Kidney stones, a prevalent urinary disease, pose significant health risks. Factors like insufficient water intake or a high-protein diet increase an individual's susceptibility to the disease. Social media platforms can be a valuable avenue for users to share their experiences in managing these risk factors. Analyzing such patient-reported information can provide crucial insights into risk factors, potentially leading to improved quality of life for other patients.

This study aims to develop a model KSrisk-GPT, based on a large language model (LLM) to identify potential kidney stone risk factors from web-based user experiences.

This study collected data on the topic of kidney stones on Zhihu in the past 5 years and obtained 11,819 user comments. Experts organized the most common risk factors for kidney stones into six categories. Then, we use the least-to-most prompting in the chain-of-thought prompting to enable GPT-4.0 to think like an expert and ask GPT to identify risk factors from the comments. Metrics, including accuracy, precision, recall, and F1-score, were used to evaluate the performance of such a model.

Our proposed method outperforms other models in identifying comments containing risk factors with 95.9% accuracy and F1-score, with a precision of 95.6% and a recall of 96.2%. Out of the 863 comments identified with risk factors, our analysis showed the most mentioned risk factors for kidney stones in Zhihu user discussions, mainly including dietary habits (high protein, high calcium intake), insufficient water intake, genetic factors, and lifestyle. In addition, new potential risk factors were discovered with GPT, such as excessive use of supplements like vitamin C and calcium, laxatives, and hyperparathyroidism.

Comments from social media users offer a new data source for disease prevention and understanding patient journeys. Our method not only sheds light on using LLMs to efficiently summarize risk factors from social media data but also on LLMs' potential to identify new potential factors from the patient's perspective.

There are limited studies on the relationship between plant-based diet indices (PDIs) including plant-based diet index (PDI), healthful plant-based diet index (hPDI) and unhealthful plant-based diet index (uPDI) and kidney stones (KS), especially in Middle Eastern populations. We aimed to investigate the relationship between these plant-based diet indices (PDI, hPDI, and uPDI) and KS in a large group of Iranian adults. This cross-sectional study was carried out on 9,839 adult participants aged 35-70 years. Dietary data were collected using a validated semi-quantitative 118-item food frequency questionnaire. The scoring method suggested by Satija et al. was applied to examine the adherence to the PDIs including PDI, hPDI, and uPDI. These indices are grounded in evidence linking plant-based foods to health outcomes such as obesity, diabetes, cancer, and cardiovascular disease. The history of KS was identified based on self-reported information provided by the participants. Approximately 16.4% (n = 1638) of study participants were found to have KS. After adjustment for a wide range of confounding variables, a significant positive association was observed between PDI and KS (OR: 1.17; 95% CI: 1.01-1.37). In the case of hPDI, we found no significant association between hPDI scores and risk of KS after adjustment for potential confounders (OR: 1.16; 95% CI: 0.98-1.38). Non-significant association was also observed for uPDI and risk of KS in the fully adjusted model (OR: 1.14; 95% CI: 0.95-1.35). In conclusion, findings of the present study showed that higher PDI score was positively associated with the risk of KS, whereas the hPDI and uPDI scores were not associated with the risk of KS. Further prospective studies are needed to establish causal relationships.

This meta-analysis aims to compare the efficacy and safety of tadalafil and silodosin as medical expulsive therapy (MET) for lower ureteric stones below 10 mm. The study also assesses the incidence of adverse effects associated with each drug.

A comprehensive search of electronic databases was conducted up to October, 2024. The study included randomized controlled trials (RCTs) and cohort studies that compared tadalafil and silodosin in patients with lower ureteric stones (5-10 mm). The primary outcomes assessed were stone expulsion time (SET), stone expulsion rate (SER), and adverse effects. Data were analyzed using a random-effects model for heterogeneity and a fixed-effect model for non-heterogeneity.

Eight studies involving 797 patients were included. The pooled analysis showed no significant difference in SET between tadalafil and silodosin (MD = 0.15, 95% CI [-0.28, 0.57], p=0.50), with significant heterogeneity. Similarly, the pooled analysis showed no significant difference in SER between the two drugs (RR = 0.92, 95% CI [0.80 to 1.05], p=0.22), with heterogeneity. However, after excluding one study, silodosin was favored over tadalafil for SER (RR 0.88, 95% CI [0.79 to 0.98], p=0.02). There were no significant differences in headache, backache, or dizziness. Silodosin was associated with a higher incidence of orthostatic hypotension, but this was resolved by excluding one study. A significant difference for abnormal ejaculation favored tadalafil (RR = 0.16, 95% CI [0.09 to 0.29], p=0.01).

While the pooled results initially showed no significant difference in SET and SER, silodosin demonstrated a superior stone expulsion rate after adjusting for heterogeneity silodosin showed a trend towards shorter SET. However, silodosin was associated with a higher risk of orthostatic hypotension and abnormal ejaculation. Further high-quality RCTs with larger sample sizes are needed to confirm these findings.

Urolithiasis, a prevalent condition characterized by a high rate of incidence and recurrence, necessitates accurate preoperative diagnostic methods to determine stone composition for effective clinical management. Current diagnostic practices, reliant on postoperative specimen analysis, often fail to facilitate timely and precise therapeutic decisions, leading to suboptimal clinical outcomes. This study introduces an artificial intelligence model developed to predict infectious and non-infectious urolithiasis preoperatively using clinical data and CT imaging.

Data from December 2014 to November 2021 involving 642 patients undergoing surgical treatment for urolithiasis were used to train and validate the model. The model integrates Visual and Textual Transformation (VTT) and Multimodal-Segmentation Attention Fusion (MSAF) modules to enhance the diagnostic process.

The model demonstrated superior accuracy and reliability in differentiating between infectious and non-infectious urolithiasis compared to traditional diagnostic methods. It achieved a classification accuracy of 79.66%, Area Under Curve of 86.74%, significantly outperforming conventional ResNet architectures and similar models. The inclusion of clinical parameters substantially improved the model's predictive capabilities.

Our model provides an efficient tool for the preoperative identification of urolithiasis type, supporting clinical decisions regarding surgical planning and postoperative care. Its ability to process and analyze complex clinical and imaging data preoperatively positions it as a valuable adjunct in urological practice, particularly in settings with limited access to specialized medical resources.

Traditional herbal remedies have been used for treating nephrolithiasis, but the relevant scientific evidence is limited. Zaleya pentandra (L.) C. Jeffrey is traditionally used for the prevention of kidney stones in various cultures. However, its efficacy has not been scientifically studied.

