Objective:Prevalence of kidney stone disease continues to increase globally with recurrence rates between 30%and 50%despite technological and scientific advances.Reduction in recurrence would improve patient outcomes ...Objective:Prevalence of kidney stone disease continues to increase globally with recurrence rates between 30%and 50%despite technological and scientific advances.Reduction in recurrence would improve patient outcomes and reduce cost and stone morbidities.Our objective was to review results of experimental studies performed to determine the efficacy of readily available compounds that can be used to prevent recurrence.Methods: All relevant literature up to October 2020,listed in PubMed is reviewed.Results: Clinical guidelines endorse the use of evidence-based medications,such as alkaline agents and thiazides,to reduce urinary mineral supersaturation and recurrence.However,there may be additional steps during stone pathogenesis where medications could moderate stone risk.Idiopathic calcium oxalate stones grow attached to Randall’s plaques or plugs.Results of clinical and experimental studies suggest involvement of reactive oxygen species and oxidative stress in the formation of both the plaques and plugs.The renin-angiotensin-aldosterone system(RAAS),nicotinamide adenine dinucleotide phosphate(NADPH)oxidase,mitochondria,and NOD-like receptor pyrin domain containing-3(NLRP3)inflammasome have all been implicated at specific steps during stone pathogenesis in animal models.Conclusion: In addition to supersaturation-reducing therapies,the use of anti-oxidants,free radical scavengers,and inhibitors of NADPH oxidase,NLRP3 inflammasome,and RAAS may prove beneficial for stone prevention.Compounds such as statins and angiotensin converting enzyme inhibitors are already in use as therapeutics for hypertension and cardio-vascular disease and have previously shown to reduce calcium oxalate nephrolithiasis in rats.Although clinical evidence for their use in stone prevention in humans is limited,experimental data support they be considered along with standard evidence-based medications and clinical expertise when patients are being counselled for stone prevention.展开更多
Effect of various counterions of tartrate on the crystallization of calcium oxalate in gel system was investigated using scanning electron microscopy and X-ray diffraction. Various tartrates with hydrogen (H2tart), ...Effect of various counterions of tartrate on the crystallization of calcium oxalate in gel system was investigated using scanning electron microscopy and X-ray diffraction. Various tartrates with hydrogen (H2tart), sodium (Na2tart), potassium (K2tart), ammonium ((NH4)2tart), and a mixture of sodium and potassium cations (NaKtart) were considered. For H2tart, Na2tart, and (NH4)2tart, calcium oxalate dihydrate (COD) was induced. However, for K2tart and NaKtart, calcium oxalate trihydrate (COT) was obtained.展开更多
This study examined the potential antilithic effects of a traditional Chinese medicine Urtica dentata Hand (UDH) in experimental rats and screened the optimal extract of UDH as a possible therapeutic agent for kidne...This study examined the potential antilithic effects of a traditional Chinese medicine Urtica dentata Hand (UDH) in experimental rats and screened the optimal extract of UDH as a possible therapeutic agent for kidney stones. The rat model of urinary calcium oxalate stones was induced by intragastric (i.g.) administration of 2 mL of 1.25% ethylene glycol (EG) and 1% ammonium chloride (AC) for 28 days and was confirmed by Color Doppler ultrasound imaging. The rats in different experimental groups were then intragastrically given petroleum ether extract (PEE), N-butanol extract (NBE), aqueous extract (AqE) of UDH, Jieshitong (positive control drug), and saline, respectively. Treatment with NBE significantly reduced the elevated levels of urinary calcium, uric acid, phosphate, as well as increased urinary output. Accordingly, the increased calcium, oxalate levels and the number of calcium oxalate crystals deposits were remarkably reverted in the renal tissue of NBE-treated rats. In addition, NBE also prevented the impairment of renal function to decrease the contents of blood urea nitrogen (BUN) and creatinine. Taken together, these data suggest that NBE of UDH has a beneficial effect on calcium oxalate urinary stones in rats by flushing the stones out and protecting renal function.展开更多
Urinary prothrombin fragment 1 (UPTFl) is a potent inhibitor of urinary stone formation. UPTF1 exerts such inhibitory effect by effective 7-carboxylation in which vitamin K epoxide reductase complex subunit 1 (VKO...Urinary prothrombin fragment 1 (UPTFl) is a potent inhibitor of urinary stone formation. UPTF1 exerts such inhibitory effect by effective 7-carboxylation in which vitamin K epoxide reductase complex subunit 1 (VKORC1), the rate-limiting enzyme, is involved. This study examined the correlation between VKORC1 expression and calcium oxalate urolithiasis. The renal cortex samples were obtained from patients undergoing nephrectomy and then divided into 3 groups: urolithiasis group, control group A [hydronephrosis-without-stone (HWS) group], control group B (normal control group), The localization and expression of VKORC1 in renal tissues were determined by using immunohistochemistry, immunofluorescence microscopy, Western blotting and SYBR Green I real-time reverse-transcription PCR. The rapid amplification of cDNA ends (RACE) were conducted to obtain the 3'- and 5'-untranslated region (UTR) of VKORC1. The results showed that VKORC1 was located in the cytoplasm of renal tubular epithelial cells. The expression of VKORC1 in the uro- lithiasis group was significantly lower than that in the other two control groups (P〈0.05). Moreover, the 3'- and 5'-UTR sequence of the VKORC1 gene was successfully cloned. No insertion or deletion was found in the 3'- and 5'-UTR. However, a 171-bp new base sequence was discovered in the up- stream of 5'-UTR end in the urolithiasis group. It was concluded that the decreased expression of VKORC 1 may contribute to the development of calcium oxalate urolithiasis in the kidney.展开更多
