Examining the Relationship between Urinary Pathogens, Antibiotic Exposure and Urolithiasis

Urinary stone disease is a highly prevalent urological condition; however, the pathophysiology remains poorly understood. Growing evidence suggests a relationship between urinary tract infections, antibiotic exposure and the development of urolithiasis. In this project, we utilized a dietary Drosophila melanogaster model and a calcium oxalate crystal adhesion assay to further investigate the impact of a urinary pathogen and antibiotics on calcium stone formation. We demonstrated that both a non-urease producing strain of Escherichia coli and the antibiotics, ciprofloxacin and trimethoprim-sulfamethoxazole, increased calcium stone formation. In addition, our preliminary work suggests that biomineralization agents such as osteopontin and zinc appear to be implicated in this process. Further research is required to better delineate the mechanisms involved and to translate these findings into potential therapeutic and prevention strategies for human stone disease including antibiotic stewardship, anti-oxidants, probiotics, and microbiome modification

A population-based retrospective cohort study analyzing contemporary trends in the surgical management of urinary stone disease in adults

Introduction: We aimed to review the trends and incidence of surgical intervention for adults with upper urinary tract stones in Ontario, Canada, and to hypothesize potential causes for the observed changes. Methods: We carried out a retrospective, population-based cohort study using administrative databases held at the Institute of Clinical Evaluative Sciences (IC/ES) to identify all adults (≥18 years) who underwent surgical treatment for urolithiasis, defined by records using a combination of both hospital and physician billing from 2002-2019. Descriptive statistics were used to summarize baseline patient demographics, and surgical trends were analyzed using the Cochrane-Armitage test for trend. Results: From 2002-2019, 140 263 patients were treated surgically for urolithiasis. During this time period, the total number of surgically treated stone disease increased by 80.5%. By type of procedure, percutaneous nephrolithotomy (PCNL) increased by 187% and ureteroscopy (URS) increased by 158%, while the number of shockwave lithotripsy (SWL) declined by 31.4%. The adult population in Ontario in the years evaluated grew by 24.4%. The number of surgical procedures per 100 000 people over this time grew by 45.3%. For every 1% increase in the population, there was a 2.6% rise in stone-related surgical procedures. Conclusions: The number of stone-related surgical procedures performed rose significantly and cannot be accounted for by population growth alone. This rise was proportionally larger in the female population, further supporting a narrowing of the gender gap in urinary stone disease. The reasons for the increase are likely multifactorial and may imply an increasing incidence of surgically treated stone disease. The change in the proportion of URS and SWL performed may demonstrate a continued shift in surgical preference or may be reflective of resource limitations and availability. The increase in PCNL volumes may also suggest a greater complexity of cases. These findings should be considered for future resource planning and require further study

Techniques - Ultrasound-guided percutaneous nephrolithotomy: How we do it.

Ultrasonography has emerged as an alternative to fluoroscopy for image-guided percutaneous nephrolithotomy (PCNL) in many countries. Compared to fluoroscopy-guided PCNL (F-PCNL), ultrasound-guided PCNL (US-PCNL) is easier to learn and reduces radiation exposure to patients and providers. Despite these advantages, uptake of ultrasound-guided PCNL (US-PCNL) in Canada has been almost nonexistent, largely because it is not incorporated into urologists' training. In this article, we seek to familiarize Canadian urologists with this approach by describing our step-by-step technique for US-PCNL. Additionally, we provide keys to successful implementation of this technique

In focus: perplexing increase of urinary stone disease in children, adolescent and young adult women and its economic impact

Background Urinary stone disease (USD) historically has affected older men, but studies suggest recent increases in women, leading to a near identical sex incidence ratio. USD incidence has doubled every 10 years, with disproportionate increases amongst children, adolescent, and young adult (AYA) women. USD stone composition in women is frequently apatite (calcium phosphate), which forms in a higher urine pH, low urinary citrate, and an abundance of urinary uric acid, while men produce more calcium oxalate stones. The reasons for this epidemiological trend are unknown. Methods This perspective presents the extent of USD with data from a Canadian Province and a North American institution, explanations for these findings and offers potential solutions to decrease this trend. We describe the economic impact of USD. Findings There was a significant increase of 46% in overall surgical interventions for USD in Ontario. The incidence rose from 47.0/100,000 in 2002 to 68.7/100,000 population in 2016. In a single United States institution, the overall USD annual unique patient count rose from 10,612 to 17,706 from 2015 to 2019, and the proportion of women with USD was much higher than expected. In the 10–17-year-old patients, 50.1% were girls; with 57.5% in the 18–34 age group and 53.6% in the 35–44 age group. The roles of obesity, diet, hormones, environmental factors, infections, and antibiotics, as well as the economic impact, are discussed. Interpretation We confirm the significant increase in USD among women. We offer potential explanations for this sex disparity, including microbiological and pathophysiological aspects. We also outline innovative solutions – that may require steps beyond typical preventive and treatment recommendations

The evolution of percutaneous nephrolithotomy : analysis of a single institution experience over 25 years

