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Keywords = urinary stone risk

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13 pages, 239 KiB  
Article
Extended-Spectrum Beta-Lactamase Production and Carbapenem Resistance in Elderly Urinary Tract Infection Patients: A Multicenter Retrospective Study from Turkey
by Çiğdem Yıldırım, Sema Sarı, Ayşe Merve Parmaksızoğlu Aydın, Aysin Kilinç Toker, Ayşe Turunç Özdemir, Esra Erdem Kıvrak, Sinan Mermer, Hasip Kahraman, Orçun Soysal, Hasan Çağrı Yıldırım and Meltem Isikgoz Tasbakan
Antibiotics 2025, 14(7), 719; https://doi.org/10.3390/antibiotics14070719 - 17 Jul 2025
Viewed by 362
Abstract
Introduction: Urinary tract infections (UTIs) remain a significant public health issue worldwide, particularly affecting the geriatric population with increased morbidity and mortality. Aging-related immune changes, comorbidities, and urogenital abnormalities contribute to the higher incidence and complexity of UTIs in elderly patients. Antimicrobial resistance, [...] Read more.
Introduction: Urinary tract infections (UTIs) remain a significant public health issue worldwide, particularly affecting the geriatric population with increased morbidity and mortality. Aging-related immune changes, comorbidities, and urogenital abnormalities contribute to the higher incidence and complexity of UTIs in elderly patients. Antimicrobial resistance, especially extended-spectrum beta-lactamase (ESBL) production and carbapenem resistance, poses a major challenge in managing UTIs in this group. Methods: This retrospective, multicenter study included 776 patients aged 65 and older, hospitalized with a diagnosis of urinary tract infection between January 2019 and August 2024. Clinical, laboratory, and microbiological data were collected and analyzed. Urine samples were obtained under sterile conditions and pathogens identified using conventional and automated systems. Antibiotic susceptibility testing was performed according to CLSI standards. Logistic regression analyses were conducted to identify factors associated with ESBL production, carbapenem resistance, and mortality. Results: Among the patients, the median age was 78.9 years, with 45.5% female. ESBL production was detected in 56.8% of E. coli isolates and carbapenem resistance in 1.2%. Klebsiella species exhibited higher carbapenem resistance (37.8%). Independent predictors of ESBL production included the presence of urogenital cancer and antibiotic use within the past three months. Carbapenem resistance was associated with recent hospitalization, absence of kidney stones, and infection with non-E. coli pathogens. Mortality was independently associated with intensive care admission at presentation, altered mental status, Gram-positive infections, and comorbidities such as chronic obstructive pulmonary disease and urinary incontinence. Discussion: Our findings suggest that urinary pathogens and resistance patterns in elderly patients are similar to those in younger adults reported in the literature, highlighting the need for age-specific awareness in empiric therapy. The identification of risk factors for multidrug-resistant organisms emphasizes the importance of targeted antibiotic stewardship, especially in high-risk geriatric populations. Multicenter data contribute to regional understanding of resistance trends, aiding clinicians in optimizing management strategies for elderly patients with UTIs. Conclusions: This study highlights that E. coli and Klebsiella species are the primary causes of UTIs in the elderly, with resistance patterns similar to those seen in younger adults. The findings also contribute important data on risk factors for ESBL production and carbapenem resistance, supported by a robust patient sample. Full article
21 pages, 1217 KiB  
Review
Beyond Infection: How Antimicrobial Therapies Influence the Urinary Microbiome and Stone Disease
by Oana Nicu-Canareica, Vlad-Octavian Bolocan, Loredana Sabina Cornelia Manolescu, Petru Armean, Cosmin Medar, Liliana Burlibașa, Maria-Luiza Băean and Viorel Jinga
Pharmaceuticals 2025, 18(7), 1038; https://doi.org/10.3390/ph18071038 - 12 Jul 2025
Viewed by 574
Abstract
The discovery of a resident urinary microbiome has significantly altered the understanding of urolithiasis, expanding its etiology beyond metabolic and dietary factors to include microbial contributions. This review highlights how specific uropathogens—particularly Proteus mirabilis, Klebsiella pneumoniae, and Escherichia coli—facilitate stone [...] Read more.