In order to compare the effects of several experimental renal calcium oxalate stones formation models in rats and to find a simple and convenient model with significant effect of calcium oxalate crystals deposition in...In order to compare the effects of several experimental renal calcium oxalate stones formation models in rats and to find a simple and convenient model with significant effect of calcium oxalate crystals deposition in the kidney, several rat models of renal calcium oxalate stones formation were induced by some crystal-inducing drugs (CID) including ethylene glycol (EG), ammonium chloride (AC), vitamin D3 [ 1 α(OH)VitD3, alfacalcidol], calcium gluconate, ammonium oxalate, gentamicin sulfate, L-hydroxyproline. The rats were fed with drugs given singly or unitedly. At the end of experiment, 24-h urines were collected and the serum creatinine (Cr), blood urea nitrogen (BUN), the extents of calcium oxalate crystal deposition in the renal tissue, urinary calcium and oxalate excretion were measured. The serum Cr levels in the stone-forming groups were significantly higher than those in the control group except for the group EG+L-hydroxyproline, group calcium gluconate and group oxalate. Blood BUN concentration was significantly higher in rats fed with CID than that in control group except for group EG+L-hydroxyproline and group ammonium oxalate plus calcium gluconate. In the group of rats administered with EG plus Vitamin D3, the deposition of calcium oxalate crystal in the renal tissue and urinary calcium excretion were significantly greater than other model groups. The effect of the model induced by EG plus AC was similar to that in the group induced by EG plus Vitamin D3. EG plus Vitamin D3 or EG plus AC could stably and significantly induced the rat model of renal calcium oxalate stones formation .展开更多
To investigate the exon mutation of vitamin K-dependent gamma-glutamyl carboxylase (GGCX or VKDC) in patients with calcium oxalate urolithasis, renal cortex and peripheral blood samples were obtained from severe hyd...To investigate the exon mutation of vitamin K-dependent gamma-glutamyl carboxylase (GGCX or VKDC) in patients with calcium oxalate urolithasis, renal cortex and peripheral blood samples were obtained from severe hydronephrosis patients (with or without calculi), and renal tumor patients undergoing nephrectomy. GGCX mutations in all 15 exons were examined in 44 patients with calcium oxalate urolithiasis (COU) by polymerase chain reaction (PCR) and denatured high pressure liquid chromatography (DHPLC), and confirmed by sequencing. Mutation was not found in all COU samples compared to the controls. These data demonstrated that functional GGCX mutations in all 15 exons do not occur in most COU patients. It was suggested that there may be no significant association between the low activity and mutation of GGCX in COU.展开更多
The influence of sulfated polysaccharide (SPS) isolated from marine algae Sargassum fusiforme on the morphology and phase compositions of urinary crystal calcium oxalate was investigated in vitro by means of scannin...The influence of sulfated polysaccharide (SPS) isolated from marine algae Sargassum fusiforme on the morphology and phase compositions of urinary crystal calcium oxalate was investigated in vitro by means of scanning electron microscopy and X-ray diffraction. SPS maybe is a potential inhibitor to CaOxa urinary stones by inhibiting the growth of calcium oxalate monohydrate (COM), preventing the aggregation of COM, and inducing the formation of calcium oxalate dihydrate (COD) crystals.展开更多
The ring patterns of calcium oxalate crystals were induced by domains in Langmuir-Blodgett (LB) films of dipalmitoylpho- sphatidylcboline (DPPC). The result was explained by the defects at the ring boundaries of l...The ring patterns of calcium oxalate crystals were induced by domains in Langmuir-Blodgett (LB) films of dipalmitoylpho- sphatidylcboline (DPPC). The result was explained by the defects at the ring boundaries of liquid condensed (LC) and liquid expanded (LE) phases of LB film. These boundaries could provide less free energy and much more nucleating sites for COM crystals.展开更多
The inducing effect of potassium citrate (K3cit) on simultaneous growth of calcium oxalate mono-(COM), di-(COD), and trihydrate (COT) crystals in synthetic urine was observed with double diffusion gelatinous t...The inducing effect of potassium citrate (K3cit) on simultaneous growth of calcium oxalate mono-(COM), di-(COD), and trihydrate (COT) crystals in synthetic urine was observed with double diffusion gelatinous technique. K3cit can induce the formation of COD and COT, inhibit the aggregation and decrease the surface area of COM crystals. It supported the clinical use of K3cit and may provide important clues to this disease in cure and in search for new drugs.展开更多
To study the relationship between polymorphism of vitamin D receptor (VDR) allele with formation of calcium oxalate calculus and find the predisposing genes of calcium oxalate calculus, we screened out 150 patients w...To study the relationship between polymorphism of vitamin D receptor (VDR) allele with formation of calcium oxalate calculus and find the predisposing genes of calcium oxalate calculus, we screened out 150 patients who suffered from calcium oxalate calculus. 36 of them had idiopathic hypercalciuria according to analysis of calculus component and assay of urine calcium. The polymorphisms of VDR gene Taq1, Apa1 and Fok1 were detected using PCR-RFLP technique and the correlation were analyzed between the polymorphism and urinary calculus or between the polymorphism and hypercalciuria. The difference in each genotypic frequency of the allele of promoter Fok1 between calculus group and healthy group or between idiopathic hypercalciuria calculus group and health group was significant. The content of 24-h urine calcium of those who had genotype ff was obviously higher than that of those who have other genotypes in the same group. There was no significant difference in the polymorphism of gene Apa1 and Taq1 between each two groups. It is concluded that hypercalciuria and calcium oxalate calculus were related to the polymorphism of VDR gene's promoter Fok1 allele, but it had nothing to do with the polymorphism of gene Apa1 and Taq1. The genotype ff was a candidate heredity marker of calcium calculus disease.展开更多
