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Kidney Stone Disease (KSD) constitutes a multifaceted disorder, emerging from a confluence of environmental and genetic determinants, and is characterized by a high frequency of occurrence and recurrence. Our objective is to elucidate potential causative proteins and identify prospective pharmacological targets within the context of KSD. This investigation harnessed the unparalleled breadth of plasma protein and KSD pooled genome-wide association study (GWAS) data, sourced from the United Kingdom Biobank Pharma Proteomics Project (UKBPPP) and the FinnGen database version R10. Through Mendelian randomization analysis, proteins exhibiting a causal influence on KSD were pinpointed. Subsequent co-localization analyses affirmed the stability of these findings, while enrichment analyses evaluated their potential for pharmacological intervention. Culminating the study, a phenome-wide association study (PheWAS) was executed, encompassing all phenotypes (2408 phenotypes) catalogued in the FinnGen database version R10. Our MR analysis identified a significant association between elevated plasma levels of proteins FKBPL, ITIH3, and SERPINC1 and increased risk of KSD based on genetic predictors. Conversely, proteins CACYBP, DAG1, ITIH1, and SEMA6C showed a protective effect against KSD, documented with statistical significance (P FDR <0.05). Co-localization analysis confirmed these seven proteins share genetic variants with KSD, signaling a shared genetic basis (PPH3 + PPH4 > 0.8). Enrichment analysis revealed key pathways including hyaluronan metabolism, collagen-rich extracellular matrix, and serine-type endopeptidase inhibition. Additionally, our PheWAS connected the associated proteins with 356 distinct diseases (P FDR <0.05), highlighting intricate disease interrelations. In conclusion, our research elucidated a causal nexus between seven plasma proteins and KSD, enriching our grasp of prospective therapeutic targets., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Calcium-containing stones represent the most common form of kidney calculi, frequently linked to idiopathic hypercalciuria, though their precise pathogenesis remains elusive. This research aimed to elucidate the molecular mechanisms involved by employing urinary exosomal microRNAs as proxies for renal tissue analysis. Elevated miR-148b-5p levels were observed in exosomes derived from patients with kidney stones. Systemic administration of miR-148b-5p in rat models resulted in heightened urinary calcium excretion, whereas its inhibition reduced stone formation. RNA immunoprecipitation combined with deep sequencing identified miR-148b-5p as a suppressor of calcitonin receptor (Calcr) expression, thereby promoting urinary calcium excretion and stone formation. Mice deficient in Calcr in distal epithelial cells demonstrated elevated urinary calcium excretion and renal calcification. Mechanistically, miR-148b-5p regulated Calcr through the circRNA-83536/miR-24-3p signaling pathway. Human kidney tissue samples corroborated these results. In summary, miR-148b-5p regulates the formation of calcium-containing kidney stones via the circRNA-83536/miR-24-3p/Calcr axis, presenting a potential target for novel therapeutic interventions to prevent calcium nephrolithiasis., (© 2024. The Author(s).)

Purpose: The aim of this study is to investigate the results and safety of retrograde intrarenal surgery (RIRS) in patients who have previously undergone percutaneous nephrolithotomy (PCNL)., Methods: A retrospective analysis included patients who underwent RIRS for kidney stones between August 2018 and April 2023. Group 1 comprised 396 patients who underwent primary RIRS, while Group 2 included 231 individuals who had RIRS after previous PCNL. Evaluation parameters included preoperative characteristics, stone attributes, operative details, treatment outcomes, stone-free status, and complications. Statistical analysis utilized Student's t test, Mann-Whitney U test, and Pearson Chi-square test (p < 0.05)., Results: The mean age, body mass index, stone number, mean stone burden, and SFS were not statistically different between the groups. Lower pole stones were identified in 144 patients in Group 1 and 88 patients in Group 2 (p = 0.315). In Group 1 and Group 2, the mean operation time and fluoroscopy time were 65.23 ± 18.1 min, 81.32 ± 14.3 min, 26.34 ± 8.31 s, 46.61 ± 7.6 s, respectively, showing statistically significant differences between the groups (p = 0.013, p < 0.001, respectively). Infundibulum stenosis was identified and treated with a laser in 12% of Group 2 cases. Complications occurred in 12 patients in Group 1 and 14 patients in Group 2 (p = 0.136)., Conclusion: A history of PCNL may contribute to extended operation times and increased fluoroscopy exposure in subsequent RIRS without significantly affecting postoperative SFS or complication rates., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Screening high-risk populations is crucial for the prevention and treatment of kidney stones. Here, we employed radiomics to screen high-risk patients for kidney stones. A total of 513 independent kidneys from our hospital between 2020 and 2022 were randomly allocated to training and validation sets at a 7:3 ratio. Radiomic features were extracted using 3Dslicer software. The least absolute shrinkage and selection operator (LASSO) method was used to select radiomic features from the 107 extracted features, and logistic regression, decision tree, AdaBoost, and support vector machine (SVM) models were subsequently used to construct radiomic feature prediction models. Among these, the logistic regression algorithm demonstrated the best predictive performance and stability. The area under the curve (AUC) of the logistic regression model based on radiomic features was 0.858 in the training cohort and 0.806 in the validation cohort. Furthermore, univariate and multivariate logistic regression analyses were performed to identify the independent risk factors for kidney stones, which were gender and body mass index (BMI). Combining these independent risk factors improved the predictive performance of the model, with AUC values of 0.860 in the training cohort and 0.814 in the validation cohort. Clinical decision curve analysis (DCA) indicated that the radiomic model provided clinical benefit when the probability ranged from 0.2 to 1.0. The radiomic model has a good ability to screen high-risk patients with kidney stones, facilitating early intervention in kidney stone cases and improving patient prognosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Retrograde intrarenal surgery (RIRS) is the recommended treatment for renal stones up to two cm in size. As digital health literacy (e-HL) has become increasingly important in promoting informed health decisions and healthy behaviors, it is necessary to investigate its impact on RIRS treatment outcomes. We aimed to explore the influence of patients' e-HL level on their postoperative quality of life (QoL). We conducted an observational prospective study of 111 patients who underwent RIRS for renal pelvis stones. Before RIRS, we evaluated patients' e-HL using the electronic health literacy scale (eHEALS). QoL was evaluated using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) one month after RIRS. SFR was determined by a negative CT scan or asymptomatic patients with stone fragments < 3 mm. Adult individuals aged 18 years or older with typical calyceal anatomy met the eligibility criteria for enrollment. Exclusion criteria for the study included patients with ureteric stones, anomalous kidneys, or bilateral renal stones. The relationship between patients' QoL and stone-free rate was explored using Spearman's rank correlation coefficient. The mean stone burden was 14 ± 3 mm (6-19 mm). The overall SFR was 83.3% after one month. The median EQ-5D-5L utility index and VAS score were 0.826 (0.41-1) and 70 (20-100) respectively, for the overall population. We found that poorer e-HL was associated with being older (p = 0.035), having less education (p = 0.005), and not having access to the internet (p < 0.001). A significant difference was observed between patients with sufficient e-HL and patients with limited e-HL in the self-care (p = 0.02) and anxiety/depression (p = 0.021) dimensions. To date, no study has examined the impact of patients' e-HL levels on postoperative QoL in patients undergoing RIRS. This study also revealed that e-HL levels in patients undergoing RIRS were related to postoperative QoL, especially self-care and anxiety/depression dimensions, whereas there was no relationship between them and SFR., (© 2024. The Author(s).)