The discovery of a resident urinary microbiome has significantly altered the understanding of urolithiasis, expanding its etiology beyond metabolic and dietary factors to include microbial contributions. This review highlights how specific uropathogens—particularly Proteus mirabilis, Klebsiella pneumoniae, and Escherichia coli—facilitate stone formation through mechanisms such as urease activity, citrate degradation, urine alkalinization, biofilm development, and inflammatory signaling. We critically examine how antibiotic therapies, while essential for treating urinary tract infections (UTIs), disrupt microbial homeostasis by depleting beneficial taxa like Lactobacillus and enabling colonization by lithogenic and resistant strains. Recurrent or broad-spectrum antibiotic use is linked to persistent dysbiosis and increased risk of stone recurrence. Additionally, this paper explores emerging microbiome-targeted strategies—such as probiotics, prebiotics, bacteriotherapy, and precision antimicrobials—as potential interventions to restore microbial balance and mitigate stone risk. Recognizing the urinary microbiome as a therapeutic target opens new avenues for personalized, microbiota-conscious strategies in the prevention and management of kidney stone disease. Full article
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45 pages, 4730 KiB  
Review
Hydration Meets Regulation: Insights into Bicarbonate Mineral Water and Acid–Base Balance
by Katharina Mansouri, Thierry Hanh and Andreas Hahn
Nutrients 2025, 17(14), 2291; https://doi.org/10.3390/nu17142291 - 10 Jul 2025
Viewed by 1031
Abstract
Acid–base balance is critical to human health and can be significantly influenced by dietary choices. The Western diet, characterized by high meat and cheese consumption, induces excess acidity, highlighting the need for strategies to mitigate this. Recent studies have focused on bicarbonate-rich mineral [...] Read more.
Acid–base balance is critical to human health and can be significantly influenced by dietary choices. The Western diet, characterized by high meat and cheese consumption, induces excess acidity, highlighting the need for strategies to mitigate this. Recent studies have focused on bicarbonate-rich mineral water as a viable solution. In this context, the present narrative review synthesizes the findings from recent scientific studies on bicarbonate-rich mineral water, specifically those with bicarbonate levels over 1300 mg/L and medium or low PRAL values. This water has been shown to exert beneficial effects on both urinary and blood parameters. The key effects include an increase in the urine pH and a profound reduction in net acid excretion as a sign for a reduced acid load. Additionally, bicarbonate mineral water has been shown to decrease the excretion of nephrolithiasis-related constituents, including calcium and oxalates, as well as inhibitory substances such as magnesium and citrates. In blood, bicarbonate-rich water has been demonstrated to stabilize pH and increase bicarbonate levels, thereby enhancing systemic buffering capacity. Clinically, these changes have been associated with a lowered risk of calcium oxalate stone formation and improved kidney health. Furthermore, bicarbonate-rich water has been shown to support bone health by reducing bone resorption markers. Consequently, the integration of bicarbonate-rich mineral water into the diet has the potential to enhance urinary and blood parameters, mitigate the risk of kidney stones, and strengthen skeletal integrity, thereby serving as a promising strategy for health promotion and disease prevention. While promising, these findings underscore the need for further research to establish long-term recommendations. Future interventional studies should be designed with rigorous randomization, larger sample sizes, cross-over methodologies, and comprehensive dietary assessments to address the methodological limitations of previous research. Full article
(This article belongs to the Section Nutrition and Public Health)
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15 pages, 1475 KiB  
Article
AI-Driven Prediction of Renal Stone Recurrence Following ECIRS: A Machine Learning Approach to Postoperative Risk Stratification Incorporating 24-Hour Urine Data
by Takahiro Yanase, Rei Unno, Theodoros Tokas, Vineet Gauhar, Yuya Sasaki, Kengo Kawase, Ryosuke Chaya, Shuzo Hamamoto, Mihoko Maruyama, Takahiro Yasui and Kazumi Taguchi
J. Clin. Med. 2025, 14(12), 4037; https://doi.org/10.3390/jcm14124037 - 7 Jun 2025
Viewed by 835
Abstract
Background/Objectives: Predicting kidney stone recurrence after active stone treatment remains challenging due to its multifactorial nature. Artificial intelligence, particularly machine learning, provides new methods for identifying hidden patterns in high-dimensional clinical data. We conducted a study applying machine learning to identify key [...] Read more.