The influence of additive Konjac Glucomannan (KGM) in a variety of con- centrations on the crystallization morphology and structure of calcium oxalate (CaOxa) has been investigated by infrared spectroscopy, scanni...The influence of additive Konjac Glucomannan (KGM) in a variety of con- centrations on the crystallization morphology and structure of calcium oxalate (CaOxa) has been investigated by infrared spectroscopy, scanning electron microscope, X-ray diffraction and so on. The results showed KGM can complex with the Ca^2+ ions; low concentration KGM prevents CaOxa from aggregating, raises the concentration of ions in the solution, reduces the quantity of crystals and inhibits their growth, and the crystals are round and blunt; while high concentration KGM promotes the growth of crystal, which appears in sheet-like or irregular shape. Only CaOxa monohydrate was observed in a certain system with or without the presence of KGM.展开更多
Summary: The vitamin K epoxide reductase complex subunit 1 (VKORC1), the rate-limiting enzyme for vitamin K recycling, is significantly down-regulated in the kidneys of urolithiasis patients. This study searched fo...Summary: The vitamin K epoxide reductase complex subunit 1 (VKORC1), the rate-limiting enzyme for vitamin K recycling, is significantly down-regulated in the kidneys of urolithiasis patients. This study searched for direct evidence to define the inhibitory activity of VKORC1 against calcium oxalate (CaOx) crystal formation. In the experiment of VKORC1 overexpression, HK-2 cells were transfected with the pFLAG-CMV-7.1-VKORC1 plasmid as a pFLAG-CMV-7.1-VKORC1 transfection group or the pFLAG-CMV-7.1 plasmid as a pFLAG-CMV-7.1 control group. In the experiment of VKORC1 knockdown, HK-2 cells were transfected with the PGPU6/GFP/Neo-VKORClshRNA-2 as a PGPU6/GFP/Neo-VKORClshRNA-2 transfection group or the PGPU6/GFP/Neo-shRNA-NC plasmid as a PGPU6/GFP/Neo-shRNA-NC control group. The expression of VKORC1 in HK-2 cells was detected by real-time quantitative PCR and Western blotting. The CaOx crystal formation was observed under the laser-scanning confocal microscope. It was found that the expression levels of VKORC1 mRNA and protein were significantly higher in the pFLAG-CMV-7.1-VKORC 1 transfection group than in the pFLAG-CMV-7.1 control group (P〈0.01). The number of CaOx crystals in HK-2 cells incubated in fluorescently labeled CaOx monohydrate (COM) crystal medium for 48 h was 14±4 per field (100×) in the pFLAG-CMV-7.1-VKORC1 transfection group and 26±5 per field (100×) in the pFLAG-CMV-7.1 control group respectively under the laser-scanning confocal microscope. The amount of CaOx crystal aggregation and formation in the pFLAG-CMV-7.1-VKORC 1 transfection group was significantly reduced as compared with the pFLAG-CMV-7.1 control group (P〈0.05). The expression levels of VKORC 1 mRNA and protein were significantly lower in the PGPU6/GFP/Neo-VKORC 1 shRNA-2 transfection group than in the PGPU6/GFP/Neo-shRNA-NC control group (P〈0.05). The number of CaOx crystals in HK-2 cells incubated in fluorescently labeled COM crystal medium was 65±11 per field (100x) in the PGPU6/GFP/Neo-VKORC 1 shRNA-2 transfection group and 24±6 per field (100×) in the PGPU6/GFP/Neo-shRNA-NC control group respectively under the laser-scanning confocal microscope. The amount of CaOx crystal aggregation and formation in the PGPU6/GFP/Neo-VKORClshRNA-2 transfection group was significantly increased as compared with the PGPU6/GFP/Neo-shRNA-NC control group (P〈0.05). These findings suggested that the VKORC 1 protein could inhibit CaOx salt crystallization, adhesion and aggregation. This research would help us to understand the mechanisms involving the interaction between crystallization and epithelial cells and the formation of CaOx. Key words: calcium oxalate crystals; kidney stone; vitamin K epoxide reduetase complex subunit 1; laser-scanning confocal microscopy展开更多
The intestinal Oxalobacter Formigenes were isolated in 30 cases of urolithiasis and in 45 controls. The biologic characters and morphology of the bacteria were also observed. The results showed that the colony counts ...The intestinal Oxalobacter Formigenes were isolated in 30 cases of urolithiasis and in 45 controls. The biologic characters and morphology of the bacteria were also observed. The results showed that the colony counts in urolith group 9 (mean 103/g. faeces) were significantly less than that of controls (mean 108/g. faeces) (P<0. 001). It is believed that the lesser amount of oxalobacter formigenes in urolith was the important factor of the calcium oxalate calculi formation.展开更多
Objective To analyze and identify the differentially expressed proteins in human renal tubular epithelial ceils ( HK-2) after injury caused by oxalic acid and calcium oxalate monohydrate ( COM ) crystal,and to explore...Objective To analyze and identify the differentially expressed proteins in human renal tubular epithelial ceils ( HK-2) after injury caused by oxalic acid and calcium oxalate monohydrate ( COM ) crystal,and to explore the potential role of renal tubular cell injury in kidney stone formation. Methods Normal HK-2 cells展开更多
Background:Dietary supplementation with citrate-containing juices may serve as an effective alternative to potassium citrate therapy for preventing calcium oxalate stone recurrence.This study was performed to evaluate...Background:Dietary supplementation with citrate-containing juices may serve as an effective alternative to potassium citrate therapy for preventing calcium oxalate stone recurrence.This study was performed to evaluate whether consumption of lemon-tomato juice can decrease the tendency for stone formation in the urine of calcium oxalate stone formers.Materials and methods:The study was conducted as a prospective interventional randomized crossover clinical trial with a repeated-measures design.Twenty-two patients with calcium oxalate stones and no metabolic abnormalities in the urine treated with lithotripsy at a tertiary care center from August 2017 to July 2018 were recruited.After a 14-hour overnight fasting,urine samples were collected after the patients consumed either milk only or milk and lemon-tomato juice.Their urine was tested for multiple parameters,including urine pH,specific gravity,calcium-creatinine ratio,and supersaturation with sodium oxalate,followed by optical density measurement via spectrophotometry.Results:There were no significant differences in the background characteristics between the 2 groups.The optical density of the urine samples obtained after consumption of milk only was significantly higher than that after consumption of milk and lemon-tomato juice(mean=0.131 for milk only vs.0.053 for milk and lemon-tomato juice,p<0.001).The urine calcium-creatinine ratio was similar between the groups(mean=0.141 for milk only vs.0.076 for milk and lemon-tomato juice,p=0.019).Conclusions:The addition of lemon-tomato juice as a source of citrate in the diet significantly decreases the established risk factors for calcium oxalate stone formation in patients.This study was prospectively registered at CTRI under number CTRI/2017/04/008312 on April 7,2017.展开更多