Purpose: To evaluate the effect of preoperative single-dose methylprednisolone use on postoperative early pain after retrograde intrarenal surgery (RIRS)., Methods: Patients who had 10-20 mm solitary kidney stones and underwent RIRS procedures were included in this prospective cohort study between February 2022 and May 2023. Patients who were administered methylprednisolone at a dose of 1 mg/kg preoperatively were included in group 1 (n: 31), and the other first 90 patients who met the inclusion criteria and did not receive methylprednisolone before surgery were included in group 2 (n: 90). Demographic data, features of stone, postoperative pain at 1, 6, 12, 18, and 24 hour, the need for analgesics, changes in serum glucose levels, and the prevalence of postoperative fever were compared., Results: Age, sex, stone laterality, localization, size, Hounsfield Unit, modified Satava scores, stone-free status, duration of the RIRS procedure, and duration of the ureteral access sheath were found to be similar between groups. Visual Analog Scale (VAS) scores at postoperative 1, 6, 12, 18, and 24 h were found to be statistically significantly lower in group 1 (p = .001, p = .001, p = .001, p = .001, and p = .001, respectively). Similarly, postoperative analgesic requirements were found to be significantly lower in group 1 (p = .048) with a similar postoperative fever rate and changes in serum glucose levels between groups., Conclusion: Giving a single dose of methylprednisolone at a dose of 1 mg/kg preoperatively for the RIRS procedure is safe and effective at preventing early pain and the need for analgesics after the RIRS procedure., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Macrophages play a role in nephrolithiasis, offering the possibility of developing macrophage-mediated preventive therapies. To establish a system for screening drugs that could prevent the formation of kidney stones, we aimed to develop a model using human induced pluripotent stem cell (iPSC)-derived macrophages to study phagocytosis of calcium oxalate monohydrate (COM) crystals. Human iPSCs (201B7) were cultured. CD14+ monocytes were recovered using a stepwise process that involved the use of growth factors and cytokines. These cells were then allowed to differentiate into M1 and M2 macrophages. The macrophages were co-cultured with COM crystals and used in the phagocytosis experiments. Live cell imaging and polarized light observation via super-resolution microscopy were used to visualize phagocytosis. Localization of phagocytosed COM crystals was observed using transmission electron microscopy. Intracellular fluorescence intensity was measured using imaging cytometry to quantify phagocytosis. Human iPSCs successfully differentiated into M1 and M2 macrophages. M1 macrophages adhered to the culture plate and moved COM crystals from the periphery to cell center over time, whereas M2 macrophages did not adhere to the culture plate and actively phagocytosed the surrounding COM crystals. Fluorescence assessment over a 24-h period showed that M2 macrophages exhibited higher intracellular fluorescence intensity (5.65-times higher than that of M1 macrophages at 4.5 h) and maintained this advantage for 18 h. This study revealed that human iPSC-derived macrophages have the ability to phagocytose COM crystals, presenting a new approach for studying urinary stone formation and highlighting the potential of iPSC-derived macrophages as a tool to screen nephrolithiasis-related drugs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Kidney stones (KSs), in fact, have been considered one of the most ancient and prevalent medical conditions that impact a significant number of human beings all around the world. Such stones can range greatly in size and can be detected in any part of the urinary system, including the kidneys, ureters, or bladder itself. The development of stones is caused by the mineral's crystallization, which then interacts with each other and adheres together. Kidney stone formation can represent a prime medical condition for which there are numerous therapies available, among them natural ones. Recurrence of stones after curing is very common, and strategies available to prevent their reoccurrence or even their development for the first time are numerous, with enhanced fluid consumption or avoiding dehydration being the most important one., Objective: The current review article aims to draw attention to the potential of natural remedies besides lifestyle modification in the management and prevention of KSs. This is not arbitrary but based on real, documented scientific evidence., Method: The natural remedies mentioned in the context of this manuscript were chosen for their availability in almost all nations, or perhaps even in every home., Results: The findings of the present article are very promising and exhibit the potential benefit of natural remedies in addition to shifting to a healthy lifestyle in both the treatment and prevention of KSs., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

In this study, we aimed to evaluate the effect of HPL on different parameters by different centers and urologists. While doing this, we evaluated different parameters by comparing HPL(High Power laser) and LPL(Low-power laser). This is an observational, retrospective, comparative, multicentric study of prospectively organised database. A total of 217 patients who underwent RIRS for kidney stones smaller than 2 cm in three different centers were included in the study. The patients were divided into two groups; LPL used (Group1, n:121 patients) and HPL used (Group2, n:96). Propensity score matching was done in the data analysis part. After matching, a total of 192 patients, 96 patients in both groups, were evaluated. There was no difference between the groups regarding age, gender, stone side, and stone location. The stone-free rate on the first day was 80.3% in Group 1, it was 78.1% in Group 2 (p = 0.9). In the third month, it was 90.7% in Group 1 and 87.5% in Group 2 (p:0.7).Hospitalization duration was significantly higher in Group 1. (2.35 ± 2.27 days vs. 1.42 ± 1.10 days; p < 0.001).The operation duration was 88.70 ± 29.72 min in Group1 and 66.17 ± 41.02 min in Group2 (p < 0.001). The fluoroscopy time (FT) was 90.73 ± 4.79 s in Group 1 and 50.78 ± 5.64 s in Group 2 (p < 0.001). Complications according to Clavien Classification, were similar between the groups(p > 0.05). According to our study similar SFR and complication rates were found with HPL and LPL. In addition, patients who used HPL had lower operation time, hospital stay, and fluoroscopy time than the LPL group. Although high-power lasers are expensive in terms of cost, they affect many parameters and strengthen the hand of urologists thanks to the wide energy and frequency range they offer., (© 2024. The Author(s).)