Background/Objectives: Predicting kidney stone recurrence after active stone treatment remains challenging due to its multifactorial nature. Artificial intelligence, particularly machine learning, provides new methods for identifying hidden patterns in high-dimensional clinical data. We conducted a study applying machine learning to identify key predictors of recurrence following endoscopic combined intrarenal surgery (ECIRS) in patients with calcium stones. Methods: This retrospective cohort analysis included 72 patients with calcium stones who underwent ECIRS between June 2019 and May 2022 and achieved a complete stone-free status on postoperative CT. Patients were followed for two years, with recurrence assessed through protocolized imaging. We collected 235 variables, including clinical data, 24 h urine collections, stone composition, imaging features, and perioperative findings. Several machine learning models were developed, and SHapley Additive exPlanations (SHAP) analysis identified features associated with recurrence. Results: Within two years, 29 of 72 patients (40.3%) experienced recurrence. The TabNet model demonstrated the highest predictive accuracy (AUC = 0.89), outperforming traditional machine learning algorithms. SHAP analysis identified urinary oxalate ≥ 25.4 mg/day and hemoglobin (Hb) drop ≥ 0.3 g/dL at 3 months postoperatively as independent predictors, even within normal limits. A simplified TabNet-based model using three key features (oxalate, urine volume, and 3-month ΔHb) maintained a strong performance (AUC = 0.75), supporting its clinical utility. Conclusions: Machine learning enabled the accurate prediction of kidney stone recurrence after ECIRS. The inclusion of 24 h urine data significantly improved the performance. Even patients with “normal” oxalate levels showed increased risk, suggesting current clinical thresholds may require re-evaluation. Full article
(This article belongs to the Special Issue Clinical Advances in Artificial Intelligence in Urology)
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9 pages, 202 KiB  
Article
Evaluation of the Largest Series of Ultramini Percutaneous Nephrolithotomy in Preschool Children: 10-Year Experience with 711 Units of Kidney Stones
by Mehmet Mazhar Utangaç and Onur Dede
J. Clin. Med. 2025, 14(10), 3355; https://doi.org/10.3390/jcm14103355 - 12 May 2025
Viewed by 358
Abstract
Background and Objectives: This study aimed to evaluate the safety, efficacy and outcomes of ultramini percutaneous nephrolithotomy (UM-PNL) in preschool-aged children with kidney stones. Materials and Methods: A retrospective analysis was conducted on 711 renal units of 676 paediatric patients aged 0–6 years [...] Read more.
Background and Objectives: This study aimed to evaluate the safety, efficacy and outcomes of ultramini percutaneous nephrolithotomy (UM-PNL) in preschool-aged children with kidney stones. Materials and Methods: A retrospective analysis was conducted on 711 renal units of 676 paediatric patients aged 0–6 years who underwent UM-PNL between April 2014 and July 2024. The children’s demographic data, stone characteristics, operative details and postoperative outcomes were analysed. The procedure was performed using a 9.5 Fr sheath and a 7.5 Fr nephroscope, with laser lithotripsy applied. Postoperative follow-up included imaging and a clinical assessment of complications. Results: The mean patient age was 34.2 months (range: 5–72 months). Haematuria (36.8%) and urinary tract infections (24.5%) were the most common presenting symptoms. The mean stone size was 16.2 mm, and the stone-free rate was 89.2% after the first session, increasing to 96.4% with additional interventions. The mean operative time was 38 min. No major complications were observed; 8.4% of cases had Clavien grade 3b complications, most of which were managed conservatively. Blood transfusion was required in 2.6% of the cases. Conclusions: UM-PNL is a safe and effective treatment method for kidney stones in preschool-aged children, characterized by high stone-free rates and a low risk of complications. With proper patient selection and experienced surgical teams, UM-PNL can be considered a first-line option in paediatric stone management. Full article
(This article belongs to the Section Nephrology & Urology)
11 pages, 959 KiB  
Article
Metabolic Differences in 24-Hour Urine Parameters Between Calcium Oxalate Monohydrate and Dihydrate Kidney Stones: A Clinical Study
by Nariman Gadzhiev, Vitaliy Gelig, Gennadii Rodionov, Vineet Gauhar and Guohua Zeng
Diagnostics 2025, 15(8), 994; https://doi.org/10.3390/diagnostics15080994 - 14 Apr 2025
Cited by 2 | Viewed by 1077
Abstract
Background: Different types of kidney stones are associated with distinct changes in urine chemistry. Methods: We assessed urinary parameters of 98 patients with calcium oxalate (CaOx) stones one month following endoscopic stone removal. The 24 h urine analysis encompassed the assessment of various [...] Read more.
