Kidney stone growth through the lens of Raman mapping.

Bulk composition of kidney stones, often analyzed with infrared spectroscopy, plays an essential role in determining the course of treatment for kidney stone disease. Though bulk analysis of kidney stones can hint at the general causes of stone formation, it is necessary to understand kidney stone microstructure to further advance potential treatments that rely on in vivo dissolution of stones rather than surgery. The utility of Raman microscopy is demonstrated for the purpose of studying kidney stone microstructure with chemical maps at ≤ 1 µm scales collected for calcium oxalate, calcium phosphate, uric acid, and struvite stones. Observed microstructures are discussed with respect to kidney stone growth and dissolution with emphasis placed on < 5 µm features that would be difficult to identify using alternative techniques including micro computed tomography. These features include thin concentric rings of calcium oxalate monohydrate within uric acid stones and increased frequency of calcium oxalate crystals within regions of elongated crystal growth in a brushite stone. We relate these observations to potential concerns of clinical significance including dissolution of uric acid by raising urine pH and the higher rates of brushite stone recurrence compared to other non-infectious kidney stones.

Tight junction and kidney stone disease.

Defects of tight junction (TJ) are involved in many diseases related to epithelial cell functions, including kidney stone disease (KSD), which is a common disease affecting humans for over a thousand years. This review provides brief overviews of KSD and TJ, and summarizes the knowledge on crystal-induced defects of TJ in renal tubular epithelial cells (RTECs) in KSD. Calcium oxalate (CaOx) crystals, particularly COM, disrupt TJ via p38 MAPK and ROS/Akt/p38 MAPK signaling pathways, filamentous actin (F-actin) reorganization and α-tubulin relocalization. Stabilizing p38 MAPK signaling, reactive oxygen species (ROS) production, F-actin and α-tubulin by using SB239063, N-acetyl-L-cysteine (NAC), phalloidin and docetaxel, respectively, successfully prevent the COM-induced TJ disruption and malfunction. Additionally, genetic disorders of renal TJ, including mutations and single nucleotide polymorphisms (SNPs) of CLDN2, CLDN10b, CLDN14, CLDN16 and CLDN19, also affect KSD. Finally, the role of TJ as a potential target for KSD therapeutics and prevention is also discussed.

The first epidemiology of urolithiasis in Northern Vietnam: Urinary stone composition, age, gender, season, and clinical features study.

OBJECTIVES: The aim of this study is to analyze the compositions of urinary stones and investigate their distributions in different ages, genders, seasons, and clinical features of Northern Vietnamese patients. METHODS: A total of 231 patients with urinary stones from Northern Vietnam were collected and analyzed composition from 1/2021-12/2022. For all patients, age, sex, stone location, stone side, urine pH, and hospitalized date (month) were collected. RESULTS: Kidney stones are more frequently found in men than women with the male: female urinary stones ratio in this study being 1.96:1. The highest stone prevalence appeared between 60 and 69 years old. The most common stone composition was calcium oxalate, followed by calcium phosphate, uric acid, struvite, and cysteine. Mix stones of CaOx and CaP were more prevalent than pure stones. Males submitted more CaOx, CaP, and UA stones, whereas females were susceptible to infectious stones. Stones were more frequently found on the left side of the upper urinary tract (51.9%) than on the right side (27.3%) and lower urinary tract (7.8%). Cultural tendency leads to a smaller number of stones during the Lunar new year (February), and Ghost month (August).

Effect of a high-citrate beverage on urine chemistry in patients with calcium kidney stones.