Artificial calcium oxalate films have been applied to protect sculptures,monuments,and buildings made of marble due to their potential protective capacities.Unfortunately,artificially prepared calcium oxalate films ar...Artificial calcium oxalate films have been applied to protect sculptures,monuments,and buildings made of marble due to their potential protective capacities.Unfortunately,artificially prepared calcium oxalate films are usually loose,and easy to peel off in contrast to the natural ones.In this paper,a new method was developed for the preparation of a compact and cohesive calcium oxalate film,using ethylene glycol as an additive.The morphology,elemental composition,structure,and crystal phase of the film were analyzed by SEM,EDX,IR,and XRD,and the protective effects were investigated by acid resistance test,while its adhesion to the underlying marble by the Scotch tape test.The porosity,water absorption,and color of treated marble were also assessed.The results showed that a calcium oxalate film with a compact structure,good adhesion,and a protective effect against acid rain can be successfully obtained by including ethylene glycol as an additive.With the new preparation method,a better bond between the stone and the film is obtained which contributes to solving the spalling problem of the artificial calcium oxalate films.展开更多
To study the activity of vitamin K-dependent γ-glutamyl carboxylase in patients with calcium oxalate (CaOx) urolithiasis compared with healthy individuals and to assess its relationship to the renal calcium oxalate u...To study the activity of vitamin K-dependent γ-glutamyl carboxylase in patients with calcium oxalate (CaOx) urolithiasis compared with healthy individuals and to assess its relationship to the renal calcium oxalate urolithiasis Methods Renal parenchymas were harvested from urolithic patients and renal tumor patients undergoing nephrectomy The renal carboxylase activity was evaluated as the radioactivity of [ 14 C] labeled sodium bicarbonate in carboxylic reactions in vitro using β-liquid scintillation counting Results Significantly reduced activity of renal vitamin K-dependent γ-glutamyl carboxylase was observed in the urolithic group as compared with normal controls (P<0 01) Conclusion It suggests that the reduced carboxylase activity observed in the urolithic patients may play an important role in the course of renal calcium oxalate urolithiasis展开更多
The adsorption of anionic surfactant sodium diisooctyl sulfosuccinate(AOT) onto calcium oxalate mono- hydrate(COM) and dihydrate(COD) with sizes of 50, 100 nm, 1, 3 and 10 μm was comparatively studied to simula...The adsorption of anionic surfactant sodium diisooctyl sulfosuccinate(AOT) onto calcium oxalate mono- hydrate(COM) and dihydrate(COD) with sizes of 50, 100 nm, 1, 3 and 10 μm was comparatively studied to simulate the interaction between urinary crystallites and urine components. The adsorption quantity of different concentrations of AOT onto COD and COM with different sizes was detected using a UV-Vis spectrophotometer. The crystalline phase transition of COM and COD before and after adsorption was analyzed by X-ray powder diffraction and Fourier transform infrared spectrometry. The zeta potential of the crystal surface after adsorption of different concentrations of AOT was measured using a zeta potential analyzer. The adsorption quantity of AOT on COM and COD with different sizes was ranked in the following order: 50 nm〉100 nm〉1μm〉3 μm〉10 μm. The adsorption quantity of COM was greater than that of COD with the same size because the density of the positive charges on the COM surface was higher than that on COD surface. With the increase of AOT concentration, the adsorption curves of the large-sized COM and COD(3 and 10μm) were S-type, whereas the adsorption curves of the small-sized COM and COD(50 nm, 100 nm and 1μm) were linear. The adsorption capacities of small-sized COM and COD were much greater than those of the 3 and 10μm crystals. On the basis of the above results, we proposed a molecular model to summarize the absorption of AOT onto COM and COD crystals. Small crystals exhibit a large specific surface area and high surface energy. Thus, the adsorption capacities of them are stronger than those of large crystals. Overall, this study implies that small crystals can easily absorb anionic molecules in urine and may easily adhere to a negatively charged cell surface, thereby increasing the severity of cell injury.展开更多
The effect of concentration of structurally-different carboxylic acids such as ethylene diamine tetraacetic acid (H4edta), citric acid (H3cit), tartaric acid (H2tart), and acetic acid (HOAc) on growth and aggr...The effect of concentration of structurally-different carboxylic acids such as ethylene diamine tetraacetic acid (H4edta), citric acid (H3cit), tartaric acid (H2tart), and acetic acid (HOAc) on growth and aggregation of calcium oxalate (CaOxa) in gel systems was comparatively investigated. H2tart and H3cit could change the morphology of cal- cium oxalate monohydrate (COM) and induce the formation of calcium oxalate dihydrate (COD). H4edta could induce the formation of COD at a lower concentration of 0.33 mmol/L and have the strongest ability to inhibit aggregation of COM. HOAc inhibited COM aggregation only at a higher concentration than 500 mmol/L. With increasing the number of carboxylic groups in an acid or increasing the concentration of carboxylic acid, the capacity of this acid to induce COD formation and to inhibit growth and aggregation of COM crystals increased. That is, this capacity followed the order: H4edta〉H3cit〉H2tart〉 〉HOAc. The result in this work suggested that the presence of H3cit and H2tart in urine played a role in the natural defense against stone formation.展开更多
