Antioxidant activity and Inhibitory effects of Cydonia oblonga Miller. leaves extracts against calcium oxalate stones.

Urinary stone disease is a widespread health problem in both adults and children, and its prevalence has been increasing worldwide. Various plants preparations have already been used since ancient times in order to treat urolithiasis. The aim of this study is to evaluate the antioxidant capacity and litholytic effect on kidney stones of Cydonia oblonga Miller. leaves. The infusion, methanol and acetone extracts were made from Cydonia oblonga Miller. leaf at different concentration. Estimation of mass fractions of total polyphenol, flavonoid, and flavonol contents, as well as the in vitro radical scavenging potential on 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH·) of the investigated extracts was carried out using colorimetric methods. The litholytic property of the extracts was performed by an in-vitro model using experimentally prepared kidney stones- calcium oxalate. As results, the quince leaf extracts revealed stronger antioxidant properties in the DPPH assay, which was proved by the semi-maximal inhibitory concentration values, being about 36.06 ± 3.55, 74.15 ± 6.29, and 142.35 ± 5.09 µg/ml for methanol, acetone and infusion extracts respectively. Furthermore, the tested extracts were found to be more effective in dissolving calcium oxalate stones compared to the control solutions, the mass loss is about 15.13 ± 1.10% with methanol extract, while it is 14.77 ± 1.74% and 11.14 ± 2.86% for acetone and infusion extracts respectively. These findings confirm the quince leaf's richness in phyto-components, offering anti-oxidant property and being able to be used as a remedy for the management of kidney stones by dissolving calcium oxalate stones in the kidneys.

Carboxymethylated Rhizoma alismatis polysaccharides reduces the risk of calcium oxalate stone formation by reducing cellular inflammation and oxidative stress.

This study aims to elucidate the mechanism and potential of Rhizoma alismatis polysaccharides (RAPs) in preventing oxidative damage to human renal proximal tubule epithelial cells. The experimental approach involved incubating HK-2 cells with 100 nm calcium oxalate monohydrate for 24 h to establish a cellular injury model. Protection was provided by RAPs with varying carboxyl group contents: 3.57%, 7.79%, 10.84%, and 15.33%. The safeguarding effect of RAPs was evaluated by analyzing relevant cellular biochemical indicators. Findings demonstrate that RAPs exhibit notable antioxidative properties. They effectively diminish the release of reactive oxygen species, lactate dehydrogenase, and malondialdehyde, a lipid oxidation byproduct. Moreover, RAPs enhance superoxide dismutase activity and mitochondrial membrane potential while attenuating the permeability of the mitochondrial permeability transition pore. Additionally, RAPs significantly reduce levels of inflammatory factors, including NLRP3, TNF-α, IL-6, and NO. This reduction corresponds to the inhibition of overproduced pro-inflammatory mediator nitric oxide and the caspase 3 enzyme, leading to a reduction in cellular apoptosis. RAPs also display the ability to suppress the expression of the HK-2 cell surface adhesion molecule CD44. The observed results collectively underscore the substantial anti-inflammatory and anti-apoptotic potential of all four RAPs. Moreover, their capacity to modulate the expression of cell surface adhesion molecules highlights their potential in inhibiting the formation of kidney stones. Notably, RAP3, boasting the highest carboxyl group content, emerges as the most potent agent in this regard.

The anti-urolithiasis activity and safety of strangury-relieving herbs: A comparative study based on fruit fly kidney stone model.