The Holmium (Ho:YAG) laser is presently the most extensively employed in laser lithotripsy for the management of kidney stones. Despite its adoption as the gold standard for laser lithotripsy, Ho:YAG laser lithotripsy poses three significant challenges, namely thermal effect, insufficient stone fragmentation, and stone displacement, which have garnered increased attention from urologic surgeons. Nowadays, the femtosecond laser is regarded as a potential alternative to the Ho:YAG laser due to its capacity to ablate diverse materials with minimal thermal effect. In our ex vivo investigation, we assessed the dimensions of ablation pits, the efficacy of ablation, the degree of stone fragmentation, the alterations in water temperature surrounding stones, and the degree of tissue damage associated with Femtosecond laser lithotripsy utilizing adjustable power settings (1-50 W). Our findings indicate that the ablation pits generated by the Femtosecond laser exhibited uniform geometries, and the effectiveness of ablation and fragmentation for Femtosecond laser lithotripsy were significantly and positively correlated with laser power. When the laser power remained constant, the Femtosecond laser with higher pulse energy demonstrated superior efficiency in stone ablation, but inferior performance in stone fragmentation. Conversely, the Femtosecond laser with higher pulse frequency exhibited the opposite behavior. Furthermore, the thermal effect increased proportionally with laser power, leading to a tentative recommendation of 10W laser power for future investigations. Our in vitro findings suggest that the Femtosecond laser holds promise as a safe and effective alternative to holmium lasers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Assessing the effects of heavy metals (HMs) on kidney stone is often limited to analyzing individual metal exposures, with studies on the effects of exposure to mixtures of HMs being scarce. To comprehensively evaluate the relationship between exposure to mixed HMs and kidney stones, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2007-2016, which included 7809 adults. We used multiple statistical methods, including multiple logistic regression models, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp) and bayesian kernel machine regression (BKMR), to assess the association between single HM and mixed exposure to HMs and kidney stones. Firstly, in single exposure analysis, urinary cadmium (Cd) and cobalt (Co) demonstrated a positive association with the risk of kidney stones. Secondly, various other approaches consistently revealed that mixed exposure to HMs exhibited a positive association with kidney stone risk, primarily driven by Cd, Co, and barium (Ba) in urine, with these associations being particularly notable among the elderly population. Finally, both BKMR and survey-weighted generalized linear models consistently demonstrated a significant synergistic effect between urinary Co and urinary uranium (Ur) in elevating the risk of kidney stones. Overall, this study provides new epidemiological evidence that mixed exposure to HMs is associated with an increased risk of kidney stones. Further prospectively designed studies are needed to confirm these findings., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Our objective was to evaluate the feasibility of a multi-section continuum robotic ureteroscope to address the difficulties with access into certain renal calyces during flexible ureteroscopy. First, the robotic ureteroscope developed in previous research, which utilizes three actuated bendable sections controlled by wires, was modified for use in this project. Second, using phantom models created from five randomly selected computer tomography urograms, the flexible ureteroscope and robotic ureteroscope were evaluated, focusing on several factors: time taken to access each renal calyx, time taken to aim at three targets on each renal calyx, the force generated in the renal pelvic wall associated with ureteroscope manipulation, and the distance and standard deviation between the ureteroscope and the target. As a result, the robotic ureteroscope utilized significantly less force during lower pole calyx access (flexible ureteroscope vs. robotic ureteroscope; 2.0 vs. 0.98 N, p = 0.03). When aiming at targets, the standard deviation of proper target access was smaller for each renal calyx (upper pole: 0.49 vs. 0.11 mm, middle: 0.84 vs. 0.12 mm, lower pole: 3.4 vs. 0.19 mm) in the robotic ureteroscope group, and the distance between the center point of the ureteroscope image and the target was significantly smaller in the robotic ureteroscope group (upper: 0.49 vs. 0.19 mm, p < 0.001, middle: 0.77 vs. 0.17 mm, p < 0.001, lower: 0.77 vs. 0.22 mm, p < 0.001). In conclusion, our robotic ureteroscope demonstrated improved maneuverability and facilitated accuracy and precision while reducing the force on the renal pelvic wall during access into each renal calyx., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Bioelectric impedance analysis (BIA) is a non-invasive method that can show the distribution of fatty and lean mass of the body. In this study, we aimed to determine the effect of BIA on extracorporeal shock wave lithotripsy (SWL) success. Our secondary aim was to determine the factors predicting transition from a single SWL session to multiple sessions. Patients who underwent SWL due to kidney stones were prospectively included. Demographics, pre-procedural BIA parameters (fat percentage, obesity degree, muscle mass, total water and metabolic rate), stone parameters, and number of SWL sessions were recorded. Univariate and multivariate regression analyzes were made to determine independent risk factors for success. Then, the successful group was divided into two subgroups according to their SWL session number as one session or multiple sessions and multivariate regression analysis was made to determine independent risk factors. Stone-free status was achieved in 114 (61.2%) of 186 patients. Stone Hounsfield Unit (HU) (OR: 0.998, p = 0.004), stone volume (OR: 0.999, p = 0.023) and fat percentage (OR: 0.933, p = 0.001) were independent risk factors for stone-free status in multivariate analysis. HU value of the stone (OR: 1.003, p = 0.005) and age (OR: 1.032, p = 0.031) were determined as independent risk factors for transition to multiple sessions in the subgroup analysis of the successful group. Fat percentage, stone volume, and stone density were determined as factors affecting success in SWL. Routine use of BIA may be considered to predict success before SWL. The probability of SWL success in a single session decreases as the age and stone's HU value increase., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study seeks to evaluate the recurrence of kidney stones (ROKS) nomogram for risk stratification of recurrence in a retrospective study. To do this, we analyzed the performance of the 2018 ROKS nomogram in a case-control study of 200 patients (100 with and 100 without subsequent recurrence). All patients underwent kidney stone surgery between 2013 and 2015 and had at least 5 years of follow-up. We evaluated ROKS performance for prediction of recurrence at 2- and 5-year via area under the receiver operating curve (ROC-AUC). Specifically, we assessed the nomogram's potential for stratifying patients based on low or high risk of recurrence at: a) an optimized cutoff threshold (i.e., optimized for both sensitivity and specificity), and b) a sensitive cutoff threshold (i.e., high sensitivity (0.80) and low specificity). We found fair performance of the nomogram for recurrence prediction at 2 and 5 years (ROC-AUC of 0.67 and 0.63, respectively). At the optimized cutoff threshold, recurrence rates for the low and high-risk groups were 20 and 45% at 2 years, and 50 and 70% at 5 years, respectively. At the sensitive cutoff threshold, the corresponding recurrence rates for the low and high-risk groups were of 16 and 38% at 2 years, and 42 and 66% at 5 years, respectively. Kaplan-Meier analysis revealed a recurrence-free advantage between the groups for both cutoff thresholds (p < 0.01, Fig. 2). Therefore, we believe that the ROKS nomogram could facilitate risk stratification for stone recurrence and adherence to risk-based surveillance protocols., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study is to evaluate the usefulness of microureteroscopy (m-URS) in the treatment of renal and ureteral stones in children younger than 3 years of age. A retrospective analysis of pediatric patients aged < 3 years with upper urinary tract calculi who underwent lithotripsy was performed. The children were divided into the m-URS group (4.85 F, n = 41) and the ureteroscopy (URS) group (4.5/6.5 F, n = 42) according to the type of ureteroscope used. The mean age of the patients was 23.5 ± 10.7 months in the m-URS group and 20.6 ± 7.1 months in the URS group (P = 0.212). The success rate of one-stage surgery was 80.5% (33/41) for m-URS and 38.1% (16/42) for URS (P < 0.001). The success rates of m-URS were 60.0%, 69.2%, and 91.3% for stones located in the renal pelvis/calix, upper ureter, and mid-lower ureter, respectively. Eight children in the m-URS group and 26 children in the URS group underwent the second-stage ureteroscopic surgery. The mean operation time was 50 (30-60) min in the m-URS group and 40 (34-60) min in the URS group (P = 0.287). The complication rates were 4.9% and 7.1% in the m-URS and URS groups, respectively (P = 1.000). The stone-free rate at 1 month after lithotripsy was 87.8% in the m-URS group and 83.3% in the URS group (P = 0.563). The mean anesthesia session was 2.1 in the m-URS group and 2.5 in the URS group (P = 0.002). M-URS can effectively reduce the number of anesthesia sessions and is considered an alternative treatment for upper urinary tract calculi in selected pediatric patients younger than 3 years of age., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study was aimed at investigating the impact of varying concentrations of strontium (Sr) on calcium (Ca) excretion via the urine and determine its impact on kidney stone formation. Twenty adult male Sprague Dawley rats weighing between 200 and 300 g were selected. The rats were randomly divided into four groups of five. One group was used as a control group while the other three groups were experimental. The diet of the rats was modulated over a 12 week period to investigate the impact of Sr on the urinary excretion of Ca. Urinary samples were collected every 2 weeks from the rats. The rats were fed water ad libitum. After the study the rats were euthanised and their kidneys harvested. Urine and kidney samples from the rats were analysed using Total Reflection X-Ray Fluorescence (TXRF). In the urine excretion of Ca increased with increased intake of Sr in the diet. Sr excretion via the urine also increased with increased dietary intake. There was a correlation of 0.835 at the significance level of 0.01 between Ca and Sr in the urine. However, for the kidneys, the varying concentration of Sr did not impact the retention of Ca in the kidneys. There was increased retention of Sr in the kidneys with increased dietary intake. In this study an increase of Sr in the diet resulted in an increase in urinary excretion of Ca., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Both shock wave lithotripsy (SWL) and flexible ureterorenoscopy (F-URS) are recommended as the first choice for non-lower pole kidney stones. Therefore, we conducted a prospective study to evaluate the efficacy, safety, and cost of SWL versus F-URS in patients with solitary non-lower pole kidney stones ≤ 20 mm under the COVID-19 pandemic. This prospective study was conducted in a tertiary hospital from June 2020 to April 2022. Patients who underwent lithotripsy (SWL or F-URS) for non-lower pole kidney stones were enrolled in this study. The stone-free rate (SFR), retreatment rate, complications, and cost were recorded. Propensity score-matched (PSM) analysis was performed. A total of 699 patients were finally included, of which 81.3% (568) were treated with SWL and 18.7% (131) underwent F-URS. After PSM, SWL showed equivalent SFR (87.9% vs. 91.1%, P = 0.323), retreatment rate (8.6% vs. 4.8%, P = 0.169), and adjunctive procedure (2.6% vs. 4.9%, P = 0.385) compared with F-URS. Complications were scarce and also comparable between SWL and F-URS (6.0% vs 7.7%, P > 0.05), while the incidence of ureteral perforation was higher in the F-URS group compared with the SWL group (1.5% vs 0%, P = 0.008). The hospital stay was significantly shorter (1 day vs 2 days, P < 0.001), and the cost was considerably less (1200 vs 30,083, P < 0.001) in the SWL group compared with the F-URS group. This prospective cohort demonstrated that SWL had equivalent efficacy with more safety and cost benefits than F-URS in treating patients with solitary non-lower pole kidney stones ≤ 20 mm. During the COVID-19 pandemic, SWL may have benefits in preserving hospital resources and limiting opportunity for virus transmission, compared to URS. These findings may guide clinical practice., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Knowledge of kidney stone composition can help in patient management; urine composition analysis and dual-energy CT are frequently used to assess stone type. We assessed if threshold-based stone segmentation and radiomics can determine the composition of kidney stones from single-energy, non-contrast abdomen-pelvis CT., Methods: With IRB approval, we identified 218 consecutive patients (mean age 64 ± 13 years; male:female 138:80) with the presence of kidney stones on non-contrast, abdomen-pelvis CT and surgical or biochemical proof of their stone composition. CT examinations were performed on one of the seven multidetector-row scanners from four vendors (GE, Philips, Siemens, Toshiba). Deidentified CT images were processed with a radiomics prototype (Frontier, Siemens Healthineers) to segment the entire kidney volumes with an AI-based organ segmentation tool. We applied a threshold of 130 HU to isolate stones in the segmented kidneys and to estimate radiomics over the segmented stone volume. A coinvestigator verified kidney stone segmentation and adjusted the volume of interest to include the entire stone volume when necessary. We applied multiple logistic regression tests with precision recall plots to obtain area under the curve (AUC) using a built-in R statistical program., Results: The threshold-based stone segmentation successfully isolated kidney stones (uric acid: n = 102 patients, calcium oxalate/phosphate: n = 116 patients) in all patients. Radiomics differentiated between calcium and uric acid stones with an AUC of 0.78 (p < 0.01, 95% CI 0.73-0.83), 0.79 sensitivity, and 0.90 specificity regardless of CT vendors (GE CT: AUC = 0.82, p < 0.01, 95% CI 0.740-0896; Siemens CT: AUC = 0.77, 95% CI 0.700-0.846, p < 0.01)., Conclusion: Automated threshold-based stone segmentation and radiomics can differentiate between calcium oxalate/phosphate and urate stones from non-contrast, single-energy abdomen CT., (© 2022. The Author(s) under exclusive licence to Japan Radiological Society.)

