Search

Remnant cholesterol (RC), a key indicator of dyslipidemia, has been validated as a contributing factor to metabolic and cardiovascular diseases, both of which are closely associated with kidney stones (KS). This study aimed to investigate the association between RC and the risk of KS in Chinese adults. A total of 8,576 KS cases (mean age 55.87, 69.37% male) and 137,523 controls (mean age 54.57, 51.62% male) were included in this case-control study. RC was calculated using the formula: RC = TC-HDL-LDL. KS was ascertained with ultrasound by well-trained physicians. Multivariable logistic and restricted cubic spline (RCS) were applied to investigate the relationship between RC and KS. A total of 146,099 subjects (weighted mean age 54.64 years and 52.66% male) were included with mean RC = 0.8 for controls and RC = 0.72 for KS cases (P < 0.001). The multivariable-adjusted OR for KS occurrence across consecutive quartiles was 1.00 (reference), 1.05 (0.98–1.12), 1.15 (1.07–1.22), and 1.44 (1.35–1.53), respectively. Moreover, each standard deviation increment of RC was associated with a 15% (OR:1.15, 95% CI: 1.12–1.19) higher risk of KS occurrence. RCS showed significant and linear dose-response relationships between RC and KS occurrence (P-overall < 0.001, P-nonlinear = 0.270). The positive associations between RC and KS risk persisted in sensitivity analyses, suggesting the robustness of the results. In this case-control study of Chinese adults, elevated RC was associated with the occurrence of KS. [ABSTRACT FROM AUTHOR]

Kidney stones are the most common urinary system diseases, and early identification is of great significance. The purpose of this study was to use routine urine and blood detection indices to build a deep learning (DL) model to identify the presence of kidney stones in the early stage. A retrospective analysis was conducted on patients with kidney stones who were treated at West China Hospital of Sichuan University from January 2020 to June 2023. A total of 1130 individuals presenting with kidney stones and 1230 healthy subjects were enrolled. The first blood and urine laboratory data of participants at our hospital were collected, and the data were divided into a training dataset (80%) and a verification dataset (20%). Additionally, a long short-term memory (LSTM)-based adaptive feature weighting model was trained for the early identification of kidney stones, and the results were compared with those of other models. The performance of the model was evaluated by the area under the subject working characteristic curve (AUC). The important predictive factors are determined by ranking the characteristic importance of the predictive factors. A total of 17 variables were screened; among the top 4 characteristics according to the weight coefficient in this model, urine WBC, urine occult blood, qualitative urinary protein, and microcyte percentage had high predictive value for kidney stones in patients. The accuracy of the kidney stone (KS-LSTM) learning model was 89.5%, and the AUC was 0.95. Compared with other models, it has better performance. The results show that the KS-LSTM model based on routine urine and blood tests can accurately identify the presence of kidney stones. And provide valuable assistance for clinicians to identify kidney stones in the early stage. [ABSTRACT FROM AUTHOR]

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 (PFDR<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 (PFDR<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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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_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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 mm3, number of auxiliary interventions increased with volumes above 1256 mm3, and success of the operation decreased with volumes above 1416 mm3. A subgroup analysis under and over 1064 mm3 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 mm3. In patients who underwent RIRS, for every 1000 mm3 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 mm3, the success rate will be higher, complication rate will be similar, and the need for auxiliary treatment will be lower. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 mm2 (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The relationship between calcium-based calculi and Randall plaques is well documented, but the role these plaques play in the early process of urinary stone formation remains unknown. The vascular hypothesis of Randall plaque formation has been proposed, and recent works support this concept. The renal papilla's vascular environment is subject to relative hypoxia, hyperosmolar surroundings, and turbulent blood flow. These factors together create an environment prone to vascular injury and may potentiate Randall plaque precipitation. Recent data support the similarity between the vascular calcification process itself and urinary stone formation. Furthermore, epidemiological studies have suggested an association between urinary stones, adverse cardiovascular events, and vascular calcification risk factors. The concept that an initial vascular insult precipitates a Randall plaque and subsequent urolithiasis is compelling and represents an area in need of continued research. This may lead to future novel treatment approaches to urolithiasis.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Various analgesic applications can be used during extracorporeal shock wave lithotripsy (SWL) for pain relief and maximal success rate. Intracutaneous sterile water injection (ISWI) has been shown to be effective in several types of pain, but a gap exists about its use during SWL. In this paper, we aimed to evaluate the effect of ISWI during SWL and compare that with diclofenac sodium injection used commonly to provide ideal patient contentment. Patients with kidney stone were randomized to have either ISWI therapy or intramuscular non-steroid anti-inflammatory drug (diclofenac sodium) injection. Using a syringe, 2–3 ml of sterile water was administered to the triangle area bounded by the 12th costal margin, the iliac crest and the vertebral spine in prone position. Visual analog scale (VAS) was employed to record pain scores of patients. Other parameters including stone size, SWL duration, total shock waves given, used energy and the necessity of rescue analgesia were also noted. A total of 524 patients were recruited, of those 216 patients were treated with ISWI and 308 patients had diclofenac sodium injections. The characteristics of the patients and shockwave therapy did not differ significantly between the two groups. Although the mean VAS scores prior to SWL and at every voltage increment during the procedure did not differ, more patients in the diclofenac sodium injection group required rescue analgesia with significantly greater side effects. ISWI is found to be as effective as the diclofenac sodium injection for pain management during SWL with lower adverse event rates. [ABSTRACT FROM AUTHOR]