A well-accepted strategy to prevent kidney stones is to increase urine volume by increasing oral intake of fluids, especially water, to lower supersaturation of the relevant, relatively insoluble salts, and thereby lower the risk of precipitation. Randomized controlled trials have shown that this strategy works. It is inexpensive, safe, and intuitively attractive to patients. However, although any beverage can increase urine volume, and citrus juices can increase urine citrate content and pH, no beverage other than water has been clearly shown by randomized controlled trial to prevent kidney stones. We designed an innovative, palatable, low-calorie, high alkali citrate beverage to prevent kidney stones, called Moonstone. One packet of Moonstone powder, mixed in 500 ml of water, contains 24.5 meq of alkali citrate. We administered one packet twice a day to ten calcium stone formers. Moonstone resulted in an increase in mean 24-h urine citrate and urine pH, and a decrease in supersaturation of calcium oxalate in calcium stone formers compared to an equal volume of water. These changes, comparable to those seen in a prior study of a similar amount of (potassium-magnesium) citrate, will likely be associated with a clinically meaningful reduction in kidney stone burden in patients with calcium stones. The effect to increase urine pH would also be expected to benefit patients with uric acid and cystine stones, groups that we hope to study in a subsequent study. The study preparation was well tolerated and was selected as a preferred preventative strategy by about half the participants. Moonstone is an alternative, over-the-counter therapy for kidney stone prevention.

Overexpression of sirtuin 1 attenuates calcium oxalate-induced kidney injury by promoting macrophage polarization.

Sirtuin 1 (SIRT1) protein is involved in macrophage differentiation, while NOTCH signaling affects inflammation and macrophage polarization. Inflammation and macrophage infiltration are typical processes that accompany kidney stone formation. However, the role and mechanism of SIRT1 in renal tubular epithelial cell injury caused by calcium oxalate (CaOx) deposition and the relationship between SIRT1 and the NOTCH signaling pathway in this urological disorder are unclear. This study investigated whether SIRT1 promotes macrophage polarization to inhibit CaOx crystal deposition and reduce renal tubular epithelial cell injury. Public single-cell sequencing data, RT-qPCR, immunostaining approaches, and Western blotting showed decreased SIRT1 expression in macrophages treated with CaOx or exposed to kidney stones. Macrophages overexpressing SIRT1 differentiated towards the anti-inflammatory M2 phenotype, significantly inhibiting apoptosis and alleviating injury in the kidneys of mice with hyperoxaluria. Conversely, decreased SIRT1 expression in CaOx-treated macrophages triggered Notch signaling pathway activation, promoting macrophage polarization towards the pro-inflammatory M1 phenotype. Our results suggest that SIRT1 promotes macrophage polarization towards the M2 phenotype by repressing the NOTCH signaling pathway, which reduces CaOx crystal deposition, apoptosis, and damage in the kidney. Therefore, we propose SIRT1 as a potential target for preventing disease progression in patients with kidney stones.

The relationship between patients' kidney stone type and demographics in Israel: analysis of 10 K patients.

PURPOSE: To analyze urinary stone composition in Israel and assess the effects of key demographic parameters (gender, age, socioeconomic status, ethnicity, medical history and geographic region) on stone composition. METHODS: A retrospective review was conducted of stone analysis of 10,633 patients from an HMO Israeli database analyzed by a central laboratory from 2014 to 2019 and subjected to Fourier-transform infrared spectroscopy. Associations between stone composition and different demographic parameters were determined using the Chi-square test. RESULTS: Calcium oxalate (CaOx) monohydrate accounted for 51.9% of the stones. Of the total sample, 5776 stones had one single component (54%), whereas 4857 (46%) had mixed components. Men had a higher frequency of CaOx stones (89.6% vs. 85.6%), whereas women had a higher frequency of calcium phosphate, infection, and cystine stones (27.2%, 17.7%, and 0.9% vs. 17.2%, 7.5%, and 0.5%, respectively). Cystine stones were more abundant in Arabs (1.2% vs. 0.5% in the Jewish population). Lower socioeconomic status was associated with a higher prevalence of calcium phosphate, uric acid, and infection stones and a lower prevalence of CaOx stones. Uric acid stones were associated with medical conditions such as diabetes, hypertension, ischemic heart disease, and obesity (28.3%, 24.9%, 25.7%, and 22.6% vs. 9.6%, 8.4%, 12.3%, and 10.3%, respectively). CONCLUSIONS: Stone types were highly influenced by patients' demographics. COM was the most common stone component in either pure or complex form. UA stone prevalence was found to increase with age and was associated with medical conditions such as diabetes, hypertension, ischemic heart disease, and obesity.

