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Background: Calcium oxalate (CaOx) kidney stones are the most common type of stones in the urinary system, and their formation involves a complex mechanism with multiple contributing factors. In recent years, with the development of bioinformatics, there has been a deeper understanding of the pathogenesis of this type of disease. This study aimed to analyze the gene expression profiles of idiopathic kidney stones composed of CaOx using bioinformatics methods. By investigating the pathogenesis at the molecular level and identifying potential therapeutic targets, the study also integrated clinical data to validate the clinical relevance of the target genes. Methods: Gene expression profiles from the GSE73680 dataset were analyzed via the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) between Randall's plaques (RPs) from kidney papillae associated with CaOx stones and normal kidney papillae tissues. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was employed to construct transcription factor (TF)-DEG-microRNA (miRNA) networks, and key genes were screened using the Molecular Complex Detection (MCODE) plugin. A gene set enrichment analysis (GSEA) was performed to investigate the possible underlying mechanisms of the key genes. The clinical data of idiopathic CaOx kidney stone patients who received treatment at the General Hospital of Northern Theater Command from January 2020 to December 2022 were retrospectively analyzed. Enzyme-linked immunosorbent assay (ELISA) kits were used to measure the transcriptional activity of the key genes in calcified kidney papillae tissues. Univariate and multivariate logistic regression analyses were employed to analyze the transcriptional activity of the key genes and their association with idiopathic kidney stones composed of CaOx. Results: In the GSE73680 dataset, 276 upregulated and 538 downregulated DEGs were identified. Protein-protein interaction network construction revealed one significant module and three candidate genes [interleukin 11 (IL-11), interleukin 16 (IL-16), and interleukin 32 (IL-32)]. The TF-DEG-miRNA network indicated that IL-11 might be regulated by 25 TFs and interact with six miRNAs. The GSEA suggested that IL-11 could influence the development of idiopathic CaOx stones through chemokine expression and via the signaling pathways of the nucleotide-binding oligomerization domain-like receptors [NOD-like receptors (NLRs)] and toll-like receptors (TLRs). The clinical data analysis revealed that the IL-11 serum levels were significantly elevated in the patients with idiopathic kidney stones composed of CaOx compared to the control subjects (P<0.001). Additionally, IL-11 was identified as an independent risk factor for the development of idiopathic CaOx kidney stones (P<0.001). Conclusions: The bioinformatically identified key genes and signaling pathways provide a deeper understanding of the potential mechanisms underlying idiopathic CaOx kidney stones. Preliminary clinical trials suggest that elevated serum IL-11 levels in idiopathic CaOx kidney stone patients could serve as a possible diagnostic biomarker and treatment target.

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Background and Objective: Percutaneous Nephrolithotomy (PCNL) is recommended for large Kidney Stones. It is mostly done in prone position. However, PCNL in Supine position is another safe option. Only few centers in country are doing it and so it is challenging task to adopt supine PCNL approach in an institution initially. In this study our purpose was to assess initial experience of Supine PCNL in our center. Methods: It is a preliminary retrospective study of our first fifty-one supine PCNL procedures, performed by a single Surgeon, over Twelve months period, from April 2021 to April 2022. We managed a retrospective review of patients' records. Analysis was completed by utilizing SPSS version 20. Implementation of Mean along with standard deviation values was utilized for continuous variables. While frequency/percentages represented categorical factors. Results: Patients mean age was 39 years, comprising of 62.74% male and 37.25% female patients. Thirty patients had their stones treated on the left side. Mean Stone burden was 3.2 cm. Most of the stones were GUYs score one and two (complexity wise). The mean procedure time 147minutes. Mean hospital stay of 2.17 days was observed in this study. Forty patients were stone free. Only seven patients (14%) had level I-II complications (Clavien-Dindo classification). Conclusion: Supine PCNL can be adopted safely in an institute if careful selection of patients is done before surgery. In our center it had acceptable success rates and few complications.