Clinical guidelines disagree on whether the identification of abnormal urine chemistries should occur before starting diet and medication interventions to prevent the recurrence of kidney stone events. We describe the rationale and design of the Urinary supersaturation in a Randomized trial among Individuals with Nephrolithiasis comparing Empiric versus selective therapy (URINE) study, a randomized trial comparing two multi-component interventions to improve urinary supersaturation. Participants are randomized (1:1 ratio) to the empiric or selective arm. The target sample size is 56 participants. Adults ≥ 18 years of age with idiopathic calcium stone disease and two symptomatic stone events within the previous 5 years. Exclusion criteria include systemic conditions predisposing to kidney stones and pharmacologic treatment for stone prevention at baseline. Participants in the empiric arm receive standard diet therapy recommendations, thiazide, and potassium citrate. Participants in the selective arm receive tailored diet and nutrient recommendations and medications based on baseline and 1-month follow-up of 24-h urine testing results. The primary endpoints are urinary supersaturations of calcium oxalate and calcium phosphate at 2 months of follow-up. Secondary endpoints include side effects, diet and medication adherence, and changes in 24-h urine volume, calcium, oxalate, citrate, and pH. Short-term changes in urinary supersaturation may not reflect changes in future risk of stone events. The URINE study will provide foundational data to compare the effectiveness of two prevention strategies for kidney stone disease., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to investigate the genotypic and phenotypic characteristics of Chinese pediatric patients with cystinuria. This was a retrospective study of 14 Chinese pediatric patients with cystine stones. All published studies of the Chinese pediatric cystinuria population were searched and enrolled based on the inclusive standard. Among the 14 pediatric patients with cystinuria, 8 were males and 6 were females. The mean age of first stone onset was 4.0 ± 3.3 years (4 months-9 years). All of the patients had multiple stones, and 57.1% (8/14) had bilateral stones. The mean maximum stone diameter was 1.7 ± 0.6 (range 0.5-2.6) cm. A total of 13 SLC3A1 gene mutations and 9 SLC7A9 gene mutations were detected, of which 41% (9/22) of mutations were novel. Patients with SLC7A9 mutations were more likely to develop bilateral stones than those with SLC3A1 mutations (100% vs. 33.3%, p = 0.03). Thirty-four SLC3A1 gene mutations and twenty-eight SLC7A9 gene mutations were found in a total of fifty-five Chinese children with cystinuria. The SLC7A9 gene mutation distribution was more dispersed, while the SLC3A1 mutation was clustered in exons 6-8. The c.647C > T (p. T216M) (4/53) and c.1113C > A (p. Y371Ter) (4/53) mutations in the SLC3A1 gene and the c.1399 + 2&#95;3insT (3/36) mutation in the SLC7A9 gene represent potential hotspots in cystinuria. Our results present a comprehensive genetic spectrum for pediatric cystinuria patients in China. Patients with SLC7A9 mutations were more likely to develop bilateral stones than those with SLC3A1 mutations. A wide mutation spectrum and the potential mutation hotspots associated with cystinuria were also identified., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study was to construct the fourth in a series of guidelines on the treatment of urolithiasis by the International Alliance of Urolithiasis (IAU) that by providing a clinical framework for the metabolic evaluation, prevention, and follow-up of patients with urolithiasis based on the best available published literature. All recommendations were summarized following a systematic review and assessment of the literature in the PubMed database from January 1976 to June 2022. Each generated recommendation was graded using a modified GRADE methodology. Guideline recommendations were developed that addressed the following topics: initial evaluation, metabolic testing, dietary measures, medical management, and follow-up of recurrent stone formers. It was emphasized by the Panel that prevention of new stone formation is as important as the surgical removal of the stones. Although general preventive measures may be effective in reducing stone recurrence rates in some patients, specific medical and dietary management should be well considered and eventually applied in an individualized manner based on the outcomes of metabolic work-up, stone analysis and some certain patient related factors. A detailed follow-up of each case is essential depending on the metabolic activity of each individual patient., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To determine whether urine cobalt (Co) is associated with the prevalence of kidney stones, we conducted a cross-sectional study of participants (≥ 20 years) involved in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. The urine Co level was divided into four groups: 0.02-0.22, 0.22-0.36, 0.36-0.58, and 0.58-37.40 μg/L. The independent correlation between urine Co and prevalence of kidney stones was determined by logistic regression analyses. A total of 10,744 participants aged over 20 years that were not pregnant were eligible. Among them, 1041 participants reported ever having developed kidney stones. Patients with kidney stones developed significantly higher urine Co than the non-stone participants. The kidney stone patients were more likely to have been smoking ≥ 100 cigarettes in life; have hypertension, diabetes, and cancer; and engage in heavy activity. Multivariate logistic regression indicated a significantly positive relationship between the urine Co level and occurrence of kidney stones (OR 1.059, 95% CI 1.018-1.102, P = 0.00430). Moreover, the outcome remained unchanged after some sophisticated factors were adjusted (OR 1.059, 95% CI 1.001-1.120, P = 0.04635), and kidney stones were significantly related to a higher level of Co (OR (95% CI) = 0.22-0.36 μg/L: 1.111 (0.869, 1.421); 0.36-0.58 μg/L: 1.392 (1.095, 1.770); 0.58-37.40 μg/L: 1.712 (1.351, 2.170), and P for trend < 0.00001). So, urine Co concentration is positively associated with the prevalence of kidney stones. However, more high-quality prospective studies are needed to elucidate the causal correlation between Co level and kidney stones., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Kidney stones are regarded as common malignant diseases in the developed world. As a result, significant research examining their formation is ongoing, with microRNAs (miRs) recently being linked with kidney stone formation. Here, we aim to define the potential role of miR-484 in regulating renal tubular epithelial cell (RTEC) viability and the attachment of calcium oxalate (CaOx) crystals to RTECs via vitamin D receptor (VDR)/forkhead box protein O1 (FoxO1) axis. The pathological condition of CaOx crystallization was induced and examined in Sprague-Dawley rats, while RTECs were isolated and cultured in vitro. Loss- and gain-function assays were performed to study the effects that miR-484, VDR, and FoxO1 on RTEC functions and CaOx crystallization in vitro and on kidney stone formation in vivo. The interaction between miR-484 and VDR was confirmed by dual-luciferase reporter gene assays. Downregulation of miR-484 and FoxO1 as well as overexpression of VDR were identified in kidney stone modelled rats. VDR was confirmed as a target gene of miR-484, while knockdown of VDR upregulated the FoxO1 expression. miR-484 overexpression or VDR suppression reduced RTEC cytotoxicity and crystal attachment to RTECs in vitro and reduced the CaOx crystallization in vivo. Taken together, these findings suggest that miR-484 overexpression may be a potential inhibitor of RTEC proliferation and CaOx crystallization through a VDR/FoxO1 regulatory axis, providing a novel therapeutic target for the treatment of kidney stone., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hypercalciuria is the main risk factor for recurrent calcium urolithiasis. The goal of our study is to determinate how useful an oral calcium load test is for stone formers to classify different forms of hypercalciuria in pathogenetic categories defined as renal or absorptive according to the current knowledge. Between June 2013 and February 2016, a prospective study was carried out on 117 documented recurrent hypercalciuric stone formers undergoing an oral calcium load test modified from the original description by Pak. After 2 days of calcium-restricted diet, urine and blood were analyzed at baseline and 120 min after receiving orally 1 g of calcium. Total and ionized calcium, parathyroid hormone from serum and urine calcium and creatinine were assessed in order to divide patients in three groups as previously described: resorptive, absorptive, and renal hypercalciuria. This allowed the identification of 19, 39, 34 and 33 patients with normocalcemic primary hyperparathyroidism (NPHPT), renal hypercalciuria aka renal calcium leak (RCL), absorptive hypercalciuria (AH) and unidentified cause, respectively. Patients with NPHPT (who required parathyroidectomy) experienced a lower PTH decrease (41.41 ± 12.82 vs. 54.06 ± 13.84% p < 0.01), higher beta-crosslaps, as well as lower TmP/GFR and distal third radius bone mineral density. RCL resulted in increased fasting urine calcium-to-creatinine ratio (Uca/Cr), i.e., > 0.37 mmol/mmol), without hyperparathyroidism. AH was diagnosed by the presence of ΔUCa/Cr > 0.60 mmol/mmol between baseline and 120 min without any other anomaly. For all remaining patients, results were inconclusive due to the lack of sufficient increase in serum calcium or because the cause of lithogenesis could not be clearly identified. The oral calcium load test is useful in nearly 80% of patients by identifying the different forms of hypercalciuria causing urolithiasis and by guiding treatment, including parathyroid surgery., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We aimed to perform a systematic review of randomized trials to summarize the evidence on the safety and stone-free rate after Tubeless percutaneous nephrolithotomy (PCNL) (ureteral stent/catheter, no nephrostomy) compared to Standard PCNL (nephrostomy, with/without ureteral stent/catheter) to evaluate if the tubeless approach is better. The inverse variance of the mean difference with a random effect, 95% Confidence Interval (CI), and p values was used for continuous variables. Categorical variables were assessed using Cochran-Mantel-Haenszel method with the random effect model, and reported as Risk Ratio (RR), 95% CI, and p values. Statistical significance was set at p < 0.05 and a 95% CI. 26 studies were included. Mean operative time was significantly shorter in the Tubeless group (MD-5.18 min, 95% CI - 6.56, - 3.80, p < 0.00001). Mean postoperative length of stay was also significantly shorter in the Tubeless group (MD-1.10 day, 95% CI - 1.48, - 0.71, p < 0.00001). Incidence of blood transfusion, angioembolization for bleeding control, pain score at the first postoperative day, the number of patients requiring postoperative pain medication, fever, urinary infections, sepsis, perirenal fluid collection, pleural breach, hospital readmission, and SFR did not differ between the two groups. Incidence of postoperative urinary fistula was significantly lower in the Tubeless group (RR 0.18, 95% CI 0.07, 0.47, p = 0.0005). This systematic review shows that tubeless PCNL can be safely performed and the standout benefits are shorter operative time and hospital stay, and a lower rate of postoperative urinary fistula., (© 2022. The Author(s).)