ETHNOPHARMACOLOGICAL RELEVANCE: Urolithiasis is one of the oldest and most widespread urological diseases suffered globally. In the long history of Traditional Chinese Medicine, there're numerous herbs documented with strangury-relieving properties playing crucial roles in treating various urological disorders, including dysuria, hematuria, and renal colic, etc., which may be caused by urolithiasis. Exploring these herbs may reveal safer, more effective, and cost-efficient drugs and therapies for urolithiasis. AIM OF THE STUDY: This study aims to assess the anti-urolithiasis efficacy and safety of 46 Chinese traditional and folk herbal drugs using the fruit fly (Drosophila melanogaster) kidney stone model, in order to identify the most valuable ethnomedicinal materials. MATERIALS AND METHODS: Water extract and 50% ethanol extract of each herb were prepared respectively. 0.2% (w/w) sodium oxalate was chosen as appropriate lithogenic agent through fruit fly life span study. Male fruit-flies within three days of emergence were aged for an additional three days, then were randomly divided into experimental groups, model group and control groups (n = 20). The flies in blank control group, model group and positive control group were fed with standard food, standard food containing 0.2% sodium oxalate, standard food containing 0.2% sodium oxalate and 3% (w/w) Garcinia cambogia extract, respectively. Meanwhile, flies in the experimental groups were raised on standard food containing 0.2% sodium oxalate and 3% (w/w) herbal extract. The anti-urolithiasis capability of the extracts was evaluated using stone area ratio (the stone area divided by the area of the Malpighian tubule) and stone-clearing rate. Additionally, the 7-day mortality rate was employed as an indicator of safety. RESULTS: Out of the 46 herbs, 24 exhibited significant anti-urolithiasis effects in their water extracts. Among them, Herba Nephrolepidis, Herba Humuli, Herba Desmodii Styracifolii, Cortex Plumeriae Rubrae, and Herba Mimosae Pudicae showed us a low 7-day mortality rate of fruit-flies as well. However, only a limited number of herbal extracts (8 out of 46) showed obvious anti-urolithiasis activity in their 50% ethanol extracts. CONCLUSION: Highly potential anti-urolithiasis candidates were discovered from strangury-relieving herbs recorded in classical Traditional Chinese Medicine works, highlighting the significant value of traditional and folk ethnopharmacological knowledge.

Tratamiento farmacológico de la litiasis renal: medicamentos actuales y monitorización del pH urinario / Pharmacologic treatment of kidney stones: Current medication and pH monitoring

La nefrolitiasis es una enfermedad urológica de prevalencia mundial asociada a una importante morbilidad y malestar para el paciente. El tratamiento actual de los cálculos renales se basa en intervenciones quirúrgicas y farmacológicas. Aunque la cirugía puede ser necesaria en casos determinados, el tratamiento farmacológico es una opción más asequible, fácilmente disponible y menos invasiva para el paciente. Se realizó una revisión exhaustiva para resumir la bibliografía disponible sobre las estrategias de manejo farmacológico de los principales tipos de litiasis: oxalato cálcico, fosfato cálcico, ácido úrico, estruvita y cistina. La regulación de factores como el pH urinario, la cristalización de los cálculos y los trastornos metabólicos del paciente que precipitan el desarrollo y el crecimiento de los cálculos es fundamental para estos enfoques terapéuticos. Esta revisión hace hincapié en las opciones farmacológicas disponibles para el tratamiento según el tipo de litiasis y destaca la importancia de un tratamiento médico personalizado para cada paciente, aspecto que debe ser tenido en cuenta por todos los médicos. (AU)

Nephrolithiasis is a globally prevalent urologic condition associated with significant morbidity and patient discomfort. Current management of kidney stones includes both surgical and pharmacologic interventions. Though surgery may be necessary under certain circumstances, pharmacologic treatment is a more affordable, readily available, and a less invasive option for patients. A comprehensive scoping review was conducted to summarize the available literature on the pharmacologic strategies for managing the predominant stone types including calcium oxalate, calcium phosphate, uric acid, struvite, and cystine stones. Central to these therapeutic approaches is the regulation of factors such as urine pH, stone crystallization, and patient metabolics that precipitate stone development and growth. This review highlights the pharmacological options available for treating each kidney stone type, emphasizing the importance of patient tailored medical management that should be considered by every physician. (AU)

Molecular mechanism of Rhizoma Polygonati in the treatment of nephrolithiasis: network pharmacology analysis and in vivo experimental verification.