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BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) is associated with increased risk of calcium-oxalate kidney stones, likely due to enteric hyperoxaluria. However, the risk of kidney stones for patients with CP after total pancreatectomy with islet autotransplantation (TPIAT) is unknown. We aimed to evaluate kidney stone risk in patients with CP after TPIAT. METHODS: A retrospective analysis of 629 patients who underwent TPIAT was conducted to identify patients who developed kidney stones post-TPIAT. Kaplan-Meier analysis estimated time to first event. An Anderson-Gill proportional-hazards analysis of all kidney stone events described key clinical associations. RESULTS: Mean age at TPIAT was 33 years (SD 15.3, range 3-69); 69.8 % (n = 439) were female. The estimated chance of any kidney stone episodes by 5 years post-TPIAT was 12.8 % (95 % CI: 8.8-16.6 %); by 10 years, 23.2 % (CI: 17.5-28.6 %); by 15 years, 29.4 % (CI: 21.8-36.2 %). Significant associations with kidney stones post-TPIAT included older age (HR 1.25 per 10 years), smoking history (HR 1.72), mild chronic kidney disease (HR 1.96), renal cysts (HR 3.67), pre-TPIAT kidney stones (HR 4.06), family history of kidney stones (HR 4.10), and Roux-en-Y reconstruction (HR 2.68). Of the 77 patients who developed kidney stones, 34 (44.1 %) had recurrent episodes. Of 143 total kidney stone events, 35 (24.5 %) required stone removal, 79 (55.2 %) resolved spontaneously, and 29 (20.3 %) were missing this data. CONCLUSIONS: Patients with CP post-TPIAT commonly have kidney stones: nearly 3 in 10 have ≥1 kidney stone episodes within 15 years. Clinicians should be aware of this risk and counsel patients on prevention.

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The interplay between crystals and epithelial cells forms the cornerstone of kidney stone development, communication between epithelial cells and macrophages emerging as a pivotal role in this process. We conducted next-generation sequencing on the secreted exosomes of TCMK-1 cells treated with calcium oxalate monohydrate (OX_EXO) or controls (NC_EXO), and on the macrophage cell line RAW264.7 stimulated with OX_EXO or NC_EXO, followed by validation of differentially expressed target proteins and miRNAs through Western blot and PCR. UPSET plots were employed to identify genes co-targeted by exosomal miRNAs. Various bioinformatic analyses were employed to predict potential mechanisms of the dysregulated genes. We integrated sequencing data from the GEO database, and validated findings using clinical patient urine and kidney tissues. We identified 665 differentially expressed exosomal miRNAs between OX_EXO and NC_EXO. Among the top 10 down-regulated miRNAs, the most targeted genes were AAK1 and NUFIP2, whereas PLCB1 was significantly targeted among the top 10 up-regulated miRNAs. In clinical specimens, we confirmed the differential expressions of five homologous miRNAs, as well as CNOT3, CNCNA1C, APEX1, and TMEM199. In conclusion, treatment of TCMK-1 cells with calcium oxalate significantly alerted the expression profile of exosomal miRNAs, subsequently influencing gene expression in macrophages, thereby modulating the processes of kidney stone formation.

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Calcium oxalate (CaOx) kidney stones are common and recurrent, lacking pharmacological prevention. Randall's plaques (RPs), calcium deposits in renal papillae, serve as niduses for some CaOx stones. This study explores the role of osteogenic-like cells in RP formation resembling ossification. CaP crystals deposit around renal tubules, interstitium, and blood vessels in RP tissues. Human renal interstitial fibroblasts (hRIFs) exhibit the highest osteogenic-like differentiation potential compared to chloride voltage-gated channel Ka positive tubular epithelial cells, aquaporin 2 positive collecting duct cells, and vascular endothelial cells, echoing the upregulated osteogenic markers primarily in hRIFs within RP tissues. Utilizing RNA-seq, osteomodulin (OMD) is found to be upregulated in hRIFs within RP tissues and hRIFs following osteogenic induction. Furthermore, OMD colocalizes with CaP crystals and calcium vesicles within RP tissues. OMD can enhance osteogenic-like differentiation of hRIFs in vitro and in vivo. Additionally, crystal deposits are attenuated in mice with Omd deletion in renal interstitial fibroblasts following CaOx nephrocalcinosis induction. Mechanically, a positive feedback loop of OMD/BMP2/BMPR1A/RUNX2/OMD drives hRIFs to adopt osteogenic-like fates, by which OMD induces osteogenic-like microenvironment of renal interstitium to participate in RP formation. We identify OMD upregulation as a pathological feature of RP, paving the way for preventing CaOx stones.

