Crystallization Of Calcium Salts Research Articles

Preliminary study of the role of nanobacteria in the formation of renal stones in experimental rats and its mechanism.

The aim of the study was to study the role of nanobacteria in the formation of renal calculi and the underlying mechanism. A total of 90 clean Wistar male rats were randomly divided into a negative control group, an experimental group, and an interference group. From the end of the first week of modelling, 10 consecutive times once a week, 3 rats in each group were randomly selected to measure the biochemical blood markers and urine metabolism. After sacrifice, the formation of kidney stones was assessed by observing the ultrastructure of the kidney by electron microscopy and pathohistology. Finally, the expression of calcium-sensitive receptor (CaSR) and claudin-14 protein in the kidney tissue was examined by western blotting. Compared with the control group, the gross structure of the kidney was changed in the model group. At the fourth week of modelling, the rats in the nanobacteria group had significantly enlarged kidneys and increased kidney-to-body ratio, and the difference had statistical significance (p < 0.05). The colour of the kidney profile was dark, the structure of the skin pulp was less clear, and the accumulation of yellowish particles was observed at the junction of the cortical pulp. The creatinine, uric acid, urea nitrogen, and urinary calcium of the rats in the nanobacteria group began to increase at the third week, and the difference between the third and eighth week had statistical significance (p < 0.05). However, the difference between the 3 groups had no statistical significance after the eighth week. At the fourth week, we observed the formation of calculi, which were mainly distributed in the renal tubules and surrounding tissues. The kidney stone formation rate was 52.4% in the nanobacteria group and 27.8% in the interference group, and the difference had statistical significance (p < 0.05). Ultrastructure observations revealed that from the fourth week, the renal tissues in the nanobacteria group showed expanded renal tubules, swollen renal tubular epithelium, granular degeneration, shedding and lymphocyte infiltration of renal tubular epithelial cells, and a small amount of calcium salt crystals in renal tubules. At the third week, the expression of CaSR and Claudin-14 protein in the nanobacteria group increased, and the difference had statistical significance (p < 0.05). The expression of CaSR and Claudin-14 was positively correlated with urinary calcium (p < 0.05). The formation of renal calculi began in the fourth week after the model was established, and the crystals were mostly located in the renal tubules. During the formation of renal calculi, the renal tubular epithelial cells were damaged, showing granular degeneration and small amounts of calcium salt crystals, accompanied by a few renal tubules beginning to expand and epithelial swelling, granular degeneration, necrosis and shedding of renal tubular epithelial cells, lymphocyte infiltration in the renal interstitium, and small amounts of calcium salt crystals in the renal tubules, which aggravated with time. The serum creatinine, serum uric acid, urea nitrogen, and urinary calcium levels increased with time from the third week and returned to normal after the eighth week. The expression of CaSR and Claudin-14 protein was upregulated and positively correlated with the 24-h urinary calcium excretion value.

Effect of Phytate (InsP6) and Other Inositol-Phosphates (InsP5, InsP4, InsP3, InsP2) on Crystallization of Calcium Oxalate, Brushite, and Hydroxyapatite.

Pathological calcifications may consist of calcium oxalate (CaOx), hydroxyapatite (HAP), and brushite (BRU). The objective of this study was to evaluate the effect of phytate (inositol hexakisphosphate, InsP6), InsP6 hydrolysates, and individual lower InsPs (InsP5, InsP4, InsP3, and InsP2) on the crystallization of CaOx, HAP and BRU in artificial urine. All of the lower InsPs seem to inhibit the crystallization of calcium salts in biological fluids, although our in vitro results showed that InsP6 and InsP5 were stronger inhibitors of CaOx crystallization, and InsP5 and InsP4 were stronger inhibitors of BRU crystallization. For the specific in vitro experimental conditions we examined, the InsPs had very weak effects on HAP crystallization, although it is likely that a different mechanism is responsible for HAP crystallization in vivo. For example, calciprotein particles seem to have an important role in the formation of cardiovascular calcifications in vivo. The experimental conditions that we examined partially reproduced the in vivo conditions of CaOx and BRU crystallization, but not the in vivo conditions of HAP crystallization.

Phytate Intake, Health and Disease: "Let Thy Food Be Thy Medicine and Medicine Be Thy Food".