Rhizoma Polygonati (RP) is the dried rhizome of the liliaceous plant. It has anti-inflammatory and anti-apoptosis effects. But its role in kidney stones has not been studied. The purpose of this study was to verify the effect of RP in the treatment of nephrolithiasis through network pharmacological analysis and in vivo experiments. The active compounds and protein targets of RP, as well as the potential targets of the nephrolithiasis were searched from the database. The protein-protein interaction (PPI) network diagram and the drug-compounds-targets-disease network were constructed. The enrichment analysis was performed by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the effect of RP on the prevention and treatment of nephrolithiasis was experimentally validated in vivo. Animal experiments showed that RP ameliorates renal function and reduced crystal deposition in a mouse model. It may act through anti-inflammation and anti-apoptosis. Our study showed that RP could prevent and treat nephrolithiasis by inhibiting apoptosis and inflammation, which provided a new efficacy and clinical application for RP.

Identification of biomarkers and potential therapeutic targets of kidney stone disease using bioinformatics.

PURPOSE: Kidney stone disease (KSD) is a common urological disease, but its pathogenesis remains unclear. In this study, we screened KSD-related hub genes using bioinformatic methods and predicted the related pathways and potential drug targets. METHODS: The GSE75542 and GSE18160 datasets in the Gene Expression Omnibus (GEO) were selected to identify common differentially expressed genes (DEGs). We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to identify enriched pathways. Finally, we constructed a hub gene-miRNA network and drug-DEG interaction network. RESULTS: In total, 44 upregulated DEGs and 1 downregulated DEG were selected from the GEO datasets. Signaling pathways, such as leukocyte migration, chemokine activity, NF-κB, TNF, and IL-17, were identified in GO and KEGG. We identified 10 hub genes using Cytohubba. In addition, 21 miRNAs were predicted to regulate 4 or more hub genes, and 10 drugs targeted 2 or more DEGs. LCN2 expression was significantly different between the GEO datasets. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses showed that seven hub gene expressions in HK-2 cells with CaOx treatment were significantly higher than those in the control group. CONCLUSION: The 10 hub genes identified, especially LCN2, may be involved in kidney stone occurrence and development, and may provide new research targets for KSD diagnosis. Furthermore, KSD-related miRNAs may be targeted for the development of novel drugs for KSD treatment.

Pharmacologic treatment of kidney stones: Current medication and pH monitoring.

Nephrolithiasis is a globally prevalent urologic condition associated with significant morbidity and patient discomfort. Current management of kidney stones includes both surgical and pharmacologic interventions. Though surgery may be necessary under certain circumstances, pharmacologic treatment is a more affordable, readily available, and a less invasive option for patients. A comprehensive scoping review was conducted to summarize the available literature on the pharmacologic strategies for managing the predominant stone types including calcium oxalate, calcium phosphate, uric acid, struvite, and cystine stones. Central to these therapeutic approaches is the regulation of factors such as urine pH, stone crystallization, and patient metabolics that precipitate stone development and growth. This review highlights the pharmacological options available for treating each kidney stone type, emphasizing the importance of patient tailored medical management that should be considered by every physician.

Tranexamic acid for percutaneous nephrolithotomy: an abridged Cochrane review.

OBJECTIVE: To assess the effects of tranexamic acid (TXA) in individuals with kidney stones undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: We performed a literature search of Cochrane Library, PubMed (including MEDLINE), Embase, Scopus, Global Index Medicus, trials registries, grey literature, and conference proceedings. We included randomised controlled trials (RCTs) that compared treatment with PCNL with administration of TXA to placebo (or no TXA) for patients aged ≥18 years. Two review authors independently classified studies and abstracted data. Primary outcomes were blood transfusion, stone-free rate (SFR), thromboembolic events (TEE). We rated the certainty of evidence (CoE) according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach using a minimally contextualised approach with pre-defined thresholds for minimally clinically important differences (MCID). RESULTS: We included 10 RCTs assessing the effect of systemic TXA in PCNL vs placebo (or no TXA). Eight studies were published as full text. Based on an adjusted baseline risk of blood transfusion of 5.7%, systemic TXA may reduce blood transfusions (risk ratio [RR] 0.45, 95% confidence interval [CI] 0.27-0.76). Based on an adjusted baseline SFR of 75.7%, systemic TXA may increase SFR (RR 1.11, 95% CI 0.98-1.27). There is probably no difference in TEEs (risk difference 0.001, 95% CI -0.01 to 0.01). Systemic TXA may increase adverse events (AEs) (RR 5.22, 95% CI 0.52-52.72). Systemic TXA may have little to no effect on secondary interventions (RR 1.15, 95% CI 0.84-1.57). The CoE for most outcomes was assessed as low or very low. CONCLUSIONS: Based on a body of evidence of 10 RCTs, we found that systemic TXA in PCNL may reduce blood transfusions, major surgical complications, and hospital length of stay, as well as improve the SFR; however, it may increase AEs. These findings should inform urologists and their patients in making informed decisions about the use of TXA in the setting of PCNL.