This study aimed to investigate the antiurolithic activity of Zaleya pentandra, and validate its traditional used for preventing kidney stones.

The crude ethanolic extract of Z. pentandra (Zp.Crd) was evaluated through in vitro and in vivo studies. In vitro experiments assessed its impact on crystal count and morphology in metastable calcium oxalate solutions. In vivo studies involved diuretic and ethylene glycol-induced calcium oxalate crystal formation in male Wistar rats.

Zp.Crd transforms calcium oxalate crystals from harmful calcium oxalate monohydrate (COM) to calcium oxalate dihydrate (COD). In vivo, Zp.Crd exhibited dose-dependent (30-300 mg/kg) diuretic activity in rats by significantly increasing urinary sodium (Na+) and potassium (K+) excretion, similar to the standard diuretic hydrochlorothiazide (HCT). In the urolithiasis model, Zp.Crd exhibited dose-dependent antiurolithic effects by reducing kidney crystals and significantly altering lithogenic factors induced by ethylene glycol, including crystalluria, oxaluria, calcium, creatinine, and urea, in the urine and serum of treated rats. Zp.Crd also exhibited antioxidant effects, effectively combating oxidative lithogenic stress in rats.

Zp.Crd has been shown to demonstrate antiurolithic activity against CaOx stones through CaOx crystal inhibition, diuretic activity, antioxidant properties, hypocalciuric effects, and hypercitrauric actions. The findings underscore Zp.Crd's potential as a viable alternative or supplemental therapy to current urolithiasis treatments, paving the door for further clinical trials and its inclusion into modern medical practices.

Kidney stones represent a significant global health challenge, with dietary habits playing a crucial role in their formation. This study investigates the association between dietary fatty acid intake-specifically saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA)-and the prevalence of kidney stones in a U.S. adult population, aiming to inform potential dietary prevention strategies. Data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007-2018 were analyzed, including 30,716 participants. Logistic regression models were used to assess the relationship between fatty acid intake and kidney stones prevalence, adjusting for demographic and health-related covariates such as age, sex, BMI, diabetes status, physical activity, and other dietary factors. Additional analyses were conducted to explore the effects of fatty acid intake as a percentage of total energy and the impact of various fatty acid ratios. Higher intakes of SFA, MUFA, and PUFA were associated with increased odds of kidney stones prevalence. Specifically, each 10 g/day increase in SFA, MUFA, and PUFA intake was linked to a 22% [OR = 1.22, 95% CI: 1.11-1.34, p = 0.002], 10% [OR = 1.10, 95% CI: 1.00-1.22, p = 0.052] and 21% [OR = 1.21, 95% CI: 1.10-1.33, p = 0.001] higher odds of kidney stones, respectively. These associations were generally consistent across various subgroups. Additional analyses examining fatty acid intake as a percentage of total energy and various fatty acid ratios yielded compatible findings. The findings suggest a modest association between higher dietary fatty acid intake and increased odds of kidney stones prevalence. While the observed odds increases were relatively small, these results highlight the importance of considering dietary fatty acid types in kidney stones prevention strategies. Future research is needed to further elucidate the underlying mechanisms and to refine dietary recommendations.

Remnant cholesterol (RC) is the cholesterol content of triglyceride-rich lipoproteins. This study aimed to investigate the association between RC levels and kidney stones in U.S. adults.

Data were obtained from the 2007 to 2016 National Health and Nutrition Examination Survey (NHANES). A total of 10,551 participants with complete data were included and analyzed in this study. Univariate and multivariate logistic regression analysis, restricted cubic spline function, subgroup analysis and mediation analysis were preformed to estimate the independent relationship between RC levels and kidney stones.

Participants with stone formation had higher levels of RC than those with without stone formation (25.78 ± 13.83 vs 23.27 ± 13.04, p< 0.001). The results of logistic regression analysis and dose-response risk curves revealed a positive nonlinear association between RC levels and risk of kidney stones [univariate: adjusted odds ratio (aOR) =2.388, 95% CI: 1.797-3.173, p< 0.001; multivariate: aOR = 1.424, 95% CI: 1.050-1.929, p = 0.023]. Compared with the discordantly low RC group, the discordantly high RC group was associated with increased risk of kidney stones (aOR = 1.185, 95% CI: 1.013-1.386, p= 0.034). Similar results were demonstrated according to the discordance of different clinical cut points. And metabolic syndrome parameters and vitamin D levels parallelly mediated the association between RC and kidney stone risk.

Higher RC levels were independently associated with an increased risk of kidney stone incidence.

The study aimed to investigate the molecular mechanisms underlying kidney stones by analyzing gene expression profiles. They focused on identifying differentially expressed genes (DEGs), performing gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and screening optimal feature genes using various machine learning algorithms.

Data from the GSE73680 dataset, comprising normal renal papillary tissues and Randall's Plaque (RP) tissues, were downloaded from the GEO database. DEGs were identified using the limma R package, followed by GSEA and WGCNA to explore functional modules. Functional enrichment analysis was conducted using KEGG and Disease Ontology. Various machine learning algorithms were used for screening the most suitable feature genes, which were then assessed for their expression and diagnostic significance through Wilcoxon rank-sum tests and ROC curves. GSEA and correlation analysis were performed on optimal feature genes, and immune cell infiltration was assessed using the CIBERSORT algorithm.

412 DEGs were identified, with 194 downregulated and 218 upregulated genes in kidney stone samples. GSEA revealed enriched pathways related to metabolic processes, immune response, and disease states. WGCNA identified modules correlated with kidney stones, particularly the yellow module. Functional enrichment analysis highlighted pathways involved in metabolism, immune response, and disease pathology. Through machine learning algorithms, KLK1 and MMP10 were identified as optimal feature genes, significantly upregulated in kidney stone samples, with high diagnostic value. GSEA further elucidated their biological functions and pathway associations.

The study comprehensively analyzed gene expression profiles to uncover molecular mechanisms underlying kidney stones. KLK1 and MMP10 were identified as potential diagnostic markers and key players in kidney stone progression. Functional enrichment analysis provided insights into their roles in metabolic processes, immune response, and disease pathology. These results contribute significantly to a better understanding of kidney stone pathogenesis and may inform future diagnostic and therapeutic strategies.

Crystalluria is an important indicator of renal stone recurrence. Mechanisms underlying urinary stone formation are still not fully understood and raising interests has been giving to intestinal commensal bacteria for their contribute in maintaining urinary solutes equilibrium. The aim of our phase II study was to examine the administration of potassium citrate, magnesium and probiotics in order to reduce crystalluria.