The purpose of this study was to evaluate the long-term outcomes of patients undergoing prophylactic intervention or active surveillance for asymptomatic kidney stones and identify factors influencing the outcomes. In this retrospective cohort study, we reviewed the medical records of patients with asymptomatic kidney stones in two institutes between November 2014 and November 2019. Standardized questions were asked via phone calls to supplement the outcomes. Pain, hydronephrosis, stone growth, serious infection, gross hematuria, and spontaneous passage were defined as stone-related events. Future intervention was also recorded to evaluate management. A total of 101 patients with 120 kidney units were enrolled in this study. The median follow-up time was 63 months. The patients were classified into the control group (79 cases) or exposure group (41 cases) according to whether they underwent prophylactic intervention before any stone-related events. Generally, the rates of stone-related events and future intervention were significantly different between the two groups (57.0 vs. 12.2%, p < 0.001; and 31.6 vs. 4.9%, p = 0.002, respectively). After applying stabilized inverse probability of treatment weighted, Cox regression suggested that patients who underwent prophylactic intervention were less likely to experience stone-related events and future intervention (HR = 0.175, and HR = 0.028, respectively). In conclusion, patients who underwent prophylactic intervention had a lower risk of stone-related events and future intervention, although they had some slight complications., (© 2022. The Author(s).)