The purpose of this work was to detect the properties of African green monkey renal epithelial cells (Vero) after oxidative injury and to study the mediation of the injured Vero on aggregation and formation of calci...The purpose of this work was to detect the properties of African green monkey renal epithelial cells (Vero) after oxidative injury and to study the mediation of the injured Vero on aggregation and formation of calcium oxalate crystals. This injury model was induced by 0.15 mmol/L H2O2 according to the pretest evaluation. The results suggested that H2O2 could injure Vero significantly and decrease cell viability in a time-dependent manner for exposure time of 0.5--2 h. After cell injury, the indexes connected with oxidative injury changed. The malondialdehyde (MDA) content and osteopontin (OPN) expression increased, while superoxide dismutase (SOD) level decreased. It resulted in the increase of both the amount of CaOxa crystals and the degree of crystal aggregation on the injured cells. This work indicated that injured cells promoted the formation of calcium oxalate monohydrate (COM) crystals, thus increased the risk of formation of urinary stone.展开更多
文摘Objective:Prevalence of kidney stone disease continues to increase globally with recurrence rates between 30%and 50%despite technological and scientific advances.Reduction in recurrence would improve patient outcomes and reduce cost and stone morbidities.Our objective was to review results of experimental studies performed to determine the efficacy of readily available compounds that can be used to prevent recurrence.Methods: All relevant literature up to October 2020,listed in PubMed is reviewed.Results: Clinical guidelines endorse the use of evidence-based medications,such as alkaline agents and thiazides,to reduce urinary mineral supersaturation and recurrence.However,there may be additional steps during stone pathogenesis where medications could moderate stone risk.Idiopathic calcium oxalate stones grow attached to Randall’s plaques or plugs.Results of clinical and experimental studies suggest involvement of reactive oxygen species and oxidative stress in the formation of both the plaques and plugs.The renin-angiotensin-aldosterone system(RAAS),nicotinamide adenine dinucleotide phosphate(NADPH)oxidase,mitochondria,and NOD-like receptor pyrin domain containing-3(NLRP3)inflammasome have all been implicated at specific steps during stone pathogenesis in animal models.Conclusion: In addition to supersaturation-reducing therapies,the use of anti-oxidants,free radical scavengers,and inhibitors of NADPH oxidase,NLRP3 inflammasome,and RAAS may prove beneficial for stone prevention.Compounds such as statins and angiotensin converting enzyme inhibitors are already in use as therapeutics for hypertension and cardio-vascular disease and have previously shown to reduce calcium oxalate nephrolithiasis in rats.Although clinical evidence for their use in stone prevention in humans is limited,experimental data support they be considered along with standard evidence-based medications and clinical expertise when patients are being counselled for stone prevention.
基金granted by the Key Project of Guangdong Province(013202,C31401)the Key Project of Natural Science Foundation of China(20031010)
文摘Effect of various counterions of tartrate on the crystallization of calcium oxalate in gel system was investigated using scanning electron microscopy and X-ray diffraction. Various tartrates with hydrogen (H2tart), sodium (Na2tart), potassium (K2tart), ammonium ((NH4)2tart), and a mixture of sodium and potassium cations (NaKtart) were considered. For H2tart, Na2tart, and (NH4)2tart, calcium oxalate dihydrate (COD) was induced. However, for K2tart and NaKtart, calcium oxalate trihydrate (COT) was obtained.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 81073124)
文摘This study examined the potential antilithic effects of a traditional Chinese medicine Urtica dentata Hand (UDH) in experimental rats and screened the optimal extract of UDH as a possible therapeutic agent for kidney stones. The rat model of urinary calcium oxalate stones was induced by intragastric (i.g.) administration of 2 mL of 1.25% ethylene glycol (EG) and 1% ammonium chloride (AC) for 28 days and was confirmed by Color Doppler ultrasound imaging. The rats in different experimental groups were then intragastrically given petroleum ether extract (PEE), N-butanol extract (NBE), aqueous extract (AqE) of UDH, Jieshitong (positive control drug), and saline, respectively. Treatment with NBE significantly reduced the elevated levels of urinary calcium, uric acid, phosphate, as well as increased urinary output. Accordingly, the increased calcium, oxalate levels and the number of calcium oxalate crystals deposits were remarkably reverted in the renal tissue of NBE-treated rats. In addition, NBE also prevented the impairment of renal function to decrease the contents of blood urea nitrogen (BUN) and creatinine. Taken together, these data suggest that NBE of UDH has a beneficial effect on calcium oxalate urinary stones in rats by flushing the stones out and protecting renal function.
基金supported by a grant from the National Natural Science Foundation of China(No.30901482)
文摘Urinary prothrombin fragment 1 (UPTFl) is a potent inhibitor of urinary stone formation. UPTF1 exerts such inhibitory effect by effective 7-carboxylation in which vitamin K epoxide reductase complex subunit 1 (VKORC1), the rate-limiting enzyme, is involved. This study examined the correlation between VKORC1 expression and calcium oxalate urolithiasis. The renal cortex samples were obtained from patients undergoing nephrectomy and then divided into 3 groups: urolithiasis group, control group A [hydronephrosis-without-stone (HWS) group], control group B (normal control group), The localization and expression of VKORC1 in renal tissues were determined by using immunohistochemistry, immunofluorescence microscopy, Western blotting and SYBR Green I real-time reverse-transcription PCR. The rapid amplification of cDNA ends (RACE) were conducted to obtain the 3'- and 5'-untranslated region (UTR) of VKORC1. The results showed that VKORC1 was located in the cytoplasm of renal tubular epithelial cells. The expression of VKORC1 in the uro- lithiasis group was significantly lower than that in the other two control groups (P〈0.05). Moreover, the 3'- and 5'-UTR sequence of the VKORC1 gene was successfully cloned. No insertion or deletion was found in the 3'- and 5'-UTR. However, a 171-bp new base sequence was discovered in the up- stream of 5'-UTR end in the urolithiasis group. It was concluded that the decreased expression of VKORC 1 may contribute to the development of calcium oxalate urolithiasis in the kidney.