Since May 2021, we enrolled 23 patients candidates for ureterorenolithotripsy for calcium oxalate kidney stones with crystalluria and a normal metabolic profile. The analysis was validated by the Institution's Ethical Committee (no. approval STS CE Lazio 1/N-823). At discharge, patients were provided with daily food supplementation for 20 days of 1 billion Lactobacillus paracasei LPC09, 1 billion Lactobacillus plantarum LP01, 1 billion Bifidobacterium breve BR03, potassium (520 mg), citrate (1400 mg), and magnesium (80 mg). Crystalluria was re-assessed at 1, 3, 6, and 12-months follow-up by polarized light microscopy.

After one month from the oral supplementation, no patient reported crystalluria; at 3 months, among the 20 participants available for re-evaluation, still no patient reported crystalluria. Instead, crystalluria was reported in three patients (15%) at 6 months, and in five patients (25%) at 12 months follow-up.

The oral supplementation with Lactobacillus spp. and Bifidobacterium spp. was found able to reduce the prevalence of crystalluria in a cohort of patients with diagnosis of calcium oxalate kidney stones with crystalluria candidate to ureterorenolithotripsy.

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.

To explore the association between representative insulin resistance (IR) indices and the risk of kidney stone disease in an American adult population. The representative IR indices referred to metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride glucose-body mass index (TyG-BMI), visceral adiposity index (VAI), and homeostatic model assessment of IR (HOMA-IR).

We investigated adult participants who joined the 2015-2018 National Health and Nutrition Examination Survey (NHANES) and reported kidney stone histories. Weighted proportions, multivariable regression analysis, and restricted cubic splines were used to evaluate the associations between IR indices and kidney stones after their adjustment for gender, age, race, education, smoking status, alcohol drinking frequency, hypertension and diabetes status, physical activity level, water intake, and levels of calcium, cholesterol, and uric acid.

A total of 19,225 participants were included. The weighted prevalence of kidney stone was 11.1%. A multivariable logistic regression model showed a dose-response relationship between the METS-IR and kidney stone [odds ratio (OR) = 1.02, 95% confidence interval (CI) (1.01, 1.04), p < 0.01]. A similar relationship was observed between the TyG-BMI and kidney stone after full adjustment [OR = 1.0, 95% CI (1.0, 1.01), p < 0.001]. Sex-stratified analyses revealed that the association between METS-IR and nephrolithiasis [OR = 1.03, 95% CI (1.01, 1.05), p < 0.01], and the association between TyG-BMI and nephrolithiasis [OR = 1.01, 95% CI (1.0, 1.01), p <0.001] was significant among the male participants in the fully adjusted model. Moreover, a significant association was found between the METS-IR levels and nephrolithiasis [OR = 1.03, 95% CI (1.01, 1.06), p < 0.01], and between the TyG-BMI levels and nephrolithiasis [OR = 1.01, 95% CI (1.0, 1.01), p < 0.05] among the diabetic participants after full adjustment. Furthermore, a potential nonlinear association was found between other IR indices (i.e., TG/HDL-C, VAI, and HOMA-IR) and the risk of kidney stone disease.

Higher METS-IR and TyG-BMI levels were associated with a higher risk of nephrolithiasis. Future investigations are required to identify the role of IR in the progress of kidney stone formation and to propose prevention measures and health guidelines.

Understanding chronic kidney disease (CKD) through the lens of evolutionary biology highlights the mismatch between our Paleolithic-optimized genes and modern diets, which led to the dramatically increased prevalence of CKD in modern societies. In particular, the Standard American Diet (SAD), high in carbohydrates and ultra-processed foods, causes conditions like type 2 diabetes (T2D), chronic inflammation, and hypertension, leading to CKD. Autosomal dominant polycystic kidney disease (ADPKD), a genetic form of CKD, is characterized by progressive renal cystogenesis that leads to renal failure. This review challenges the fatalistic view of ADPKD as solely a genetic disease. We argue that, just like non-genetic CKD, modern dietary practices, lifestyle, and environmental exposures initiate and accelerate ADPKD progression. Evidence shows that carbohydrate overconsumption, hyperglycemia, and insulin resistance significantly impact renal health. Additionally, factors like dehydration, electrolyte imbalances, nephrotoxin exposure, gastrointestinal dysbiosis, and renal microcrystal formation exacerbate ADPKD. Conversely, carbohydrate restriction, ketogenic metabolic therapy (KMT), and antagonizing the lithogenic risk show promise in slowing ADPKD progression. Addressing disease triggers through dietary modifications and lifestyle changes offers a conservative, non-pharmacological strategy for disease modification in ADPKD. This comprehensive review underscores the urgency of integrating diet and lifestyle factors into the clinical management of ADPKD to mitigate disease progression, improve patient outcomes, and offer therapeutic choices that can be implemented worldwide at low or no cost to healthcare payers and patients.

This study aims to uncover the molecular mechanisms underlying pediatric kidney stone formation induced by renal calcium deposition by utilizing high-throughput sequencing data to reveal the regulation of PINK1 by MyoD1. We performed transcriptome sequencing on peripheral blood samples from healthy children and children with kidney stones to obtain differentially expressed genes (DEGs). Genes related to mitochondrial oxidative stress were obtained from the Genecards website and intersected with DEGs to obtain candidate target genes. Additionally, we conducted protein-protein interaction (PPI) analysis using the STRING database to identify core genes involved in pediatric kidney stone disease (KSD) and predicted their transcription factors using the hTFtarget database. We assessed the impact of MyoD1 on the activity of the PINK1 promoter using dual-luciferase reporter assays and investigated the enrichment of MyoD1 on the PINK1 promoter through chromatin immunoprecipitation (ChIP) experiments. To validate our hypothesis, we selected HK-2 cells and established an in vitro kidney stone model induced by calcium oxalate monohydrate (COM). We evaluated the expression levels of various genes, cell viability, volume of adherent crystals in each group, as well as mitochondrial oxidative stress in cells by measuring mitochondrial membrane potential (Δψm), superoxide dismutase (SOD) activity, reactive oxygen species (ROS), and malondialdehyde (MDA) content. Mitochondrial autophagy was assessed using mtDNA fluorescence staining and Western blot analysis of PINK1-related proteins. Apoptosis-related proteins were evaluated using Western blot analysis, and cell apoptosis was measured using flow cytometry. Furthermore, we developed a rat model of KSD and assessed the expression levels of various genes, as well as the pathologic changes in rat renal tissues using H&E and von Kossa staining, transmission electron microscopy (TEM), and the expression of creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) to evaluate the mitochondrial oxidative stress in vivo (through measurement of Δψm, SOD activity, ROS, and MDA content). Mitochondrial autophagy was evaluated by Western blot analysis of PINK1-associated proteins. Apoptosis-related proteins were detected using Western blot analysis, and cellular apoptosis was examined using cell flow cytometry and TUNEL staining. Bioinformatics analysis revealed that the PINK1 gene is upregulated and vital in pediatric kidney stone patients. Our in vitro and in vivo experiments demonstrated that silencing PINK1 could inhibit kidney stone formation by suppressing mitochondrial oxidative stress both in vitro and in vivo. We identified MyoD1 as an upstream transcription factor of PINK1 that contributes to the occurrence of pediatric kidney stones through the activation of PINK1. Our in vivo and in vitro experiments collectively confirmed that silencing MyoD1 could inhibit mitochondrial oxidative stress, mitochondrial autophagy, and cellular apoptosis in a rat model of kidney stones by downregulating PINK1 expression, consequently suppressing the formation of kidney stones. In this study, we discovered that MyoD1 may promote kidney stone formation and development in pediatric patients by transcriptionally activating PINK1 to induce mitochondrial oxidative stress.