Introduction: Over time, the incidence of nephrolithiasis has risen significantly, and patient populations have become increasingly complex. Our study aimed to determine the impact of changes in patient demographics on percutaneous nephrolithotomy (PCNL) outcomes.
 Methods: A retrospective analysis of a prospectively collected database was carried out from 1990–2015. Patient demographics, comorbidities, stone and procedure characteristics were analyzed. Multivariate logistic regression was used to evaluate differences in operative duration, complications, stone-free rate, and length of stay.
 Results: A total of 2486 patients with a mean age of 54±15 years, body mass index (BMI) of 31±8, and stone surface area of 895±602 mm2 were analyzed; 47% of patients had comorbidities, including hypertension (22%), diabetes mellitus (14%), and cardiac disease (13%). Complication rate was 19%, including a 2% rate of major complications (Clavien grade III–V). There was a statistically significant increase in patient age, BMI, and comorbidities over time, which was correlated with an increased complication rate (odds ratio [OR] 1.15; p=0.010). The overall transfusion rate was 1.0% and remained stable (p=0.131). With time, both OR duration (mean Δ 16 minutes; p<0.001) and hospital length of stay (mean Δ 2.4 days; p<0.001) decreased significantly. Stone-free rate of 1873 patients with available three-month followup was 87% and decreased significantly over time (OR 1.09; p<0.001), but was correlated with an increased use of computed tomography (CT) scans for followup imaging.
 Conclusions: Despite an increasingly complex patient population, PCNL remains a safe and effective procedure with a high stone-free rate and low risk of complications

Techniques - Ultrasound-guided percutaneous nephrolithotomy: How we do it.

Ultrasonography has emerged as an alternative to fluoroscopy for image-guided percutaneous nephrolithotomy (PCNL) in many countries. Compared to fluoroscopy-guided PCNL (F-PCNL), ultrasound-guided PCNL (US-PCNL) is easier to learn and reduces radiation exposure to patients and providers. Despite these advantages, uptake of ultrasound-guided PCNL (US-PCNL) in Canada has been almost nonexistent, largely because it is not incorporated into urologists training. In this article, we seek to familiarize Canadian urologists with this approach by describing our step-by-step technique for US-PCNL. Additionally, we provide keys to successful implementation of this technique

Oxalate-degrading bacillus subtilis mitigates urolithiasis in a drosophila melanogaster model

Kidney stones affect nearly 10% of the population in North America and are associated with high morbidity and recurrence, yet novel prevention strategies are lacking. Recent evidence suggests that the human gut microbiota can influence the development of nephrolithiasis, although clinical trials have been limited and inconclusive in determining the potential for microbially based interventions. Here, we used an established Drosophila melanogaster model of urolithiasis as a highthroughput screening platform for evaluation of the therapeutic potential of oxalatedegrading bacteria in calcium oxalate (CaOx) nephrolithiasis. The results demonstrated that Bacillus subtilis 168 (BS168) is a promising candidate based on its preferential growth in high oxalate concentrations, its ability to stably colonize the D. melanogaster intestinal tract for as long as 5 days, and its prevention of oxalate-induced microbiota dysbiosis. Single-dose BS168 supplementation exerted beneficial effects on D. melanogaster for as long as 14 days, decreasing stone burden in dissected Malpighian tubules and fecal excreta while increasing survival and behavioral markers of health over those of nonsupplemented lithogenic controls. These findings were complemented by in vitro experiments using the established MDCK renal cell line, which demonstrated that BS168 pretreatment prevented increased CaOx crystal adhesion and aggregation. Taking our results together, this study supports the notion that BS168 can functionally reduce CaOx stone burden in vivo through its capacity for oxalate degradation. Given the favorable safety profile of many B. subtilis strains already used as digestive aids and in fermented foods, these findings suggest that BS168 could represent a novel therapeutic adjunct to reduce the incidence of recurrent CaOx nephrolithiasis in high-risk patients. IMPORTANCE Kidney stone disease is a morbid condition that is increasing in prevalence, with few nonsurgical treatment options. The majority of stones are composed of calcium oxalate. Unlike humans, some microbes can break down oxalate, suggesting that microbial therapeutics may provide a novel treatment for kidney stone patients. This study demonstrated that Bacillus subtilis 168 (BS168) decreased stone burden, improved health, and complemented the microbiota in a Drosophila melanogaster urolithiasis model, while not exacerbating calcium oxalate aggregation or adhesion to renal cells in vitro. These results identify this bacterium as a candidate for ameliorating stone formation; given that other strains of B. subtilis are components of fermented foods and are used as probiotics for digestive health, strain 168 warrants testing in humans. With the severe burden that recurrent kidney stone disease imposes on patients and the health care system, this microbial therapeutic approach could provide an inexpensive therapeutic adjunct

Techniques - Ultrasound-guided percutaneous nephrolithotomy: How we do it.

Ultrasonography has emerged as an alternative to fluoroscopy for image-guided percutaneous nephrolithotomy (PCNL) in many countries. Compared to fluoroscopy-guided PCNL (F-PCNL), ultrasound-guided PCNL (US-PCNL) is easier to learn and reduces radiation exposure to patients and providers. Despite these advantages, uptake of ultrasound-guided PCNL (US-PCNL) in Canada has been almost nonexistent, largely because it is not incorporated into urologists' training. In this article, we seek to familiarize Canadian urologists with this approach by describing our step-by-step technique for US-PCNL. Additionally, we provide keys to successful implementation of this technique