Dynamics of differentiated-renal epithelial cell monolayer after calcium oxalate injury: The role of cyclooxygenase-2.

AIMS: Calcium oxalate (Oxa), constituent of most common kidney stones, damages renal tubular epithelial cells leading to kidney disease. Most in vitro studies designed to evaluate how Oxa exerts its harmful effects were performed in proliferative or confluent non-differentiated renal epithelial cultures; none of them considered physiological hyperosmolarity of renal medullary interstitium. Cyclooxygenase 2 (COX2) has been associated to Oxa deleterious actions; however, up to now, it is not clear how COX2 acts. In this work, we proposed an in vitro experimental system resembling renal differentiated-epithelial cells that compose medullary tubular structures which were grown and maintained in a physiological hyperosmolar environment and evaluated whether COX2 â†’ PGE2 axis (COX2 considered a cytoprotective protein for renal cells) induces Oxa damage or epithelial restitution. MAIN METHODS: MDCK cells were differentiated with NaCl hyperosmolar medium for 72 h where cells acquired the typical apical and basolateral membrane domains and a primary cilium. Then, cultures were treated with 1.5 mM Oxa for 24, 48, and 72 h to evaluate epithelial monolayer restitution dynamics and COX2-PGE2 effect. KEY FINDINGS: Oxa completely turned the differentiated phenotype into mesenchymal one (epithelial-mesenchymal transition). Such effect was partially and totally reverted after 48 and 72 h, respectively. Oxa damage was even deeper when COX2 was blocked by NS398. PGE2 addition restituted the differentiated-epithelial phenotype in a time and concentration dependence. SIGNIFICANCE: This work presents an experimental system that approaches in vitro to in vivo renal epithelial studies and, more important, warns about NSAIDS use in patients suffering from kidney stones.

Meta-data analysis of kidney stone disease highlights ATP1A1 involvement in renal crystal formation.

Nephrolithiasis is a complicated disease affected by various environmental and genetic factors. Crystal-cell adhesion is a critical initiation process during kidney stone formation. However, genes regulated by environmental and genetic factors in this process remain unclear. In the present study, we integrated the gene expression profile data and the whole-exome sequencing data of patients with calcium stones, and found that ATP1A1 might be a key susceptibility gene involved in calcium stone formation. The study showed that the T-allele of rs11540947 in the 5'-untranslated region of ATP1A1 was associated with a higher risk of nephrolithiasis and lower activity of a promoter of ATP1A1. Calcium oxalate crystal deposition decreased ATP1A1 expression in vitro and in vivo and was accompanied by the activation of the ATP1A1/Src/ROS/p38/JNK/NF-κB signaling pathway. However, the overexpression of ATP1A1 or treatment with pNaKtide, a specific inhibitor of the ATP1A1/Src complex, inhibited the ATP1A1/Src signal system and alleviated oxidative stress, inflammatory responses, apoptosis, crystal-cell adhesion, and stone formation. Moreover, the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine reversed ATP1A1 down-regulation induced by crystal deposition. In conclusion, this is the first study to show that ATP1A1, a gene modulated by environmental factors and genetic variations, plays an important role in renal crystal formation, suggesting that ATP1A1 may be a potential therapeutic target for treating calcium stones.

Ferroptosis in calcium oxalate kidney stone formation and the possible regulatory mechanism of ANKRD1.