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Kidney stones, a prevalent urological disorder, are closely associated with oxidative stress (OS) and the inflammatory response. Recent research in the field of kidney stone treatment has indicated the potential of natural active ingredients to modulate OS targets and the inflammatory response in kidney stones. Oxidative stress can occur through various pathways, increasing the risk of stone formation, while the inflammatory response generated during kidney stone formation further exacerbates OS, forming a detrimental cycle. Both antioxidant systems related to OS and inflammatory mediators associated with inflammation play roles in the pathogenesis of kidney stones. Natural active ingredients, abundant in resources and possessing antioxidative and anti-inflammatory properties, have the ability to decrease the risk of stone formation and improve prognosis by reducing OS and suppressing pro-inflammatory cytokine expression or pathways. Currently, numerous developed natural active ingredients have been clinically applied and demonstrated satisfactory therapeutic efficacy. This review aims to provide novel insights into OS and inflammation targets in kidney stones as well as summarize research progress on potential therapeutic strategies involving natural active ingredients. Future studies should delve deeper into exploring efficacy and mechanisms of action of diverse natural active ingredients, proposing innovative treatment strategies for kidney stones, and continuously uncovering their potential applications.

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OBJECTIVE: Renal calculi are solid crystals that form in the kidneys and cause severe pain and discomfort. This study aims to investigate risk factors for postoperative recurrence of renal calculi in elderly patients and provide background knowledge on the prevalence and management of renal calculi in this demographic. METHODS: The clinical data of 123 elderly patients with renal calculi were included from 1 June 2021 to 1 June 2023 for their 6-month follow-up study. The patients were divided into recurrence group and non-recurrence group according to whether they had recurrence after surgery. The general sociological characteristics and disease-related characteristics of the two groups were counted. Logistic regression equation was used to calculate differences, and the influencing factors of postoperative recurrence in elderly patients with kidney stones were obtained. A receiver operating characteristic (ROC) curve was drawn to analyse the value of the factors in predicting postoperative recurrence in patients with kidney stones. RESULTS: A total of 123 elderly patients with renal calculi were enrolled. The patients were divided according to the presence or absence of stone recurrence into the recurrence group (25 cases, 20.33%) and the non-recurrence group (98 cases, 79.67%). Postoperative water intake, excessive intake of animal protein, exercise and postoperative complications significantly differed between the recurrence group and the non-recurrence group (p < 0.001). Logistic regression analysis showed that the above-mentioned indicators were the influencing factors of postoperative recurrence. The area under the curve (AUC) values of postoperative water intake (AUC = 0.767), animal protein intake (AUC = 0.752), exercise (AUC = 0.707) and postoperative complications (AUC = 0.727) were statistically significant, and they were identified as the most important factors with high sensitivity and specificity and were of high value in predicting postoperative recurrence of renal calculi. CONCLUSIONS: Elderly patients with kidney stones are prone to recurrence after surgery. Influencing factors should be given attention, and corresponding measures should be formulated for intervention as soon as possible.