Background: Different types of kidney stones are associated with distinct changes in urine chemistry. Methods: We assessed urinary parameters of 98 patients with calcium oxalate (CaOx) stones one month following endoscopic stone removal. The 24 h urine analysis encompassed the assessment of various parameters, including volume, sodium, chloride, sulfate, nitrate, fluoride, phosphate, calcium, potassium, magnesium, oxalate, uric acid, citrate, creatinine, and pH levels. Results: Hypocitraturia was the most prevalent urinary abnormality (61.2%, n = 63), followed by low urine volume (53%, n = 52) and hypercalciuria (50%, n = 49). We did not find any statistically significant differences between patients with whewellite (COM) (n = 69) and weddellite (COD) stones (n = 29) (p > 0.05). However, oxalate concentration was the only parameter with a statistically significant intergroup difference (p = 0.0297). Additionally, in univariate linear regression analysis, urinary phosphate levels ≥ 48.0 mmol/d showed a trend towards significance (OR 0.17, 95% CI 0.02–1.15, p = 0.0692), indicating that phosphaturia is associated with a significant increase in the odds ratio of COD stones. To further explore metabolic heterogeneity among stone formers, we conducted cluster analysis, which revealed three distinct metabolic subgroups. Cluster 1 was predominantly associated with COM stones (80.5%) and exhibited significantly higher urinary excretion of sodium, calcium, oxalate, phosphate, and uric acid compared to Cluster 2, which had a more balanced distribution of monohydrate and dihydrate stones. Conclusions: These findings suggest that a specific metabolic phenotype may be linked to COM stone formation, providing a framework for risk stratification and personalized prevention strategies in calcium oxalate stone formers. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Management of Urologic Diseases)
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12 pages, 243 KiB  
Article
Prospective Study of Urinary Stone Formation in Pediatric Patients with Acquired Brain Injury: A Focus on Incidence and Analysis of Risk Factors
by Sara Galbiati, Federica Locatelli, Fabio Alexander Storm, Marco Pozzi and Sandra Strazzer
Nutrients 2025, 17(5), 883; https://doi.org/10.3390/nu17050883 - 28 Feb 2025
Viewed by 690
Abstract
Background/Objectives: Little is known about the factors linked with nutrition, infections, and physical activity, which may influence urinary stone formation in patients with acquired brain injury. Previous studies have demonstrated that enteral nutrition mixtures rich in sodium and poor in calcium may [...] Read more.
Background/Objectives: Little is known about the factors linked with nutrition, infections, and physical activity, which may influence urinary stone formation in patients with acquired brain injury. Previous studies have demonstrated that enteral nutrition mixtures rich in sodium and poor in calcium may promote stone formation in pediatric patients, but a confirmation study is lacking. Moreover, the occurrence of urinary stones and heterotopic ossifications has not been studied regarding incidence. We thus conducted a prospective observational study in an unselected pediatric population with acquired brain injury, to estimate the incidence of urinary stones and heterotopic ossifications and analyze the associated factors. Methods: Prospective observational study: We recruited all patients with enteral nutrition consecutively admitted to our brain injury rehabilitation unit during a 5-year time-frame. We collected clinical data regarding nutrition, infections, blood and urine exams performed, neurological examinations, and physical examinations. Results: The prospective design allowed us to observe that no patient developed heterotopic ossifications, while urinary stones were found in 12.5% of patients and gravel in 14.6%. Factors associated with stone formation were having a worse subacute GCS, having done intense physical activity before injury, receiving bladder catheterizations, having a higher urine pH, and having higher blood potassium levels. The composition of the enteral nutrition did not influence stone formation, although the nutrition mixtures contained levels of vitamin C and proteins considerably higher than the recommended reference ranges. Conclusions: We have provided an observation of the incidence of urolithiasis in pediatric patients in rehabilitation, which was lacking from the literature. Enteral nutrition, at the amounts received by the patients studied herein, does not seem to have a role in stone formation. We identified a set of risk factors that can be useful for clinicians to pinpoint patients at an increased risk of developing stones. Full article
14 pages, 2611 KiB  
Article
Low Serum and Urine Fetuin-A Levels and High Composite Dietary Antioxidant Index as Risk Factors for Kidney Stone Formation
by Mehmet Arif Icer, Tevfik Koçak, Yusuf Icer, Emine Kocyigit, Duygu Ağagündüz, Makbule Gezmen-Karadag, Suleyman Yesil and Ferenc Budán
J. Clin. Med. 2025, 14(5), 1487; https://doi.org/10.3390/jcm14051487 - 23 Feb 2025
Cited by 3 | Viewed by 1016
Abstract
Background: Fetuin-A prevents the precipitation of hydroxyapatite in supersaturated solutions of calcium and phosphate; however, its relationship with nephrolithiasis has yet to be clarified. The aim of this study was to investigate the protective and predictive roles of serum and urine fetuin-A levels [...] Read more.
