Prevalence and characteristics of genetic disease in adult kidney stone formers.

BACKGROUND: Molecular mechanisms of kidney stone formation remain unknown in most patients. Previous studies showed high a heritability of nephrolithiasis, but data on prevalence and characteristics of genetic disease in unselected adults with nephrolithiasis are lacking. This study was conducted to fill this important knowledge gap. METHODS: We performed whole exome sequencing in 787 participants of the Bern Kidney Stone Registry, an unselected cohort of adults with ≥ 1 past kidney stone episode (KSF), and 114 non-stone-forming individuals (NKSF). An exome-based panel of 34 established nephrolithiasis genes was analyzed and variants assessed according to ACMG criteria. Pathogenic (P) or likely pathogenic (LP) variants were considered diagnostic. RESULTS: Mean age of KSF was 47±15 years, and 18% were first time KSF. A Mendelian kidney stone disease was present in 2.9% (23 of 787) of KSF. The most common genetic diagnoses were cystinuria (SLC3A1, SLC7A9; n=13), Vitamin D-24 hydroxylase deficiency (CYP24A1; n=5) and primary hyperoxaluria (AGXT, GRHPR, HOGA1; n=3). 8.1% (64 of 787) of KSF were monoallelic for LP/P variants predisposing to nephrolithiasis, most frequently in SLC34A1/A3 or SLC9A3R1 (n=37), CLDN16 (n=8) and CYP24A1 (n=8). KSF with Mendelian disease had a lower age at the first stone event (30±14 years vs. 36±14 years, p=0.003), were more likely to have cystine stones (23.4% vs. 1.4%) and less likely to have calcium oxalate monohydrates stones (31.9% vs. 52.5%) compared to KSF without genetic diagnosis. The phenotype of KSF with variants predisposing to nephrolithiasis was subtle and showed significant overlap with KSF without diagnostic variants. In NKSF, no Mendelian disease was detected, and LP/P variants were significantly less prevalent compared to KSF (1.8% vs. 8.1%). CONCLUSION: Mendelian disease is uncommon in unselected adult KSF, yet variants predisposing to nephrolithiasis are significantly enriched in adult KSF.

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.

Variations in the mineral content of bottled 'carbonated or sparkling' water across Europe: a comparison of 126 brands across 10 countries.

INTRODUCTION: Kidney stone disease is a common disease with high recurrence rates. Sufficient intake of water is the cornerstone in primary prevention of stone disease. However, the mineral composition of water can affect urinary minerals and influence stone formation. The aim of this study is to assess the variation in the mineral composition of bottled sparkling or carbonated drinking water across Europe. MATERIAL AND METHODS: The two largest supermarket chains in each participating country were visited to obtain data on mineral composition regarding bicarbonate, calcium, magnesium, potassium, sodium and sulphates of sparkling or carbonated waters by reading the ingredient labels on the bottles supplied by the manufacturers. Alternatively, the web-shops of these supermarkets were consulted. RESULTS: In total, 126 sparkling water brands across ten European countries were analysed regarding mineral composition. The median concentrations per mineral varied greatly. The greatest variation in median mineral content was found for sodium and sulphates with levels ranging from 3.1 mg/l to 63.0 mg/l and 6.0 mg/l to 263.0 mg/l respectively. A wide distribution of calcium content was found in Switzerland, with calcium levels reaching up to 581.6 mg/l. CONCLUSIONS: This study confirms that the mineral composition of sparkling or carbonated water varies greatly across Europe. Patients with kidney stone disease should be aware that the mineral content of water may influence stone formation and be mindful of the great variation that exists between different water brands. Mineral water can be a source of potential promotors or inhibitors of stone formation and patients and urologists need to be mindful of this.

Machine Learning Models for Predicting Stone-Free Status after Shockwave Lithotripsy: A Systematic Review and Meta-Analysis.

We performed a systematic review and meta-analysis to investigate the use of machine learning techniques for predicting stone-free rates following Shockwave Lithotripsy (SWL). Eight papers (3264 patients) were included. Two studies used decision-tree approaches, five studies utilised Artificial Neural Networks (ANN), and one study combined a variety of approaches. The summary true positive rate was 79%, summary false positive rate was 14%, and Receiver Operator Characteristic (ROC) was 0.90 for machine learning approaches. Machine learning algorithms were at least as good as standard approaches. Further prospective evidence is needed to routinely apply machine learning algorithms in clinical practice.

Can the Use of Serial Multiparametric Magnetic Resonance Imaging During Active Surveillance of Prostate Cancer Avoid the Need for Prostate Biopsies?-A Systematic Diagnostic Test Accuracy Review.