Phytate (myo-inositol hexakisphosphate or InsP6) is the main phosphorus reservoir that is present in almost all wholegrains, legumes, and oilseeds. It is a major component of the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets. Phytate is recognized as a nutraceutical and is classified by the Food and Drug Administration (FDA) as Generally Recognized As Safe (GRAS). Phytate has been shown to be effective in treating or preventing certain diseases. Phytate has been shown to inhibit calcium salt crystallization and, therefore, to reduce vascular calcifications, calcium renal calculi and soft tissue calcifications. Moreover, the adsorption of phytate to the crystal faces can inhibit hydroxyapatite dissolution and bone resorption, thereby playing a role in the treatment/prevention of bone mass loss. Phytate has a potent antioxidation and anti-inflammatory action. It is capable of inhibiting lipid peroxidation through iron chelation, reducing iron-related free radical generation. As this has the effect of mitigating neuronal damage and loss, phytate shows promise in the treatment/prevention of neurodegenerative disease. It is reported that phytate improves lipid and carbohydrate metabolism, increases adiponectin, decreases leptin and reduces protein glycation, which is linked with macrovascular and microvascular diabetes complications. In this review, we summarize the benefits of phytate intake as seen in in vitro, animal model, epidemiological and clinical trials, and we also identify questions to answer in the future.

Multidisciplinary management of patients affected with pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE, OMIM # 264800) is an autosomal recessive, multisystemic disorder, associated with mutations of the ABCC6 gene. Ectopic mineralization is in the background of the clinical manifestations of the disease. Calcium-salt crystals are deposited primarily in the skin, in the Bruch membrane of the eyes, and in the vascular endothelium. Thus, in addition to the skin lesions, visual impairment and cardiovascular involvement also occur. Clinical symptoms show varying severity and display heterogeneous appearance. The identification of the phenotype and care of the patients require a multidisciplinary perspective based on the collaboration of a dermatologist, ophthalmologist, cardiologist, and clinical geneticist. The aim of our work is to describe the development of symptoms of the disease, in order to facilitate the diagnosis. In addition, we aim to draw attention to the importance of early diagnosis of pseudoxanthoma elasticum, and to present modern diagnostic methods. Considering the development of severe systemic complications, the early diagnosis with the collaboration between related specialists is crucial to provide optimal clinical care and management of the patients.

Randomized Clinical Study, Comparative of Parallel Groups, to Evaluate the Effectiveness of Three Preparations of Potassium Citrate in Producing an Increase in Urinary pH in Patients with a History of Kidney Stones

Background: A very strict control of urinary pH is recommended to maintain it between 5.5 and 6.2, preventing formation or recurrence of crystals. Kidney stones are a common problem, with a high rate of recurrence, not altered by the success of surgery. Medical treatment prevents recurrence. Potassium Citrate inhibits crystallization of calcium salts. It influences calculogenesis by increasing urinary citrates and alkalinizing the urine. Purpose: to evaluate the similarity in the effect of three K citrate products, K citrate reference product Urocit® 10 mEq, and K citrate from Laboratorios LETI S.A.V., 10 mEq and 15 mEq, on urinary pH. Materials and Methods: We carried out a prospective, randomized study of three parallel groups. We admitted female and male patients with history of kidney stones or evidence of lithiasis (grit, microlithiasis) in the renal echosonogram. Laboratory assessments: urine, 24-hour urine, urinary pH, Calcium, uric acid, Phosphorus, Sodium, protein and urinary creatinine at times: start, day 7, day 21, 30 of treatment. Results: all three products produced a slight increase in urinary pH in the simple urine test and 24-hour urine, with no differences between groups or their logarithmically transformed means and their CI95, which did not exceed the range between 80% and 125%. Conclusions: K Citrate, 10 mEq and 7.5 mEq, from Laboratorios LETI, S.A.V., at a dose of 30 mEq daily in patients with history of kidney stones are equivalent to the reference product Urocit®, in its effects on urinary pH in 24-hour urine, and in the simple urine test.

Complex character of the influence of polycarboxylic and phosphonic acids on the crystallization of calcium and magnesium salts in dynamic conditions

The influence of water-soluble organic compounds (adipic, polyaspartic and phosphonic acids) and their compositions on the crystallization of calcium and magnesium salts in dynamic conditions has been studied. It is found that the induction period of phase formation increases in the presence of polyaspartic and phosphonic acids 2.3–5.2 times in the range of their content from 0.05 to 0.2 ppm. The results of XRD and electron microscopic studies confirm the change in the phase composition and morphology of the crystalline precipitate that is formed. The dibasic carboxylic acid influence on the induction period, composition and structure of the precipitate is much less. It is established that the composition of organic acids also increases the induction period of phase formation. The complex inhibitor provides an increase in the critical supersaturation level in the system. The phosphonic and carboxyl groups of the inhibitor interact with calcium and magnesium ions and block the crystallization nuclei. When interacting with the dicarboxylic acid and polyacid adsorption on the surface of the formed crystals, the microcrystals dissolve.