Background: Fetuin-A prevents the precipitation of hydroxyapatite in supersaturated solutions of calcium and phosphate; however, its relationship with nephrolithiasis has yet to be clarified. The aim of this study was to investigate the protective and predictive roles of serum and urine fetuin-A levels in nephrolithiasis and their relationships with the composite dietary antioxidant index (CDAI). Methods: This study involved 75 adult patients with kidney stone disease and 71 healthy adults without kidney stone disease in the control group. Participants had specific anthropometric measurements taken, and three-day food records were kept. The CDAI was calculated by summing six standard antioxidants, including vitamins A, C, and E, manganese, selenium, and zinc, representing participants’ antioxidant profile. In addition to some analyzed serum and urine parameters of the participants, fetuin-A levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. Results: In patients with kidney stones, both serum and urine fetuin-A levels (676.3 ± 160.14 ng/mL; 166.6 ± 128.13 ng/mL, respectively) were lower than in the control group (1455.6 ± 420.52 ng/mL; 2267.5 ± 1536.78 ng/mL, respectively) (p < 0.00001). In contrast, the CDAI was higher in patients with kidney stones compared to those without kidney stones (p < 0.001). Besides, several dietary parameters had significant positive correlations with serum and/or urinary fetuin-A. Conclusions: The present study suggests that serum and urinary fetuin-A levels may serve as protective factors against kidney stones and could potentially be used as predictive markers for the development of nephrolithiasis. Furthermore, our results suggest that the CDAI above a certain level may increase the risk of stone formation and that some dietary parameters may affect the levels of this biomarker in serum and urine. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Kidney Stones)
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7 pages, 980 KiB  
Article
Canada-Wide Distribution of Environmental and Occupational Risk Factors for Urinary Stone Disease: Insights for Equitable Resource Allocation and Fighting Health Disparities
by Mohammadali Saffarzadeh, Anna Black, Michael Ordon, Ben H. Chew and Connor M. Forbes
Soc. Int. Urol. J. 2025, 6(1), 9; https://doi.org/10.3390/siuj6010009 - 12 Feb 2025
Viewed by 834
Abstract
Abstract: Objectives: This study aimed to map the distribution of nephrolithiasis’ environmental risk factors (occupational heat and heavy metal exposure and ambient seasonal temperature) and to assess the correlations of these exposures with the best estimates of the reported nephrolithiasis incidence in [...] Read more.
Abstract: Objectives: This study aimed to map the distribution of nephrolithiasis’ environmental risk factors (occupational heat and heavy metal exposure and ambient seasonal temperature) and to assess the correlations of these exposures with the best estimates of the reported nephrolithiasis incidence in Canada. Methods: The regional average heat burden was defined as the mean temperature in the hottest three months of the year for 2020, 2021, and 2022. The employment rates in the top five industries with occupational heavy metal (cadmium, lead, and arsenic) and heat exposure were obtained from the Statistics Canada 2021 database. Statistical significance was calculated based on the 95% confidence interval difference from the null hypothesis. Correlation analysis was performed between our rates of nephrolithiasis risk factors and previously published estimates of the stone incidence: kidney stone interventions and acute kidney stone event rates. Results: Lower-latitude provinces had higher overall mean temperatures in 2020 to 2022, with Ontario, Manitoba, and Prince Edward Island having the highest seasonal heat burdens, in this order. Nunavut had the lowest rate of occupational heat exposure, while the remaining regions had similar rates. Yukon, the Northwest Territories, and Nunavut had significantly higher rates of occupational heavy metal exposure compared to the remaining regions. The ambient temperature and occupation heavy metal and heat exposure showed no significant correlation with the estimates of the stone incidence. Conclusions: The occupational heat exposure was relatively similar between regions. Northern Canada had higher occupational heavy metal exposure compared to other regions. Occupational exposures and temperature variations were not associated with the nephrolithiasis incidence in Canada. Full article
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21 pages, 2745 KiB  
Article
Preliminary Investigation on Biodegradable Ureteral Stents Using 3D Printing
by Chirag Chetan and Sagil James
J. Manuf. Mater. Process. 2025, 9(2), 52; https://doi.org/10.3390/jmmp9020052 - 6 Feb 2025
Cited by 1 | Viewed by 2104
Abstract
The prevalence of kidney stones, a significant urological health concern, necessitates advancements in the management and treatment methods, particularly in the domain of ureteral stents. This study explores the feasibility and potential benefits of utilizing three biodegradable polymers—Polylactic Acid (PLA), Tough Polylactic Acid [...] Read more.
