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BackgroundKidney stone formers (SFs) are at increased risk of stroke, myocardial infarction, and atherosclerosis of the carotid and coronary arteries. These cardiovascular and urologic pathologies can result from ectopic biomineral deposition. The objectives of this study are: (I) to evaluate risk factors for ectopic biomineralization, and (II) to characterize the overall burden of ectopic minerals in known SFs compared to non-stone formers (NSFs) matched for these risk factors.MethodsPresence and quantity of biominerals at eight anatomic locations (abdominal aorta, common iliac arteries, pelvic veins, prostate or uterus, mesentery, pancreas, and spleen) were determined in a case control study by retrospective analysis of clinical non-contrast computed tomography scans obtained from 190 SFs and 190 gender- and age-matched NSFs (renal transplant donors). Predictors of biomineralization were determined using negative binomial regression. A subgroup of 140 SFs and 140 NSFs were matched for risk factors for systemic biomineralization, and mineralization was compared between these matched SFs and NSFs using ordinal logistic regression.ResultsHypertension, hyperlipidemia, diabetes mellitus, and smoking were more common amongst SFs. Risk factors for increased systemic biomineralization included history of nephrolithiasis, male gender, older age, and history of hyperlipidemia. When controlling for these comorbidities, SFs had significantly increased biomineralization systemically and at the abdominal aorta, iliac arteries, prostate, mesentery, pancreas, and spleen compared to NSFs.ConclusionsThe current study provides evidence that SFs are at increased risk of biomineralization systemically, independent of common risk factors of atherosclerosis.

Nephrolithiasis is a significant source of morbidity, and its incidence has increased significantly over the last decades. This rise has been attributed to concurrent increasing rates of obesity, associated with a 3-time risk of developing NL. To date, the mechanism by which obesity is linked to stone formation has not been elucidated. We aimed to utilize a transcriptomics approach to discover the missing link between these two epidemic diseases. We investigated gene expression profiling of nephrolithiasis patients by two RNA-sequencing approaches: comparison between renal papilla tissue with and without the presence of calcified Randall's plaques (RP), and comparison between the papilla, medulla, and cortex regions from within a single recurrent stone forming kidney. Results were overlaid between differently expressed genes found in the patient cohort and in the severely lithogenic kidney to identify common genes. Overlay of these two RNA-sequencing datasets demonstrated there is impairment of lipid metabolism in renal papilla tissue containing RP linked to downregulation of fatty acid binding protein (FABP) 4. Immunohistochemistry of human kidney specimens and microarray analysis of renal tissue from a nephrolithiasis mouse model confirmed that FABP4 downregulation is associated with renal stone formation. In a FABP4 knockout mouse model, FABP4 deficiency resulted in development of both renal and urinary crystals. Our study revealed that FABP4 plays an important, previously unrecognized role in kidney stone formation, providing a feasible mechanism to explain the link between nephrolithiasis and metabolic syndrome.

ObjectivesTo compare perioperative outcomes of robotic-assisted partial nephrectomy (RaPN) with open partial nephrectomy (OPN).MethodsSystematically search through PubMed, Embase, ClinicalKey, Cochrane Library, ProQuest, ScienceDirect, Web of Science, and ClinicalTrials.gov for eligible studies was performed to April 11, 2018. A meta-analysis was conducted for studies comparing RaPN and OPN. Confounding variables were assessed by meta-regression or subgroup analysis.ResultsThis study included 34 studies with 60 808 patients. Meta-analysis revealed less blood loss, less transfusion, longer operative time, less postoperative complications, lower readmission rate, shorter length of stay, and less estimated glomerular filtration rate (eGFR) decline in RaPN groups. The superiority of RaPN in blood loss was attenuated with highly complex renal masses. The superiority of RaPN in intraoperative complications was strengthened with renal hilar control. The advantage of RaPN in surgical margin was increased in patient with body mass index (BMI)

STUDY OBJECTIVES:To delineate the relationship between sleep apnea and subsequent risk of nephrolithiasis. METHODS:We conducted a retrospective cohort analysis of a general population sample from Taiwan National Health Insurance Research Database (NHIRD) from January 1, 2000 to December 31, 2012. Patients with sleep apnea without prior diagnosis of nephrolithiasis (n = 7,831) were identified and subsequent development of nephrolithiasis was compared to an age- and sex-matched control group (n = 31,293) without sleep apnea. The Cox proportional hazard regression models were used to evaluate the association between sleep apnea and subsequent nephrolithiasis development. RESULTS:After adjusting for age, sex, and comorbidities, the risk of nephrolithiasis remained significantly increased in the sleep apnea group (hazard ratio [HR] = 1.35; 95% confidence interval [CI] = 1.23-1.48; P < .001). Compared to controls, elevated HRs of nephrolithiasis were observed for male patients (HR = 1.22; 95% CI 1.09-1.36; P < .001) and those aged 20-39 years (HR = 1.28; 95% CI 1.09-1.49; P < .01) and 40-59 years (HR = 1.17, 95% CI 1.03-1.34, P < .05) in the sleep apnea cohort. Risk of nephrolithiasis in patients with sleep apnea increased significantly with concomitant metabolic-related comorbidities, gouty arthritis, and urinary tract infection. CONCLUSIONS:Sleep apnea is associated with an increased subsequent risk of the development of nephrolithiasis. Young male patients with sleep apnea and concomitant comorbidities are at the greatest risk for nephrolithiasis formation.

