SLIPS-LAB-A bioinspired bioanalysis system for metabolic evaluation of urinary stone disease.
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ABSTRACT:
SUBMITTER: Li H
PROVIDER: S-EPMC7244315 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
Publications
SLIPS-LAB-A bioinspired bioanalysis system for metabolic evaluation of urinary stone disease.
Li Hui H Shkolyar Eugene E Wang Jing J Conti Simon S Pao Alan C AC Liao Joseph C JC Wong Tak-Sing TS Wong Pak Kin PK
Science advances 20200522 21
Urinary stone disease is among the most common medical conditions. Standard evaluation of urinary stone disease involves a metabolic workup of stone formers based on measurement of minerals and solutes excreted in 24-hour urine samples. Nevertheless, 24-hour urine testing is slow, expensive, and inconvenient for patients, which has hindered widespread adoption in clinical practice. Here, we demonstrate SLIPS-LAB (Slippery Liquid-Infused Porous Surface Laboratory), a droplet-based bioanalysis sys ...[more]
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Project description:PurposeRecent observational studies reporting a lack of benefit from 24-hour urine testing for urinary stone disease (USD) prevention assumed testing included all components recommended from clinical guidelines. We sought to assess the completeness of 24-hour urine testing in the VA population.Materials and methodsFrom the VHA Corporate Data Warehouse (2012-2019), we identified patients with USD (n=198,621) and determined those who saw a urologist and/or nephrologist, and received 24-hour urine testing within 12 months of their index USD encounter. Through Logical Observation Identifiers Names and Codes, we evaluated each collection's completeness, defined as including all of urine volume, calcium, oxalate, citrate, uric acid, and creatinine. We then fit a multilevel logistic regression model with random effects for VHA facility to evaluate factors associated with specialist follow-up, testing, and testing completeness.ResultsSpecialist follow-up occurred in 54.3% and was stable over time. Testing occurred in 8.4%, declining from 9.3% in 2012 to 7.2% in 2019. Of tests performed, 54.6% were complete (43.7% increasing to 62.7% from 2012-2019). In adjusted analysis, there was high between-facility variation in specialist follow-up (median OR 2.0; 95% CI 1.7-2.0), testing (median OR 2.2, 95% CI 1.9-2.4), and testing completeness (median OR, 6.0, 95% CI 4.5-7.3). Individual facilities contributed 52% (intraclass correlation coefficient, 0.52; 95% CI, 0.44-0.57) towards the observed variation in testing completeness.ConclusionsApproximately 1 in 12 U.S. Veterans with USD receive metabolic testing and half of these tests are complete. Addressing facility level variation in testing completeness may improve USD care.
| S-EPMC9762689 | biostudies-literature
Project description:Background: Employing advanced machine learning models, we aim to identify biomarkers for urolithiasis from 24-h metabolic urinary abnormalities and study their associations with urinary stone diseases. Methods: We retrospectively recruited 468 patients at Peking Union Medical College Hospital who were diagnosed with urinary stone disease, including renal, ureteral, and multiple location stones, and had undergone a 24-h urine metabolic evaluation. We applied machine learning methods to identify biomarkers of urolithiasis from the urinary metabolite profiles. In total, 148 (34.02%) patients were with kidney stones, 34 (7.82%) with ureter stones, and 163 (34.83%) with multiple location stones, all of whom had detailed urinary metabolite data. Our analyses revealed that the Random Forest algorithm exhibited the highest predictive accuracy, with AUC values of 0.809 for kidney stones, 0.99 for ureter stones, and 0.775 for multiple location stones. The Super Learner Ensemble Method also demonstrated high predictive performance with slightly lower AUC values compared to Random Forest. Further analysis using multivariate logistic regression identified significant features for each stone type based on the Random Forest method. Results: We found that 24-h urinary magnesium was positively associated with both kidney stones and multiple location stones (OR = 1.195 [1.06-1.3525] and 1.3258 [1.1814-1.4949]) due to its high correlation with urinary phosphorus, while 24-h urinary creatinine was a protective factor for kidney stones and ureter stones, with ORs of 0.9533 [0.9117-0.996] and 0.8572 [0.8182-0.8959]. eGFR was a risk factor for ureter stones and multiple location stones, with ORs of 1.0145 [1.0084-1.0209] and 1.0148 [1.0077-1.0223]. Conclusion: Machine learning techniques show promise in revealing the links between urological stone disease and 24-h urinary metabolic data. Enhancing the prediction accuracy of these models leads to improved dietary or pharmacological prevention strategies.