Renal calculi (kidney stones) are mainly made by calcium oxalate and can cause different complications including malfunction of the kidney. The most important urinary stone inhibitors are citrate molecules. Unfortunately, the amount of citrate reaching the kidney after oral ingestion is low. We hypothesized that nanoparticles of polyallylamine hydrochloride (CIT-PAH) carrying citrate ions could simultaneously deliver citrates while PAH would complex oxalate triggering dissolution and removal of CaOx nanocrystals.

We successfully prepared nanoparticles of citrate ions with polyallylamine hydrochloride (CIT-PAH), PAH with oxalate (OX-PAH) and characterize them by Small Angle X ray Scattering (SAXS), Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS) and NMR. Dissolution of CaOx nanocrystals in presence of CIT-PAH have been followed with Wide Angle Xray Scattering (WAXS), DLS and Confocal Raman Microscopy. Raman spectroscopy was used to study the dissolution of crystals in synthetic urine samples. The release of citrate from CIT-PAH was followed by diffusion NMR. Molecular dynamics (MD) simulations were carried out to study the interaction of CIT and OX ions with PAH.

CIT-PAH nanoparticles dissolves CaOx nanocrystals as shown by NMR, DLS, TEM and WAXS in water and by Raman spectroscopy in artificial human urine. WAXS and Raman show that the crystal structure of CaOx disappears in the presence of CIT-PAH. DLS shows that the time required for CaOX dissolution will depend on the concentration of CIT-PAH NPs. NMR proves that citrate ions are released from the CIT PAH NPs during CaOX dissolution, MD simulations showed that oxalates exhibit a stronger interaction for PAH than citrate, explaining the removal of oxalate ions and replacement of the citrate in the polymer nanoparticles.

This study was to investigate the correlation between oxidative balance score (OBS) and the prevalence of kidney stones in the general adult population.

We conducted an analysis using data from the 2007-2018 National Health and Nutrition Examination Survey (NHANES) project, including 17,988 participants. The OBS was computed based on previous research, combining 16 dietary factors and 4 lifestyle factors. Multiple logistic regressions and restricted cubic spline (RCS) regressions were utilized to explore the associations between OBS and kidney stone prevalence.

Our analysis included 1,622 adults with kidney stones and 16,366 adults without kidney stones. The average age of participants was 46.86 ± 0.27 years, with 50.72% being male. The median OBS was 22.00 (17.00, 27.00). After adjusting for all covariates, each one-unit increase in OBS was associated with a 3% decrease in kidney stone prevalence (odds ratio [OR] = 0.97 [0.96-0.98], P < 0.001). Moreover, compared to the first quartile, the fourth quartile of OBS (OR = 0.65 [0.50-0.84], P = 0.001) exhibited a negative association with kidney stone prevalence after adjusting for multiple variables. Furthermore, we observed a non-linear negative relationship between OBS and kidney stone prevalence, with inflection points at 18.2 (P for nonlinearity = 0.048). Stratified analysis did not identify any variables significantly affecting the results.

Our findings indicate that a higher OBS is associated with a decreased prevalence of kidney stones in the general adult population.

The ratio of monocyte to high-density lipoprotein cholesterol (MHR) has surfaced as a novel biomarker indicative of inflammation and oxidative stress. The aim of our study was to evaluate the association between MHR and the risk of kidney stones.

This study analyzed data from individuals aged 20-79 who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. The MHR was assessed as the exposure variable, while a self-reported history of kidney stones was used as the outcome variable. The independent relationship between MHR and the risk of kidney stones was thoroughly evaluated.

This study included 28,878 participants, and as the quartile range of the MHR increased, the proportion of kidney stones also rose progressively (7.20% to 8.89% to 10.88% to 12.05%, P<0.001). After adjusting for confounding factors, MHR was independently associated with an increased risk of kidney stones (OR=1.31, 95%CI=1.11-1.54, P=0.001), also independent of some common inflammatory indices. Subgroup analysis suggested that the relationship between MHR and kidney stones was more pronounced in female and individuals aged 20-49. Further restricted cubic spline (RCS) analysis indicated a nonlinear relationship between MHR and the risk of kidney stones.

Our results indicate a positive correlation between MHR and an increased risk of kidney stones in US adults, underscoring the need for further large-scale prospective cohort studies to validate these findings.

Numerous studies have shown that intestinal and urinary tract flora are closely related to the formation of kidney stones. The removal of probiotics represented by lactic acid bacteria and the colonization of pathogenic bacteria can directly or indirectly promote the occurrence of kidney stones. However, currently existing natural probiotics have limitations. Synthetic biology is an emerging discipline in which cells or living organisms are genetically designed and modified to have biological functions that meet human needs, or even create new biological systems, and has now become a research hotspot in various fields. Using synthetic biology approaches of microbial engineering and biological redesign to enable probiotic bacteria to acquire new phenotypes or heterologous protein expression capabilities is an important part of synthetic biology research. Synthetic biology modification of microorganisms in the gut and urinary tract can effectively inhibit the development of kidney stones by a range of means, including direct degradation of metabolites that promote stone production or indirect regulation of flora homeostasis. This article reviews the research status of engineered microorganisms in the prevention and treatment of kidney stones, to provide a new and effective idea for the prevention and treatment of kidney stones.