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BACKGROUND/OBJECTIVES: Studies on the impact of dietary fiber intake on kidney stones are few, and their results were controversial. This study aimed to explore the association between dietary fiber intake and kidney stones in the nationally representative population of the USA. SUBJECTS/METHODS: This cross-sectional research included 8,588 participants from the National Health and Nutrition Examination Survey, 2011 to 2018. Information regarding dietary fiber intake was obtained from a 24-h recall survey. Participants were categorized into different dietary fiber intake tertiles according to the average of 2 days of dietary recall data. The outcome was self-reported kidney stones. After adjusting for the traditional risk factors, a multivariate logistic regression model was used to examine the association between dietary fiber intake and kidney stones. RESULTS: Eight hundred seventy-two participants had kidney stones. The weighted prevalence (SE) of kidney stones in the lowest tertile, medium tertile, and highest tertile of dietary fiber intake was 11.8% (0.8%), 10.3% (0.8%), and 9.1% (0.8%), respectively. After adjusting for age, sex, race and ethnicity, education level, smoking status, alcohol consumption, physical activity, body mass index, hypertension, diabetes, dyslipidemia, daily water intake, chronic kidney disease stage 3-5, and total energy intake, participants with the highest tertile of fiber intake had a significantly lower risk of kidney stones (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.48-0.95) compared to those in the lowest tertile. Every 5 g/day increment in dietary fiber intake was associated with a significant decrease in risk of kidney stones (OR, 0.90; 95% CI, 0.83-0.98). CONCLUSION: An increase in dietary fiber intake was associated with a lower risk of kidney stones, suggesting adults should be encouraged to maintain an adequate dietary fiber intake to prevent the development of kidney stones. Our results provide evidence to formulate nutrition management strategies for the prevention of kidney stones.

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Robotic pyelolithotomy continues to gain attention as an alternative to percutaneous nephrolithotomy (PCNL) for managing complex renal stones. We performed a single-arm meta-analysis and systematically searched the English-language literature published in PubMed, Web of Science, Scopus, and Google Scholar databases up to June 2024. The risk of non-randomized bias was assessed using ROBINS-I, and the quality of the literature was assessed using MINORS (Methodological Index for Non-Randomized Studies). Merger parameters were calculated using Stata16/SE under a random-effects model. Five non-comparative single-arm studies were included in the meta-analysis. Results showed that the operative time for robotic pyelolithotomy was 168.10 min (95% CI 133.63, 202.56). The hospital stay was 2.63 days (95% CI 0.96, 4.29), and blood loss was 44.13 ml (95% CI 19.76, 68.51). The stone clearance rate was 87% (95% CI 79-93%). The incidence of minor postoperative complications (Clavien grade I-II) was 23.7% (95% CI 13.4-35.8%), and the incidence of major complications (Clavien grade ≥ III) was 7% (95% CI 0.3-20.7%).The safety and efficacy of robotic pyelolithotomy in treating complex renal stones are acceptable, but future large prospective cohort studies are needed to validate the treatment.

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There remains a lack of effective drugs to alleviate the kidney stones caused by oxidative stress and inflammatory damage. The MOF-818 nanozyme is utilized to lessen the generation of reactive oxygen species (ROS) effectively, restore the membrane potential of mitochondria, regulate the cell cycle, decrease cell death, hinder the recruitment of macrophages, and mitigate the release of inflammatory factors in macrophages. These effects are attributed to the nanozyme's ability to mimic the enzyme properties of catalase (CAT) and superoxide dismutase (SOD). It is demonstrated that this nanozyme can reduce kidney calcium oxalate crystal deposition by reducing the renal injury caused by high concentration oxalate, upregulate the expression levels of SOD and CAT in tissues, downregulate adhesion proteins and inflammatory factor IL-6 and TNF-α, and promote the polarization of macrophages from M1 to M2 phenotype in the rat model induced by ethylene glycol. Overall, MOF-818 has the potential to effectively suppress oxidative stress and inflammatory harm caused by high levels of oxalate, hence lowering the likelihood of stone formation. MOF-818 nanozyme is also expected to be used as an alternative drug for the treatment of calcium oxalate kidney stones and provide an experimental theoretical basis for the development of new nanomedicines.