Nonopioid Pain Management Pathways for Stone Disease.

Introduction: New opioid dependency after urologic surgery is a serious adverse outcome that is well-described in the literature. Patients with stone disease often require multiple procedures because of recurrence of disease and hence are at greater risk for repeat opioid exposures. Despite this, opioid prescribing after urologic surgery remains highly variable and in an emergency setting, opioids are still used commonly in management of acute renal colic. Methods: Two literature searches were performed using PubMed. First, we searched available literature concerning opioid-sparing pathways in acute renal colic. Second, we searched available literature for opioid-sparing pathways in ureteroscopy and percutaneous nephrolithotomy (PCNL). Abstracts were reviewed for inclusion in our narrative review. Results: In the setting of acute renal colic, multiple randomized control trials have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) attain greater reduction in pain scores, decreased need for rescue medications, and decreased vomiting events in comparison with opioids. NSAIDs also form a core component in management of postureteroscopy pain and have been demonstrated in randomized trials to have equivalent to improved pain control outcomes compared with opioids. Multiple opioid-free pathways have been described for postureteroscopy analgesia with need for rescue narcotics falling under 20% in most studies, including in patients with ureteral stents. Enhanced Recovery After Surgery protocols after percutaneous nephrolithotomy are less well described but have yielded a reduction in postoperative opioid requirements. Conclusions: In select patients, both acute renal colic and after kidney stone surgery, adequate pain management can usually be obtained with minimal or no opioid medication. NSAIDs form the core of most described opioid-sparing pathways for both ureteroscopy and PCNL, with the contribution of other components to postoperative pain outcomes limited because of lack of head-to-head comparisons. However, medications aimed specifically at targeting stent-related discomfort form a key component of most multimodal postsurgical pain management pathways. Further investigation is needed to develop pathways in patients unable to tolerate NSAIDs.

Is it Safe to Continue Aspirin in Patients Undergoing Percutaneous Nephrolithotomy?

OBJECTIVE: To evaluate peri-operative outcomes in patients on chronic aspirin therapy undergoing percutaneous nephrolithotomy (PCNL), with and without discontinuation of aspirin. Anti-coagulation and anti-platelet therapy are contraindications for PCNL per American Urological Association guidelines due to bleeding risk. However, there is potentially increased cardiovascular risk with peri-procedural aspirin withdrawal. METHODS: Patients on chronic aspirin undergoing PCNL between January 2014 and May 2019 were retrospectively reviewed and stratified by continued or discontinued aspirin >5 days preoperatively. Hematologic complications, transfusions, and thrombotic complications were assessed with logistic regression model. RESULTS: Three hundred twenty-five patients on chronic aspirin therapy underwent PCNL-85 continued and 240 discontinued aspirin. There were no significant differences in hemoglobin change, estimated blood loss, transfusions, creatinine change, thrombotic complications, 30-days re-admissions, complications, or 30-day emergency department visits. Patients who continued aspirin had longer length of stay (1.6 vs 1.9 days, P = .03). American Society of Anesthesiologists (ASA) score of 3 (OR 3.2, P = .02, 95% confidence intervals (CI) [1.2-8.4]), ASA score of 4 (OR 4.0, P = .02, 95% CI [1.2-13.1]), Black race, and previous smoking (OR 2.1, P = .02, 95% CI [1.1-3.9]) was associated with continued aspirin. Body mass index ≥30 was associated with aspirin discontinuation (OR 0.9, P = .004, 95% CI [0.9-1.0]). Increased postoperative hematologic complications were associated with additional anticoagulation medication (OR 2.9, P = .04, 95% CI [1.0-4.4]). CONCLUSION: Continued aspirin use did not increase in postoperative complications in patients undergoing PCNL. Patients who are on additional anticoagulation medication are at risk of hematologic complications.