| S-EPMC11678200 | biostudies-literature
Project description:Introduction: In complex microbial communities, the importance of microbial species at very low abundance levels and their prevalence for overall community structure and function is increasingly being recognized. Clinical microbiome studies on urinary stone disease (USD) have indicated that both the gut and urinary tract microbiota are associated with the onset of the disease and that kidney stones them-selves harbor a complex, yet consistent and viable, microbiome. However, how rare phylotypes contribute to this association remains unclear. Delineating the contribution of rare and common phylotypes to urinary stone disease is important for the development of bacteriotherapies to promote urologic health. Methods: The objectives of the current report were to conduct a metaanalysis of 16S rRNA datasets derived from the kidney stone, stool, and urine samples of participants with or without urinary stone disease. To delineate the impact of rare and common phylotypes, metaanalyses were conducted by first separating rare and common taxa determined by both the frequency and abundance of amplicon sequence variants. Results: Consistent with previous analyses, we found that gut, upper urinary, and lower urinary tract microbiomes were all unique. Rare phylotypes comprised the majority of species observed in all sample types, with kidney stones exhibiting the greatest bias toward rarity, followed by urine and stool. Both rare and common fractions contributed significantly to the differences observed between sample types and health disparity. Furthermore, the rare and common fractions were taxonomically unique across all sample types. A total of 222 and 320 unique rare phylotypes from urine and stool samples were found to be significantly associated with USD. A co-occurrence correlation analysis revealed that rare phylotypes are most important for microbiome structure in stones, followed by urine and stool. Discussion: Collectively, the results indicate that rare phylotypes may be important for the pathophysiology of USD, particularly in the kidney stone matrix, which is inherently a very low microbial biomass niche that can have implications for the diagnosis and treatment of kidney stones. Further studies are needed to investigate the functional significance of rare phylotypes in kidney stone pathogenesis.
| S-EPMC10436313 | biostudies-literature
Project description:BackgroundKidney stones or nephrolithiasis is a chronic metabolic disease characterized by renal colic and hematuria. Currently, a pathogenetic mechanism resulting in kidney stone formation remains elusive. We performed a multi-omic study investigating urinary microbial compositions and metabolic alterations during nephrolithiasis.MethodUrine samples from healthy and individuals with nephrolithiasis were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectroscopy. Microbiome and metabolome profiles were analyzed individually and combined to construct interactome networks by bioinformatic analysis.ResultsDistinct urinary microbiome profiles were determined in nephrolithiasis patients compared with controls. Thirty-nine differentially abundant taxa between controls and nephrolithiasis patients were identified, and Streptococcus showed the most significant enrichment in nephrolithiasis patients. We also observed significantly different microbial compositions between female and male nephrolithiasis patients. The metabolomic analysis identified 112 metabolites that were differentially expressed. Two significantly enriched metabolic pathways, including biosynthesis of unsaturated fatty acids and tryptophan metabolism, were also identified in nephrolithiasis patients. Four potentially diagnostic metabolites were also identified, including trans-3-hydroxycotinine, pyroglutamic acid, O-desmethylnaproxen, and FAHFA (16:0/18:2), and could function as biomarkers for the early diagnosis of nephrolithiasis. We also identified three metabolites that contributed to kidney stone size. Finally, our integrative analysis of the urinary tract microbiome and metabolome identified distinctly different network characteristics between the two groups.ConclusionsOur study has characterized important profiles and correlations among urinary tract microbiomes and metabolomes in nephrolithiasis patients for the first time. These results shed new light on the pathogenesis of nephrolithiasis and could provide early clinical biomarkers for diagnosing the disease.
