Prospective Multicenter Evaluation of Pain Before and After Removal of Nonobstructing Renal Calculi: A CoRE Initiative.

PURPOSE: Flank pain associated with stone disease is typically caused by a stone that obstructs urine flow. However, it is plausible that nonobstructing kidney stones may still cause pain. We performed a multicenter, observational trial to evaluate whether treatment of small nonobstructing calyceal stones improves pain and kidney stone-specific health-related quality of life. MATERIALS AND METHODS: Patients aged 18 years or older with nonobstructing renal stone(s) up to 10 mm in longest diameter and moderate to severe pain were recruited. All participants completed 3 questionnaires: the Brief Pain Inventory (BPI), the Patient-Reported Outcomes Measurement Information System pain interference form 6a, and the Wisconsin Stone Quality of Life questionnaire. Thereafter, all participants underwent ureteroscopy for renal stone treatment. All 3 questionnaires were repeated at 2, 6 to 8, and at 12 weeks postprocedure. The primary outcomes were change in preoperative to 12-week postoperative mean BPI score and worst BPI pain score. RESULTS: A total of 43 patients with nonobstructing kidney stones and associated flank pain were recruited. All stones were removed. Preoperatively, BPI scores for mean pain and worst pain were 5.5 and 7.2, respectively which decreased to 1.8 and 2.8 respectively at 12 weeks postoperatively. Wisconsin Stone Quality of Life questionnaire mean score increased from 70.4 to 115.3 at 12 weeks postoperatively. A total of 86% and 69% of patients had at least a 20% and 50% reduction in their mean pain scores, respectively. CONCLUSIONS: This study determined that patients benefit significantly from the removal of calyceal nonobstructing kidney stones for at least 12 weeks with a reduction in pain and an increase in quality of life. Therefore, surgical removal of these stones in this patient population should be offered as a treatment option.

Evaluation of augmented reality technology in global urologic surgery.

BACKGROUND: The COVID-19 pandemic drastically reduced opportunities for surgical skill sharing between high-income and low to middle-income countries. Augmented reality (AR) technology allows mentors in one country to virtually train a mentee in another country during surgical cases without international travel. We hypothesize that AR technology is an effective live surgical training and mentorship modality. METHODS: Three senior urologic surgeons in the US and UK worked with four urologic surgeon trainees across the continent of Africa using AR systems. Trainers and trainees individually completed post-operative questionnaires evaluating their experience. RESULTS: Trainees rated the quality of virtual training as equivalent to in-person training in 83% of cases (N = 5 of 6 responses). Trainers reported the technology's visual quality as "acceptable" in 67% of cases (N = 12 of 18 responses). The audiovisual capabilities of the technology had a "high" impact in the majority of the cases. CONCLUSION: AR technology can effectively facilitate surgical training when in-person training is limited or unavailable.

Redlining has led to increasing rates of nephrolithiasis in minoritized populations: a hypothesis.

PURPOSE OF REVIEW: The persistent rise in kidney stone prevalence in recent decades has prompted much speculation as to the causes. There has been some discussion about the effect of heat on nephrolithiasis. Here, we review recent data and postulate that heat may play a role in stone formation on a large scale and among African-Americans in particular. RECENT FINDINGS: African-Americans are the race/ancestry group with faster rates of increasing incidence and prevalence of kidney stones. We make the observation that urban heat islands in the United States have resulted in part from the effects of redlining, a practice of systematic segregation and racism in housing that led to the development of neighborhoods with substantial disparities in environmental conditions. SUMMARY: In this thought experiment, we propose that the disproportionate rise in the prevalence of nephrolithiasis in minoritized populations correlates with increased temperatures specifically in neighborhoods adversely affected by the practice of redlining. We discuss phenomena in support of this hypothesis and ongoing work to test this theory.

Indwelling stents cause obstruction and induce ureteral injury and fibrosis in a porcine model.