The objective of this study was to explore the role of ferroptosis in the formation of calcium oxalate (CaOx) kidney stones and the regulatory mechanism of the ankyrin repeat domain 1 (ANKRD1) gene. The study found that the Nrf2/HO-1 and p53/SLC7A11 signaling pathways were activated in the kidney stone model group, and the expression of the ferroptosis marker proteins SLC7A11 and GPX4 was significantly reduced, while the expression of ACSL4 was significantly increased. The expression of the iron transport-related proteins CP and TF increased significantly, and Fe2+ accumulated in the cell. The expression of HMGB1 increased significantly. In addition, the level of intracellular oxidative stress was increased. The gene with the most significant difference caused by CaOx crystals in HK-2 cells was ANKRD1. Silencing or overexpression of ANKRD1 by lentiviral infection technology regulated the expression of the p53/SLC7A11 signaling pathway, which regulated the ferroptosis induced by CaOx crystals. In conclusion, CaOx crystals can mediate ferroptosis through the Nrf2/HO-1 and p53/SLC7A11 pathways, thereby weakening the resistance of HK-2 cells to oxidative stress and other unfavorable factors, enhancing cell damage, and increasing crystal adhesion and CaOx crystal deposition in the kidney. ANKRD1 participates in the formation and development of CaOx kidney stones by activating ferroptosis mediated by the p53/SLC7A11 pathway.

Detection of Cadmium and Lead in Kidney Stones. Associations with Patient Demographics, Stone Composition, and Smoking.

BACKGROUND: Kidney stones are a highly prevalent disease worldwide. Additionally, both environmental and occupational exposure to Pb and Cd continue to be prevalent globally and can result in renal toxicity. The objective of this study was to examine the potential presence of Pb and Cd in kidney stones, and to assess for correlation with demographic factors including smoking, gender, age, and kidney stone matrix composition. METHODS: Patient kidney stones (n = 96) were analyzed using Fourier transform infrared spectroscopy to identify the stone constituents. Cd and Pb concentrations (µg/g) were determined by inductively coupled plasma mass spectrometry. Cd and Pb concentrations were correlated using bivariable and multivariable statistical analysis with demographic factors (age, gender, smoking status), and kidney stone composition. RESULTS: Kidney stone Cd (median 0.092 µg/g, range 0.014 to 2.46) and Pb concentrations (median 0.95 µg/g, range 0.060 to 15.4) were moderately correlated (r = 0.56, P < 0.0001). Cd concentrations were positively associated with patient history of smoking, patient age, and calcium oxalate monohydrate levels while negatively associated with struvite and uric acid/uric acid dihydrate. Pb concentrations were positively associated with females and apatite levels while negatively associated with uric acid/uric acid dihydrate. After holding constant other stone type composition levels, smoking status, and age, both Pb and Cd were positively associated with apatite and negatively associated with uric acid/uric acid dihydrate, struvite, and calcium carbonate. CONCLUSIONS: Cd and Pb kidney stone concentrations are associated with specific kidney stone types. Cd and Pb kidney stone concentrations are both associated with smoking.

The SLC6A19 gene mutation in a young man with hyperglycinuria and nephrolithiasis: a case report and literature review.

BACKGROUND: Hyperglycinuria is a rare disorder, with few reported cases, caused by either a defect in glycine metabolism or a disturbance in renal glycine reabsorption. Genetic findings of hyperglycinuria are rare and have not previously been reported in Chinese young men. CASE PRESENTATION: A 24-year-old man presented with a compliant of bilateral lumbago for 1 month. Abdominal computed tomography revealed bilateral kidney stones and right upper ureteral dilatation. The 24-h urine analysis showed high urine oxalate levels of 63 mg/day. Analysis of amino acids in urine revealed that his urinary glycine levels were abnormally high (2.38 µmol/mg creatinine). Whole-exome sequencing detected the SLC6A19 variant c.1278 C > T p. (Cys426). Flexible ureteroscopy with holmium laser lithotripsy was conducted twice to remove his bilateral nephrolithiasis. Postoperative stone biochemical composition analysis revealed that the stones were composed of approximately 70% calcium oxalate monohydrate and 30% calcium oxalate dihydrate. The patient was subsequently diagnosed with hyperglycinuria. Three months after the stone surgery, ultrasonography revealed one nodule under the right thyroid lobe during a health checkup. His serum parathyroid hormone (PTH) levels increased to 392.3 pg/mL. Resection of the right parathyroid nodule was performed, and the histopathological examination confirmed right parathyroid adenoma. During the 2-year follow-up period, nephrolithiasis did not relapse, and serum PTH, calcium, and phosphorus levels were normal. CONCLUSION: The SLC6A19 gene may have been significant in the development of hyperglycinuria in a Chinese young man. Further evaluation for the possibility of a glycine excretion disorder could be considered when encountering nephrolithiasis.