Composition for rock grouting based on insoluble calcium salts for groundwater protection

Importance to reduce permeability of rocks arises safety of mining operations and protecting the soil and underground water in the area of industrial waste storage with high contents of water-soluble salts. Disadvantage of the existing methods of grouting rocks by soluble salts is either their dissolution with changing of the composition or diluting of the contacting solution. The paper considers the composition of the grouting mixture for the deposition of insoluble calcium salts and its effectiveness in laboratory conditions. The eutonic solution of a four-component KCl–NaCl–CaCl2–H2O system was used as the initial solution, while saturated solutions of sodium sulfate and carbonate, and sulfuric acid were applied as the precipitators. Efficiency of rock grouting was estimated according to the water or solution filtration rate through the rock (sand, sylvinite, and halite) before and after calcium salt crystallization. Laboratory experiments showed that the precipitation of calcium sulfate responds to the challenge of plugging rocks. The paper proposes some recommendations of protective screens at the bed of the salt tailing piles and slurry storage facilities.

Structure and elemental composition of Ceftriaxone induced pediatric nephrolithiasis.

Ceftriaxone is a widely used antibiotic because to its broad-spectrum gram-negative coverage, safety, and biological half life (5-9h) permit dose once-daily administration. It is specifically used in pediatric patients in developing countries. Ceftriaxone forms insoluble sludge/stone when combined with calcium in the urinary system. In this study, Ceftriaxone induced sludge/stones from pediatric patients were collected to identify its microstructure and composition to gather insights into the mechanism of Ceftriaxone induced sludge/stone formation. The results illustrated that Ceftriaxone induced stones formed rapidly following antibiotic administration. Ceftriaxone calcium salt crystals could easily be broken with minimal intervention. However, Ceftriaxone combined with calcium phosphate formed an insoluble stone aggregate.

Chelator Regulation of In Situ Calcium Availability to Enable Spray-Dry Microencapsulation in Cross-Linked Alginates.

A recently patented one-step in situ cross-linked alginate microencapsulation (CLAM) by spray-drying (i.e., the UC Davis CLAMs technology) can overcome the high cost of scale-up that limits commercial applications. While increasing calcium loading in the CLAMs process can increase the extent of cross-linking and improve retention and protection of the encapsulated cargo, the potential for residual undissolved calcium salt crystals in the final product can be a concern for some applications. Here, we demonstrate an alternate one-step spray-dry CLAMs process using pH-responsive chelation of calcium. The “Chelate CLAMs” process is an improvement over the patented process that controls ion availability based on pH-responsive solubility of the calcium salt. Hyaluronic acid was encapsulated in CLAMs to minimize swelling and release in aqueous formulations. CLAMs with 61% (d.b.) hyaluronic acid (HA-CLAMs) demonstrated restricted plumping, limited water absorption capacity, and reduced leaching, retaining up to 49% hyaluronic acid after 2 h in water. Alternatively, “Chelate HA-CLAMs” formed by the improved process exhibited nearly full retention of hyaluronic acid over 2 h in water and remained visibly insoluble after 1 year of storage in water at 4 °C. Successful hyaluronic acid retention in CLAMs is likely due in part to its ability to cross-link with calcium.

Key Aspects of Myo-Inositol Hexaphosphate (Phytate) and Pathological Calcifications.

Phytate (myo-inositol hexaphosphate, InsP6) is an important component of seeds, legumes, nuts, and whole cereals. Although this molecule was discovered in 1855, its biological effects as an antinutrient was first described in 1940. The antinutrient effect of phytate results because it can decrease the bioavailability of important minerals under certain circumstances. However, during the past 30 years, researchers have identified many important health benefits of phytate. Thus, 150 years have elapsed since the discovery of phytate to the first descriptions of its beneficial effects. This long delay may be due to the difficulty in determining phytate in biological media, and because phytate dephosphorylation generates many derivatives (InsPs) that also have important biological functions. This paper describes the role of InsP6 in blocking the development of pathological calcifications. Thus, in vitro studies have shown that InsP6 and its hydrolysates (InsPs), as well as pyrophosphate, bisphosphonates, and other polyphosphates, have high capacity to inhibit calcium salt crystallization. Oral or topical administration of phytate in vivo significantly decreases the development of pathological calcifications, although the details of the underlying mechanism are uncertain. Moreover, oral or topical administration of InsP6 also leads to increased urinary excretion of mixtures of different InsPs; in the absence of InsP6 administration, only InsP2 occurs at detectable levels in urine.