The prevalence of kidney stones, a significant urological health concern, necessitates advancements in the management and treatment methods, particularly in the domain of ureteral stents. This study explores the feasibility and potential benefits of utilizing three biodegradable polymers—Polylactic Acid (PLA), Tough Polylactic Acid (Tough PLA), and Polylactic Acid/Poly-hydroxybutyrate (PLA/PHB)—for the fabrication of 3D-printed ureteral stents tailored to patient-specific needs. Through the integration of CAD and Fused Deposition Modeling (FDM) 3D printing technology, ureteral stents were successfully produced, demonstrating key advantages in terms of biodegradability and mechanical properties. The study involved a rigorous evaluation of the biodegradability, tensile strength, and hardness of the stents. Biodegradability tests performed in a simulated physiological environment revealed that PLA/PHB and Tough PLA stents exhibited higher degradation rates compared to PLA, aligning with the requirements for temporary urinary tract support. Tensile strength testing indicated that while PLA showed the highest strength, PLA/PHB and Tough PLA stents provided beneficial ductility, reducing the risk of blockage due to material breakage. Hardness assessments classified PLA/PHB stents as medium soft, optimizing patient comfort during the stenting period. These findings demonstrate the potential of using biodegradable polymers to produce ureteral stents that could eliminate the need for removal procedures, thereby enhancing patient recovery and comfort. Full article
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19 pages, 4176 KiB  
Hypothesis
Advanced Glycation End-Product-Modified Heat Shock Protein 90 May Be Associated with Urinary Stones
by Takanobu Takata, Shinya Inoue, Kenshiro Kunii, Togen Masauji, Junji Moriya, Yoshiharu Motoo and Katsuhito Miyazawa
Diseases 2025, 13(1), 7; https://doi.org/10.3390/diseases13010007 - 2 Jan 2025
Cited by 1 | Viewed by 1569
Abstract
Background: Urinary stones (urolithiasis) have been categorized as kidney stones (renal calculus), ureteric stones (ureteral calculus and ureterolith), bladder stones (bladder calculus), and urethral stones (urethral calculus); however, the mechanisms underlying their promotion and related injuries in glomerular and tubular cells remain unclear. [...] Read more.
Background: Urinary stones (urolithiasis) have been categorized as kidney stones (renal calculus), ureteric stones (ureteral calculus and ureterolith), bladder stones (bladder calculus), and urethral stones (urethral calculus); however, the mechanisms underlying their promotion and related injuries in glomerular and tubular cells remain unclear. Although lifestyle-related diseases (LSRDs) such as hyperglycemia, type 2 diabetic mellitus, non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, and cardiovascular disease are risk factors for urolithiasis, the underlying mechanisms remain unclear. Recently, heat shock protein 90 (HSP90) on the membrane of HK-2 human proximal tubular epithelium cells has been associated with the adhesion of urinary stones and cytotoxicity. Further, HSP90 in human pancreatic and breast cells can be modified by various advanced glycation end-products (AGEs), thus affecting their function. Hypothesis 1: We hypothesized that HSP90s on/in human proximal tubular epithelium cells can be modified by various types of AGEs, and that they may affect their functions and it may be a key to reveal that LSRDs are associated with urolithiasis. Hypothesis 2: We considered the possibility that Japanese traditional medicines for urolithiasis may inhibit AGE generation. Of Choreito and Urocalun (the extract of Quercus salicina Blume/Quercus stenophylla Makino) used in the clinic, Choreito is a Kampo medicine, while Urocalun is a characteristic Japanese traditional medicine. As Urocalun contains quercetin, hesperidin, and p-hydroxy cinnamic acid, which can inhibit AGE generation, we hypothesized that Urocalun may inhibit the generation of AGE-modified HSP90s in human proximal tubular epithelium cells. Full article
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16 pages, 2013 KiB  
Article
Machine Learning Models Decoding the Association Between Urinary Stone Diseases and Metabolic Urinary Profiles
by Lin Ma, Yi Qiao, Runqiu Wang, Hualin Chen, Guanghua Liu, He Xiao and Ran Dai
Metabolites 2024, 14(12), 674; https://doi.org/10.3390/metabo14120674 - 3 Dec 2024
Cited by 2 | Viewed by 1172
Abstract
Background: Employing advanced machine learning models, we aim to identify biomarkers for urolithiasis from 24-h metabolic urinary abnormalities and study their associations with urinary stone diseases. Methods: We retrospectively recruited 468 patients at Peking Union Medical College Hospital who were diagnosed with urinary [...] Read more.