Recent evidence has suggested that recurrent urinary tract infection (UTI) can cause not only infection stones but also metabolic stones (e.g., those containing calcium oxalate monohydrate or COM). However, precise mechanisms underlying UTI-induced metabolic stones remained unknown. In this study, Escherichia coli, the most common bacterium found in recurrent UTI was used to establish the in vitro model for persistent infection of renal epithelial cells. The promoting effects of persistent E. coli infection on kidney stone formation were validated by COM crystal-cell adhesion assay, followed by immunofluorescence study for changes in surface expression of the known COM crystal receptors. Among the five receptors examined, only ezrin had significantly increased level on the surface of persistently infected cells without change in its total level. Such translocation of ezrin to apical membranes was confirmed by Western blotting of apical membrane and cytosolic fractions and confocal microscopic examination. Additionally, persistent infection increased phosphorylation (Thr 567 ) of ezrin. However, all of these changes induced by persistent E. coli infection were significantly inhibited by small-interfering RNA (siRNA) specific for ezrin or a Rho-associated kinase (ROCK)-specific inhibitor (Y-27632). In summary, this study provides a piece of evidence demonstrating that persistent infection by E. coli, one of the non-urease-producing bacteria, may contribute to COM metabolic stone formation by translocation of ezrin to apical membranes, thereby promoting COM crystal-cell adhesion. Such ezrin translocation was mediated via Rho/ROCK signaling pathway. These findings may, at least in part, explain the pathogenic mechanisms underlying recurrent UTI-induced metabolic kidney stone disease., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Genetic renal phosphate leak is one of the rare disorders in recurrent stone formers with absorptive hypercalciuria. Diagnosis and appropriate management may change the life of patients. To provide answers on how and when to make the diagnosis of genetic renal phosphate leak and how medical management prevents the recurrences and changes patients' life, we conducted a retrospective study including nine patients with recurrent nephrolithiasis and a confirmed genetic mutation of a phosphate transporter between 2008 and 2019 in our multidisciplinary center at the Pitié Salpetriere Hospital, Paris, France. We compared the number and the annual rate of urological intervention before and after the diagnosis and management using the Wilcoxon test. A qualitative survey was done to evaluate the quality of life of patients. A total of 9 patients were included in this study. Patient baseline characteristics and elements supporting the diagnosis are described. We showed an effective decrease in urological intervention number (p = 0.0078) and annual rate (p = 0.0117) after the diagnosis and the appropriate management, and an improvement in the patients' quality of life. The diagnosis and the appropriate management of genetic renal phosphate leak disorder improve the quality of life by preventing stone recurrence and decreasing the number of surgical intervention., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim of this study is to categorize stones between 10 and 20 mm according to stone diameter or volume and compare mini percutaneous nephrolithotomy (mPNL) and retrograde intrarenal surgery (RIRS) outcomes. Files of 515 patients who underwent surgery for kidney stones with sizes 10-20 mm were reviewed. Patients were divided into RIRS or mPNL groups. An attempt was made to find the diameter and volume threshold values above which the success of the operation, complication rates and the number of auxiliary treatments deteriorated. Subgroup analysis was performed below and above the threshold value to reveal the optimal treatment methods. RIRS complications increased with volumes above 1064 mm 3 , number of auxiliary interventions increased with volumes above 1256 mm 3 , and success of the operation decreased with volumes above 1416 mm 3 . A subgroup analysis under and over 1064 mm 3 was performed in RIRS group. Complication and auxiliary treatment rates were higher, operative success was lower in patients with a stone volume greater than 1064 mm 3 . In patients who underwent RIRS, for every 1000 mm 3 increase in stone volume success of the operation decreased by 2.1 times, while the probability of auxiliary treatment increased by 2.8 times. In patients with kidney stones between 10 and 20 mm, it is more meaningful to use volume instead of diameter to determine the success rate. When mPNL is used instead of RIRS for volumes greater than 1064 mm 3 , the success rate will be higher, complication rate will be similar, and the need for auxiliary treatment will be lower., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To explore the roles microbiome of urinary tract played in calcium oxalate stones (CaOx) formation, we collected two sides' pelvis urine of patients with unilateral CaOx stones to set self-control to diminish the influence of systemic factors. Patients with unilateral CaOx stones were recruited in our study according to strict criteria. 16S rRNA gene sequencing was applied to every pair of pelvis urine. Bacterial genome sequencing of Enterobacter cloacae was conducted and bioinformatic analysis was applied to explore the possible pathways of Enterobacter cloacae inducing CaOx stones formation. In vivo experiments were conducted to validate our claims. Von Kossa staining, TUNEL assay and Western Blot were applied to SD rats exploring the mechanism of stone formation. We found 26 significantly different bacteria between stone sides and non-stone sides' pelvis urine, among which Enterobacter cloacae ranked the most different. Bacterial genome sequencing of Enterobacter cloacae revealed that its virulence factors included Flagellin, LPS and Fimbrial. GO and KEGG analysis revealed it probably induced CaOx stone formation via ion binging and signaling transduction pathways. The results of animal experiments indicated that Glyoxylic Acid could promote apoptosis and crystal depositions of kidney comparing with control group while pre-injected with Enterobacter cloacae could apparently compound the effects. While Western Blot demonstrated that Glyoxylic Acid or Enterobacter cloacae could increase the expression of IL-6, Mcp-1, BMP2 and OPN in rats' kidney, Glyoxylic Acid and Enterobacter cloacae together could aggravate these increases. These findings indicated that Enterobacter cloacae might play important roles in CaOx stones formation. However, this study is just a preliminary exploration; further studies still need to be conducted., (© 2022. The Author(s).)

During the development of urinary stone disease, the formation of tiny crystals that adhere to the renal tubular epithelium induces epithelial cell damage. This damage and repair of the epithelium is associated with the establishment of more crystal adhesion sites, which in turn stimulates further crystal adhesion and, eventually, stone formation. Deposited crystals typically cause changes in epithelial cell gene expression, such as transcriptome changes and alternative splicing events. Although considered important for regulating gene expression, alternative splicing has not been reported in studies related to kidney stones. To date, whether alternative splicing events are involved in the regulation of stone formation and whether crystallographic cell interactions are regulated by alternative splicing at the transcriptional level have remained unknown. Therefore, we conducted RNA sequencing and alternative splicing-related bioassays by modeling the in vitro stone environment. Many alternative splicing events were associated with crystallographic cell interactions. Moreover, these events regulated transcription and significantly affected the capacity of crystals to adhere to renal tubular epithelial cells and regulate apoptosis., (© 2021. The Author(s).)

Fictional portrayals of medical conditions on television have been shown to significantly shape understanding and management expectations of the viewing public. Given the high prevalence of kidney stone disease, we aimed to assess the frequency of its portrayal on US television and assess whether its depiction was reflective of the current epidemiology or management of urolithiasis in the US. A detailed search was conducted for English language depictions of kidney stones in fictional television using internet, movie and television database search engines. Television episodes with characters depicting a kidney stone occurrence were independently reviewed by two reviewers and analyzed for genre, initial air date on US television, character age, gender, race and management strategy. Seventeen episodes from 13 different television series portrayed a character with a symptomatic kidney stone. The majority were male (88%). Surgical intervention was performed in 7/17 cases (shockwave lithotripsy n = 1, ureteroscopy n = 2, nephrectomy n = 1, transurethral removal n = 1, unknown n = 2), spontaneous passage or medical expulsive therapy in 7/17 cases and no treatment or resolution portrayed in 3/17 cases. The only surgical complication shown was ureteral avulsion during ureteroscopy. Inpatient management was seen in 9/14 (64%) cases with event resolution. This study identified a number of kidney stone depictions that may be misleading or misrepresent the presentation and management of this condition. Although likely portrayed for plot development and dramatic effect, this could potentially reinforce inaccurate beliefs or misconceptions and future depictions should be mindful of this., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To evaluate the efficacy of a unique imaging software "OptiVision" on the confidence of stone identification using X-ray imaging during shockwave lithotripsy. A total of 57 patients with solitary radio-opaque kidney stones sized < 15 mm were included and evaluated with appropriate radiological imaging and laboratory studies before undergoing shockwave lithotripsy (SWL). The size of the stones was measured on KUB and CT images using maximal stone diameters. All patients were evaluated with radiography on the Dornier Delta III immediately before SWL and at the end of the SWL session with fluoroscopy, a snapshot image, and the OptiVision modality (applied over the acquired snapshot image without additional radiation exposure) for precise identification of the stone. All images obtained with these three different imaging modalities (fluoroscopy, snapshot, and OptiVision) were comparatively evaluated for confidence levels in stone identification using a five-point Likert scale (1 = poor diagnostic confidence, 5 = excellent diagnostic confidence). These confidence levels were also used to differentiate between stones and bony structures using these same imaging modalities. Results were evaluated for statistical significance regarding their impact on the precise identification of renal stones. A total of 57 patients with solitary stones were evaluated using flouroscopy, snapshot, and OptiVision images before and after SWL to ascertain the efficacy of these 3 imaging modalities on the precise identification of the calculi. Stone sizes ranged from 4 to 15 mm, with a mean of 8.30 mm in the longest dimension. Evaluation of the findings demonstrated that while the pre- and post-SWL confidence of fluoroscopic stone identification was from 29.51 to 31.15%, the values using snapshot ranged from 31.15 to 39.34%. Pre- and post-SWL confidence of stone identification with OptiVision post-processing imaging was approximately 89%. In the majority of cases (n = 43), the use of OptiVision image processing enabled urologists to identify the stone with a higher level of confidence rating than the use of both fluoroscopy (n = 0) and snapshot (n = 0) image processing tools. While a rating level of 4 or higher was given in 89% of images obtained by OptiVision during the pre- and post-SWL phase, this value was only 37% (4 or more points) using fluoroscopy and Snapshot image processing techniques. For all the radiography image processing tools, the distribution of the Likert score differed significantly among the OptiVision, fluoroscopy, and snapshot imaging modalities (p < 0.001). Precise and reliable identification of stone(s) located in the kidney is essential in delivering shock waves to the desired focal point and achieving higher stone-free rates. Our findings demonstrated that using the specially designed imaging modality OptiVision was significantly helpful in identifying and localizing stones with high-quality images before SWL for effective stone disintegration during this procedure., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The mechanism underlying phosphatidylserine eversion in renal tubule cells following calcium oxalate-mediated damage remains unclear; therefore, we investigated the effects of TGF-β1/Smad signaling on phosphatidylserine eversion in the renal tubule cell membrane during the early stage of kidney stone development. In a rat model of early stage of calcium oxalate stone formation, phosphatidylserine eversion on the renal tubular cell membrane was detected by flow cytometry, and the expression of TGF-β1 (transforming growth factor-β1), Smad7, and phospholipid scramblase in the renal tubular cell membrane was measured by western blotting. We observed that the TGF-β1/Smad signaling pathway increased phosphatidylserine eversion at the organism level. The results of in vitro studies demonstrated that oxalate exposure to renal tubule cells induced TGF-β1 expression, increasing phospholipid scramblase activity and phosphatidylserine eversion in the renal tubule cell membrane. These results indicate that TGF-β1 stimulates phosphatidylserine eversion by increasing the phospholipid scramblase activity in the renal tubule cell membrane during the early stage of kidney stone development. The results of this study form a basis for further detailed research on the development of therapeutic agents that specifically treat urolithiasis and exert fewer adverse effects., (© 2021. The Author(s).)