Constituent transformation mechanism of concentrated leachate after incineration at different temperatures.

Spraying concentrated leachate into an incineration furnace and burning is encouraged by the Chinese government as a harmless method for leachate treatment. In this research, the constituent transformation mechanism was studied, by X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive spectrometry (EDS), of residues after burning the concentrated leachate in a muffle furnace at different temperatures (750 °C, 850 °C, 900 °C, 1000 °C, and 1100 °C). XRD results showed that the main components of the residues were metal chlorides and calcium salt crystals and that the peak position of most of these crystals changed little because their crystal structure was stable at high temperatures. SEM results illustrated that the higher the burning temperature, the smaller the solid particles, and the looser the structures of the residues. EDS analysis showed that S atoms in the concentrated leachate were usually transformed into gaseous compounds during incineration, whereas most of the Cl atoms could be fastened onto solid residues if an appropriate temperature was maintained. This study concluded that 900 °C was the best burning temperature for spraying concentrated leachate into the furnace. In addition, this study suggested that material selection for the nozzle and flue gas pipelines must pay more attention to corrosion caused by gaseous sulfur compounds. Similarly, material selection for the inner wall of the incinerator furnace should pay more attention to corrosion caused by Cl atoms. This means that the municipal solid waste (MSW) incineration power plants should incorporate various and appropriate corrosion-resistant materials according to the different regions of the incinerator.

Major innovations and clinical applications of disodium-levofolinate: a review of available preclinical and clinical data.

The association of folinate salts with 5-fluorouracil (5-FU) represents a gold standard in the treatment of many cancers. In several clinical trials, the simultaneous administration of calcium–folinic acid (Ca-FA) and the prolonged infusion of 5-FU resulted in a better clinical response compared with fluoropyrimidine alone and 5-FU bolus. However, the simultaneous infusion of 5-FU and Ca-FA mixed in the same infusion pump is hindered by the crystallization of calcium salts, which eventually leads to catheter obstruction and damage. The sodium salt of leucovorin-disodium levofolinate (Na-Lv) is a novel molecule with a pharmacological profile similar to Ca-FA. Owing to its higher solubility, it can be safely mixed with 5-FU in a single pump without the risk of precipitation and catheter occlusion. The efficacy and safety of Na-Lv have been widely examined in preclinical and clinical phase II studies in combination with various schedules of 5-FU and in several cancer types. PubMed, EMBASE, SCOPUS and Web of Science databases were searched from inception to November 2018 to retrieve available published phase I and II series, including Western patients. Compared with Ca-FA, Na-Lv shows a more favourable efficacy and toxicity profile in terms of overall response rate, progression-free survival, time to progression and occurrence of severe adverse events. Moreover, it allows treatment time to be shortened, decreasing the number of required human resources for drug administration and limiting the occurrence of catheter damage.

Meso-scale mechanical deterioration of mortar due to sodium chloride attack

Salt frost deterioration of concrete is an important durability problem to concern. Prior to clarifying the salt frost damage mechanisms, the salt effect on mechanical behavior of concrete needs to be clarified. To quantitatively understand the damage effects, this paper experimentally investigated meso-scale mortar samples suffered from sodium chloride (NaCl) attack, including mechanical degradation in meso scale and chemical analysis of calcium hydroxide and Friedel's salt in micro scale. The test results showed that calcium (Ca2+) leaching and salt crystallization occur along with the solution absorption process, and the kinetics is depending on water to cement ratio (W/C) and solution concentrations. Higher W/C has more severe Ca2+ leaching and strength loss, while the leaching amount and strength loss are changed in fluctuating manner with the solution concentrations. The amount of crystallized salt is increasing with the solution concentration. The mechanical degradation degree agrees with the Ca2+ leaching amount. The results indicated that the deterioration of mortar is mainly resulting from increasing porosity due to Ca2+ leaching.