Inhibitory role of microRNA-484 in kidney stone formation by repressing calcium oxalate crystallization via a VDR/FoxO1 regulator axis.

Kidney stones are regarded as common malignant diseases in the developed world. As a result, significant research examining their formation is ongoing, with microRNAs (miRs) recently being linked with kidney stone formation. Here, we aim to define the potential role of miR-484 in regulating renal tubular epithelial cell (RTEC) viability and the attachment of calcium oxalate (CaOx) crystals to RTECs via vitamin D receptor (VDR)/forkhead box protein O1 (FoxO1) axis. The pathological condition of CaOx crystallization was induced and examined in Sprague-Dawley rats, while RTECs were isolated and cultured in vitro. Loss- and gain-function assays were performed to study the effects that miR-484, VDR, and FoxO1 on RTEC functions and CaOx crystallization in vitro and on kidney stone formation in vivo. The interaction between miR-484 and VDR was confirmed by dual-luciferase reporter gene assays. Downregulation of miR-484 and FoxO1 as well as overexpression of VDR were identified in kidney stone modelled rats. VDR was confirmed as a target gene of miR-484, while knockdown of VDR upregulated the FoxO1 expression. miR-484 overexpression or VDR suppression reduced RTEC cytotoxicity and crystal attachment to RTECs in vitro and reduced the CaOx crystallization in vivo. Taken together, these findings suggest that miR-484 overexpression may be a potential inhibitor of RTEC proliferation and CaOx crystallization through a VDR/FoxO1 regulatory axis, providing a novel therapeutic target for the treatment of kidney stone.

How Reliable Is Endoscopic Stone Recognition? A Comparison Between Visual Stone Identification and Formal Stone Analysis.

Objective: To assess the diagnostic accuracy and intra-observer agreement of endoscopic stone recognition (ESR) compared with formal stone analysis. Introduction: Stone analysis is a corner stone in the prevention of stone recurrence. Although X-ray diffraction (XRD) and infrared spectroscopy are the recommended techniques for reliable formal stone analysis, this is not always possible, and the process takes time and is costly. ESR could be an alternative, as it would give immediate information on stone composition. Materials and Methods: Fifteen endourologists predicted stone composition based on 100 videos from ureterorenoscopy. Diagnostic accuracy was evaluated by comparing the prediction from visual assessment with stone analysis by XRD. After 30 days, the videos were reviewed again in a random order to assess intra-observer agreement. Results: The median diagnostic accuracy for calcium oxalate monohydrate was 54% in questionnaire 1 (Q1) and 59% in questionnaire 2 (Q2), whereas calcium oxalate dihydrate had a median diagnostic accuracy of 75% in Q1 and 50% in Q2. The diagnostic accuracy for calcium hydroxyphosphate was 10% in Q1 and 13% in Q2. The median diagnostic accuracy for calcium hydrogen phosphate dihydrate and calcium magnesium phosphate was 0% in both questionnaires. The median diagnostic accuracy for magnesium ammonium phosphate was 20% in Q1 and 40% in Q2. The median diagnostic accuracy for uric acid was 22% in both questionnaires. Finally, there was a diagnostic accuracy of 60% in Q1 and 80% in Q2 for cystine. The intra-observer agreement ranged between 45% and 72%. Conclusion: Diagnostic accuracy of ESR is limited and intra-observer agreement is below the threshold of acceptable agreement.

Effect of theobromine on dissolution of uric acid kidney stones.

