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"Stern, Joshua M"
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Evidence for a distinct gut microbiome in kidney stone formers compared to non-stone formers
2016
The trillions of microbes that colonize our adult intestine are referred to as the gut microbiome (GMB). Functionally it behaves as a metabolic organ that communicates with, and complements, our own human metabolic apparatus. While the relationship between the GMB and kidney stone disease (KSD) has not been investigated, dysbiosis of the GMB has been associated with diabetes, obesity and cardiovascular disease. In this pilot study we sought to identify unique changes in the GMB of kidney stone patients compared to patients without KSD. With an IRB-approved protocol we enrolled 29 patients into our pilot study. 23 patients were kidney stone formers and six were non-stone forming controls. Specimens were collected after a 6h fast and were flash frozen in dry ice and then stored at -80 °C. Microbiome: determination of bacterial abundance was by analysis of 16 s rRNA marker gene sequences using next generation sequencing. Sequencing of the GMB identified 178 bacterial genera. The five most abundant enterotypes within each group made up to greater than 50 % of the bacterial abundance identified. Bacteroides was 3.4 times more abundant in the KSD group as compared to control (34.9 vs 10.2 %; p = 0.001). Prevotella was 2.8 times more abundant in the control group as compared to the KSD group (34.7 vs 12.3 %; p = 0.005). In a multivariate analysis including age, gender, BMI, and DM, kidney stone disease remained an increased risk for high prevalence for Bacteroides (OR = 3.26, p = 0.033), whereas there was an inverse association with Prevotella (OR = 0.37, p = 0.043). There were no statistically significant differences in bacterial abundance levels for Bacteroides or Prevotella when comparing patients with and without DM, obesity (BMI >30), HTN or HLD. 11 kidney stone patients completed 24 h urine analysis at the time of this writing. Looking at the bacterial genuses with at least 4 % abundance in the kidney stone group, Eubacterium was inversely correlated with oxalate levels (r = -0.60, p < 0.06) and Escherichia trended to an inverse correlation with citrate (r = -0.56, p < 0.08). We also compared bacterial abundance between uric acid (UA) stone formers (n = 5) and non UA stone formers (n = 18) and found no significant difference between them. We identified two genus of bacteria in the GMB that had significant association with KSD. Interestingly, components of the 24-h urine appear to be correlated to bacterial abundance. These preliminary studies for the first time associate differences in the GMB with kidney stone formation. Further studies are warranted to evaluate the potential causative role of preexisting dysbiosis in kidney stone disease.
Journal Article
Development of Quantum Dot-Mediated Fluorescence Thermometry for Thermal Therapies
by
Hanson, Willard L
,
Bensalah, Karim
,
Stern, Joshua M
in
Animals
,
Biochemistry
,
Biological and Medical Physics
2009
As thermal therapies are frequently employed for management of tumors in various organs, there are growing demands for reliable and accurate intraoperative monitoring techniques of the thermal lesion. However, current monitoring techniques have limited accuracy, accessibility and are not capable of monitoring the thermal lesion in real-time during the procedure. In the present study, quantum dot-mediated fluorescence thermometry was developed and its performance was characterized to demonstrate the feasibility of spatiotemporal monitoring of thermal lesions. First, the temperature dependency of two different types of CdTe/ZnS quantum dots (QDs) were characterized in a temperature range relevant to hyperthermic therapies, and a temperature-intensity relationship was established for each QD. The spatial and temporal resolutions of the system were characterized by exposing QDs to a pre-determined spatial temperature gradient, and by monitoring the spatiotemporal temperature during gold nanoshell-mediated heating. The results demonstrated that QD-mediated thermometry is capable of measuring spatiotemporally varying temperature fields relevant for hyperthermic thermal therapies. Its implication for intraoperative image-guidance of thermal therapy was also discussed.