OBJECTIVES: To investigate global changes in ureters at the transcriptional, translational and functional levels, both while stents are indwelling and after removal and recovery, and to study the effects of targeting pathways that play a potential role. METHODS: Pig ureters were stented for varying amounts of time (48 h, 72 h, 14 days) and the impact on peristalsis, dilatation and hydronephrosis were assessed. RNAseq, proteomic, histological and smooth muscle (SM) function analyses were performed on ureteric and kidney tissues to assess changes induced by stenting and recovery. Pathway analysis was performed using Ingenuity Pathway Analysis software. To study the impact of possible interventions, the effects of erythropoeitin (EPO) and a Gli1 inhibitor were assessed. RESULTS: Stenting triggers massive ureteric dilatation, aperistalsis and moderate hydronephrosis within 48 h. Pathways associated with obstruction, fibrosis and kidney injury were upregulated by stenting. Increased expression of GLI1, clusterin-α (a kidney injury marker) and collagen 4A2 (a fibrosis marker) was found in stented vs contralateral unstented ureters. EPO did not improve peristalsis or contraction force but did decrease non-purposeful spasming seen exclusively in stented ureters. Tamsulosin administration increased contractility but not rate of peristalsis in stented ureters. CONCLUSIONS: Ureters respond to stents similarly to how they respond to an obstruction, that is, with activation of pathways associated with hydronephrosis, fibrosis and kidney injury. This is driven by significant dilatation and associated ureteric SM dysfunction. EPO and tamsulosin induced mild favourable changes in SM physiology, suggesting that targeting specific pathways has potential to address stent-induced complications.

The Uniform grading tooL for flexIble ureterorenoscoPes (TULIP-tool): a Delphi consensus project on standardised evaluation of flexible ureterorenoscopes.

OBJECTIVE: To develop a standardised tool to evaluate flexible ureterorenoscopes (fURS). MATERIALS AND METHODS: A three-stage consensus building approach based on the modified Delphi technique was performed under guidance of a steering group. First, scope- and user-related parameters used to evaluate fURS were identified through a systematic scoping review. Then, the main categories and subcategories were defined, and the expert panel was selected. Finally, a two-step modified Delphi consensus project was conducted to firstly obtain consensus on the relevance and exact definition of each (sub)category necessary to evaluate fURS, and secondly on the evaluation method (setting, used tools and unit of outcome) of those (sub)categories. Consensus was reached at a predefined threshold of 80% high agreement. RESULTS: The panel consisted of 30 experts in the field of endourology. The first step of the modified Delphi consensus project consisted of two questionnaires with a response rate of 97% (n = 29) for both. Consensus was reached for the relevance and definition of six main categories and 12 subcategories. The second step consisted of three questionnaires (response rate of 90%, 97% and 100%, respectively). Consensus was reached on the method of measurement for all (sub)categories. CONCLUSION: This modified Delphi consensus project reached consensus on a standardised grading tool for the evaluation of fURS - The Uniform grading tooL for flexIble ureterorenoscoPes (TULIP) tool. This is a first step in creating uniformity in this field of research to facilitate future comparison of outcomes of the functionality and handling of fURS.

Prospective randomized trial of 2 versus 12-weeks of postoperative antibiotics after percutaneous nephrolithotomy in complex patients with infection-related kidney stones.