CONTEXT: The role of multiparametric magnetic resonance imaging (mp-MRI) during active surveillance (AS) of prostate cancer needs evaluation. It remains unclear whether mp-MRI can replace prostate biopsies completely during AS. OBJECTIVE: To evaluate the diagnostic performance of mp-MRI for disease progression in men on AS for prostate cancer. EVIDENCE ACQUISITION: This systematic review was performed in accordance with the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Cross-sectional studies that evaluate the diagnostic performance of mp-MRI (index test) for disease progression compared with systematic and targeted prostate/template biopsies or a composite of this (reference standard) were included. A meta-analysis was performed using STATA with "metandi" and "midas" commands. EVIDENCE SYNTHESIS: Seven studies with 800 patients were included in this systematic review. The pooled pathological progression rate was 27%. The pooled sensitivity and specificity of mp-MRI for disease progression were 0.61 (95% confidence interval [CI]: 0.46-0.74) and 0.78 (95% CI: 0.54-0.91), respectively. Adjusting for a prevalence of disease progression of 30% results in a positive predictive value of 0.43 (95% CI: 0.39-0.46) and a negative predictive value of 0.81 (95% CI: 0.78-0.84). Significant heterogeneity was observed. The meta-regression analysis did not demonstrate any significant outliers. CONCLUSIONS: It is not possible to supplant prostate biopsies with mp-MRI in AS protocols with the current level of evidence. There is significant institutional variation in the diagnostic performance of mp-MRI during AS. Institutions must internally audit the diagnostic performance of mp-MRI in the AS setting. AS protocols must be based on local diagnostic performance, rather than on international AS protocols that may have limited applicability at individual settings. PATIENT SUMMARY: In this review, we explored the accuracy of multiparametric magnetic resonance imaging in diagnosing disease progression for patients who were enrolled in active surveillance programmes for prostate cancer.

Variations in the Mineral Content of Bottled "Still" Water Across Europe: Comparison of 182 Brands Across 10 Countries.

Introduction: Kidney stone disease (KSD) is a highly prevalent disease worldwide. As water intake and its mineral content influence stone formation and recurrence, patients and physicians must be aware of the mineral content of drinkable water. We analyzed commercial bottled still water within Europe to assess the variation in its mineral composition across different manufacturers and countries. Materials and Methods: Data on the mineral composition of bottled still water regarding bicarbonate, calcium, magnesium, potassium, sodium, and sulfate concentration (mg/L) were collected from ten European countries. To collect the data, the two main supermarket chains in each participating country were either visited to check for the ingredient label on bottles or the online shop was consulted through the website of the supermarket in question. Descriptive statistics such as simple boxplots were used to illustrate the variation in mineral content. Results: One hundred eighty-two different commercial water brands were analyzed. Up to a fivefold variation in average concentrations per mineral between countries was observed. For calcium, a wide distribution was found in France and Switzerland compared with other countries with calcium levels ranging from 10.5 to 565 mg/L and 8.4 to 579 mg/L, respectively. By consuming 2 L of water with such high calcium levels, the daily reference intake for calcium is already achieved. Conclusions: The mineral content of bottled still water across Europe varies greatly. For patients with KSD it is important to be aware of the mineral content of the water they drink, as it might influence stone recurrence rates and necessitate alterations of their diet.

Trends in surgical and ablative treatment of localised renal cell carcinoma: A review of publication trends over 16 years (2000-2015).

Objective: To investigate the bibliometric (publication) trends in surgical and ablative treatment of localised renal cell carcinoma (RCC) over a period of 16-years, from 2000 to 2015, as publication trends reflect clinical practice and new innovations. Material and methods: We performed a systematic review using PubMed over a 16-year period from 2000 to 2015 for all published papers on surgical and ablative management of renal tumours. Data were further analysed in two time periods, period-1 (2000-2007) and period-2 (2008-2015). Results: During the last 16 years a total of 2415 papers were published on surgical (n = 1662, 69%) and ablative (n = 753, 31%) management of RCC. This included partial nephrectomy (PN; n = 1662, 69%), cryoablation (CA; n = 405, 17%), and radiofrequency ablation (RFA; n = 348, 14%). When comparing the two time periods for PN, during period-2, the change was +189% (P < 0.001), +69% (P = 0.004) and +4600% (P < 0.001) for open PN, laparoscopic PN and robotic PN, respectively. Regarding ablative techniques, a change of +109% (P = 0.002) and +78% (P = 0.036) was seen for CA and RFA, respectively. There was also a significant rise in percutaneous CA when compared to laparoscopic CA (P < 0.002). Conclusions: There has been a rise in all forms of PN and ablative techniques over the last 16 years. This rise has been particularly steep for robotic PN potentially reflecting a change in surgical practice. Abbreviations: CA: cryoablation; CC: correlation coefficient; MIS: minimally invasive surgery/surgical; NSS: nephron-sparing surgery; (L)(O)(R)PN: (laparoscopic) (open) (robotic) partial nephrectomy; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RFA: radiofrequency ablation; RN: radical nephrectomy; SRM: small renal mass.