Kidney stone is a chronic metabolic disease that caused by many factors, especially by the metabolic disturbances of urine compositions, but the metabolic profiling of the urine from kidney stone patients remains poorly explored. In the present study, 1H NMR spectroscopy and multivariate pattern recognition analytical techniques were combined to explore the metabolic profiling of the urine from kidney stone patients. A total of 216 urine samples obtained from kidney stone patients (n = 110) and healthy controls (n = 106) were investigated. The results indicated that principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) models were capable of distinguishing kidney stone patients from healthy controls. In addition, a total of 15 metabolites was obviously different in concentration between the two groups. Furthermore, four metabolic pathways, including glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism, phenylalanine metabolism and citrate cycle (TCA cycle), were closely associated with kidney stone. Together, our results established a preliminary metabolic profiling of the urine from kidney stone patients via using 1H NMR-based analytical techniques for the first time and provided a novel method for recognizing and observing the kidney stone disease. [ABSTRACT FROM AUTHOR]

To compare renal functional outcomes in patients with and without chronic kidney disease (CKD) to identify predictors of change in renal function after percutaneous nephrolithotomy (PCNL). We reviewed patients who underwent PCNL by a single surgeon over 3.5 years. Patients' pre- and post-operative Glomerular Filtration Rate (GFR) was calculated. Baseline GFR < 60 ml/min/1.73 m2 (stage ≥ 3 CKD) defined our CKD cohort. Patients' baseline renal function, comorbidities, stone parameters, and intra-operative variables were analyzed to determine the relationship with post-operative renal function after PCNL by multivariate analysis. 202 patients were analyzed. Mean follow-up time was 16 months. At baseline, 163 (80.7%) patients were free of CKD and 39 (19.3%) had CKD. Patients without CKD had an overall decrease in GFR from 105.6 to 103.3 ml/min/1.73 m2 (p = 0.494). 14/163 (8.6%) non-CKD patients experienced a significant decline in renal function after PCNL; 7/163 (4.3%) developed de novo CKD and 7 had a ≥ 30% decline in GFR. Patients with CKD had an overall increase in mean GFR post-operatively, from 47.3 to 54.0 ml/min/m2 (p = 0.067). Two in this cohort (5.1%) experienced a > 30% decline in renal function post-operatively. Age, gender, African American race, presence of comorbidities and pre-operative CKD were not significant predictors of renal function post-operatively on multivariate analysis. PCNL in this cohort appears GFR neutral in the setting of baseline CKD. CKD was not predictive of renal functional decline after PCNL. Given that stone disease carries a high recurrence rate and that CKD is associated with stone formers, further investigation into predictors of renal function change after PCNL is warranted. [ABSTRACT FROM AUTHOR]

To study the expression profiles of lncRNA and mRNA in the calcium oxalate monohydrate-attached HK-2 cells, and investigate the association between critical lncRNA expression level and renal injury. The HK-2 cells were treated with crystal suspension of calcium oxalate. The effects of calcium oxalate crystals on the growth of HK-2 cells were determined by MTT assay. Total RNA was extracted and the lncRNA and mRNA expression profiles were analyzed by high-throughput transcriptase sequencing platform HiSeq 2500. The profile of identified lncRNAs and mRNAs were verified by real-time PCR and their potential function was analyzed by Gene Ontology database and KEGG signal pathway analysis. Calcium oxalate crystals adhered to the surface of HK-2 cells in few minutes and showed obvious cytotoxicity. RNA seq results showed that there were 25 differentially expressed lncRNAs in HK-2 cells treated with calcium oxalate crystals, of which 9 were up-regulated and 16 were down-regulated. The difference was verified by real-time PCR which showed statistically significant (P < 0.05). Calcium oxalate crystals have a significant effect on lncRNA and mRNA expression in human renal epithelial cells, which may play critical roles in kidney stone-mediated renal injury. [ABSTRACT FROM AUTHOR]