PURPOSE: Treatment of struvite kidney stones requires complete surgical stone removal combined with antibiotic therapy to eliminate urinary tract infections and preventive measures to reduce stone recurrence. The optimal duration of antibiotic therapy is unknown. We sought to determine if 2- or 12-weeks of antibiotics post percutaneous nephrolithotomy (PNL) for infection stones resulted in better outcomes for stone recurrence and positive urine cultures. MATERIAL AND METHODS: This multi-center, prospective randomized trial evaluated patients with the clinical diagnosis of infection stones. Patients were randomized to 2- or 12-weeks of postoperative oral antibiotics (nitrofurantoin or culture-specific antibiotic) and included if residual fragments were ≤4 mm on computed tomography imaging after PNL. Imaging and urine analyses were performed at 3-, 6-, and 12-months post-procedure. RESULTS: Thirty-eight patients were enrolled and randomized to either 2-weeks (n = 20) or 12-weeks (n = 18) of antibiotic therapy post-PNL. Eleven patients were excluded due to residual fragments >4 mm, and 3 patients were lost to follow-up. The primary outcome was the stone-free rate (SFR) at 6 months post-PNL. At 3-, 6-, and 12-months follow-up, SFRs were 72.7% versus 80.0%, 70.0% versus 57.1%, 80.0% versus 57.1% (p = ns), between 2- and 12-week-groups, respectively. At 3-, 6-, and 12-months follow-up, positive urine cultures were 50.0% versus 37.5%, 50.0% versus 83.3%, and 37.5% versus 100% between 2- and 12-week groups, respectively (p = ns). CONCLUSIONS: For patients with stone removal following PNL, neither 2-weeks nor 12-weeks of postoperative oral antibiotics is superior to prevent stones and recurrent positive urine cultures.

Stone disease in low- and middle-income countries: could augmented reality have a role in its management?

Urolithiasis is a global phenomenon. Cystolithiasis is common in parts of Africa due to low protein intake and dehydration from endemic diarrhoeal illnesses. Nephrolithiasis is less prevalent than in high-income countries, probably due to a variety of lifestyle issues, such as a more elemental diet, higher physical activity, and less obesity. Although renal stones are less common in low- and middle-income countries (LMICs), the social and economic impacts of nephrolithiasis are still considerable; many stones present late or with complications such as upper urinary tract obstruction or urosepsis. These may lead to the development of chronic kidney disease, or end-stage renal failure in a small proportion of cases, conditions for which there is very poor provision in most LMICs. Early treatment of nephrolithiasis by the least invasive method possible can, however, reduce the functional consequences of urinary stone disease. Although extracorporeal lithotripsy is uncommon, and endoscopic interventions for stone are not widespread in most of Africa, percutaneous nephrolithotomy and ureteroscopic renal surgery are viable techniques in those regional centres with infrastructure to support them. Longitudinal mentoring has been shown to be a key step in the adoption of these minimally invasive procedures by local surgeons, something that has been difficult during the coronavirus disease 2019 (COVID-19) pandemic due to travel restriction. Augmented reality (AR) technology is an alternative means of providing remote mentoring, something that has been trialled by Urolink, the MediTech Trust and other global non-governmental organisations during this period. Our preliminary experience suggests that this is a viable technique for promulgating skills in LMICs where appropriate connectivity exists to support remote communication. AR may also have long-term promise for decreasing the reliance upon short-term surgical visits to consolidate competence, thereby reducing the carbon footprint of global surgical education.

Over-the-Counter Alkali Agents to Raise Urine pH and Citrate Excretion: A Prospective Crossover Study in Healthy Adults.

OBJECTIVE: To assess the effect of 2 over-the-counter alkalizing agents on 24 hour urinary parameters. MATERIALS AND METHODS: Ten healthy volunteers without a history of kidney stones were recruited to complete a baseline 24 hour urinalysis with a 4 day diet inventory. Participants then maintained the same diet on either LithoLyte (20 mEq 2 times per day) or KSPtabs (1 tablet 2 times per day) and submitted another 24 hour urinalysis. The process was repeated with the other supplement. Urinary alkali parameters were compared to baseline, and side effects were elicited with a questionnaire. RESULTS: LithoLyte intake resulted in a non-significant increase in citrate (597-758 mg/day, P =.058, an increase in urine pH (6.46-6.66, P =.028), and a decrease in urine ammonium (41-36 mmol/day, P =.005) compared to baseline. KSPtabs resulted in an increase in citrate (597-797 mg/day, P =.037) and urine pH (6.46-6.86, P =.037), with a non-significant decrease in ammonium (41-34 mmol/day, P =.059). No significant differences were seen comparing urinary analytes between LithoLyte and KSPtabs. With Litholyte, no side effects, mild, moderate, and severe side effects were seen in 50%, 40%, 10%, and 0%, respectively. With KSPtabs, rates were 60%, 20%, 10%, and 10%, respectively. CONCLUSION: In healthy participants without a history of kidney stones, LithoLyte and KSPtabs are effective over-the-counter alkali supplements, with a similar side effect profile to prescription potassium citrate.