Lipidomics based on liquid chromatography-high resolution mass spectrometry reveals the protective role of peroxisome proliferator-activated receptor alpha on kidney stone formation in mice treated with glyoxylate.

Few studies have examined the relationship between lipid metabolism and kidney stone formation, particularly the role of key lipid regulatory factors in kidney stone formation. We evaluated the effect of the lipid regulatory factor-peroxisome proliferator-activated receptor alpha on the formation of renal stones in mice by injecting them with glyoxylate followed by treatment with either a peroxisome proliferator-activated receptor alpha agonist fenofibrate or an antagonist GW6471 (GW). Liquid chromatography coupled with trapped ion mobility spectrometry-quadrupole-time-of-flight mass spectrometry-based lipidomics was used to determine the lipid profile in the mouse kidneys. Histological and biochemical analyses showed that the mice injected with glyoxylate exhibited crystal precipitation and renal dysfunction. Crystallization decreased significantly in the fenofibrate group, whereas it increased significantly in the GW group. A total of 184 lipids, including fatty acyls, glycerolipids, glycerophospholipids, and sphingolipids differed significantly between the mice in the model and control groups. Peroxisome proliferator-activated receptor alpha activity negatively correlated with glyoxylate-induced kidney stone formation in mice, which may be related to improved fatty acid oxidation, maintenance of ceramide/complex sphingolipids cycle balance, and alleviation of disorder in phospholipid metabolism.

Synergistic effect of doxycycline and aqueous extract of irradiated khella on structure of nanobacteria isolated from kidney stones: In vitro and in vivo studies.

Kidney stones have been associated with an increased risk of chronic kidney diseases, end-stage renal failure. This study is devoted to isolate nanobacteria from patients with active urolithiasis and investigate the in vitro and in vivo antinanobacterial activity of some antibiotics alone or in combination with extracts of irradiated herbs from certain medicinal plants. Nanobacteria were detected using scanning (SEM) and transmission (TEM) electron microscopy, protein electrophoresis (SDS-PAGE) and DNA profile. The antimicrobial susceptibility of some biofilm-producing nanobacterial isolates was evaluated. The effect of medicinal plant extracts on growth was tested. A combination treatment between the most potent extracts and antibiotics was tested on biofilm production, protein profile, release of 260 nm absorbing material, protein content, and ultrastructure of the strongest biofilm producers. In vivo study of nanobacteria and its treatment by the most potent agents was evaluated on male rats. Renal function was measured in serum; histological examination and oxidative stress parameters were determined in kidney tissues. Results showed that streptomycin, trimethoprim/sulfamethoxazole, doxycycline, and water extracts of irradiated khella at 6 kGy had antinanobacterial activity. Meanwhile, the synergistic effect of the aqueous extract of irradiated Khella and doxycycline showed higher inhibition activity on microbial growth and biofilm production. They affected dramatically the strength of its cell membrane and subsequently its ultrastructure. Moreover, these results are confirmed by ameliorations in renal function and histological alterations. It could be concluded that the combination of DO and an aqueous extract of irradiated khella has an antinephrotoxic effect against nanobacteria-induced renal toxicity.

Association of low-dose aspirin use for primary prevention with self-reported kidney stones prevalence: a cross-sectional study.

OBJECTIVE: To investigate the association between low-dose aspirin use for primary prevention and self-reported kidney stones prevalence in the 40-79 years old population. METHODS: We conducted a cross-sectional study based on the United States population data from the National Health and Nutrition Examination Survey 2011-2018. Baseline demographical and clinical data were collected. The univariate and multivariate regression was performed to identify confounding factors and assess the relationship between aspirin use for primary prevention and the prevalence of self-reported kidney stones. A propensity-score matching was used to identify patients with similar baseline characteristics to adjust for the bias caused by confounding factors. RESULTS: A total of 10,256 low-dose aspirin-use participants were included in this study. 10.4% of participants reported a history of kidney stones, and 18.5% reported a continuous use of low-dose prophylactic aspirin. Multivariate logistic regression analysis showed that low-dose preventive aspirin use had significantly increased the odds of self-reported kidney stones (OR = 1.245; 95% CI: 1.063-1.459; p = 0.007). In subgroup analysis, this finding was primarily limited to males (OR = 1.311), non-hypertensive participants (OR = 1.443), diabetic participants (OR = 1.380), and older (60 ≤ Age < 80) (OR = 1.349). The propensity-score matched analyses supported this result after adjusting for the bias caused by potential confounders (OR = 1.216; 95% CI: 1.011-1.462; p = 0.038). CONCLUSION: In this study, there exists a significant relationship between low-dose aspirin for primary prevention and self-reported kidney stones, primarily among males, no hypertensive participants, diabetics, or older adults. Further studies are needed to elucidate the mechanisms underlying these findings in the future.