Calcifying nanoparticles (CNPs) play an important role in kidney stone formation, but the mechanism(s) are unclear. CNPs were isolated and cultured from midstream urine of patients with kidney stones. CNP morphology and characteristics were examined by electron microscopy and electrophoresis analysis. Chemical composition was analyzed using energy-dispersive X-ray microanalysis and Western blotting. Human renal proximal convoluted tubule cell (HK-2) cultures were exposed to CNPs for 0, 12 and 72 h, and production of reactive oxygen species (ROS), mitochondrial membrane potential and apoptosis levels were evaluated. CNPs isolated from patients showed classical morphology, the size range of CNPs were 15-500 nm and negative charge; they were found to contain fetuin-A. Exposure of HK-2 cells to CNPs induced ROS production, decreased mitochondrial membrane potential and decreased cell viability. Transmission electron microscopy showed that CNPs can enter the cell by phagocytosis, and micrographs revealed signs of apoptosis and autophagy. CNPs increased the proportion of apoptotic cells, down-regulated Bcl-2 expression and up-regulated Bax expression. CNPs also up-regulated expression of LC3-B, Beclin-1and p-JNK.CNPs are phagocytosed by HK-2 cells, leading to autophagy, apoptosis and ROS production, in part through activation of JNK signaling pathways. ROS and JNK pathways may contribute to CNP-induced cell injury and kidney stone formation. [ABSTRACT FROM AUTHOR]

Twin and genealogy studies suggest a strong genetic component of nephrolithiasis. Likewise, urinary traits associated with renal stone formation were found to be highly heritable, even after adjustment for demographic, anthropometric and dietary covariates. Recent high-throughput sequencing projects of phenotypically well-defined cohorts of stone formers and large genome-wide association studies led to the discovery of many new genes associated with kidney stones. The spectrum ranges from infrequent but highly penetrant variants (mutations) causing mendelian forms of nephrolithiasis (monogenic traits) to common but phenotypically mild variants associated with nephrolithiasis (polygenic traits). About two-thirds of the genes currently known to be associated with nephrolithiasis code for membrane proteins or enzymes involved in renal tubular transport. The thick ascending limb of Henle and connecting tubules are of paramount importance for renal water and electrolyte handling, urinary concentration and maintenance of acid-base homeostasis. In most instances, pathogenic variants in genes involved in thick ascending limb of Henle and connecting tubule function result in phenotypically severe disease, frequently accompanied by nephrocalcinosis with progressive CKD and to a variable degree by nephrolithiasis. The aim of this article is to review the current knowledge on kidney stone disease associated with inherited defects in the thick ascending loop of Henle and the connecting tubules. We also highlight recent advances in the field of kidney stone genetics that have implications beyond rare disease, offering new insights into the most common type of kidney stone disease, i.e., idiopathic calcium stone disease. [ABSTRACT FROM AUTHOR]

Taraxasterol is one of the important constituents of Taraxacum officinale L. (Compositae) with antioxidant potential. The present study was designed to evaluate and compare the antiurolithiatic effects of taraxasterol and potassium citrate in the ethylene glycol induced urolithiatic rat. Urolithiasis was induced by ammonium chloride and ethylene glycol in adult male rats. Taraxasterol (2, 4 and 8 mg/kg) and potassium citrate (2.5 g/kg) were treated for 33 days by gavage. Then, the animals were anesthetized and weighted and blood, urine, liver and kidney sampling were done. The kidney sections were prepared by hematoxylin & eosin staining. The liver and kidney coefficients, urine pH, calcium, magnesium, oxalate and citrate levels, serum albumin, calcium and magnesium levels, serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, superoxide dismutase and glutathione peroxidase activities in serum, kidney and liver, number of calcium oxalate crystal deposits, score of crystal deposits, score of histopathological damages and score of inflammation in kidney sections were evaluated. The results showed that taraxasterol decreased liver and kidney coefficients (p < 0.001), serum calcium (p < 0.01) level, serum alanine aminotransferase (p < 0.001), aspartate aminotransferase (p < 0.001), lactate dehydrogenase (p < 0.05) activities, urine magnesium (p < 0.05) and oxalate (p < 0.001) levels, number of crystal deposits (p < 0.001), score of crystal deposits (p < 0.01), score of histopathological damages (p < 0.001) and score of inflammation (p < 0.01) in kidney sections, while increased urine pH (p < 0.01), calcium (p < 0.001) and citrate (p < 0.05), serum magnesium (p < 0.001) and albumin (p < 0.01) levels, superoxide dismutase and glutathione peroxidase in serum (p < 0.01), kidney (p < 0.05 and p < 0.001, respectively) and liver (p < 0.01 and p < 0.001, respectively) tissue homogenates in treated urolithiatic rats in comparison to the control urolithiatic rats. The effect of potassium citrate is the same as taraxasterol in treated urolithiatic rats. In conclusion, the effect of taraxasterol could be by improving liver function, changing serum and urine parameters, maintaining the antioxidant environment, reducing crystal deposition, excretion of small deposits from kidney and reducing the chance of them being retained in the urinary tract. [ABSTRACT FROM AUTHOR]