The causal genetic relationship between common parenteral manifestations of inflammatory bowel disease (IBD) and urolithiasis remains unclear because their timing is difficult to determine. This study investigated the causal genetic association between IBD and urolithiasis using Mendelian randomization (MR) based on data from large population-based genome-wide association studies (GWASs).

A two-sample MR analysis was performed to assess the potential relationship between IBD and urolithiasis. Specific single nucleotide polymorphism data were obtained from GWASs, including IBD (n = 59957) and its main subtypes, Crohn's disease (CD) (n = 40266) and ulcerative colitis (UC) (n = 45975). Summarized data on urolithiasis (n = 218792) were obtained from different GWAS studies. A random-effects model was analyzed using inverse-variance weighting, MR-Egger, and weighted medians.

Genetic predisposition to IBD and the risk of urolithiasis were significantly associated [odds ratio (OR), 1.04 (95% confidence interval [CI], 1.00-.08), P = 0.01]. Consistently, the weighted median method yielded similar results [OR, 1.06 (95% CI, 1.00-1.12), P = 0.02]. The MR-Egger method also demonstrated comparable findings [OR, 1.02 (95% CI, 0.96-1.08), P = 0.45]. Both funnel plots and MR-Egger intercepts indicated no directional pleiotropic effects between IBD and urolithiasis. CD was strongly associated with it in its subtype analysis [OR, 1.04 (95% CI, 1.01-1.07), P = 0.01], and UC was also causally associated with urolithiasis, although the association was not significant [OR, 0.99 (95% CI, 0.95-1.03), P = 0.71].

A unidirectional positive causal correlation was identified between IBD and urolithiasis, with varying degrees of association observed among the different subtypes of IBD. Recognizing the increased incidence of urolithiasis in patients with IBD is crucial in clinical practice. Early detection and surveillance of IBD, improved patient awareness, adoption of preventive strategies, and promotion of collaborative efforts among healthcare providers regarding treatment methodologies are vital for improving patient outcomes.

To provide a comprehensive review on the existing literature on medical management of urolithiasis.

A thorough literature review was performed using Medline, PubMed/PMC, Embase, and the Cochrane Database of Systematic Reviews up to December 2022 to identify publications on the medical management of urolithiasis. Studies that assessed dietary and pharmacologic management of urolithiasis were reviewed; studies on medical expulsive therapy were not included in this review.

Medical management of urolithiasis ranges from the prophylactic management of kidney stone disease to dissolution therapies. While most treatment concepts have been long established, large randomized controlled trials are scarce. Dietary modification and increased fluid intake remain cornerstones in the conservative management of urolithiasis. A major limitation for medical management of urolithiasis is poor patient compliance.

Medical management of urolithiasis is more important in patients with recurrent urolithiasis and patients with metabolic abnormalities putting them at higher risk of developing stones. Although medical management can be effective in limiting stone recurrence, medical interventions often fail due to poor compliance.

There is some evidence to suggest that there may be a link between body mass index (BMI) and the development of kidney stones, it remains unclear whether weight change was associated with the presence of kidney stone.

The objective of this study was to investigate the potential association between changes patterns in weight during adulthood and the incidence of kidney stone.

This study included 14472 participants aged 30-75 years, whose BMI was recorded at both baseline and 10 years prior to the survey. We categorized individuals into five weight change patterns: stable healthy, non-obesity to obesity, obesity to non-obesity, stable obesity, and maximum overweight. Odds ratios (OR) and 95% confidence intervals (CI) relating weight change to incident kidney stone were calculated using logistic regression models adjusting for covariates. The non-linear association between absolute weight change was investigated using the restricted cubic spline (RCS) regression. The supposed population attributable fraction (PAF) for the weight change patterns was calculated.

After adjusting for all confounders, participants changing from non-obesity to obesity, obesity to non-obesity, and stable obesity had significantly higher risks of kidney stone than those with healthy weight during adulthood (OR = 1.59, 95% CI:1.18-2.13; OR = 1.78, 95% CI: 1.47-2.16; OR = 1.80, 95% CI: 1.48-2.19, respectively). A U-shaped association was observed, and the risk of kidney stone was lowest in participants with stable healthy BMI. If the population had maintained a healthy BMI, a 28.7% (95% CI: 18.6%-37.5%) lower incidence of kidney stones was observed.

This study found that changes in weight during adulthood are linked to the risk of developing kidney stones. Maintaining healthy weight during adulthood is important for reducing the risk of developing kidney stones.

Evidence from observational studies and clinical trials suggests that the allergic diseases (ADs) are associated with kidney diseases (KDs). However, the causal association between them remains to be determined. We used bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the potential causality between them.

Mendelian randomization (MR) was performed using publicly available genome-wide association study (GWAS) summary datasets. Inverse variance weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode methods are used to evaluate the causality between ADs and KDs. Sensitivity and heterogeneity analyses were used to ensure the stability of the results.

The MR results indicated that genetic susceptibility to ADs was associated with a higher risk of CKD [odds ratio (OR) = 1.124, 95% CI = 1.020-1.239, p = 0.019] and unspecified kidney failure (OR = 1.170, 95% CI = 1.004-1.363, p = 0.045) but not with kidney stone, ureter stone or bladder stone (OR = 1.001, 95% CI = 1.000-1.002, p = 0.216), other renal or kidney problem (OR = 1.000, 95% CI = 1.000-1.001, p = 0.339), urinary tract or kidney infection (OR = 1.000, 95% CI = 0.999-1.001, p = 0.604), kidney volume (OR = 0.996, 95% CI = 0.960-1.033, p = 0.812) and cyst of kidney (OR = 0.914, 95% CI = 0.756-1.105, p = 0.354). No causal evidence of KDs on ADs was found in present study.

Results from MR analysis indicate a causal association between ADs and CKD and unspecified kidney failure. These findings partly suggest that early monitoring of CKD risk in patients with ADs is intentional.

Type 2 diabetes mellitus (T2DM) commonly complicates kidney stone disease (KSD). Our objective is to investigate the variations in the urinary microbiota between individuals with KSD alone and those with KSD plus T2DM. This exploration could have implications for disease diagnosis and treatment strategies.

During lithotripsy, a ureterscope was employed, and 1 mL of urine was collected from the renal pelvis after bladder disinfection. Sequencing targeting the V3-V4 hypervariable region was performed using the 16S rRNA and Illumina Novaseq platform.