Migration time correction for dual pressure capillary electrophoresis in semi-targeted metabolomics study.

Migration time fluctuation strongly affects peak alignment and identification of unknown compounds, making migration time correction an essential step in capillary electrophoresis (CE)-based metabolomics. To obtain more reliable information, metabolites with different apparent mobilities are analyzed by tandem mass spectrometry. Applying a small pressure is a common practice for reducing the analysis time of anions in a positive mode CE, known as the pressure-assisted CE. However, applying pressure may reduce the separation efficiency and can be undesirable for cation analysis. A simple way to address this issue is to increase the pressure after a certain time, during the separation. We term this practice as dual pressure CE. However, changing the pressure during the CE separation complicates migration time correction. Previous migration time correction methods were established based on a consistent electroosmotic flow and a constant pressure-driven bulk-flow velocity. We proposed a new correction method to support the peak alignment when dual pressure CE is used. A Python-based script was developed to implement dual pressure CE migration time correction for semi-targeted metabolomics study performed by a multiple reaction monitoring-based method. This script can help select suitable endogenous metabolites as correction markers, perform migration time correction, and conduct peak alignment. A case study showed that migration time precision of 156 metabolites in 32 samples can be improved from 4.8 to 11.4%RSD (relative standard deviation) to less than 1.8%RSD.

Kidney Stone Surgery: Assessing Public Interest and Evaluating Social Media Content.

An increasing number of patients are utilizing the internet to answer their medical questions. Given the lack of verified stone treatment resources on the web, we sought to evaluate online interest in kidney stone surgical interventions and assess the quality of the most popular resources on social media. Google Trends was used to evaluate public interest in different kidney stone interventions between March 2016 and February 2021 and reported as search volume index (SVI). Next, the social media analysis tool, BuzzSumo, was used to identify stone surgery content online on the social media platforms, YouTube, Instagram, Pinterest, Reddit, and Twitter. To evaluate the quality of health information presented in the online resources, the DISCERN instrument was employed by three individual raters. Ureteroscopy (URS), percutaneous nephrolithotomy (PCNL), and extracorporeal shockwave lithotripsy (SWL) were identified as the top search terms on Google Trends with mean SVIs of 47.75, 42.98, and 45.74, respectively (p = 0.012). On YouTube, URS, PCNL, and SWL had 12,549, 116,222, and 20,717 views, respectively. Nine articles and fifteen videos were chosen for analysis using the DISCERN tool with a mean score of 2.82 and 2.27, respectively, among three independent evaluators. The result of our study suggests that online users are interested in URS but engaged more often with PCNL content on social media platforms. We found that the quality of online resources related to stone surgery highlights the need for involvement of urologists in creation of engaging high-quality content and sharing of accurate information in a social media-driven society.

Consensus Statement on Urinary Stone Treatment During a Pandemic: A Delphi Process from the Endourological Society TOWER Research Initiative.

Introduction: The novel coronavirus disease (COVID-19) pandemic has had a significant impact on the care of patients with urolithiasis. Recommendations and prioritization of endourologic surgical procedures vary among regions, and a comprehensive overall international directive is needed. We used the Delphi method to obtain international consensus on managing urolithiasis patients during the pandemic. Methods: A three-round Delphi process was used to elicit expert consensus (53 global key opinion leaders within the Endourological Society from 36 countries) on an extensive survey on management of endourologic patients in a pandemic. Questions addressed general management, inpatient and outpatient procedures, clinic visits, follow-up care, and best practices for suspension and resumption of routine care. Results: Consensus was achieved in 64/84 (76%) questions. Key consensus findings included the following: consultations should be delivered remotely when possible. Invasive surgical procedures for urolithiasis patients should be reserved for high-risk situations (infection, renal failure, etc.). To prevent aerosolization, spinal anesthesia is preferred over general, whenever feasible. Treatment of asymptomatic renal stones should be deferred. Primary definitive treatment of obstructing or symptomatic stones (both renal and ureteral) is preferred over temporizing drainage. Extracorporeal shockwave lithotripsy should be continued for obstructive ureteral stones. There was consensus on treatment modalities and drainage strategies depending on location and size of the stone. Conclusion: International endourologist members of the Endourological Society participated in this Delphi initiative to provide expert consensus on management of urolithiasis during a pandemic. These results can be applied currently and during a future pandemic.