Most of kidney stones are supposed to originate from Randall’s plaque at the tip of the papilla or from papillary tubular plugs. Nevertheless, the frequency and the composition of crystalline plugs remain only partly described. The objective was to assess the frequency, the composition and the topography of papillary plugs in human kidneys. A total of 76 papillae from 25 kidneys removed for cancer and without stones were analysed by immunohistochemistry combined with Yasue staining, field emission-scanning electron microscopy and Fourier transformed infrared micro-spectroscopy. Papillary tubular plugs have been observed by Yasue staining in 23/25 patients (92%) and 52/76 papillae (68%). Most of these plugs were made of calcium phosphate, mainly carbonated apatite and amorphous calcium phosphate, and rarely octacalcium phosphate pentahydrate. Calcium and magnesium phosphate (whitlockite) have also been observed. Based upon immunostaining coupled to Yasue coloration, most of calcium phosphate plugs were located in the deepest part of the loop of Henle. Calcium oxalate monohydrate and dihydrate tubular plugs were less frequent and stood in collecting ducts. At last, we observed calcium phosphate plugs deforming and sometimes breaking adjacent collecting ducts. Papillary tubular plugging, which may be considered as a potential first step toward kidney stone formation, is a very frequent setting, even in kidneys of non-stone formers. The variety in their composition and the distal precipitation of calcium oxalate suggest that plugs may occur in various conditions of urine supersaturation. Plugs were sometimes associated with collecting duct deformation. [ABSTRACT FROM AUTHOR]

Urinary stones composed of uric acid can be treated medically. Prediction of uric acid stone type is, therefore, desirable when a urinary stone is diagnosed with unenhanced CT. The purpose of the present study was to describe single-energy thin slice quantitative CT parameters of urinary stones correlated to chemical stone type and to develop a method to distinguish pure uric acid stones (UA) from other stones (non-UA/Mix). Unenhanced thin slice single-energy CT images of 126 urinary stones (117 patients) with known chemical stone type were retrospectively included in the study. Among the included stones, 22 were UA and 104 were non-UA/Mix. The included CT images and Laplacian filtered images of the stones were quantitatively analyzed using operator-independent methods. A post hoc classification method for pure UA stones was created using a combination of cutoff values for the peak attenuation and peak point Laplacian. The stone types differed in most quantitative image characteristics including mean attenuation (p < 0.001), peak attenuation (p < 0.001), and peak point Laplacian (p < 0.001). The sensitivity for the post hoc-developed peak attenuation—peak point Laplacian method for classifying pure UA stones was 95% [21/22, 95% CI (77-100%)] and the specificity was 99% [103/104, 95% CI (95-100%)]. In conclusion, quantitative image analysis of thin slice routine single-energy CT images is promising for predicting pure UA content in urinary stones, with results comparable to double energy methods. [ABSTRACT FROM AUTHOR]

Our previous study has shown that lime powder (LP) had an inhibitory effect against calcium oxalate stone formation. However, the precise mechanisms underlying such beneficial effect remained unclear. Our present study thus aimed to address the effect of LP on excretory level and compositions of urinary proteins using a proteomics approach. From a total of 80 calcium oxalate stone formers recruited into our 2-year randomized clinical trial of LP effect, 10 patients with comparable age and clinical parameters were selected for this proteomic study. 24-h urine specimens were collected from all subjects, at baseline (before) and after LP treatment for 6 months, and then subjected to quantitative proteomics analysis and subsequent validation by ELISA. Total urinary protein excretion was significantly decreased by LP treatment, but unaffected by placebo. Nanoflow liquid chromatography coupled to tandem mass spectrometry (nanoLC-MS/MS) followed by quantitative analysis revealed 17 proteins whose levels were significantly altered (16 decreased and 1 increased) exclusively by LP treatment. Among these, the decrease of transferrin and increase of uromodulin were validated by ELISA. Moreover, there was a significant correlation between microalbuminuria and urinary transferrin level by Pearson’s correlation test. In summary, LP treatment caused significant reduction in total urinary protein excretion and changes in urinary protein compositions that could be linked to stone inhibitory effects and might be relevant mechanisms responsible for the beneficial effects of LP to prevent kidney stone formation and recurrence. [ABSTRACT FROM AUTHOR]