The effectiveness of citrates and pyridoxine in the treatment of kidney stones.

The prevalence of nephrolithiasis is increasing across all demographic groups. Apart from the morbidity associated with an acute occurrence, preventative treatment is essential for stone disease, which can become a long-term problem. Simple interventions like fluid intake optimization and dietary modification are effective for most stone types. However, patients with specific metabolic abnormalities may require pharmaceutical therapy if lifestyle changes are insufficient to reduce the risk of stone recurrence. The treatment of citrates and/or pyridoxines may help eliminate or prevent recurrences of kidney stones, especially when they are composed of uric acid, calcium oxalate, calcium phosphate, or the latter two together. In cases of struvite stones, which often necessitate a surgical approach, acetohydroxamic acid emerges as a valuable second-line treatment option. Thiol-binding agents may be needed for cystinuria, as well as lifestyle modifications. Successful treatment reduces stone recurrence and the need to remove stones surgically.

PPARG: A Novel Target for Yellow Tea in Kidney Stone Prevention.

Kidney stones are a common urological disorder with increasing prevalence worldwide. The treatment of kidney stones mainly relies on surgical procedures or extracorporeal shock wave lithotripsy, which can effectively remove the stones but also result in some complications and recurrence. Therefore, finding a drug or natural compound that can prevent and treat kidney stones is an important research topic. In this study, we aimed to investigate the effects of yellow tea on kidney stone formation and its mechanisms of action. We induced kidney stones in rats by feeding them an ethylene glycol diet and found that yellow tea infusion reduced crystal deposits, inflammation, oxidative stress, and fibrosis in a dose-dependent manner. Through network pharmacology and quantitative structure-activity relationship modeling, we analyzed the interaction network between the compounds in yellow tea and kidney stone-related targets and verified it through in vitro and in vivo experiments. Our results showed that flavonoids in yellow tea could bind directly or indirectly to peroxisome proliferator-activated receptor gamma (PPARG) protein and affect kidney stone formation by regulating PPARG transcription factor activity. In conclusion, yellow tea may act as a potential PPARG agonist for the prevention and treatment of renal oxidative damage and fibrosis caused by kidney stones.

Elucidating shared biomarkers and pathways in kidney stones and diabetes: insights into novel therapeutic targets and the role of resveratrol.

BACKGROUND: The pathogenic mechanisms shared between kidney stones and diabetes at the transcriptional level remain elusive, and the molecular mechanisms by which resveratrol exerts its protective effects against these conditions require further investigation. METHODS: To address these gaps in knowledge, we conducted a comprehensive analysis of microarray and RNA-seq datasets to elucidate shared biomarkers and biological pathways involved in the pathogenesis of kidney stones and diabetes. An assortment of bioinformatic approaches was employed to illuminate the common molecular markers and associated pathways, thereby contributing to the identification of innovative therapeutic targets. Further investigation into the molecular mechanisms of resveratrol in preventing these conditions was conducted using molecular docking simulation and first-principles calculations. RESULTS: The study identified 11 potential target genes associated with kidney stones and diabetes through the intersection of genes from weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) screening. Among these, Interleukin 11 (IL11) emerged as a pivotal hub gene and a potential diagnostic biomarker for both conditions, particularly in males. Expression analysis of IL11 demonstrated elevated levels in kidney stones and diabetes groups compared to controls. Additionally, IL11 exhibited correlations with specific cell types and differential expression in normal and pathological conditions. Gene set enrichment analysis (GSEA) highlighted significant disparities in biological processes, pathways, and immune signatures associated with IL11. Moreover, molecular docking simulation of resveratrol towards IL11 and a first-principles investigation of Ca adsorption on the resveratrol surface provided structural evidence for the development of resveratrol-based drugs for these conditions. CONCLUSIONS: Overall, this investigation illuminates the discovery of common molecular mechanisms underlying kidney stones and diabetes, unveils potential diagnostic biomarkers, and elucidates the significance of IL11 in these conditions. It also provides insights into IL11 as a promising therapeutic target and highlights the role of resveratrol. Nonetheless, further research is warranted to enhance our understanding of IL11 targeting mechanisms and address any limitations in the study.