The Shannon index showed a significant decrease in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.041). Principal Coordinate Analysis (PCoA) demonstrated a distinct bacterial community in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.027). The abundance of Sphingomonas, Corynebacterium, and Lactobacillus was significantly higher in the KSD plus T2DM group than in the KSD-only group (false discovery rate < 0.05). Furthermore, Enhydrobacter, Chryseobacterium, and Allobaculum were positively correlated with fasting blood glucose and HbA1c values (P < 0.05).

The urinary microbiota in the renal pelvis exhibits differences between patients with KSD plus T2DM and those with KSD alone. Further studies employing animal models are necessary to validate these distinctions, potentially paving the way for therapeutic developments based on the urinary microbiota.

The aim of this study was to investigate the functional role of phosphodiesterase enzymes (PDE) in the isolated porcine ureter. Distal ureteral strips were mounted in organ baths and pre-contracted with 5-HT (100 μM). Upon generation of stable phasic contractions, PDE-4 and PDE-5 inhibitors were added cumulatively to separate tissues. PDE-4 inhibitors, such as rolipram (10 nM and greater) and roflumilast (100 nM and greater), resulted in significant attenuation of ureteral contractile responses, while a higher concentration of piclamilast (1 μM and greater) was required to induce a significant depressant effect. The attenuation effect by rolipram was abolished by SQ22536 (100 μM). PDE-5 inhibitors, such as sildenafil and tadalafil, were not nearly as effective and were only able to suppress the 5-HT-induced contractions at higher concentrations of 1 μM. Rolipram significantly enhanced the depressant effect of forskolin, while sodium nitroprusside-induced attenuation of contractile responses remained unchanged in the presence of tadalafil. In summary, our study demonstrates that PDE-4 inhibitors are effective in attenuating 5-HT-induced contractility in porcine distal ureteral tissues, while PDE-5 inhibitors are less effective. These findings suggest that PDE-4 inhibitors, such as rolipram, may hold promise as potential therapeutic agents for the treatment of ureteral disorders attributable to increased intra-ureteral pressure.

The lifetime incidence of kidney stones is 6%-12% in the general population. Nephrolithiasis is a known cause of acute and chronic kidney injury, mediated via obstructive uropathy or crystal-induced nephropathy, and several modifiable and non-modifiable genetic and lifestyle causes have been described. Evidence for epidemiology and management of nephrolithiasis after kidney transplantation is limited by a low number of publications, small study sizes and short observational periods. Denervation of the kidney and ureter graft greatly reduces symptomatology of kidney stones in transplant recipients, which may contribute to a considerable underdiagnosis. Thus, reported prevalence rates of 1%-2% after kidney transplantation and the lack of adverse effects on allograft function and survival should be interpreted with caution. In this narrative review we summarize current state-of-the-art knowledge regarding epidemiology, clinical presentation, diagnosis, prevention and therapy of nephrolithiasis after kidney transplantation, including management of asymptomatic stone disease in kidney donors. Our aim is to strengthen clinical nephrologists who treat kidney transplant recipients in informed decision-making regarding management of kidney stones. Available evidence, supporting both surgical and medical treatment and prevention of kidney stones, is presented and critically discussed. The specific anatomy of the transplanted kidney and urinary tract requires deviation from established interventional approaches for nephrolithiasis in native kidneys. Also, pharmacological and lifestyle changes may need adaptation to the specific situation of kidney transplant recipients. Finally, we point out current knowledge gaps and the need for additional evidence from future studies.

Infected urolithiasis is a serious condition that carries with it a high rate of morbidity and mortality.

This review highlights the pearls and pitfalls of infected urolithiasis, including presentation, diagnosis, and management in the emergency department based on current evidence.

Although urolithiasis is common and the vast majority can be treated conservatively, the presence of a concomitant urinary tract infection significantly increases the risk of morbidity, to include sepsis and mortality. Identification of infected urolithiasis can be challenging as patients may have symptoms similar to uncomplicated urolithiasis and/or pyelonephritis. However, clinicians should consider infected urolithiasis in toxic-appearing patients with fever, chills, dysuria, and costovertebral angle tenderness, especially in those with a history of recurrent urinary tract infections. Positive urine leukocyte esterase, nitrites, and pyuria in conjunction with an elevated white blood cell count may be helpful to identify infected urolithiasis. Patients should be resuscitated with fluids and broad-spectrum antibiotics. Additionally, computed tomography and early urology consultation are recommended to facilitate definitive care.

An understanding of infected urolithiasis can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

Enteric hyperoxaluria is a medical condition characterized by elevated urinary oxalate excretion due to increased gastrointestinal oxalate absorption. Causative features include fat malabsorption and/or increased intestinal permeability to oxalate. Enteric hyperoxaluria has long been known to cause nephrolithiasis and nephrocalcinosis, and, more recently, an association with CKD and kidney failure has been shown. Currently, there are no US Food and Drug Administration-approved therapies for enteric hyperoxaluria, and it is unclear what end points should be used to evaluate the efficacy of new drugs and biologics for this condition. This study represents work of a multidisciplinary group convened by the Kidney Health Initiative to review the evidence supporting potential end points for clinical trials in enteric hyperoxaluria. A potential clinical outcome is symptomatic kidney stone events. Potential surrogate end points include ( 1 ) an irreversible loss of kidney function as a surrogate for progression to kidney failure, ( 2 ) asymptomatic kidney stone growth/new stone formation observed on imaging as a surrogate for symptomatic kidney stone events, ( 3 ) urinary oxalate and urinary calcium oxalate supersaturation as surrogates for the development of symptomatic kidney stone events, and ( 4) plasma oxalate as a surrogate for the development of the clinical manifestations of systemic oxalosis. Unfortunately, because of gaps in the data, this Kidney Health Initiative workgroup was unable to provide definitive recommendations. Work is underway to obtain robust information that can be used to inform trial design and medical product development in this space.