Obesity increases the risk of several diseases, including kidney stone disease (KSD). The study aimed to explore the relationship between KSD and various obesity-related indices. A total of 121,605 participants in the Taiwan Biobank from December 2008 to February 2020 were analyzed. The association between self-reported history of KSD and eight obesity-related indices, including body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), abdominal volume index (AVI), body roundness index (BRI), conicity index, and triglyceride glucose index was examined in cross-sectional analysis; additionally, the risk of developing kidney stones was analyzed in a longitudinal cohort of 25,268 participants without KSD at baseline, which was a subset of the main cohort. Of all participants, 77,904 (64.1%) were female. Overall, 10.7% of males and 4.0% of females had KSD. Multivariate-adjusted logistic regression showed that all obesity-related indices were significantly associated with KSD. During a mean follow-up of 47 months, kidney stones occurred in 642 (2.5%) participants, and after adjusting for confounders, the risk of developing kidney stones was higher in participants with higher BMI, WC, WHtR, WHR, AVI and BRI. BMI, WC, WHtR, WHR, AVI, and BRI were found to be associated with a higher prevalence of kidney stones as well as development of incident kidney stones, which could be used as predictive factors for development of KSD in clinical practice., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of the current prospective pilot study was to describe a hyperaccuracy three-dimensional (HA3D ™ ) model reconstruction technique, specifically developed to maximize the visualization of the renal collecting system's anatomy, and its relationship with the stones, vessels and renal parenchyma, and to compare the HA3D ™ virtual models with the intraoperative findings. The image acquisition was performed using a CT scanner (Toshiba, Aquilion Prime) and included the unenhanced, arterial, venous and excretory phases. The DICOM format CT images were processed by MEDICS Srl ( www.medics3d.com , Turin, Italy). In total, study included three patients with renal stone scheduled for non-papillary prone percutaneous nephrolithotomy (PCNL). The median age and BMI were 51 (range 49-54) and 25.5 (range 25.0-32.7), respectively. The median stone size was 1170 mm 2 (range 830-1520) and median stone density was 1130 HU (range 600-1340). In all cases, the quality of the CT images acquired with our protocol was adequate to perform the HA3D ™ reconstruction. Median operative and puncture time were 39.4 (range 35.2-44.0) and 1.9 (range 1.8-2.1) mins, respectively. The success rate for the first attempt of the percutaneous puncture was 100%, and only one PCNL tract was sufficient to complete the surgery. All three patients were stone-free on the third postoperative day. A dedicated imaging acquisition protocol and a tailored 3D model reconstruction process specifically developed for kidney stones treatment allow obtaining HA3D ™ highly relevant models to greatly match intraoperative findings during PCNL with the potential of minimizing bleeding and organ injury complications., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Previous clinical studies have shown that Escherichia coli (E. coli) predominated in urine and stone culture from calcium oxalate (CaOx) stone disease. The characteristic and relationship between E. coli isolated from urine cultures (EUC) and stone cultures (ESC) are compared. 83 E. coli (33 EUC and 50 ESC, respectively) from 66 CaOx stone patients were recruited in the study. E. coli in urine and stones from those patients were assessed by antimicrobial susceptibility test, genotyping and phylogenetic grouping. Furthermore, whole genome sequencing and comparative genomic analysis in paired ESC and EUC isolated strains from eight patients were carried out. The E. coli strains from ESC and EUC were not only multidrug resistant (MDR), but also had the similar pattern of resistant genes. The dominant phylogenetic group was B2, which was found in 54.0% of the ESC samples and 69.7% of the EUC samples, respectively. The virulence genes of E. coli, which isolated from stones and urine in the same patients, were highly homologous and largely consistent. Meanwhile, these E. coli strains were located in the same clade originated from a common ancestor. ESC and EUC isolated from patients with CaOx stones had a high prevalence of phylogenetic groups B2. Bacterial strains isolated from urine and stones in the same patient had consistent antimicrobial susceptibility profiles, genotyping, phylogenetic groups, virulence and resistance genes, also with high sequence co-linearity and close relationships., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: The effect of urolithiasis on pregnancy-related outcomes remains unknown. The aim of this study was to determine the risk of adverse maternal and neonatal outcomes., Methods: We searched PubMed, Embase, and the Cochrane Library through December 2020 for studies reporting on adverse maternal and neonatal outcomes in patients with urolithiasis. Risk ratios (ORs) with 95% confidence intervals (CIs) were calculated for these outcomes in pregnant mothers with urolithiasis and compared to healthy controls., Results: Eight studies comprising 26,577 mothers with urolithiasis were included in our analysis. Preterm birth (OR = 1.63; 95% CI 1.37-1.95, p < 0.001) or very preterm birth risk (OR = 1.49, 95% CI 1.06-2.11, p = 0.02) was more common in patients with urolithiasis compared to healthy controls. Mothers with urolithiasis had an increased incidence of preeclampsia (OR = 1.75, 95% CI 1.33-2.3, p < 0.001), hypertension (OR = 2.97, 95% CI 1.31-6.71, p = 0.009), caesarean section (OR 1.31, 95% CI 1.11-1.55, p = 0.001), and gestational diabetes mellitus (OR 1.84, 95% CI 1.37-2.46, p < 0.001)., Conclusion: Patients with urolithiasis may be at increased risk of developing adverse maternal or neonatal outcomes., (© 2021. Italian Society of Nephrology.)

Purpose: To assess the impact of interactions between kidney stone formation and conventional risk factors on incident chronic kidney disease (CKD)., Methods: A total of 11,402 subjects (men 30-69 years of age, Japanese) without CKD at baseline were observed over an average period of 4 years. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to determine the association between incident CKD, kidney stone formation, and conventional risk factors (diabetes mellitus, hypertension, overweight/obesity, dyslipidemia, and hyperuricemia/gout). We also examined the interactions of renal stones and the conventional risk factors for CKD., Results: In total, 2301 men (20.2%) developed incident CKD during the follow-up period. After multivariable adjustment, kidney stones were found to increase the risk of incident CKD (HR 1.16; 95% CI 1.03-1.32). Kidney stone formers with hypertension, dyslipidemia, or hyperuricemia/gout presented a greater risk for incident CKD than those who had either kidney stones or other risk factors. However, no significant interactions between kidney stones and other risk factors were found to increase CKD risk. On the other hand, a negative interactive effect between kidney stones and overweight/obesity was observed, leading to reversed risk of incident CKD in coexistence of both factors., Conclusion: Kidney stones were linked to a higher risk for the development of CKD. However, no positive interactive effects were identified between renal stones and conventional risk factors on the risk of incident CKD.

Purpose: To develop and validate a deep learning and thresholding-based model for automatic kidney stone detection and scoring according to S.T.O.N.E. nephrolithometry., Procedures: Abdominal noncontrast computed tomography (NCCT) images were retrospectively archived from February 2018 to April 2019 for three parts: a segmentation dataset (n = 167), a hydronephrosis classification dataset (n = 282), and test dataset (n = 117). The model consisted of four steps. First, the 3D U-Nets for kidney and renal sinus segmentation were developed. Second, the deep 3D dual-path networks for hydronephrosis grading were developed. Third, the thresholding methods were used to detect and segment stones in the renal sinus region. The stone size, CT attenuation, and tract length were calculated from the segmented stone region. Fourth, the stone's location was determined. The stone detection performance was estimated with sensitivity and positive predictive value (PPV). The hydronephrosis grading and stone size, tract length, number of involved calyces, and essence grading were estimated with the area under the curve (AUC) method and linear-weighted κ statistics, respectively., Results: The stone detection algorithm reached a sensitivity of 95.9 % (236/246) and a PPV of 98.7 % (236/239). The hydronephrosis classification algorithm achieved an AUC of 0.97. The scoring model results showed good agreement with radiologist results for the stone size, tract length, number of involved calyces, and essence grading (κ = 0.95, 95 % confidence interval [CI]: 0.92, 0.98; κ = 0.97, 95 % CI: 0.95, 1.00; κ = 0.95, 95 % CI: 0.92, 0.98; and κ = 0.97, 95 % CI: 0.94, 1.00), respectively., Conclusions: The scoring model was constructed that can automatically detect and score stones in NCCT images.