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SCOPE: This study aims to assess the association between intake of different types of fruit (citrus, pomes, tropical fruits, berries, gourds, drupes, dried fruits, and other fruits), the intake diversity of fruit types, and risk of new-onset kidney stones in general population. METHODS AND RESULTS: A total of 205 896 participants with at least one completed 24-h dietary recall from the UK Biobank are included. During a median follow-up of 11.6 years, 2074 cases of kidney stones are documented. Compared with nonconsumers, participants with higher intake of citrus (50-<100 g day-1; hazards ratio [HR] = 0.78; 95% confidence interval [CI], 0.66-0.91; ≥100 g day-1; HR = 0.75; 95%CI, 0.63-0.89), pomes (≥100 g day-1; HR = 0.86; 95%CI, 0.77-0.96), or tropical fruits (50-<100 g day-1; HR = 0.86; 95%CI, 0.75-0.99; ≥100 g day-1; HR = 0.88; 95%CI, 0.79-0.99) have a lower risk of new-onset kidney stones. However, there is no significant association of intake of berries, gourds, drupes, dried fruits, and other fruits with kidney stones. A higher fruit variety score is significantly associated with a lower risk of new-onset kidney stones (per 1-score increment, HR = 0.86; 95%CI, 0.81-0.91). CONCLUSIONS: Higher intake of citruses (≥50 g day-1), pomes (≥100 g day-1), and tropical fruits (≥50 g day-1), as well as increasing diversity of intake of these three fruits, are associated with a lower risk of new-onset kidney stones.

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Randall's plaques (RP) serve as anchoring sites for calcium oxalate (CaOx) stones, but the underlying mechanism remains unclear. Renal interstitium with a high-calcium environment is identified as pathogenesis of RP formation where the role of human renal interstitial fibroblasts (hRIFs) was highlighted. Our study aims to elucidate the potential mechanism by which a high-calcium environment drives ectopic calcification of hRIFs to participate in RP formation. Alizarin Red staining demonstrated calcium nodules in hRIFs treated with high-calcium medium. Utilizing transcriptome sequencing, tissue factor pathway inhibitor-2 (TFPI-2) was found to be upregulated in high-calcium-induced hRIFs and RP tissues, and TFPI-2 promoted high-calcium-induced calcification of hRIFs. Subsequently, the downstream regulator of TFPI2 was screened by transcriptome sequencing analysis of hRIFs with TFPI-2 knockdown or overexpressed. Dachsous Cadherin Related 1 (DCHS1) knockdown was identified to suppress the calcification of hRIFs enhanced by TFPI-2. Further investigation revealed that TFPI-2/DCHS1 axis promoted high-calcium-induced calcification of hRIFs via disturbing the balance of ENPP1/ALP activities, but without effect on the canonical osteogenic markers, such as osteopontin (OPN), osteogenic factors runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2). In summary, our study mimicked the high-calcium environment observed in CaOx stone patients with hypercalciuria, and discovered that the high-calcium drove ectopic calcification of hRIFs via a novel TFPI-2-DCHS1-ALP/ENPP1 pathway rather than adaption of osteogenic phenotypes to participate in RP formation.