Purpose: To investigate the relationship between the Oxidative Balance Score (OBS) and kidney stone risk using NHANES 2007-2018 data, and to explore potential mechanisms and population-specific effects. Materials and methods: Data from the NHANES 2007-2018 were analyzed. OBS was calculated based on 16 dietary components and 4 lifestyle components. Multivariate logistic regression was employed to investigate the relationship between OBS and kidney stone. Further stratified analyses were conducted to examine the associations across different subgroups. Results: A total of 19,799 participants were included in the study. There was a consistent inverse association between OBS and the risk of kidney stones (OR = 0.97; 95% CI: 0.96-0.99). After dividing the participants into quartiles based on OBS, compared to the lowest quartile of OBS, the risk of kidney stones in the highest quartile of OBS was reduced by 33% (95% CI 0.50-0.89; p = 0.002). This association was consistent across both dietary and lifestyle OBS scores. The protective effect of OBS was notably pronounced among Non-Hispanic white and Other race groups, and among individuals with a higher level of education. However, the association was not significant among individuals with diabetes. Conclusion: A higher OBS, indicating a balance skewed towards antioxidants, is associated with a reduced risk of kidney stones, especially among specific population subgroups. These findings underscore the potential role of oxidative balance in kidney stone pathogenesis and highlight the importance of considering individual and population-specific factors in future research and preventive strategies.

Existing evidence shows that there is an independent correlation between nephrolithiasis and gout, and hyperuricemia is the most important risk factor for gout. However, hyperuricemia was often used as an accompanying symptom of gout to explore its association with nephrolithiasis, there were few studies to explore whether hyperuricemia itself or serum uric acid (SUA) is related to the risk of nephrolithiasis. Evidence on the relationship between hyperuricemia and nephrolithiasis is still insufficient.

A total of 22,303 participants aged 30 to 79 years who participated in the China Multi-Ethnic Cohort (CMEC) study in Yunnan Province from May 2018 to September 2019 were included in the study. All participants received standardized face-to-face interviews, medical examinations, and biochemical examinations. Logistic regression was used to estimate the association between hyperuricemia and nephrolithiasis, and a restricted cubic spline (RCS) model was used to explore the dose-response relationship between SUA and the risk of nephrolithiasis.

14.5% of all participants were diagnosed with hyperuricemia, and 12.1% were diagnosed with nephrolithiasis. After adjusting for all potential confounders, the OR (95%CI) for nephrolithiasis in participants with hyperuricemia compared with participants without hyperuricemia was 1.464 (1.312,1.633), p < 0.001. Restricted cubic spline regression analysis showed that the risk of nephrolithiasis increased with the increase of SUA, and when the level of SUA is higher than 356 μmol/L in males and higher than 265 μmol/L in females, there is a dose-response relationship between the increase of SUA and the risk of nephrolithiasis in both males and females (p for nonlinearity = 0.1668, p for nonlinearity = 0.0667).

Asymptomatic hyperuricemia is associated with an increased risk of developing nephrolithiasis. Before reaching the diagnostic criteria for hyperuricemia, the risk of nephrolithiasis rises with the increase in SUA. This suggests that controlling SUA levels may be significant for the prevention of nephrolithiasis.

Elevated levels of the intracellular second messenger cAMP can stimulate intestinal oxalate secretion however the membrane transporters responsible are unclear. Oxalate transport by the chloride/bicarbonate (Cl-/HCO3-) exchanger Slc26a6 or PAT-1 (Putative Anion Transporter 1), is regulated via cAMP when expressed in Xenopus oocytes and cultured cells but whether this translates to the native epithelia is unknown. This study investigated the regulation of oxalate transport by the mouse intestine focusing on transport at the apical membrane hypothesizing PAT-1 is the target of a cAMP-dependent signaling pathway. Adopting the Ussing chamber technique we measured unidirectional 14C-oxalate and 36Cl- flux ([Formula: see text] and [Formula: see text]) across distal ileum, cecum and distal colon, employing forskolin (FSK) and 3-isobutyl-1-methylxanthine (IBMX) to trigger cAMP production. FSK/IBMX initiated a robust secretory response by all segments but the stimulation of net oxalate secretion was confined to the cecum only involving activation of [Formula: see text] and distinct from net Cl- secretion produced by inhibiting [Formula: see text]. Using the PAT-1 knockout (KO) mouse we determined cAMP-stimulated [Formula: see text] was not directly dependent on PAT-1, but it was sensitive to mucosal DIDS (4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid), although unlikely to be another Cl-/HCO3- exchanger given the lack of trans-stimulation or cis-inhibition by luminal Cl- or HCO3-. The cAMP-activated oxalate efflux was reliant on CFTR (Cystic Fibrosis Transmembrane conductance Regulator) activity, but only in the presence of PAT-1, leading to speculation on the involvement of a multi-transporter regulatory complex. Further investigations at the cellular and molecular level are necessary to define the mechanism and transporter(s) responsible.

Stone analysis by physical methods is critical to determine their chemical nature and to diagnose the underlying conditions affecting kidney stone formers. This analysis should be completed by a morphologic examination of stone surface and section, leading to the diagnosis of anatomical or metabolic disorders and of specific diseases. Crystalluria study, the analysis of urine crystals, provides complementary information and is extremely useful for both diagnosis and patient follow-up. This review describes briefly how these techniques may be used and in which conditions stone morphology and urine crystal description are particularly relevant for patients medical care.

To assess the effects of pharmacological interventions in patients with idiopathic hypercalciuria.

We performed a search of multiple databases, trial registries, grey literature and conference proceedings up to October 2019. We included randomized and quasi-randomized controlled trials that examined any pharmacological intervention for preventing complications of idiopathic hypercalciuria (given for at least four months and six of follow-up). The primary outcomes were stone-free patients, urinary symptoms and severe adverse events.

We included five RCTs (n=446 patients, all adults, 4 in individuals with kidney stones and 1 in postmenopausal women with osteoporosis). Diuretics were likely to increase the number of stone-free patients (RR 1.61, 95% CI 1.33-1.96, moderate quality of evidence (QoE)); 274 more stone-free patients/1000 patients treated (95% CI: 148-432) and produced a slight decrease in the stone formation rate (mean difference -0.18, 95% CI -0.30 to -0.06, low QoE); 180 fewer stones/year/1000 patients treated (95% CI: 300 r to 60). No data on urinary symptoms were reported. The association between diuretic use and severe adverse events was uncertain (RR 5.00, 95% CI 0.60-41.88, very low QoE); 4 more severe adverse events/1000 patients treated (95% CI: 0 fewer to 39 more).

The addition of diuretics to a normal or modified diet probably reduces the number of stone recurrences and may decrease the stone formation rate. It is uncertain whether diuretics increase the occurrence of severe adverse events. There were no studies investigating other outcomes or in children.

Whether longitudinal changes in metabolic status influence the effect of kidney stones on cardiovascular disease (CVD) remains unclarified. We investigated the modification effect of status changes in metabolic syndrome (MetS) in the association of kidney stones with risk of incident CVD events.