The role of cell-crystal reaction mediated inflammation in the formation of intrarenal calcium oxalate crystals

Calcium oxalate nephrolithiasis is the common disease of urinary surgery, its exact pathogenesis is still unclear.It is believed that the renal inflammatory injury induced by cell-crystal reaction plays an important role in the formation of intrarenal calcium oxalate crystals. Recent studies indicated that inflammation induced by cell-crystal reaction can cause renal cell damage, stimulate intracellular expression of NADPH oxidase, trigger the massive production of reactive oxygen species, activate nuclear factor-κB signaling pathway, release a large number of inflammatory factors, and cause inflammatory cascade effect of the kidney, thus promoting the accumulation, nucleation and growth of calcium salt crystals, eventually leading to the formation of intrarenal crystals and even stones. In this process, the regulatory factors and mechanisms involved include macrophages, NLRP3-high mobility group box-1 protein inflammation network, fetuin A, autophagy activation and other factors.

Construction and characterization of osteogenic and vascular endothelial cell sheets from rat adipose-derived mesenchymal stem cells

In this study, adipose-derived mesenchymal stem cells (ADSCs) were isolated from adipose tissues of rats. Flow cytometry identification showed that ADSCs of passage 3 highly expressed CD29 and CD44, but hardly expressed CD31 and CD45. Adipogenic, osteogenic, and chondrogenic differentiation were confirmed by the results of oil red O staining, alkaline phosphatase (ALP), and alcian blue staining, respectively. ADSCs at a density of 1×10(6)/cm(2) were cultured in the osteogenic medium and the osteogenic cell sheets could be obtained after 14 d. The cell sheets were positive with von kossa staining. The transmission electron microscopy (TEM) result showed that needle-like calcium salt crystals were deposited on the ECM. These results suggested that the osteogenic cell sheets may have potential osteogenesis ability. ADSCs at a density of 1×10(6)/cm(2) were cultured in the endothelial cell growth medium-2 and the endothelial cell sheets can be formed after 16 d of culture. The TEM image confirmed that the Weibel-Palade corpuscle was seen in the cells. The expression of CD31 was positive, suggesting that the endothelial cell sheets may have a strong ability to form blood vessels. In this study, two types of cell sheets with the potential abilities of osteogenesis and blood vessels formation were obtained by induced culture of ADSCs in vitro, which lays a foundation to build vascularized tissue engineered bone for the therapy of bone defects.

Mesoscale study of water transport in mortar influenced by sodium chloride

Transport properties of mortar exposed to salt solution are fundamental information for understanding the durability of mortar. In this paper, change in moisture uptake behaviors due to sodium chloride (NaCl) contamination was studied. To understand the salt contamination effect, mortar samples with different water-to-cement ratios (w/c) in meso scale were immersed into deionized (DI) water, intermediate (3%wt), and high (20%wt) concentration of NaCl solutions for three days. After immersion, the re-dried samples were sequentially immersed in DI water at room temperature for seven days. Based on the test results, two-stage solution diffusion model was developed, which can describe the solution absorption process efficiently. The salt contamination may be due to calcium (Ca2+) leaching and salt crystallization. As found, when exposed to low concentration NaCl solution, the diffusivity of mortar would increase due to faster Ca2+ leaching. However, for high concentration NaCl solution, it would be reduced since pores filled by crystallized salt have dominant effect in this case. The salt crystallization mainly occurs at small pores because there is little difference at initial absorption but the difference becomes significant for long time absorption.

Animal Protein and the Risk of Kidney Stones: A Comparative Metabolic Study of Animal Protein Sources

We compared the effect of 3 animal protein sources on urinary stone risk. A total of 15 healthy subjects completed a 3-phase randomized, crossover metabolic study. During each 1-week phase subjects consumed a standard metabolic diet containing beef, chicken or fish. Serum chemistry and 24-hour urine samples collected at the end of each phase were compared using mixed model repeated measures analysis. Serum and urinary uric acid were increased for each phase. Beef was associated with lower serum uric acid than chicken or fish (6.5 vs 7.0 and 7.3 mg/dl, respectively, each p <0.05). Fish was associated with higher urinary uric acid than beef or chicken (741 vs 638 and 641 mg per day, p = 0.003 and 0.04, respectively). No significant difference among phases was noted in urinary pH, sulfate, calcium, citrate, oxalate or sodium. Mean saturation index for calcium oxalate was highest for beef (2.48), although the difference attained significance only compared to chicken (1.67, p = 0.02) but not to fish (1.79, p = 0.08). Consuming animal protein is associated with increased serum and urine uric acid in healthy individuals. The higher purine content of fish compared to beef or chicken is reflected in higher 24-hour urinary uric acid. However, as reflected in the saturation index, the stone forming propensity is marginally higher for beef compared to fish or chicken. Stone formers should be advised to limit the intake of all animal proteins, including fish.