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Introduction: Endoscopic combined intrarenal surgery (ECIRS) is a combination of both retrograde and antegrade approaches for treatment of large or complex renal stones in one procedure, that are currently being treated with multiple tracts or sessions of percutaneous nephrolithotomy, increasing the complications. The aim of our study is to describe the clinical outcomes of Mini-ECIRS in a pediatric population. Material and Methods: A retrospective study was performed in pediatric patients with lithiasis disease treated with mini-ECIRS between 2006 and 2023 in 2 referral centers in Europe. Demographic data, clinical data, stone size and location, laser settings, intraoperative variables, stone-free rate (SFR) and complications were collected. Pearson's chi-squared test, Fishers test and logistic regression, were performed. Results: A total of 32 mini-ECIRS were included. The mean age was 9,8 years, 56.3% girls. The mean size and volume of the stone were 21.5mm and 3298, 2mm3, 53.1% were multiple. Ureteral access sheath was used in 93.8% of the surgeries and only 37.5% had preoperative JJ stent. 53.1% of percutaneous access were with 14 Fr sheath. High power laser was the most frequent energy source for lithotripsy, including thulium fiber laser. The mean operative time was 166,6 minutes. There was one perforation of the collecting system that was managed with JJ stent and in the postoperative period 81.2% of the patients had no complications. Three presented fever, 1 developed urinary sepsis, and 1 required reintervention. The SFR was 75% and the size, volume, hardness, and complexity of the lithiasis, as well as the non-use of lithotripsy in the retrograde approach were statistically significant in decreasing the success of the surgery. Conclusions: ECIRS is a feasible, safe, and efficient procedure in children with complex renal lithiasis, decreasing the number of procedures needed for stone free. Multicenter studies are required to validate these results on a population scale.

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The critical role of the human gut microbiota in kidney stone formation remains largely unknown, due to the low taxonomic resolution of previous sequencing technologies. Therefore, this study aimed to explore the gut microbiota using high-throughput sequencing to provide valuable insights and identify potential bacterial species and metabolite roles involved in kidney stone formation. The overall gut bacterial community and its potential functions in healthy participants and patients were examined using PacBio sequencing targeting the full-length 16S rRNA gene, coupled with stone and statistical analyses. Most kidney stones comprised calcium oxalate and calcium phosphate (75%), pure calcium oxalate (20%), and calcium phosphate and magnesium phosphate (5%), with higher content of Ca (130,510.5 ± 108,362.7 ppm) followed by P (18,746.4 ± 23,341.2 ppm). The microbial community structure was found to be weaker in patients' kidney stone samples, followed by patients' stool samples, than in healthy participants' stool samples. The most abundant bacterial species in kidney stone samples was uncultured Morganella, whereas that in patient and healthy participant stool samples was Bacteroides vulgatus. Similarly, Akkermansia muciniphila was significantly enriched in patient stool samples at the species level, whereas Bacteroides plebeius was significantly enriched in kidney stone samples than that in healthy participant stool samples. Three microbial metabolic pathways, TCA cycle, fatty acid oxidation, and urea cycle, were significantly enriched in kidney stone patients compared to healthy participants. Inferring bacteria at the species level revealed key players in kidney stone formation, enhancing the clinical relevance of gut microbiota.

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Background: To investigate the effect of percutaneous nephrolithotomy (PCNL) guided by holographic image technology on stress response and renal injury factors in patients with complex renal calculi. Methods: A retrospective analysis was conducted on the clinical data of 70 patients admitted to our hospital between August 2022 and June 2023 who had complex kidney stones. The patients were divided into two groups, namely, group A and group B, based on whether they received guidance from preoperative holographic imaging technology. Group A consisted of forty patients who underwent PCNL after undergoing renal CT examination prior to surgery, while Group B included thirty patients who underwent PCNL guided by holographic imaging technology. Various indexes, including operative factors, stress response, inflammatory response, renal injury factors, renal function, complication rate, and the rate of achieving complete stone clearance in a single procedure, were compared between the two groups. Results: In group B, the puncture time and operation time of the target calyces were shorter compared to group A, additionally, the intraoperative blood loss in group B was lower than that in group A (P<0.05). 24 h after surgery, group B exhibited higher levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) compared to group A, additionally, the level of malondialdehyde (MDA) in group B was lower than that in group A (P<0.05). 24 h after surgery, group B exhibited lower levels of tumor necrosis factor a (TNF-a), interleukin-6 (IL-6), IL-1, and hypersensitive C-reactive protein (hs-CRP) compared to group A (P<0.05). Furthermore, group B showed lower levels of neutrophil gelatinase-associated lipid carrier protein (NGAL), inducible protein-8-like molecule 2 (TIPE2), and b2-microglobulin (b2-MG) than group A at the 7-day mark (P<0.05). 24 h after the operation, There was no statistically significant difference observed in the levels of SCr, BUN, between group A and group B group (P > 0.05); however, exhibited lower levels of CysC compared to group A (P < 0.05). Additionally, there were no significant differences in postoperative complications between group B and group A (P>0.05). Furthermore, one month after surgery, the one-time stone clearance rate in group B was significantly higher than that in group A (P<0.05). Conclusions: PCNL under the guidance of hologram technology can shorten the time of puncture target calyce and operation, reduce the amount of intraoperative blood loss, effectively reduce the postoperative stress reaction and inflammatory reaction of patients, reduce the level of renal injury factors, improve renal function, and increase the one-time stone clearance rate.