We performed a prospective association and interaction study in a nationwide cohort including 129,172 participants aged ≥ 40 years without CVDs at baseline and followed up for an average of 3.8 years. Kidney stones information was collected by using a questionnaire and validated by medical records. The repeated biochemical measurements were performed to ascertain the metabolic status at both baseline and follow-up.

4,017 incident total CVDs, 1,413 coronary heart diseases (CHDs) and 2,682 strokes were documented and ascertained during follow-up. Kidney stones presence was significantly associated with 44%, 70% and 31% higher risk of CVDs, CHDs and stroke, respectively. The stratified analysis showed significant associations were found in the incident and sustained MetS patients, while no significant associations were found in the non-MetS at both baseline and follow-up subjects or the MetS remission ones, especially in women. For the change status of each single component of the MetS, though the trends were not always the same, the associations with CVD were consistently significant in those with sustained metabolic disorders, except for the sustained high blood glucose group, while the associations were consistently significant in those with incident metabolic disorders except for the incident blood pressure group. We also found a significant association of kidney stone and CVD or CHD risk in the remain normal glucose or triglycerides groups; while the associations were consistently significant in those with incident metabolic disorders except for the incident blood pressure group. We also found a significant association of kidney stone and CVD or CHD risk in the remain normal glucose or triglycerides groups.

A history of kidney stones in women with newly developed MetS or long-standing MetS associated with increased risk of CVD. The mechanisms link kidney stones and CVD risk in the metabolic and non-metabolic pathways were warranted for further studies.

BACKGROUND: Enteric hyperoxaluria is caused by increased intestinal oxalate absorption and can lead to kidney stones, chronic kidney disease, and kidney failure. Reloxaliase is an orally administered recombinant enzyme that degrades oxalate along the gastrointestinal tract, thereby preventing its absorption. METHODS: We randomly assigned participants with enteric hyperoxaluria to reloxaliase or placebo, three to five times per day with food for 4 weeks. The primary end point was percent change from baseline in 24-hour urinary oxalate (UOx) excretion during weeks 1 to 4. Secondary end points included the proportion of participants with more than a 20% reduction in 24-hour UOx and an efficacy assessment in the bariatric surgery subgroup. RESULTS: A total of 115 patients underwent randomization. The 24-hour UOx decreased from a baseline geometric mean of 83.2 to 67.4 mg/24 hr during weeks 1 to 4 in reloxaliase-treated participants. Corresponding data for placebo-treated participants were 84.2 to 78.1 mg/24 hr. Estimates from the mixed-effect model repeated-measures (MMRM) analysis showed a 22.6% reduction in geometric mean UOx during weeks 1 to 4 for reloxaliase and 9.7% for placebo, a difference of 14.3 percentage points (95% confidence interval [CI], 4.9 to 22.8; P=0.004). A 20% or greater reduction in 24-hour UOx was observed in 48.3% of reloxaliase-treated participants and 31.6% of placebo-treated participants (P=0.06). In the bariatric surgery subgroup, MMRM analysis showed a 21.2% reduction in geometric mean UOx for reloxaliase and a 6.0% reduction for placebo, for a difference of 16.2 percentage points (95% CI, 4.2% to 26.7%). Adverse events occurred in 69% of reloxaliase-treated participants versus 53% of individuals taking placebo and were most commonly gastrointestinal. All but one of the adverse events were grade 1 or 2 in severity; no reloxaliase-treated participants discontinued the study. CONCLUSIONS: Reloxaliase treatment for 4 weeks reduced UOx excretion in patients with enteric hyperoxaluria; adverse events were relatively common, but not dose-limiting. These data establish the foundation for a clinical trial to determine the impact of reloxaliase on nephrolithiasis in patients with enteric hyperoxaluria. (Funded by Allena Pharmaceuticals; ClinicalTrials.gov number, NCT03456830.)

Evidence exists reporting that Pyrrosia lingua (PL, Xinhui Pharmaceutical, Polypodiaceae) alleviates nephrolithiasis in rat models. The precipitation of calcium oxalate may result in kidney stones, and the intestinal microbiota is critical for oxalate metabolism. Therefore, we attempt to delineate the molecular mechanism underlying the effect of PL on nephrolithiasis and its association with gut microbiota.

Following differential flora analysis in gutMEGA, the network relationship of PL and nephrolithiasis was analyzed based on the TCMSP, DisGeNET and STRING databases. Moreover, the kidney stone model rats were fed with different doses of PL powder and PL extract. In addition, metabolomics technology was employed to identify the active ingredients in PL extract and the microbial metabolites in rat feces.

The effect of PL on the nephrolithiasis was based on quercetin and kaempferol by mediating the toll-like receptor signaling pathway and regulating the expression levels of interleukin 6, tumor necrosis factor, mitogen activated protein kinase 8, and secreted phosphoprotein 1. PL significantly reduced the levels of urine oxalic acid, urine calcium, and osteopontin (OPN) levels in rat models of nephrolithiasis. Notably, PL extract decreased these two indicators to lower levels. Furthermore, contents of Oxalobacter formigenes, Bacteriodetes, Bifidobacterium and Fecalibacterium were obviously reduced after treatment with PL extract.

PL powder and its active extracts reduce the oxalate level in urine by regulating oxalate metabolism, thus ameliorating the damage of kidney tissues and preventing kidney stone formation. This study suggests the use of PL and its extracts as an alternative source of promising agents that might directly or indirectly inhibit the progression of kidney stone diseases.

Evaluation of the kidney stone patient includes measurement of 24 h urine chemistries. This review summarizes the application of physiologic principles to the interpretation of urine chemistries, using sulfate and ammonium to estimate diet acid load, and the renal response.

There has been increased recognition of the need to measure urine ammonium excretion in the clinical setting in order to understand renal acid excretion. Some 24 h urine kidney stone panels include ammonium measurements, providing an opportunity to apply this measurement to clinical practice. In order to better interpret ammonium excretion, one needs an estimate of dietary acid load to understand the driving forces for ammonium excretion. Sulfate is also included in some kidney stone panels and functions as an estimate of diet acid load. Combining these analytes with urine pH, the clinician can quickly estimate dietary stone risk as well as potential bowel disease, acidification disorders, and the presence of urease producing bacteria; all of which can affect stone risk.

Measurement of ammonium and sulfate excretion along with urine pH provide important insights into the acid/alkali content of diet, presence and severity of bowel disease, presence of renal acidification disorders, and urinary infection.