The present study is intended to investigate the usability of shear wave elastography (SWE) in predicting the success of extracorporeal shock-wave lithotripsy (ESWL) used in kidney stone treatment. ESWL was performed on a total number of 52 patients diagnosed with kidney stones between May 2019 and July 2020. The presence of a residual stone greater than 4 mm was accepted as failure. The patients were divided into two groups as ESWL success and ESWL failure. SWE and Hounsfield unit (HU) measurements of stones were performed in all patients before ESWL. The two groups were compared in terms of age, gender, stone localisation, stone size, body mass index (BMI), skin-to-stone distance, HU, and SWE values of the stones. ESWL was successful in 30 of the 52 patients included in the study, while it failed in 22 of them. While the mean SWE value was 7.3 (7.9 ± 2.2) kPa in patients with success in ESWL, it was 14.6 (17.9 ± 10.2) kPa in those with failed ESWL. The mean HU was 883.5 (841.4 ± 191.1) in patients with success in ESWL and 1078 (1115.5 ± 183) in those with failed ESWL. Both SWE and HU values of the stones were found to be statistically significantly lower in the successful group (p < 0.05). It was seen that SWE and HU values were correlated to each other. The groups of successful and failed ESWL did not differ significantly in terms of age, gender distribution, stone size, BMI, and skin-to-stone distance (p > 0.05). With SWE, the hardness of the stone can be measured and its suitability for ESWL can be evaluated. It can be used as an alternative parameter to HU before ESWL treatment, since it has a lower cost compared to computed tomography (CT) and does not contain radiation.

Antibiotics can alter the gut microbiome (GMB), which may be associated with stone disease. We sought to determine the effect that antibiotics have on the GMB, urine ion excretion and stone formation in genetic hypercalciuric stone-forming (GHS) rats. 116th generation GHS rats were fed a fixed amount of a normal calcium (1.2%) and phosphate (0.65%) diet, and divided into three groups (n = 10): control (CTL) diet, or supplemented with ciprofloxacin (Cipro, 5 mg/day) or Bactrim (250 mg/day). Urine and fecal pellets were collected over 6, 12 and 18 weeks. Fecal DNA was amplified across the 16S rRNA V4 region. At 18 weeks, kidney stone formation was visualized by Faxitron and blindly assessed by three investigators. After 18 weeks, urine calcium and oxalate decreased with Bactrim compared to CTL and Cipro. Urine pH increased with Bactrim compared to CTL and Cipro. Urine citrate increased with Cipro compared to CTL and decreased by half with Bactrim. Calcification increased with Bactrim compared to CTL and Cipro. Increased microbial diversity correlated with decreased urinary oxalate in all animals (R = - 0.46, p = 0.006). A potential microbial network emerged as significantly associated with shifts in urinary pH. Bactrim and Cipro differentially altered the GMB of GHS rats. The Bactrim group experienced a decrease in urine calcium, increased CaP supersaturation and increased calcification. The GMB is likely a contributing factor to changes in urine chemistry, supersaturation and stone risk. Further investigation is required to fully understand the association between antibiotics, the GMB and kidney stone formation.

Purpose: Nephrolithiasis is a urological pathology that occurs at high rates and carries a great burden in terms of costs. The probability of recurrence is significant, necessitating improvements in prophylaxis and understanding of the disease mechanism. Despite the high heritability of this disease, only five genome-wide association studies (GWAS) of nephrolithiasis have been published., Methods: We selected 335 unrelated confirmed nephrolithiasis cases from two major sample collection projects (blood and buccal swabs) in Romania. DNA was extracted from whole blood and buccal swabs at deCODE Genetics (Reykjavik, Iceland) and genotyped., Results: Single-nucleotide polymorphisms identified from this GWAS implicated biological pathways and gene ontologies involving solute transport, renal physiology, and calcium homeostasis. Three loci especially emerged as candidates with a highly significant association with nephrolithiasis: RS10917682 in Regulator of G protein signaling 5, which has crucial roles in mRNA regulation and has been linked to renal cell carcinoma; RS1118528 in Solute carrier family 25 member 24, which encodes a mitochondrial ATP-Mg/phosphate carrier protein that likely influences a variety of important cellular pathways; and the TOX2-associated locus rs4437026, because TOX2 is upregulated in several tumor types and linked to tumor progression., Conclusion: This study is the largest kidney stone-related GWAS reported in an Eastern European population and the first GWAS performed in a Romanian population to investigate the genetic risk factors for nephrolithiasis. We identified several loci that warrant further investigation for a better understanding of this highly heritable condition.

The overall prevalence of kidney stones (KS) in the US rose from 3.2% in 1980 to 10.1% in 2016, but the trends in important subgroups have not been reported. We examined the prevalence trends of KS in subgroups of age, sex and race in the US and identified relevant laboratory factors associated with a history of KS using National Health and Nutrition Examination Survey (NHANES) data. We conducted a cross-sectional study among 28,209 US adults aged ≥ 20 years old in the NHANES from 2007 to 2016. We calculated the prevalence of a self-reported history of KS by using weights and standardized to the 2010 US Census population. We also compared relevant laboratory values according to the history of KS. The prevalence of KS decreased from 8.7% in 2007-2008 to 7.2% in 2011-2012 but then increased to 9.0% in 2013-2014 and 10.1% in 2015-2016. However, the overall prevalence of KS increased over 2007-2016 (p-trend = 0.02). Prevalence of KS among men was higher than women. Among men aged 20-79, there were significant quadratic trends in the prevalence of KS. Whereas, the prevalence of KS increased as a linear trend among women aged 20-59 years over 2007-2016. There were no consistent trends in the prevalence of KS by race. The prevalence trend of KS among non-Hispanic whites was 9.8% from 2007 to 2010 then dropped to 7.9% in 2011-2012 and increased to 10.6% in 2013-2014 and 12.1% in 2015-2016. A similar trend was also observed among non-Hispanic blacks. Among Hispanic, the prevalence of KS was 7.6% in 2007-2008 and 7.4% in 2009-2010 and then fluctuated over the next several time periods. For non-Hispanic Asians, the range was 4.4-4.6%. Regarding relevant laboratory factors, after adjusting for sex, race, age, BMI, smoking status, alcohol drinking, history of diabetes and gout, urine albumin-creatinine ratio and serum osmolality were independently associated with the history of KS in women and men. In conclusion, there was substantial variability in KS prevalence across individual 2-year time periods. This variation of period-specific prevalence values emphasizes the importance of looking at long-term trends and using more than a single 2-year cycle in analyses to increase the precision of the estimate. However, there was an overall increase in the prevalence of KS over 2007-2016.

The aim of this work was to determine which part of a double-J ureteral stent (DJ stents) showed the highest tendency to crystal, calculi, and biofilm deposition after ureterorenoscopic-lithotripsy procedure (URS-L) to treat calcium oxalate stones. Additionally, the mechanical strength and the stiffness of DJ stents were evaluated before and after exposure to urine. Obtained results indicated that the proximal (renal pelvis) and distal (urinary bladder) part is the most susceptible for post-URS-L fragments and urea salt deposition. Both, the outer and inner surfaces of the DJ ureteral stents were completely covered even after 7 days of implantation. Encrustation of DJ stents during a 31-day period results in reducing the Young's modulus by 27-30%, which confirms the loss of DJ stent elasticity and increased probability of cracks or interruption. Performed analysis pointed to the need to use an antibacterial coating in the above-mentioned part of the ureteral stent to prolong its usage time and to prevent urinary tract infection.