文摘In order to compare the effects of several experimental renal calcium oxalate stones formation models in rats and to find a simple and convenient model with significant effect of calcium oxalate crystals deposition in the kidney, several rat models of renal calcium oxalate stones formation were induced by some crystal-inducing drugs (CID) including ethylene glycol (EG), ammonium chloride (AC), vitamin D3 [ 1 α(OH)VitD3, alfacalcidol], calcium gluconate, ammonium oxalate, gentamicin sulfate, L-hydroxyproline. The rats were fed with drugs given singly or unitedly. At the end of experiment, 24-h urines were collected and the serum creatinine (Cr), blood urea nitrogen (BUN), the extents of calcium oxalate crystal deposition in the renal tissue, urinary calcium and oxalate excretion were measured. The serum Cr levels in the stone-forming groups were significantly higher than those in the control group except for the group EG+L-hydroxyproline, group calcium gluconate and group oxalate. Blood BUN concentration was significantly higher in rats fed with CID than that in control group except for group EG+L-hydroxyproline and group ammonium oxalate plus calcium gluconate. In the group of rats administered with EG plus Vitamin D3, the deposition of calcium oxalate crystal in the renal tissue and urinary calcium excretion were significantly greater than other model groups. The effect of the model induced by EG plus AC was similar to that in the group induced by EG plus Vitamin D3. EG plus Vitamin D3 or EG plus AC could stably and significantly induced the rat model of renal calcium oxalate stones formation .
文摘To investigate the exon mutation of vitamin K-dependent gamma-glutamyl carboxylase (GGCX or VKDC) in patients with calcium oxalate urolithasis, renal cortex and peripheral blood samples were obtained from severe hydronephrosis patients (with or without calculi), and renal tumor patients undergoing nephrectomy. GGCX mutations in all 15 exons were examined in 44 patients with calcium oxalate urolithiasis (COU) by polymerase chain reaction (PCR) and denatured high pressure liquid chromatography (DHPLC), and confirmed by sequencing. Mutation was not found in all COU samples compared to the controls. These data demonstrated that functional GGCX mutations in all 15 exons do not occur in most COU patients. It was suggested that there may be no significant association between the low activity and mutation of GGCX in COU.
基金granted by the National Natural Science Foundation of China(20471024)the Project-sponsored by SRF for ROCS,SEMthe Key project of Natural Science Foundation of China(20031010).
文摘The influence of sulfated polysaccharide (SPS) isolated from marine algae Sargassum fusiforme on the morphology and phase compositions of urinary crystal calcium oxalate was investigated in vitro by means of scanning electron microscopy and X-ray diffraction. SPS maybe is a potential inhibitor to CaOxa urinary stones by inhibiting the growth of calcium oxalate monohydrate (COM), preventing the aggregation of COM, and inducing the formation of calcium oxalate dihydrate (COD) crystals.
基金This research work was granted by the National Natural Science Foundation of China(No.20471024).
文摘The ring patterns of calcium oxalate crystals were induced by domains in Langmuir-Blodgett (LB) films of dipalmitoylpho- sphatidylcboline (DPPC). The result was explained by the defects at the ring boundaries of liquid condensed (LC) and liquid expanded (LE) phases of LB film. These boundaries could provide less free energy and much more nucleating sites for COM crystals.
基金This research work was granted by the National Natural Science Foundation of China (No 20471024).
文摘The inducing effect of potassium citrate (K3cit) on simultaneous growth of calcium oxalate mono-(COM), di-(COD), and trihydrate (COT) crystals in synthetic urine was observed with double diffusion gelatinous technique. K3cit can induce the formation of COD and COT, inhibit the aggregation and decrease the surface area of COM crystals. It supported the clinical use of K3cit and may provide important clues to this disease in cure and in search for new drugs.
基金This project was supported by the National Natural ScienceFoundation of China ( Serial No:3 0 2 0 0 2 83 )
文摘To study the relationship between polymorphism of vitamin D receptor (VDR) allele with formation of calcium oxalate calculus and find the predisposing genes of calcium oxalate calculus, we screened out 150 patients who suffered from calcium oxalate calculus. 36 of them had idiopathic hypercalciuria according to analysis of calculus component and assay of urine calcium. The polymorphisms of VDR gene Taq1, Apa1 and Fok1 were detected using PCR-RFLP technique and the correlation were analyzed between the polymorphism and urinary calculus or between the polymorphism and hypercalciuria. The difference in each genotypic frequency of the allele of promoter Fok1 between calculus group and healthy group or between idiopathic hypercalciuria calculus group and health group was significant. The content of 24-h urine calcium of those who had genotype ff was obviously higher than that of those who have other genotypes in the same group. There was no significant difference in the polymorphism of gene Apa1 and Taq1 between each two groups. It is concluded that hypercalciuria and calcium oxalate calculus were related to the polymorphism of VDR gene's promoter Fok1 allele, but it had nothing to do with the polymorphism of gene Apa1 and Taq1. The genotype ff was a candidate heredity marker of calcium calculus disease.
基金Supported by the National Natural Science Foundation of China (31071518 and 31271837)the doctoral program of higher education of the specialized research fund for the project funded by the United (20113515110010)+2 种基金Science and Technology Planning Project of technological department (2012GA7200022)the Natural Science Foundation of Fujian Province (2011J01285)the funding (type A, No. JA11167) from the Fujian Education Department
文摘The influence of additive Konjac Glucomannan (KGM) in a variety of con- centrations on the crystallization morphology and structure of calcium oxalate (CaOxa) has been investigated by infrared spectroscopy, scanning electron microscope, X-ray diffraction and so on. The results showed KGM can complex with the Ca^2+ ions; low concentration KGM prevents CaOxa from aggregating, raises the concentration of ions in the solution, reduces the quantity of crystals and inhibits their growth, and the crystals are round and blunt; while high concentration KGM promotes the growth of crystal, which appears in sheet-like or irregular shape. Only CaOxa monohydrate was observed in a certain system with or without the presence of KGM.
