggregation inhibitors.


2009 ◽  
Vol 42 (4) ◽  
pp. 629-635 ◽  
Author(s):  
Soumen Ghosh ◽  
Sharmila Basu ◽  
Santu Chakraborty ◽  
Alok K. Mukherjee

Structural and microstructural characterizations of eight human kidney stones (KS1–KS8) from eastern India have been carried out using IR spectroscopy, X-ray powder diffraction, scanning electron microscopy and thermogravimetric methods. An X-ray diffraction phase quantification revealed that three of the renal stones (KS1–KS3) were composed exclusively of calcium oxalate monohydrate (COM) and the remaining five (KS4–KS8) contained varying amounts of calcium oxalate dihydrate (40.1–53.0 wt%) and hydroxyapatite (1.3–17.3 wt%), in addition to the COM phase. The crystalline structure of COM (whewellite) at the atomic scale was redetermined through an X-ray powder diffraction study at room temperature using Rietveld analysis. Thermogravimetric analysis of KS1 reveals that COM (whewellite) is stable up to around 439 K, above which temperature anhydrous calcium oxalate is formed. The oxalate transforms to calcium carbonate at 751 K and finally to calcium oxide above 969 K. It should be emphasized that meaningful statistics in total number or gender specificity cannot be achieved with eight kidney stones.


1995 ◽  
Vol 268 (4) ◽  
pp. F604-F612 ◽  
Author(s):  
J. C. Lieske ◽  
R. Leonard ◽  
F. G. Toback

Adhesion of urinary crystals to the apical surface of renal tubular cells could be a critical step in the formation of kidney stones. The interaction between renal epithelial cells (BSC-1 line) and the most common crystal in kidney stones, calcium oxalate monohydrate (COM), was studied in a tissue culture model system. COM crystals bound to the cell surface within seconds in a concentration-dependent manner to a far greater extent than did brushite, another calcium-containing crystal found in urine. Adhesion of COM crystals to cells was blocked by the polyanion, heparin. Other glycosaminoglycans including chondroitin sulfate A or B, heparan sulfate, and hyaluronic acid, but not chondroitin sulfate C, prevented binding of COM crystals. Two nonsulfated polyanions, polyglutamic acid and polyaspartic acid, also blocked adherence of COM crystals. Three molecules found in urine, nephrocalcin, uropontin, and citrate, each inhibited binding of COM crystals, whereas Tamm-Horsfall glycoprotein (THP) did not. Prior exposure of crystals but not cells to inhibitory molecules blocked adhesion, suggesting that these agents exert their effect at the crystal surface. Inhibition of crystal binding followed a linear Langmuir adsorption isotherm for each inhibitor identified, suggesting that these molecules bind to a single class of sites on the crystal that are important for adhesion to the cell surface. Inhibition of crystal adhesion by heparin was rapidly overcome by the polycation protamine, suggesting that the glycosaminoglycan regulates cell-crystal interactions in a potentially reversible manner.(ABSTRACT TRUNCATED AT 250 WORDS)


Urolithiasis ◽  
2016 ◽  
Vol 45 (3) ◽  
pp. 235-248 ◽  
Author(s):  
Ingo Sethmann ◽  
Gunnar Wendt-Nordahl ◽  
Thomas Knoll ◽  
Frieder Enzmann ◽  
Ludwig Simon ◽  
...  

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