Journal Article
Disparities in care among patients presenting to the emergency department for urinary stone disease
2020
To determine whether patients with ureteral stones received different standard of care in the emergency department (ED) according to various sociodemographic factors. We conducted a retrospective study of patients presenting to EDs in a large tertiary-care hospital in the Bronx, New York with a diagnosis of ureteral stones. Electronic chart review was used to assess each patient’s ED course and to gather socio-demographic information. The primary outcomes of interest were administration of pain medication, prescription of alpha-1 antagonists to facilitate stone passage, and whether or not patients received CT scan or ultrasound. Associations of these outcomes with age categories, sex, race/ethnicity, BMI category, socioeconomic status and insurance status were examined using multivariate logistic regression models. 1200 patients were included in this analysis of which 616 (51%) were women. A large proportion of patients were minorities: 40% Hispanic, 15% non-Hispanic Black, and 20% other/multiracial. Patients aged 55–64 years and those 65 or older were less likely to receive pain medication compared to patients < 35 years (OR = 0.48, 95% CI 0.27–0.86, p = 0.01 and OR = 0.46, 95% CI 0.21–1.00, p = 0.05, respectively). Women were less likely than men to undergo any form of diagnostic imaging (OR = 0.52, 95% CI 0.35–0.76, p = 0.001). Similarly, patients in the lowest quintile of SES received less imaging than patients in the highest SES group (OR = 0.50, 95% CI 0.27–0.90, p = 0.02). Finally, women were less likely to receive alpha blockade compared to men (OR = 0.68, 95% CI 0.49–0.92, p = 0.014). Multiple disparities exist among patients presenting to the emergency department for ureteral stones.
Journal Article
The relationship between vascular calcifications and urolithiasis in a large, multiethnic patient population
2021
Several studies have reported associations between vascular calcifications and urinary stone disease (USD). However, results have been inconsistent and the majority of studies did not report on race/ethnicity. We examined the association between vascular calcifications and USD in a large, racially/ethnically diverse patient population. We identified 672 USD cases and 672 controls (i.e., patients without a history of USD) from patients who underwent non-contrast CT imaging at Montefiore Medical Center in Bronx, New York between 2004 and 2013. Controls were matched to cases on age, sex and race/ethnicity. The non-contrast CT imaging was used to measure abdominal aortic calcification (AAC) and calculate the AAC severity score. Logistic regression models were used to examine associations of AAC presence and severity score with risks of USD and stone types. Cases and controls had similar AAC prevalence (45.2% vs. 44.8%, p = 0.87), and AAC severity score (median 10 vs. 9.3, p = 0.47). The presence of AAC (OR = 0.98, 95% CI 0.78–1.23; p = 0.86) or AAC severity score were not associated with risk of USD: ORs of 0.96, 0.87, 1.07 and 1.03 for increasing AAC quartiles (p-trend = 0.54). There were also no associations in the stratified analyses by race/ethnicity or by sex. However, when USD patients were stratified by stone type, brushite/apatite stone formers had an inverse association with the lowest quartile of AAC severity score (OR = 0.35, 95% CI 0.11–0.84, p = 0.04) in comparison to patients without AAC. Overall, we found no association between vascular calcifications and risk of urinary stone disease in this large, hospital-based, case–control study.
Journal Article
Baseline chronic kidney disease does not predict long-term renal functional decline after percutaneous nephrolithotomy
by
Watts, Kara L
,
Abramowitz, Matthew
,
Schoenfeld, Daniel
in
Kidney diseases
,
Kidney stones
,
Mortality
2019
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.
Journal Article
Fecal transplant modifies urine chemistry risk factors for urinary stone disease
2019
Urinary stone disease (USD) is a major health concern. There is a need for new treatment modalities. Recently, our group provided evidence for an association between the GMB composition and USD. The accessibility of the Gut Microbiome (GMB) makes it an attractive target for investigation and therefore, in these studies we have evaluated the extent to which the whole gut microbial community in fecal transplants can affect urinary stone risk parameters in an animal model. Fresh fecal pellets were collected from Zucker lean rats, homogenized in PBS (100 mg/mL), filtered through a 70 μm strainer and then orally gavaged into C57BL/6NTac germ‐free mice. Twenty‐four hours urine collections and GMB analysis were performed over time for 1 month. Kidney and gut tissue were harvested from transplanted mice for western blot analysis of expression levels of the Slc26a6 transporter involved in oxalate balance. Urinary calcium decreased after fecal transplant by 55% (P < 0.001). Urinary oxalate levels were on average 24% lower than baseline levels (P < 0.001). Clostridiaceae family was negatively correlated with urinary oxalate at 4 weeks after transplant (r = −0.83, P < 0.01). There was a 0.6 unit average increase in urinary pH from a baseline of 5.85 (SE ± 0.028) to 6.49 (SE ± 0.04) (P < 0.001) after transplant. There was a concomitant 29% increase in gastrointestinal alkali absorption (P < 0.001) 4‐weeks after fecal transplant. Slc26a6 expression increased by 90% in the cecum after transplant. Our results suggest that the gut microbiome may impact metabolism, alters urinary chemistry, and thereby may influence USD; the accessibility of the GMB can potentially be leveraged for therapeutic interventions. This paper represents a very early publication in this field of urology suggesting that the GMB can alter urinary stone parameters important for stone risk.