The European Urology Residents Education Programme Hands-on Training Format: 4 Years of Hands-on Training Improvements from the European School of Urology.

BACKGROUND: The European School of Urology (ESU) started the European Urology Residents Education Programme (EUREP) in 2003 for final year urology residents, with hands-on training (HOT) added later in 2007. OBJECTIVE: To assess the geographical reach of EUREP, trainee demographics, and individual quality feedback in relation to annual methodology improvements in HOT. DESIGN, SETTING, AND PARTICIPANTS: From September 2014 to October 2017 (four EUREP courses) several new features have been applied to the HOT format of the EUREP course: 1:1 training sessions (2015), fixed 60-min time slots (2016), and standardised teaching methodology (2017). The resulting EUREP HOT format was verified by collecting and prospectively analysing the following data: total number of participants attending different HOT courses; participants' age; country of origin; and feedback obtained annually. RESULTS AND LIMITATIONS: A total of 796 participants from 54 countries participated in 1450 HOT sessions over the last 4 yr. This included 294 (20%) ureteroscopy (URS) sessions, 237 (16.5%) transurethral resection (TUR) sessions, 840 (58%) basic laparoscopic sessions, and 79 (5.5%) intermediate laparoscopic sessions. While 712 residents (89%) were from Europe, 84 (11%) were from non-European nations. Of the European residents, most came from Italy (16%), Germany (15%), Spain (15%), and Romania (8%). Feedback for the basic laparoscopic session showed a constant improvement in scores over the last 4 yr, with the highest scores achieved last year. This included feedback on improvements in tutor rating (p=0.017), organisation (p<0.001), and personal experience with EUREP (p<0.001). Limitations lie in the difficulties associated with the use of an advanced training curriculum with wet laboratory or cadaveric courses in this format, although these could be performed in other training centres in conjunction with EUREP. CONCLUSIONS: The EUREP trainee demographics show that the purpose of the course is being achieved, with excellent feedback reported. While European trainees dominate the demographics, participation from a number of non-European countries suggests continued ESU collaboration with other national societies and wider dissemination of simulation training worldwide. PATIENT SUMMARY: In this paper we look at methodological improvements and feedback for the European Urology Residents Education Programme hands-on-training over the last 4 yr.

Trends of 'urolithiasis: interventions, simulation, and laser technology' over the last 16 years (2000-2015) as published in the literature (PubMed): a systematic review from European section of Uro-technology (ESUT).

PURPOSE: To look at the bibliometric publication trends on 'Urolithiasis' and aspects of treatment and training associated with it over a period of 16 years from 2000 to 2015. To this end, we conducted this study to look at the publication trends associated with urolithiasis, including the use of simulation, laser technology, and all types of interventions for it. MATERIALS AND METHODS: We performed a systematic review of the literature using PubMed over the last 16 years, from January 2000 to December 2015 for all published papers on 'Urolithiasis'. While there were no language restrictions, English language articles and all non-English language papers with published English abstracts were also included. Case reports, animal and laboratory studies, and those studies that did not have a published abstract were excluded from our analysis. We also analyzed the data in two time periods, period-1 (2000-2007) and period-2 (2008-2015). RESULTS: During the last 16 years, a total of 5343 papers were published on 'Urolithiasis', including 4787 in English language and 556 in non-English language. This included papers on URS (n = 1200), PCNL (n = 1715), SWL (n = 887), open stone surgery (n = 87), laparoscopic stone surgery (n = 209), pyelolithotomy (n = 35), simulation in Endourology (n = 82), and use of laser for stone surgery (n = 406). When comparing the two time periods, during period 2, the change was +171% (p = 0.007), +279% (p < 0.001), and -17% (p = 0.2) for URS, PCNL, and SWL, respectively. While there was a rise in laparoscopic surgery (+116%), it decreased for open stone surgery (-11%) and pyelolithotomy (-47%). A total of 82 papers have been published on simulation for stone surgery including 48 papers for URS (67% rise in period-2, p = 0.007), and 34 papers for PCNL (480% rise in period-2, p < 0.001). A rising trend for the use of laser was also seen in period 2 (increase of 126%, p < 0.02, from 124 papers to 281 papers). CONCLUSIONS: Published papers on intervention for Urolithiasis have risen over the last 16 years. While there has been a steep rise of URS and minimally invasive PCNL techniques, SWL and open surgery have shown a slight decline over this period. A similar increase has also been seen for the use of simulation and lasers in Endourology.