Social Determinants of Kidney Stone Disease: The Impact of Race, Income and Access on Urolithiasis Treatment and Outcomes.

The medical and surgical management of kidney stones is one of the most common functions of the urologist. Management choices are often nuanced, involving the decision to embark on one surgical plan among several options. As the wider medical community critically evaluates the care we provide to an increasingly diverse population, it will be important to examine patient outcomes with a particular focus on ensuring equitable care. This review examines the influence of social parameters on the care of kidney stone patients. The dearth of literature in this area warrants rigorous studies on the relationship between race as well as socioeconomic status and the management of kidney stone disease.

Online Engagement with Surgical Treatments for Benign Prostatic Hyperplasia: Are Minimally Invasive Surgical Therapies Outpacing the Gold Standard?

Background: Patients suffering from progressive symptoms of benign prostatic hyperplasia (BPH) increasingly turn to the internet for information on invasive and minimally invasive surgical therapies (MIST). This study aimed to identify online articles accessed by patients seeking guidance on said options and to evaluate the quality and readability of their content. Methods: Social media analytics tool Buzzumo was used to identify the most shared articles on Facebook, Twitter, Reddit, and Pinterest related to BPH surgical treatments from 2016 to 2021. The content quality was graded using the DISCERN tool; a questionnaire that assesses the quality of written information on treatment choices for a health problem. An online Automatic Readability Checker was used to evaluate the readability of the written transcripts. Google Trends data were used to evaluate search term popularity for BPH procedures from 2016 to 2021. Google Trends data and DISCERN ratings were analyzed with ANOVA and paired t-test, respectively. Results: Thirty-nine percent of identified articles were rated as low quality, 39% as moderate quality, and 22% as high quality using the DISCERN tool, with no significant difference among reviewer ratings (p = 0.0561). The median reading level of all articles was 12th grade. Google Trends data illustrated a rising popularity of MIST such as Rezum and urethral lift (Urolift), exceeding interest in more invasive procedures such as Holmium laser enucleation of the prostate (HoLEP) and laser surgery. Transurethral resection of the prostate (TURP) remained popular with no significant difference between MIST and TURP on Google Trends (p = 3.46). Conclusions: The most accessed articles on BPH treatments have important shortcomings, including risks of treatment and other available options for treatment. Article transcripts exceed the reading level of the average adult patient. TURP has remained a popular procedure online, but there is a notable rising interest in MIST, especially Urolift.

Mediators of human ureteral smooth muscle contraction-a role for erythropoietin, tamsulosin and Gli effectors.

BACKGROUND: Ureteral contractility is a poorly understood process. Contractions have been demonstrated to occur in the smooth muscle layers of the ureter. Previous work suggests the involvement of Gli family proteins and erythropoietin (EPO) in regulating mammalian ureteral smooth muscle contraction. We sought to devise a method by which the effects of these proteins and tamsulosin on distal human ureteral tissue contractility could be investigated to better understand mechanisms regulating human ureteral function. METHODS: IRB approval was obtained to procure portions of extraneous distal ureteral tissue from living donor renal transplants. Contractility was measured by placing the tissue in Krebs buffer and stimulating via a uniform electric current. Contractile force was recorded with each stimulation with and without the presence of a Gli inhibitor (GANT61) or EPO. Each ureteral specimen was subsequently fixed and tested by immunohistochemistry to determine Gli, EPO and alpha-adrenergic receptor activity. RESULTS: Electrical field stimulation successfully elicited contractions in the ureteral tissue. Administering tamsulosin decreased force and duration of ureteral contractions. Inhibiting Gli signaling decreased contractility and EPO decreased ureteral contractile forces within 5 minutes of administration versus untreated controls. Staining confirmed Gli1 protein and α-adrenergic receptor expression in ureteral smooth muscle and epithelial tissue with EPO receptor expression confined to the epithelial layer. CONCLUSIONS: Distal ureteral contractile forces are decreased by inhibition of Gli family proteins and the α-adrenergic receptor. EPO acts within five minutes, suggesting ion channel involvement instead of changes in gene expression. Continuing work will elucidate the role of these proteins in coordinating ureteral contractions. This has implications for the use of pharmacologic methods to address ureteral contractility and dysfunctional peristalsis during stone passage, ureteroscopy, in transplant patients and potentially to reduce symptoms from ureteral stents.