基金supported by grants from the Scientific Research Starting Foundation for Young Scientist from ShanghaiMedical College of Fudan University(No.11L-33)theShanghai Municipal Key Specialist Construction Projects(No.ZK2012A22)
文摘Summary: The vitamin K epoxide reductase complex subunit 1 (VKORC1), the rate-limiting enzyme for vitamin K recycling, is significantly down-regulated in the kidneys of urolithiasis patients. This study searched for direct evidence to define the inhibitory activity of VKORC1 against calcium oxalate (CaOx) crystal formation. In the experiment of VKORC1 overexpression, HK-2 cells were transfected with the pFLAG-CMV-7.1-VKORC1 plasmid as a pFLAG-CMV-7.1-VKORC1 transfection group or the pFLAG-CMV-7.1 plasmid as a pFLAG-CMV-7.1 control group. In the experiment of VKORC1 knockdown, HK-2 cells were transfected with the PGPU6/GFP/Neo-VKORClshRNA-2 as a PGPU6/GFP/Neo-VKORClshRNA-2 transfection group or the PGPU6/GFP/Neo-shRNA-NC plasmid as a PGPU6/GFP/Neo-shRNA-NC control group. The expression of VKORC1 in HK-2 cells was detected by real-time quantitative PCR and Western blotting. The CaOx crystal formation was observed under the laser-scanning confocal microscope. It was found that the expression levels of VKORC1 mRNA and protein were significantly higher in the pFLAG-CMV-7.1-VKORC 1 transfection group than in the pFLAG-CMV-7.1 control group (P〈0.01). The number of CaOx crystals in HK-2 cells incubated in fluorescently labeled CaOx monohydrate (COM) crystal medium for 48 h was 14±4 per field (100×) in the pFLAG-CMV-7.1-VKORC1 transfection group and 26±5 per field (100×) in the pFLAG-CMV-7.1 control group respectively under the laser-scanning confocal microscope. The amount of CaOx crystal aggregation and formation in the pFLAG-CMV-7.1-VKORC 1 transfection group was significantly reduced as compared with the pFLAG-CMV-7.1 control group (P〈0.05). The expression levels of VKORC 1 mRNA and protein were significantly lower in the PGPU6/GFP/Neo-VKORC 1 shRNA-2 transfection group than in the PGPU6/GFP/Neo-shRNA-NC control group (P〈0.05). The number of CaOx crystals in HK-2 cells incubated in fluorescently labeled COM crystal medium was 65±11 per field (100x) in the PGPU6/GFP/Neo-VKORC 1 shRNA-2 transfection group and 24±6 per field (100×) in the PGPU6/GFP/Neo-shRNA-NC control group respectively under the laser-scanning confocal microscope. The amount of CaOx crystal aggregation and formation in the PGPU6/GFP/Neo-VKORClshRNA-2 transfection group was significantly increased as compared with the PGPU6/GFP/Neo-shRNA-NC control group (P〈0.05). These findings suggested that the VKORC 1 protein could inhibit CaOx salt crystallization, adhesion and aggregation. This research would help us to understand the mechanisms involving the interaction between crystallization and epithelial cells and the formation of CaOx. Key words: calcium oxalate crystals; kidney stone; vitamin K epoxide reduetase complex subunit 1; laser-scanning confocal microscopy
文摘The intestinal Oxalobacter Formigenes were isolated in 30 cases of urolithiasis and in 45 controls. The biologic characters and morphology of the bacteria were also observed. The results showed that the colony counts in urolith group 9 (mean 103/g. faeces) were significantly less than that of controls (mean 108/g. faeces) (P<0. 001). It is believed that the lesser amount of oxalobacter formigenes in urolith was the important factor of the calcium oxalate calculi formation.
文摘Objective To analyze and identify the differentially expressed proteins in human renal tubular epithelial ceils ( HK-2) after injury caused by oxalic acid and calcium oxalate monohydrate ( COM ) crystal,and to explore the potential role of renal tubular cell injury in kidney stone formation. Methods Normal HK-2 cells
基金grant from the State Board for Medical Research,Government Medical College,Thiruvananthapuram,Kerala,India,a government funding agency,under grant number A2/SBMR(2016-2017)/27717/2016/MCT.
文摘Background:Dietary supplementation with citrate-containing juices may serve as an effective alternative to potassium citrate therapy for preventing calcium oxalate stone recurrence.This study was performed to evaluate whether consumption of lemon-tomato juice can decrease the tendency for stone formation in the urine of calcium oxalate stone formers.Materials and methods:The study was conducted as a prospective interventional randomized crossover clinical trial with a repeated-measures design.Twenty-two patients with calcium oxalate stones and no metabolic abnormalities in the urine treated with lithotripsy at a tertiary care center from August 2017 to July 2018 were recruited.After a 14-hour overnight fasting,urine samples were collected after the patients consumed either milk only or milk and lemon-tomato juice.Their urine was tested for multiple parameters,including urine pH,specific gravity,calcium-creatinine ratio,and supersaturation with sodium oxalate,followed by optical density measurement via spectrophotometry.Results:There were no significant differences in the background characteristics between the 2 groups.The optical density of the urine samples obtained after consumption of milk only was significantly higher than that after consumption of milk and lemon-tomato juice(mean=0.131 for milk only vs.0.053 for milk and lemon-tomato juice,p<0.001).The urine calcium-creatinine ratio was similar between the groups(mean=0.141 for milk only vs.0.076 for milk and lemon-tomato juice,p=0.019).Conclusions:The addition of lemon-tomato juice as a source of citrate in the diet significantly decreases the established risk factors for calcium oxalate stone formation in patients.This study was prospectively registered at CTRI under number CTRI/2017/04/008312 on April 7,2017.