PURPOSE: Uric acid renal lithiasis has a high prevalence and a high rate of recurrence. Removal of uric acid stones can be achieved by several surgical techniques (extracorporeal shock wave lithotripsy, endoscopy, laparoscopy, open surgery). These stones can also be eliminated by dissolution within the kidneys, because the solubility of uric acid is much greater when the pH is above 6. At present, N-acetylcysteine with a urinary basifying agent is the only treatment proposed to increase the dissolution of uric acid stones. In this paper, we compare the effect of theobromine and N-acetylcysteine on the in vitro dissolution of uric acid calculi in artificial urine at pH 6.5. METHODS: The dissolution of uric acid renal calculi was performed in a temperature-controlled (37 °C) chamber. A peristaltic pump was used to pass 750 mL of synthetic urine (pH 6.5) through a capsule every 24 h. Stone dissolution was evaluated by measuring the change in weight before and after each experiment. RESULTS: N-acetylcysteine increased the dissolution of uric acid calculi, but the effect was not statistically significant. Theobromine significantly increased the dissolution of uric acid calculi. Both substances together had the same effect as theobromine alone. The addition of theobromine to a basifying therapy that uses citrate and/or bicarbonate is a potential new strategy for the oral chemolysis of uric acid stones. CONCLUSION: Theobromine may prevent the formation of new stones and increase the dissolution of existing stones.

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Kidney stone is a disease with complex etiology and high incidence, and the most common chemical composition type of it is calcium oxalate stone. The formation of calcium oxalate stones includes crystal formation, crystal growth and aggregation, crystal interaction with renal tubular epithelial cells, and crystal invasion of renal interstitial extracellular matrix and so on. In these processes, crystal-cell interactions are essential for kidney crystal retention and kidney stone formation. Recently many studies have found that the interaction between crystal and renal tubular epithelial cells is closely related to various key binding molecules, endoplasmic reticulum stress of tubular cells, extracellular matrix proteins, and various lithotriptic drugs. Understanding the mechanism of crystal-cell interaction is of great significance for the prevention and early treatment of calcium oxalate stones.

Disrupting Crystal Growth through Molecular Recognition: Designer Therapies for Kidney Stone Prevention.

Aberrant crystallization within the human body can lead to several disease states or adverse outcomes, yet much remains to be understood about the critical stages leading to these events, which can include crystal nucleation and growth, crystal aggregation, and the adhesion of crystals to cells. Kidney stones, which are aggregates of single crystals with physiological origins, are particularly illustrative of pathological crystallization, with 10% of the U.S. population experiencing at least one stone occurrence in their lifetimes. The human record of kidney stones is more than 2000 years old, as noted by Hippocrates in his renowned oath and much later by Robert Hooke in his treatise Micrographia. William Hyde Wollaston, who was a physician, chemist, physicist, and crystallographer, was fascinated with stones, leading him to discover an unusual stone that he described in 1810 as cystic oxide, later corrected to cystine. Despite this long history, however, a fundamental understanding of the stages of stone formation and the rational design of therapies for stone prevention have remained elusive.This Account reviews discoveries and advances from our laboratories that have unraveled the complex crystal growth mechanisms of l-cystine, which forms l-cystine kidney stones in at least 20 000 individuals in the U.S. alone. Although l-cystine stones affect fewer individuals than common calcium oxalate stones, they are usually larger, recur more frequently, and are more likely to cause chronic kidney disease. Real-time in situ atomic force microscopy (AFM) reveals that the crystal growth of hexagonal l-cystine is characterized by a complex mechanism in which six interlaced anisotropic spirals grow synchronously, emanating from a single screw dislocation to generate a micromorphology with the appearance of stacked hexagonal islands. In contrast, proximal heterochiral dislocations produce features that appear to be spirals but actually are closed loops, akin to a Frank-Read source. These unusual and aesthetic growth patterns can be explained by the coincidence of the dislocation Burgers vector and the crystallographic 61 screw axis. Inhibiting l-cystine crystal growth is key to preventing stone formation. Decades of studies of "tailor-made additives", which are imposter molecules that closely resemble the solute and bind to crystal faces through molecular recognition, have demonstrated their effects on crystal properties such as morphology and polymorphism. The ability to visualize crystal growth in real time by AFM enables quantitative measurements of step velocities and, by extension, the effect of prospective inhibitors on growth rates, which can then be used to deduce inhibition mechanisms. Investigations with a wide range of prospective inhibitors revealed the importance of precise molecular recognition for binding l-cystine imposters to crystal sites, which results in step pinning and the inhibition of step advancement as well as the growth of bulk crystals. Moreover, select inhibitors of crystal growth, measured in vitro, reduce or eliminate stone formation in knockout mouse models of cystinuria, promising a new pathway to l-cystine stone prevention. These observations have wide-ranging implications for the design of therapies based on tailor-made additives for diseases associated with aberrant crystallization, from disease-related stones to "xenostones" that form in vivo because of the crystallization of low-solubility therapeutic agents such as antiretroviral agents.