Global Variations in the Mineral Content of Bottled Still and Sparkling Water and a Description of the Possible Impact on Nephrological and Urological Diseases.

Kidney stone disease (KSD) is a complex disease. Besides the high risk of recurrence, its association with systemic disorders contributes to the burden of disease. Sufficient water intake is crucial for prevention of KSD, however, the mineral content of water might influence stone formation, bone health and cardiovascular (CVD) risk. This study aims to analyse the variations in mineral content of bottled drinking water worldwide to evaluate the differences and describes the possible impact on nephrological and urological diseases. The information regarding mineral composition (mg/L) on calcium, bicarbonate, magnesium, sodium and sulphates was read from the ingredients label on water bottles by visiting the supermarket or consulting the online shop. The bottled waters in two main supermarkets in 21 countries were included. The evaluation shows that on a global level the mineral composition of bottled drinkable water varies enormously. Median bicarbonate levels varied by factors of 12.6 and 57.3 for still and sparkling water, respectively. Median calcium levels varied by factors of 18.7 and 7.4 for still and sparkling water, respectively. As the mineral content of bottled drinking water varies enormously worldwide and mineral intake through water might influence stone formation, bone health and CVD risk, urologists and nephrologists should counsel their patients on an individual level regarding water intake.

Predictors of urosepsis in struvite stone patients after percutaneous nephrolithotomy.

PURPOSE: This study aims to identify clinical factors that may predispose struvite stone patients to urosepsis following percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: A retrospective review was conducted on patients who received PCNL for struvite stones. The Systemic Inflammatory Response Syndrome (SIRS) criteria and quick-Sepsis Related Organ Failure Assessment (q-SOFA) criteria were used to identify patients who were at an increased risk for urosepsis. Statistical analysis was performed using Fisher's exactness test, Wilcoxon rank test, and logistic regression. RESULTS: Chart review identified 99 struvite stone patients treated with PCNL. Post-operatively, 40 patients were SIRS positive (≥2 criteria) and/or q-SOFA positive (score ≥2). Using SIRS as an approximation for urosepsis, longer operative times (p<0.001), higher pre-operative white blood cell counts (p=0.01), greater total stone surface area (p<0.0001), and pre-operative stenting (OR, 5.75; p=0.01) were identified as independent risk factors for urosepsis. Multivariate analysis demonstrated pre-operative stenting (OR, 1.46; p=0.01) to be a risk factor. With q-SOFA, univariable analysis found that antibiotic use within 3 months prior to a PCNL (OR, 4.44; p=0.04), medical comorbidities (OR, 4.80; p=0.02), longer operative times (p<0.001), lengthier post-operative hospitalization (p<0.01), and greater total stone surface area (p<0.0001) were risk factors for urosepsis. Multivariate analysis revealed that bladder outlet obstruction (OR, 2.74; p<0.003) and pre-operative stenting (OR, 1.27; p=0.01) significantly increased odds of being q-SOFA positive. CONCLUSIONS: Several risk factors for urosepsis following PCNL for struvite stones have been identified. These risk factors should be taken into consideration in peri-operative care to mitigate the risks of urosepsis.