Synthesis and Characterisation of Hydrated Calcium Pyrophosphate Phases of Biological Interest

AbstractThe details of a synthesis method for biologically relevant hydrated calcium pyrophosphates (CPPs, Ca2P2O7·nH2O) has been elucidated. Control of the pH (from 3.6 to 5.8) and the temperature (from 25 to 90 °C) during the synthesis enabled the preparation of four pure CPP phases within one hour without intermediates: monoclinic and triclinic calcium pyrophosphate dihydrate (CPPD, Ca2P2O7·2H2O), which are the two CPP phases detected in vivo in joints of arthritic patients, monoclinic tetrahydrate β (CPPT, Ca2P2O7·4H2O) and an amorphous phase (a‐CPP, Ca2P2O7·nH2O). Four domains corresponding to the four different phases of hydrated calcium pyrophosphate were identified; a‐CPP was synthesised over a very wide pH and temperature range (up to 90 °C) within the domain of synthesis conditions explored, including physiological conditions (pH 7.4 and 37 °C). The as‐synthesised hydrated CPP phases were characterised by complementary techniques (powder X‐ray diffraction, FTIR and Raman spectroscopy, scanning electron microscopy and thermogravimetry) and chemical analyses. Rietveld refinement analyses of the as‐synthesised crystalline phases were performed, and there were significant differences between the m‐CPPD X‐ray diffraction pattern observed and previously published cell parameters. Vibrational spectroscopy allowed the crystalline and amorphous phases synthesised to be clearly distinguished and identified owing to the high flexibility of the pyrophosphate anion. Chemical analyses showed that the synthesis conditions used in this study did not allow significant hydrolysis of the pyrophosphate ions into phosphate ions, and the number of water molecules associated with each synthesised CPP phase was determined by thermogravimetric analysis. Different mechanisms of dehydration were also identified. The study of the formation of synthetic and well‐characterised hydrated calcium pyrophosphate phases and their availability in large amounts in vitro could allow progress to be made on the biological role of these phases and their possible transformations. This could also aid their detection in patients suffering from disease caused by calcium salt crystals and could clarify the mechanism by which CPP crystals form and evolve in vivo.

Amniotic membrane transplantation in cases of corneal calcification – follow up with ultrasound biomicroscopy

BACKGROUND: To show and demonstrate amniotic membrane transplantation as a useful therapic tool to treat corneal calcification. To demonstrate the usefulness of ultrasound biomicroscopy in evaluation and following up patients with corneal calcification. MATERIAL AND METHODS: Three patients with corneal calcification were treated with amniotic membrane transplantation. The diagnostic tools included basic ophthalmological examinations and UBM. Histological examinations were also carried out after removal of the calcified corneal part. RESULTS: After surgery, the amniotic membrane integrated in the corneal structure. The intraoperatively removed cornea pieces proved to contain calcium salt crystals. CONCLUSIONS: The presence of corneal calcifications correlated with chronic administration of phosphate- buffered eye drops. After removing the calcified corneal area, amniotic membrane transplantation induced satisfactory epithelial growth.

A hypothesis of calcium stone formation: an interpretation of stone research during the past decades

An interpretation of previous and recent observation on calcium salt crystallization and calcium stone formation provide the basis for formulation of a hypothetical series of events leading to calcium oxalate (CaOx) stone formation in the urinary tract. The various steps comprise a primary precipitation of calcium phosphate (CaP) at high nephron levels, establishment of large intratubular and/or interstitial (sub-epithelial) aggregates of CaP. These crystal masses subsequently might be dissolved during periods with low urine pH. On the denuded surface of subepithelial or intratubularly trapped CaP, release of calcium ions can result in very high ion-activity products of CaOx, particularly during simultaneous periods with peaks of CaOx supersaturation. Crystals of CaOx may result from nucleation in the macromolecular environment surrounding the apatite crystal phase. In the presence of low pH, low citrate and high ion-strength of urine, formation of large CaOx crystal masses can be accomplished by self-aggregation of Tamm-Horsfall mucoprotein. Following dislodgment of the initially fixed CaOx stone embryo, the further development into to clinically relevant stone is accomplished by CaOx crystal growth and CaOx crystal aggregation of the retained stone material. The latter process is modified by a number of inhibitors and promoters present in urine. The retention of the stone is a consequence of anatomical as well as hydrodynamic factors.