| S-EPMC9484321 | biostudies-literature
Project description:IntroductionBecause of phenotypic overlap between monogenic urinary stone diseases (USD), gene-specific analyses can result in missed diagnoses. We used targeted next generation sequencing (tNGS), including known and candidate monogenic USD genes, to analyze suspected primary hyperoxaluria (PH) or Dent disease (DD) patients genetically unresolved (negative; N) after Sanger analysis of the known genes. Cohorts consisted of 285 PH (PHN) and 59 DD (DDN) families.MethodsVariants were assessed using disease-specific and population databases plus variant assessment tools and categorized using the American College of Medical Genetics (ACMG) guidelines. Prior Sanger analysis identified 47 novel PH or DD gene pathogenic variants.ResultsScreening by tNGS revealed pathogenic variants in 14 known monogenic USD genes, accounting for 45 families (13.1%), 27 biallelic and 18 monoallelic, including 1 family with a copy number variant (CNV). Recurrent genes included the following: SLC34A3 (n = 13), CLDN16 (n = 8), CYP24A1 (n = 4), SLC34A1 (n = 3), SLC4A1 (n = 3), APRT (n = 2), CLDN19 (n = 2), HNF4A1 (n = 2), and KCNJ1 (n = 2), whereas ATP6V1B1, CASR, and SLC12A1 and missed CNVs in the PH genes AGXT and GRHPR accounted for 1 pedigree each. Of the 48 defined pathogenic variants, 27.1% were truncating and 39.6% were novel. Most patients were diagnosed before 18 years of age (76.1%), and 70.3% of biallelic patients were homozygous, mainly from consanguineous families.ConclusionOverall, in patients suspected of DD or PH, 23.9% and 7.3% of cases, respectively, were caused by pathogenic variants in other genes. This study shows the value of a tNGS screening approach to increase the diagnosis of monogenic USD, which can optimize therapies and facilitate enrollment in clinical trials.
| S-EPMC8589729 | biostudies-literature
Project description:IntroductionIn this study, a survey was prepared for urologists that asked about their primary choice of treatment for urolithiasis in daily practice and their answers were evaluated.MethodsThe survey was prepared on the Google Docs website and it was sent to 1,016 urologists via email with 752 confirmed deliveries. In addition to the demographic questions about each participant's age, gender, and institution, the survey presented case scenarios focusing on their preferred treatment modalities for distal ureteric, proximal ureteric, and renal calculi. The participating urologists were divided into two groups according to the frequency that they treat urolithiasis patients.ResultsOf the 752 surveys delivered, 211 urologists (28.05%) responded and 204 answered all questions. According to the results, there were no significant differences between the treatment approaches and the other localizations, but there was a statistically significant difference for treatment approaches to lower pole stones between two groups. In response to the question of which stone treatment method was used less frequently, 124 (60.7%) participants answered that they used shock wave lithotripsy less in the last 10 years.ConclusionThe present study has shown that while the management of renal and ureteric calculi by Turkish urologists is highly varied, the overall treatment patterns are in accordance with the European Association of Urology guidelines. However, similar to the global trend extracorporeal shock wave lithotripsy is less preferred by Turkish urologists.
| S-EPMC6074772 | biostudies-literature
Project description:IntroductionUrinary stone disease (USD) is associated with cardiovascular disease (CVD) in Western populations. However, the prevalence and relationship between USD and CVD risk have not been fully examined in the Chinese population.MethodsWe performed a cross-sectional study of 10,281 participants in rural China. All subjects underwent renal ultrasound to detect USD, brachial-ankle pulsewave velocity (baPWV) measurement to estimate arterial stiffness, and ankle-brachial index (ABI) examination to detect peripheral arterial disease (PAD) (defined as ABI <0.9 on at least 1 side of the body).ResultsMean age of the study population was 55.4 ± 10.0 years; 47.1% were men. Among all participants, 5.7% (n = 582) had USD, mean baPWV was 15.6 ± 3.2 m/s, and 4.0% had PAD. The prevalence of USD increased in parallel with mean arterial pressure, albuminuria, Framingham risk score, and baPWV. In multivariate analyses after adjustment for demographic characteristics, USD was significantly associated with an increased risk of hypertension (odds ratio [OR]: 1.32; 95% confidence interval [CI]: 1.08-1.62), albuminuria (OR: 2.17; 95% CI: 1.74-2.69), chronic kidney disease (OR: 2.11; 95% CI: 1.70-2.62), increased arterial stiffness (OR: 1.24; 95% CI: 1.01-1.52), and PAD (OR: 1.50; 95% CI: 1.04-2.16).DiscussionIn rural China, USD was associated with a high prevalence of traditional CVD risk factors, increased arterial stiffness, and PAD. The presence of USD should increase physician awareness of the concomitant presence of CVD risk factors.