Background: Employing advanced machine learning models, we aim to identify biomarkers for urolithiasis from 24-h metabolic urinary abnormalities and study their associations with urinary stone diseases. Methods: We retrospectively recruited 468 patients at Peking Union Medical College Hospital who were diagnosed with urinary stone disease, including renal, ureteral, and multiple location stones, and had undergone a 24-h urine metabolic evaluation. We applied machine learning methods to identify biomarkers of urolithiasis from the urinary metabolite profiles. In total, 148 (34.02%) patients were with kidney stones, 34 (7.82%) with ureter stones, and 163 (34.83%) with multiple location stones, all of whom had detailed urinary metabolite data. Our analyses revealed that the Random Forest algorithm exhibited the highest predictive accuracy, with AUC values of 0.809 for kidney stones, 0.99 for ureter stones, and 0.775 for multiple location stones. The Super Learner Ensemble Method also demonstrated high predictive performance with slightly lower AUC values compared to Random Forest. Further analysis using multivariate logistic regression identified significant features for each stone type based on the Random Forest method. Results: We found that 24-h urinary magnesium was positively associated with both kidney stones and multiple location stones (OR = 1.195 [1.06–1.3525] and 1.3258 [1.1814–1.4949]) due to its high correlation with urinary phosphorus, while 24-h urinary creatinine was a protective factor for kidney stones and ureter stones, with ORs of 0.9533 [0.9117–0.996] and 0.8572 [0.8182–0.8959]. eGFR was a risk factor for ureter stones and multiple location stones, with ORs of 1.0145 [1.0084–1.0209] and 1.0148 [1.0077–1.0223]. Conclusion: Machine learning techniques show promise in revealing the links between urological stone disease and 24-h urinary metabolic data. Enhancing the prediction accuracy of these models leads to improved dietary or pharmacological prevention strategies. Full article
(This article belongs to the Special Issue Metabolomics-Based Biomarkers for Nutrition and Health)
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6 pages, 366 KiB  
Proceeding Paper
In Silico Studies of Khellin and Related Furochromenes by Modified POM Analysis
by Renata Gašparová
Chem. Proc. 2024, 16(1), 2; https://doi.org/10.3390/ecsoc-28-20203 - 14 Nov 2024
Viewed by 846
Abstract
POM (Petra/Osiris/Molinspiration) analysis and related in silico tools are well-established methods used to evaluate the potential of molecules to become drug candidates by predicting their biological activity and calculating various physicochemical properties, ADME parameters, or toxicity. Khellin 1 is a well-known component of [...] Read more.
POM (Petra/Osiris/Molinspiration) analysis and related in silico tools are well-established methods used to evaluate the potential of molecules to become drug candidates by predicting their biological activity and calculating various physicochemical properties, ADME parameters, or toxicity. Khellin 1 is a well-known component of the Ammi visnaga (khella) plant used for centuries in folk medicine for the treatment of urinary tract pain associated with kidney stones. Modern medicine has found the importance of khellin in the treatment of psoriasis, angina pectoris, or vitiligo. However, the oral use of khellin is limited by its potential adverse effects, such as dizziness, constipation, headache, itching, or lack of appetite. Many natural or synthetic furopyrrole derivatives have been extensively studied and reported to possess numerous biological effects, including anticancer, anti-inflammatory, or antimicrobial. The present in silico study is aimed at revealing the most promising drug candidates based on favorable pharmacokinetic parameters and toxicological characteristics. A modified POM analysis of sixteen furochromenes was performed using Molinspiration, Osiris, and SwissADME software. Studied structures were selected due to the modifications of the khellin skeleton. Substitution of the furan or pyran ring, modification of one or both methoxy groups, or hydrogenation of one or both heterocyclic rings were included. The results of this preliminary in silico investigation suggest all furopyrroles have good oral bioavailability and a high level of gastrointestinal absorption. The bioactivity score prediction shows their ability to act predominantly as ion channel modulators or enzyme inhibitors. All compounds exhibit a low risk of being irritants; nine of them exhibit a low risk of being mutagenic, tumorigenic, or having reproductive effects. Full article
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16 pages, 268 KiB  
Review
SGLT2 Inhibitors and Their Effect on Urolithiasis: Current Evidence and Future Directions
by Živka Dika, Marijana Živko, Marina Kljajić and Bojan Jelaković
J. Clin. Med. 2024, 13(19), 6017; https://doi.org/10.3390/jcm13196017 - 9 Oct 2024
Cited by 3 | Viewed by 2747
Abstract
Urolithiasis (UL) is increasingly prevalent due to rising cardiorenometabolic diseases, posing significant management challenges despite advances in urological techniques. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, primarily used for type 2 diabetes mellitus, chronic kidney disease, and heart failure, have emerged as a potential novel approach [...] Read more.