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Urinothorax is a rare complication of urological procedures. This report presents a case of a patient who developed urinothorax following nephrostomy tube placement and percutaneous nephrolithotomy (PCNL). The patient was managed conservatively with chest tube and Foley catheter placement, without the need for surgery. Computed tomography (CT) and chest tube output indicated that the urinothorax occurred immediately after nephrostomy tube placement but resolved within a couple of days without further intervention. Unlike some other cases that required surgical intervention due to persistent urine leakage, this case underscores the importance of prompt identification and tailored management of this rare condition based on clinical judgment.

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Background: Clinical studies have indicated a comorbidity between sepsis and kidney diseases. Individuals with specific mutations that predispose them to kidney conditions are also at an elevated risk for developing sepsis, and vice versa. This suggests a potential shared genetic etiology that has not been fully elucidated. Methods: Summary statistics data on exposure and outcomes were obtained from genome-wide association meta-analysis studies. We utilized these data to assess genetic correlations, employing a pleiotropy analysis method under the composite null hypothesis to identify pleiotropic loci. After mapping the loci to their corresponding genes, we conducted pathway analysis using Generalized Gene-Set Analysis of GWAS Data (MAGMA). Additionally, we utilized MAGMA gene-test and eQTL information (whole blood tissue) for further determination of gene involvement. Further investigation involved stratified LD score regression, using diverse immune cell data, to study the enrichment of SNP heritability in kidney-related diseases and sepsis. Furthermore, we employed Mendelian Randomization (MR) analysis to investigate the causality between kidney diseases and sepsis. Results: In our genetic correlation analysis, we identified significant correlations among BUN, creatinine, UACR, serum urate, kidney stones, and sepsis. The PLACO analysis method identified 24 pleiotropic loci, pinpointing a total of 28 nearby genes. MAGMA gene-set enrichment analysis revealed a total of 50 pathways, and tissue-specific analysis indicated significant enrichment of five pairs of pleiotropic results in kidney tissue. MAGMA gene test and eQTL information (whole blood tissue) identified 33 and 76 pleiotropic genes, respectively. Notably, genes PPP2R3A for BUN, VAMP8 for UACR, DOCK7 for creatinine, and HIBADH for kidney stones were identified as shared risk genes by all three methods. In a series of immune cell-type-specific enrichment analyses of pleiotropy, we identified a total of 37 immune cells. However, MR analysis did not reveal any causal relationships among them. Conclusions: This study lays the groundwork for shared etiological factors between kidney and sepsis. The confirmed pleiotropic loci, shared pathogenic genes, and enriched pathways and immune cells have enhanced our understanding of the multifaceted relationships among these diseases. This provides insights for early disease intervention and effective treatment, paving the way for further research in this field.