| S-EPMC5733875 | biostudies-literature
Project description:PurposeStone composition can provide valuable information for the diagnosis, treatment and recurrence prevention of urolithiasis. The aim of this study was to evaluate the distribution of urinary stone components and the impact of different crystal forms according to gender and age of patients in Germany.MethodsA total of 45,783 urinary stones submitted from 32,512 men and 13,271 women between January 2007 and December 2020 were analyzed by infrared spectroscopy. Only the first calculus obtained per patient was included in the analysis.ResultsThe most common main stone component was calcium oxalate (CaOx) (71.4%), followed by carbonate apatite (CA) (10.2%) and uric acid (UA) (8.3%). Struvite (2.1%), brushite (1.3%), protein (0.5%) and cystine (0.4%) stones were only rarely diagnosed. CaOx (75%) and UA stones (81%) were more frequently obtained from men than women (p < 0.001). Weddellite (COD) and uric acid dihydrate (UAD) were more common in younger ages than whewellite (COM) and anhydrous uric acid (UAA), respectively, in both men and women. The ratios of COM-to-COD and UAA-to-UAD calculi were approximately 4:1 and 8:1, respectively. The peak of stone occurrence was between the ages of 40 and 59 years.ConclusionStone composition is strongly associated with gender and age. The peak incidence of calculi in both women and men was in the most active phase of their working life. The distinction between different crystal forms could provide clues to the activity and mechanisms of lithogenesis. Further research is needed in understanding the causative factors and the process of stone formation.
| S-EPMC9236976 | biostudies-literature
Project description:PurposeWe determined the association between urology consultation and emergency department revisits for children with urinary stones.Materials and methodsThis retrospective cohort study included patients 18 years old or younger who presented to an emergency department in South Carolina with a urinary stone from 1997 to 2015. The primary exposure was urology consultation during the index emergency department visit. The primary outcome was a stone related emergency department revisit occurring within 180 days of discharge from an index emergency department visit. Secondary outcomes included computerized tomography use, inpatient admission and emergent surgery.ResultsOf 5,642 index emergency department visits for acute urinary stones 11% resulted in at least 1 stone related emergency department revisit within 180 days. Of revisits 59% occurred within 30 days of discharge and 39% were due to pain. The odds of emergency department revisit were highest within the first 48 hours of discharge home (OR 22.6, 95% CI 18.0 to 28.5) and rapidly decreased thereafter. Urology consultation was associated with a 37% lower adjusted odds of emergency department revisit (OR 0.63, 95% CI 0.44 to 0.90) and 68% lower odds of computerized tomography use across all emergency department visits (OR 0.32, 95% CI 0.15 to 0.69). Among patients who revisited the emergency department the frequency of pain complaints was 27% in those with a urological consultation at the index visit and 39% in those without.ConclusionsUrology consultation was associated with decreased emergency department revisits and computerized tomography use in pediatric patients with urinary stones. Future studies should identify patients who benefit most from urology consultation and ascertain processes of care that decrease emergency department revisits among high risk patients.
| S-EPMC6002942 | biostudies-literature
Project description:ObjectiveTo bridge the gap between evidence and clinical judgement, we defined scenarios appropriate for ureteral stent omission after uncomplicated ureteroscopy (URS) using the RAND/UCLA Appropriateness Method (RAM). We retrospectively assessed rates of appropriate stent omission, with the goal to implement these criteria in clinical practice.MethodsA panel of 15 urologists from the Michigan Urological Surgery Improvement Collaborative (MUSIC) met to define uncomplicated URS and the variables that influence stent omission decision-making. Over two rounds, they scored clinical scenarios for Appropriateness Criteria (AC) for stent omission based on a combination of variables. AC were defined by median scores: 1 to 3 (inappropriate), 4 to 6 (uncertain), and 7 to 9 (appropriate). Multivariable analysis determined the association of each variable with AC scores. Uncomplicated URS cases in the MUSIC registry were assigned AC scores and stenting rates assessed.ResultsSeven variables affecting stent decision-making were identified. Of the 144 scenarios, 26 (18%) were appropriate, 88 (61%) inappropriate, and 30 (21%) uncertain for stent omission. Most scenarios appropriate for omission were pre-stented (81%). Scenarios with ureteral access sheath or stones >10mm were only appropriate if pre-stented. Stenting rates of 5,181 URS cases correlated with AC scores. Stents were placed in 61% of cases appropriate for omission (practice range, 25% to 98%).ConclusionWe defined objective variables and AC for stent omission following uncomplicated URS. AC scores correlated with stenting rates but there was substantial practice variation. Our findings demonstrate that the appropriate use of stent omission is underutilized.
| S-EPMC9432824 | biostudies-literature