基金supported by the National Natural Science Foundation of China(Grant Nos.B050121975202,52108031)the Natural Science Foundation of Shaanxi Province(Grant No.2023-JC-YB-097)the 111Project(Grant No.D18004)。
文摘Artificial calcium oxalate films have been applied to protect sculptures,monuments,and buildings made of marble due to their potential protective capacities.Unfortunately,artificially prepared calcium oxalate films are usually loose,and easy to peel off in contrast to the natural ones.In this paper,a new method was developed for the preparation of a compact and cohesive calcium oxalate film,using ethylene glycol as an additive.The morphology,elemental composition,structure,and crystal phase of the film were analyzed by SEM,EDX,IR,and XRD,and the protective effects were investigated by acid resistance test,while its adhesion to the underlying marble by the Scotch tape test.The porosity,water absorption,and color of treated marble were also assessed.The results showed that a calcium oxalate film with a compact structure,good adhesion,and a protective effect against acid rain can be successfully obtained by including ethylene glycol as an additive.With the new preparation method,a better bond between the stone and the film is obtained which contributes to solving the spalling problem of the artificial calcium oxalate films.
基金TheworkwassupportedbyagrantfromtheNationalNaturalScienceFoundationofChina (No .3990 70 740 )
文摘To study the activity of vitamin K-dependent γ-glutamyl carboxylase in patients with calcium oxalate (CaOx) urolithiasis compared with healthy individuals and to assess its relationship to the renal calcium oxalate urolithiasis Methods Renal parenchymas were harvested from urolithic patients and renal tumor patients undergoing nephrectomy The renal carboxylase activity was evaluated as the radioactivity of [ 14 C] labeled sodium bicarbonate in carboxylic reactions in vitro using β-liquid scintillation counting Results Significantly reduced activity of renal vitamin K-dependent γ-glutamyl carboxylase was observed in the urolithic group as compared with normal controls (P<0 01) Conclusion It suggests that the reduced carboxylase activity observed in the urolithic patients may play an important role in the course of renal calcium oxalate urolithiasis
基金Supported by the National Natural Science Foundation of China(No.21371077).
文摘The adsorption of anionic surfactant sodium diisooctyl sulfosuccinate(AOT) onto calcium oxalate mono- hydrate(COM) and dihydrate(COD) with sizes of 50, 100 nm, 1, 3 and 10 μm was comparatively studied to simulate the interaction between urinary crystallites and urine components. The adsorption quantity of different concentrations of AOT onto COD and COM with different sizes was detected using a UV-Vis spectrophotometer. The crystalline phase transition of COM and COD before and after adsorption was analyzed by X-ray powder diffraction and Fourier transform infrared spectrometry. The zeta potential of the crystal surface after adsorption of different concentrations of AOT was measured using a zeta potential analyzer. The adsorption quantity of AOT on COM and COD with different sizes was ranked in the following order: 50 nm〉100 nm〉1μm〉3 μm〉10 μm. The adsorption quantity of COM was greater than that of COD with the same size because the density of the positive charges on the COM surface was higher than that on COD surface. With the increase of AOT concentration, the adsorption curves of the large-sized COM and COD(3 and 10μm) were S-type, whereas the adsorption curves of the small-sized COM and COD(50 nm, 100 nm and 1μm) were linear. The adsorption capacities of small-sized COM and COD were much greater than those of the 3 and 10μm crystals. On the basis of the above results, we proposed a molecular model to summarize the absorption of AOT onto COM and COD crystals. Small crystals exhibit a large specific surface area and high surface energy. Thus, the adsorption capacities of them are stronger than those of large crystals. Overall, this study implies that small crystals can easily absorb anionic molecules in urine and may easily adhere to a negatively charged cell surface, thereby increasing the severity of cell injury.
基金Project supported by the National Natural Science Foundation of China (Nos. 30672103, 20471024) and the Key Project of Guangdong Province (Nos. 2005B30701003, 2006B36501001).
文摘The effect of concentration of structurally-different carboxylic acids such as ethylene diamine tetraacetic acid (H4edta), citric acid (H3cit), tartaric acid (H2tart), and acetic acid (HOAc) on growth and aggregation of calcium oxalate (CaOxa) in gel systems was comparatively investigated. H2tart and H3cit could change the morphology of cal- cium oxalate monohydrate (COM) and induce the formation of calcium oxalate dihydrate (COD). H4edta could induce the formation of COD at a lower concentration of 0.33 mmol/L and have the strongest ability to inhibit aggregation of COM. HOAc inhibited COM aggregation only at a higher concentration than 500 mmol/L. With increasing the number of carboxylic groups in an acid or increasing the concentration of carboxylic acid, the capacity of this acid to induce COD formation and to inhibit growth and aggregation of COM crystals increased. That is, this capacity followed the order: H4edta〉H3cit〉H2tart〉 〉HOAc. The result in this work suggested that the presence of H3cit and H2tart in urine played a role in the natural defense against stone formation.
文摘The purpose of this work was to detect the properties of African green monkey renal epithelial cells (Vero) after oxidative injury and to study the mediation of the injured Vero on aggregation and formation of calcium oxalate crystals. This injury model was induced by 0.15 mmol/L H2O2 according to the pretest evaluation. The results suggested that H2O2 could injure Vero significantly and decrease cell viability in a time-dependent manner for exposure time of 0.5--2 h. After cell injury, the indexes connected with oxidative injury changed. The malondialdehyde (MDA) content and osteopontin (OPN) expression increased, while superoxide dismutase (SOD) level decreased. It resulted in the increase of both the amount of CaOxa crystals and the degree of crystal aggregation on the injured cells. This work indicated that injured cells promoted the formation of calcium oxalate monohydrate (COM) crystals, thus increased the risk of formation of urinary stone.