On the protein content of kidney stones: an explorative study.

OBJECTIVES: Kidney stone formation is complex; urinary protein inhibitors play a major role in natural defense against stone formation. Using attenuated total-reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy of kidney stones, proteins are usually not quantified and often reported as 'organic matrix', for which there is little attention: treatment of urolithiasis is based on the nature of the major organic/inorganic stone compound. Literature no longer regards urinary proteins as innocent bystander, but highlights the role of proteins as urolithiasis modulators. We explored the potential significance of the protein content of kidney stones. METHODS: 800 stones were analyzed using ATR-FTIR spectroscopy; spectra were corrected for protein content. The ratio of the amide I peak (1655 cm-1) divided by the maximum peak was calculated. A subgroup of stones (n = 43) was weighed; protein concentration was assayed. Kidney stone composition was taken into account when calculating protein concentration. Electrophoresis was implemented to investigate the protein bands. Multiple regression analysis was carried out to study the influence of various demographic variables (age, gender, stone type) on protein concentration. RESULTS: Protein concentration showed a marked variation according to the stone composition. High relative protein content (>0.4% stone mass) was found in mixed calcium apatite/calcium oxalate dihydrate stones, mixed calcium oxalate dihydrate/calcium oxalate monohydrate/calcium apatite stones, and mixed calcium oxalate monohydrate/brushite stones, whereas lower protein percentages were found in cystine, urate, and calcium oxalate monohydrate stones. Protein concentration was dependent of the patient's age. CONCLUSION: ATR-FTIR is a practical way for assessing protein concentration in kidney stones. LIST OF ABBREVIATIONS: A: absorbance; as, asymmetric vibrations; ATR-FTIR, attenuated total-reflectance Fourier-transform infrared; ß, standardized regression coefficient; CAP, calcium apatite; COD, calcium oxalate dihydrate; COM, calcium oxalate monohydrate; CV, coefficient of variation; δ, bending vibrations; ELISA, enzyme-linked immunosorbent assay; IQR, interquartile range; IR, infrared; LOD, limit of detection; LOQ, limit of quantification; MIR, mid-infrared; N or n, amount; r, correlation; r2, coefficient of determination; s, symmetric vibrations; SD, standard deviation; SE, standard error; THP, Tamm-Horsfall protein; UA, uric acid; V, stretching vibrations; VIF: variance inflation factor; ZnSe, zinc selenide.

Association between aortic calcification and the presence of kidney stones: calcium oxalate calculi in focus.