Urolithiasis (UL) is increasingly prevalent due to rising cardiorenometabolic diseases, posing significant management challenges despite advances in urological techniques. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, primarily used for type 2 diabetes mellitus, chronic kidney disease, and heart failure, have emerged as a potential novel approach for UL treatment. These inhibitors may help reduce the risk of urolithiasis, particularly in patients with diabetes, by improving glycemic control and altering urinary chemistry, which are crucial factors in stone formation. However, the changes in urinary composition induced by SGLT2 inhibitors might also increase the risk of uric acid stone formation. This review evaluates the potential of SGLT2 inhibitors in managing UL, highlighting both the benefits and the risks. While these inhibitors show promise in reducing new and recurrent urinary stones in patients with diabetes, data on their effects in patients without diabetes who form stones are limited. Current human evidence largely comes from post hoc analyses of randomized controlled trials (RCTs) and large-scale database studies, with only one study providing detailed stone composition data. Experimental studies in animal models and cell lines have focused on calcium oxalate (CaOx) stones, showing that SGLT2 inhibitors specifically target CaOx stone formation and related renal inflammation. Although primarily studied for CaOx stones, their potential impact on other calcium-containing stones, such as calcium phosphate, remains promising. Further research is needed to explore their therapeutic potential and optimize treatment strategies. Full article
8 pages, 981 KiB  
Case Report
A Rare Case and Literature Review of Pyelo-Hepatic Abscess in an Immunocompetent Patient: When Effective Source Control and Targeted Antimicrobial Therapy Might Not Be Enough
by Anita Sforza, Andrea Bonito, Giorgio Tiecco, Giovanni Moioli, Samuele Storti, Marco Lechiara, Francesco Castelli and Eugenia Quiros-Roldan
Microorganisms 2024, 12(10), 1989; https://doi.org/10.3390/microorganisms12101989 - 30 Sep 2024
Cited by 2 | Viewed by 1410
Abstract
Pyelo-hepatic abscess is a rare complication of upper urinary tract infections (UTIs). We describe a case of polymicrobial pyelo-hepatic abscess in an immunocompetent patient. A 71-year-old male patient with a double-J stent for right ureteral lithiasis was admitted in our Infectious Diseases Department [...] Read more.
Pyelo-hepatic abscess is a rare complication of upper urinary tract infections (UTIs). We describe a case of polymicrobial pyelo-hepatic abscess in an immunocompetent patient. A 71-year-old male patient with a double-J stent for right ureteral lithiasis was admitted in our Infectious Diseases Department for a pyelo-hepatic abscess. Despite a targeted antibiotic therapy against an extended spectrum betalactamase-negative Escherichia coli, the patient did not improve. Further examinations revealed a possible polymicrobial aetiology, including Candida spp. and E. coli resistant to piperacillin/tazobactam but sensitive to third-generation cephalosporins. To date, a paucity of articles regarding pyelo-hepatic abscess exist, consisting mostly of case reports. Urinary stones and a ureteral stent indwelling time exceeding 90 days are known risk factors for upper UTIs and for bacterial dissemination in contiguous organs. Pyelo-hepatic abscesses usually involve Gram-negative bacilli, but they can be polymicrobial, including fungi. As a range of factors could limit the efficacy of antibiotics inside an encapsulated lesion and might contribute to the selection of resistant species during treatment, clinicians should be aware of this complication and try to prevent this event by acting on the main modifiable risk factor. Full article
(This article belongs to the Special Issue Recent Research on Antimicrobial Stewardship)
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