Journal Article
Kidney stone formation and the gut microbiome are altered by antibiotics in genetic hypercalciuric stone-forming rats
by
Wang, Yi
,
Suadicani, Sylvia O
,
Becker, Jennifer
in
Antibiotics
,
Calcification
,
Digestive system
2021
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.
Journal Article
Geographic location is an important determinant of risk factors for stone disease
2017
Some regions are known to have an increased burden of urolithiasis. Urolithiasis is known to be affected by weather patterns, particularly high ambient temperatures. To identify geographic differences in risk factors, we compared metabolic information for 1254 patients in two geographically distinct regions, New York and Florida, with per sample adjustment for ambient weather. We observed that patients in New York were more likely to have low urine volume, but also lower total urinary calcium (168 vs 216 mg, p = 0.005), urate (376 vs 678 mg, p < 0.001), and phosphate (0.8 vs 0.9 g, p 0.007). Temperature was a predictor of urine pH (B = −0.07, p = 0.024). Geographic region was a predictive factor (p < 0.01) for urine calcium, volume, serum bicarbonate, and anion gap. Increased anion gap and serum HCO3 − were also predicted by temperature (B = 0.065, p = 0.035). Interestingly, urine volume was not affected by temperature. Our finding that temperature is a determining factor of urine pH and anion gap may help to explain the finding that hot weather is associated with increases in urolithiasis. Anion gap has also been previously associated with poor health measures and represents an interesting target for future research. Geographic location may independently contribute to urine composition, through regional diets, sun exposure, and groundwater. This study highlights the impact geographic location plays in determining risk factors for stone disease and the value of regional knowledge to the treating physician in preventing stone disease.
Journal Article
The visceral fat compartment is independently associated with changes in urine constituent excretion in a stone forming population
2015
The objective of this study was to identify the independent effect of visceral fat on urine constituent excretion in a stone forming population. Using a database of 382 kidney stone patients with available visceral fat quantification, we created multiple linear regression models predicting changes in urinary solutes based on visceral fat area and body mass-index, divided by gender. Chi-square tests were used to compare stone composition by body mass-index and visceral fat area. Visceral fat predicts increases in urinary creatinine, sodium, and volume in men, but only urinary phosphate in women. In women, total body mass-index does not appear to modify this effect, but in men it is more pronounced in overweight patients for creatinine and volume only. Elevated visceral fat is associated with increased probability of uric acid stone composition. Different fat compartments likely effect urine composition in different ways. This effect appears to be different in men and women. Understanding and quantifying the effects of different fat compartments is probably important to understanding the metabolism of urolithiasis.
Journal Article
Nanotechnology
2017
The treatment of urologic malignancies has evolved toward tissue‐sparing and targeted therapies. Nanotechnology is at the forefront of these advances, particularly in the diagnosis and treatment of prostate and renal cancers. In diagnostics, computed tomography (CT) and magnetic resonance imaging (MRI) combined with lymphotropic nanoparticles significantly improve the detection of metastatic lymph nodes and cancer staging. In therapeutics, nanoparticles passively and actively target tumor cells to focally ablate using a variety of thermal ablative techniques. Targeted therapy using nanoparticles labeled with chemotherapeutic agents has also shown success. The field of nanotechnology holds considerable promise for the future of urologic cancer therapy in the era of tissue preservation. Future studies are needed to improve the development and use of these particles to further advance urologic cancer theranostics.
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