PURPOSE: The current research is aimed at analyzing the relationship between kidney stone (KS) and abdominal aortic calcification (AAC) and the relationship between KS components and AAC. METHODS: This is a retrospective, case-control study. Kidney stone formers (KSFs) were treated at the Department of Urology, West China Hospital, Sichuan University for urological calculus disease from January 2014 to January 2020. Matched non-stone formers (non-SFs) were drawn from the same hospital for routine health examination from January 2018 to February 2019. Research-related information was collected and reviewed retrospectively from the hospital's computerized records. AAC were evaluated using available results of computed tomography imaging and abdominal vascular ultrasound. The relationships of AAC between KSFs and non-SFs were compared. The composition of renal calculi was analyzed by Fourier-transform infrared spectrophotometer. KSFs were divided into AAC groups and non-AAC based on AAC. The relationship of the composition of renal calculi between AAC and non-AAC were compared. The independent-sample t test, the chi-squared test and binary logistics regression were performed. RESULTS: Altogether, 4516 people were included, with 1027 KSFs and 3489 non-SFs. There were no significant differences in the laboratory parameters between KSFs and non-SFs. The association between the presence of AAC and KS was significant in multivariable model 2 [adjusting hypertension, diabetes mellitus, fasting blood glucose, uric acid, serum triglyceride (TG), serum calcium, and urine pH] (OR 5.756, 95% CI 4.616-7.177, p < 0.001). The result of KSFs showed that calcium oxalate calculi (CaOx) was significantly associated with AAC in multivariable model 3 (adjusting age, hypertension, diabetes mellitus, drinking history, smoking history, and TG) (OR 1.351, 95% CI 1.002-1.822, p = 0.048). CONCLUSIONS: The current study pioneered the revelation of the relationship between CaOx and AAC. Through an elimination of the confounding factors, the study demonstrated that KS and AAC were connected.

High-Throughput in vitro Gel-Based Plate Assay to Screen for Calcium Oxalate Stone Inhibitors.

OBJECTIVE: Kidney stones are a common medical condition that is increasing in prevalence worldwide. Approximately, ∼80% of urinary calculi are composed of calcium oxalate (CaOx). There is a growing interest toward identifying therapeutic compounds that can inhibit the formation of CaOx crystals. However, some chemicals (e.g., antibiotics and bacterial metabolites) may directly promote crystallization. Current knowledge is limited regarding crystal promoters and inhibitors. Thus, we have developed an in vitro gel-based diffusion model to screen for substances that directly influence CaOx crystal formation. MATERIALS AND METHODS: We used double diffusion of sodium oxalate and calcium chloride-loaded paper disks along an agar medium to facilitate the controlled formation of monohydrate and dihydrate CaOx crystals. A third disk was used for the perpendicular diffusion of a test substance to assess its influence on CaOx crystal formation. RESULTS: We confirmed that citrates and magnesium are effective inhibitors of CaOx crystals. We also demonstrated that 2 strains of uropathogenic Escherichia coli are able to promote crystal formation. While the other tested uropathogens and most antibiotics did not change crystal formation, ampicillin was able to reduce crystallization. CONCLUSION: We have developed an inexpensive and high-throughput model to evaluate substances that influence CaOx crystallization.

Prophylactic and curative potential of peppermint oil against calcium oxalate kidney stones.

Mentha piperita L., a well-known traditional herb, constitutes essential oil as one of its important constituent, used for its flavor, aroma and therapeutic applications. Based on the antioxidant, antispasmodic and nephroprotective potential, the essential oil of Mentha piperita was evaluated for its preventive and curative effects against ethylene glycol induced urolithiasis. Peppermint oil (Mp.Eo) was evaluated for its antioxidant potential by DPPH method. Urolithiasis was developed in male rats by the administration of ammonium chloride and ethylene glycol in drinking water. Different doses of Mp.Eo (10, 30 and 50 mg/kg) and cystone, the standard antiurolithic drug (500 mg/kg), were given along with stone-inducing regimen in prophylactic model and after intoxication for the next fourteen days in curative model. Urine and serum were analyzed for various biochemical parameters. One representative kidney from each group was studied for changes in histological parameters. Mp.Eo was found to be effective against urolithiasis-associated changes including crystalluria, polyuria and acidic urine. Mp.Eo also neutralized the altered levels of urinary uric acid, magnesium, total protein, serum creatinine and serum BUN. The data obtained from the present study demonstrated the therapeutic importance of peppermint oil against urolithiasis.