Effect of two vitamin D repletion protocols on 24-h urine calcium in patients with recurrent calcium kidney stones and vitamin D deficiency: a randomized clinical trial.

OBJECTIVES: To evaluate the effects of two vitamin D repletion therapies (cholecalciferol) on serum levels of 25-hydroxyvitamin D (25(OH)D) and 24-h urine calcium in patients with recurrent calcium kidney stones and vitamin D deficiency (VDD). DESIGN, SETTING, PARTICIPANTS: A parallel-group randomized controlled clinical trial on patients who referred to Labbafinejad kidney stone prevention clinic, Tehran, Iran. From 88 recurrent calcium stone formers, 62 patients completed the study. The age of participants was 18-70 years who had serum 25(OH)D levels of 10-20 ng/ml. INTERVENTION: Participants received oral cholecalciferol 2000 IU daily for 12 weeks or 50,000 IU weekly for 8 weeks. MAIN OUTCOME MEASURES: Study variables including 24-h urine calcium, supersaturations of calcium oxalate and calcium phosphate, serum 25(OH)D and parathyroid hormone were measured at the beginning of the study and after 12 weeks. RESULTS: The 24-h urine calcium significantly increased in both groups (ß = 69.70, p < 0.001), with no significant difference between treatments. Both groups showed no significant change in the supersaturation levels of calcium oxalate and calcium phosphate. Serum levels of 25(OH)D increased significantly (ß = 12.53, p < 0.001), with more increase in the 50,000 IU group (ß = 3.46, p = 0.003). Serum parathyroid hormone decreased in both groups (p < 0.001). CONCLUSIONS: Although both treatment protocols increased 24-h urine calcium, they did not increase the supersaturation state of calcium oxalate or calcium phosphate. Trial registration IRCT20160206026406N4, 13/08/2019.

Sanjin Paishi Decoction improves the imbalance of gut microbiota and regulates MAPK signaling pathway to inhibit calcium oxalate stones in rats.

INTRODUCTION: Sanjin Paishi Decoction (SJPSD) has positive effects on stone prevention; however, there is a lack of convincing evidence in the prevention of calcium oxalate stones. This study aimed investigates the effect of SJPSD on calcium oxalate stones and to explore its mechanism. METHODS: The rat model of calcium oxalate stones was established and rats were treated with different doses of SJPSD. The pathological damage of kidney tissues was observed by HE staining, the deposition of calcium oxalate crystals in kidney tissues was examined by Von Kossa staining, and the levels of creatinine (CREA), urea (UREA), calcium (Ca), phosphorus (P), and magnesium (Mg) in serum were analyzed biochemically, the levels of IL-1ß, IL-6, and TNF-α in serum were measured by ELISA, and the protein expression of Raf1, MEK1, p-MEK1, ERK1/2, p-ERK1/2, and Cleaved caspase-3 in kidney tissues was analyzed by Western blot. Moreover, the changes in gut microbiota were analyzed by 16S rRNA sequencing. RESULTS: SJPSD attenuated the pathological damage of renal tissues, reduced the levels of CREA, UREA, Ca, P, and Mg, and inhibited the expression of Raf1, p-MEK1, p-ERK1/2, and Cleaved caspase-3 in renal tissues (P < 0.05). SJPSD treatment affected the composition of intestinal microbiota in rats with calcium oxalate stones. CONCLUSION: The mechanism of SJPSD inhibition of calcium oxalate stone injury in rats may be related to the inhibition of the MAPK signaling pathway and regulation of gut microbiota imbalance.