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Mitochondria are essential organelles because they generate the energy required for cellular functions. Kidney stones, as one of the most common urological diseases, have garnered significant attention. In this study, we first collected peripheral venous blood from patients with kidney stones and used qRT-PCR to detect mitochondrial DNA (mtDNA) copy number as a means of assessing mitochondrial function in these patients. Subsequently, through Western blotting, qPCR, immunofluorescence, immunohistochemistry, and transmission electron microscopy, we examined whether calcium oxalate crystals could cause mitochondrial dysfunction in the kidney in both in vitro and in vivo. We then examined the intersection of the DEGs obtained by transcriptome sequencing of the mouse kidney stone model with mitochondria-related genes, and performed KEGG and GO analyses on the intersecting genes. Finally, we administered the mitochondrial ROS scavenger Mito-Tempo in vivo and observed its effects. Our findings revealed that patients with kidney stones had a reduced mtDNA copy number in their peripheral venous blood compared to the control group, suggesting mitochondrial dysfunction in this population. This conclusion was further validated through in vitro and in vivo experiments. Enrichment analyses revealed that the intersecting genes were closely related to metabolism. We observed that after mitochondrial function was preserved, the deposition of calcium oxalate crystals decreased, and the kidney damage and inflammation caused by them were also alleviated. Our research indicates that kidney stones can cause mitochondrial dysfunction. After clearing mtROS, the damage and inflammation caused by kidney stones are reversed, providing new insights into the prevention and treatment of kidney stones.

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This study investigated the risk profile and the impact of dietary intervention in calcium oxalate stone formers with enteric hyperoxaluria under controlled, standardized conditions. Thirty-seven patients were included in the study. Dietary and 24-h urinary parameters were obtained on the self-selected diet and a balanced, standardized diet. Tests for [13C2]oxalate absorption, calcium- and ammonium chloride-loading were performed. Mean [13C2]oxalate absorption was 18.8%. A significant positive association was observed between urinary oxalate excretion and intestinal oxalate absorption. In addition, urinary oxalate excretion was significantly correlated with dietary oxalate intake. Mean urinary oxalate excretion decreased from 0.841 mmol/24 h on the usual diet to 0.662 mmol/24 h on the balanced diet, corresponding to a reduction of 21.3%. Besides hyperoxaluria, hypocitraturia and hypomagnesuria were the most common urinary abnormalities at baseline, being present in 83.8% and 81.1% of patients, respectively. Urinary citrate increased by 50.9% and magnesium excretion increased by 25.2% on the balanced diet. As a result, the relative supersaturation of calcium oxalate declined significantly (by 36.2%) on the balanced diet. Since 41% of patients on the balanced diet still had a urine volume of less than 2.0 L/24 h, efforts should be made to increase urine volume by increasing fluid intake and reducing intestinal fluid losses. Dietary intervention proved to be effective in reducing urinary oxalate excretion and should be a cornerstone of the treatment of patients with enteric hyperoxaluria.

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Purpose: To evaluate the efficacy and safety of a novel zero-intrarenal pressure (IRP) percutaneous nephrolithotomy (PCNL) technique for one-stage treatment of non-acute infectious calculous pyonephrosis. Patients and Methods: This retrospective study analyzed 12 patients (4 males, 8 females; mean age 56.4 years) who underwent zero-IRP PCNL. The technique utilized a double-sheath vacuum suction system, with the outer sheath allowing for gravity irrigation and the inner sheath facilitating continuous suction. Keeping the height of gravity perfusion at the level of the kidney inherently prevented high IRP and achieved zero-IRP PCNL, even when stone fragments obstructed the suction channel. Results: The procedure demonstrated a high initial stone-free rate of 75%, improving to 91.7% after 1 month. The average operative time was 50.7 minutes. The mean hemoglobin drop was 6.1 g/L, managed without transfusions. Complications were minimal, with low-grade fever in two patients. No significant intraoperative or postoperative complications, such as sepsis, were noted. Conclusions: The zero-IRP PCNL technique, characterized by its double-sheath vacuum suction system and zero-pressure gravity perfusion, shows promise in safely and effectively managing non-acute infectious calculous pyonephrosis. Preliminary results are encouraging, but further research with larger sample sizes is essential for broader clinical validation.