Dietary polyphenol caffeic acid (1) has been reported for various pharmacological activities. The aim of the current study was to investigate the effect of caffeic acid (1) on ethylene glycol-induced renal stones in rats. For the study, male Wistar rats were divided into seven groups; normal, pathological, and standard drug controls, and preventive and curative groups. Normal control group received drinking water for 8 weeks. Pathological, standard drug, preventive, and curative groups received 0.75% ethylene glycol in drinking water for the induction of calcium oxalate stone formation, along with the regular diet. Standard drug group received Urocit-K by gavage from day 1, while preventive and curative groups received caffeic acid (1) by gavage at doses of 20 and 40 mg/kg on day 1 and day 14, respectively. At the end of the experiment, urine analysis and kidney histopathology were performed. Real-time PCR was performed to evaluate the renal expression of the most important genes involved in urolithiasis, i.e., osteopontin, Tamm-Horsfall, prothrombin fragment 1, and bikunin genes. The results indicated that in both the preventive and curative groups, treatment of rats with caffeic acid (1) significantly regulated the altered biochemical parameters, along with the remarkable reduction of calcium oxalate deposits in the kidneys, as compared to the pathological group. Treatment with compound 1 also resulted in down-regulation of the osteopontin gene, and up-regulation of the prothrombin fragment 1, Tamm-Horsfall, and bikunin genes. These results suggest that caffeic acid (1) can be further investigated for the prevention, and treatment of kidney stones. [ABSTRACT FROM AUTHOR]

Idiopathic calcium oxalate nephrolithiasis is a highly recurrent disease that is increasing in prevalence. Decades of research have not identified effective methods to consistently prevent the formation of nephroliths or induce medical dissolution. Idiopathic calcium oxalate nephroliths form in association with renal papillary subepithelial calcium phosphate deposits called Randall's plaques (RPs). Rodent models are commonly used to experimentally induce calcium oxalate crystal and stone formation, but a rodent model that conclusively forms RPs has not been identified. Both dogs and cats form calcium oxalate uroliths that can be recurrent, but the etiopathologic mechanisms of stone formation, especially renal pathologic findings, are a relatively unexploited area of study. A large animal model that shares a similar environment to humans, along with a shorter lifespan and thus shorter time to recurrence, might provide an excellent means to study preventative and therapeutic measures, along with enhancing the concepts of the one health initiative. This review article summarizes and compares important known features of idiopathic calcium oxalate stone disease in humans, dogs, and cats, and emphasizes important knowledge gaps and areas for future study in the quest to discover a naturally occurring animal model of idiopathic calcium oxalate stone disease. [ABSTRACT FROM AUTHOR]

The objective of this study is to assess the utility of the Guy, S.T.O.N.E., and CROES nephrolithometry scoring systems (SS), and compare the capability of each system to predict percutaneous nephrolithotomy (PNL) outcome in patients with anatomical abnormalities. We retrospectively collected medical records of patients with anatomical abnormalities who underwent PNL for the treatment of renal calculi by experienced surgical teams in four referral centers. All of the patients were graded by a single observer from each department based on preoperative computed tomography images using each SS. Patient demographics and outcomes were compared according to the complexity of the procedure as graded by each scoring system. A total of 137 cases with anatomical abnormalities [horseshoe kidney ( n = 46), malrotation ( n = 33), kypho and/or scoliosis ( n = 31) and ectopic kidney ( n = 27)] were assessed retrospectively. The mean stone burden, number, and density were 708.5 mm, 1.7, and 791.8 HU, respectively. The mean procedure, fluoroscopy, and hospitalization times were 75.2 ± 35.3 min, 133.4 ± 92.3 s, and 3.5 ± 2.1 days, respectively. Stone-free status was achieved in 106 cases (77.4 %). A total of 17 (13.6 %) complications occurred postoperatively. The mean scores were 2.7, 7.2, and 219.1, for the Guy, S.T.O.N.E., and CROES systems, respectively. CROES score was the independent predictor of PNL success in cases with anatomical abnormalities [ p: 0.001, OR 1.01, (95 % CI 1005-1021)]. The CROES scoring system is well correlated with the success of PNL in cases with anatomical abnormalities; the S.T.O.N.E. and Guy scoring systems failed to predict the outcomes of PNL in this specific patient population. [ABSTRACT FROM AUTHOR]