Laparoscopic heminephrectomy was performed in a 64-year-old woman with a chronically obstructed horseshoe kidney moiety. More than 3000 cc of pyonephrosis was drained through two percutaneous nephrostomy tubes for infection control before left moiety laparoscopic resection. This case report attests to the feasibility of laparoscopic resection of a massively obstructed horseshoe kidney when performed in a staged manner after prolonged drainage. Since an incision was required for removal of the large specimen, ligation of the horseshoe isthmus was completed through the same incision after hilar control and laparoscopic mobilization of the moiety were completed.

INTRODUCTION:Reusable ureteroscope durability and need for repair are significant sources of expense and inefficiency for patients and urologists. Utilization of LithoVue™, a disposable flexible digital ureteroscope, may address some of these concerns. To identify its economic impact on clinical care, we performed a micro-cost comparison between flexible reusable fiberoptic ureteroscopes (URF-P6™) and LithoVue. PATIENTS AND METHODS:For this prospective, single-center micro-costing study, all consecutive ureteroscopies performed during 1 week each in July and August 2016 utilized either URF-P6 or LithoVue ureteroscopes respectively. Workflow data were collected, including intraoperative events, postoperative reprocessing cycle timing, consumables usage, and ureteroscope cost data. RESULTS:Intraoperative data analysis showed mean total operating room time for URF-P6 and LithoVue cases were 93.4 ± 32.3 and 73.6 ± 17.4 minutes, respectively (p = 0.093). Mean cost of operating room usage per case was calculated at $1618.72 ± 441.39 for URF-P6 and $1348.64 ± 237.40 for LithoVue based on institutional cost rates exclusive of disposables. Postoperative data analysis revealed costs of $107.27 for labor and consumables during reprocessing for URF-P6 cases. The costs of ureteroscope repair and capital acquisition for each URF-P6 case were $957.71 and $116.02, respectively. The total ureteroscope cost per case for URF-P6 and LithoVue were $2799.72 and $2852.29, respectively. CONCLUSIONS:Micro-cost analysis revealed that the cost of LithoVue acquisition is higher per case compared to reusable fiberoptic ureteroscopes, but savings are realized in labor, consumables, and repair. When accounting for these factors, the total cost per case utilizing these two ureteroscopes were comparable.

The development of new modalities for kidney stone prevention rests upon understanding the progression of mineralization within the renal pyramid. The progression from small foci of mineralized volumes within the renal pyramid to larger interstitial plaques that ultimately lead into clinically detectable calcium-based stones on calcium phosphate stems will be presented through correlative microscopy approach. High resolution X-ray computed tomography (micro-XCT), electron microscopy, and energy dispersive X-ray (EDX) compositional analyses of interstitial plaques, stems, and attached stones were performed. Increase in mineral density progressed with mineralization severity, with the highest mineral densities detected within mature Randall's plaque and stems to which kidney stones were attached. EDX analyses revealed variable elemental composition within interstitial plaque, stems, and stones. Micro-XCT reconstructions of stones with stems enabled visualization of unoccluded tubules within stems, with average tubule diameters corresponding to thin limbs of Henle, blood vessels, and collecting ducts. Correlative microscopy confirmed that the progression of mineralization leading to calcium-based nephrolithiasis occurs through a continuum involving four anatomically and structurally distinct biomineralization regions: 1) proximal intratubular mineralization within the renal pyramid; 2) interstitial Randall's plaque near the tip of the papilla; 3) emerging plaque (stems); and, 4) the body of heterogeneous stones.Statement of significanceNephrolithiasis is a common condition affecting nearly 1 in 11 Americans. The most common type of stone, calcium oxalate is known to form on a calcium phosphate deposit on the renal papilla known as Randall's plaque. Novel imaging techniques have identified distinct regions of biomineralization not just at the tip, but throughout the renal papilla. The classic understanding of Randall's plaque formation is reformulated using correlative imaging techniques. This study establishes a stepwise progression of anatomically-specific biomineralization events including, 1) proximal intratubular mineralization within the renal pyramid; 2) interstitial Randall's plaque near the tip of the papilla; 3) emerging plaque (stems); and, 4) the body of heterogeneous stones, and provides insights into the need for plausible site-specific therapeutic intervention.

INTRODUCTION:Cystinuria is a genetic disorder marked by elevated urinary cystine excretion and recurrent cystine nephrolithiasis. Interestingly, despite seemingly similar contralateral renal anatomy, a subset of cystinuric patients consistently form stones in only one kidney. The aim of this study is to evaluate clinical outcomes in unilateral vs bilateral cystine stone formers. PATIENTS AND METHODS:We performed a retrospective case-control study of cystinuric patients evaluated and treated at the University of California, San Francisco between 1994 and 2015 and categorized patients as either unilateral or bilateral stone formers. Clinical presentation, baseline patient demographics, stone procedures, medical therapy regimens, and long-term renal function were compared between the two groups. RESULTS:A total of 42 cystine stone patients (22 female, 20 male) were included in the analysis. The median age at first presentation was 18.5 years and median age at study conclusion was 45.5 years. Two-thirds of patients (n = 28) had a history of bilateral stones, whereas one-third (n = 14) had unilateral stones. Medical therapy regimens were similar between groups. Despite an increased average number of lifetime surgeries (7.5 sessions for bilateral vs 3.7 sessions for unilateral, p

OBJECTIVE:To compare the measured stone burden recorded between urologists and radiologists, and examine how these differences could potentially impact stone management. As current urologic stone surgery guideline recommendations are based on stone size, accurate stone measurements are crucial to direct appropriate treatment. This study investigated the discrepant interpretation that often exists between urologic surgeons and radiologists' estimation of patient urinary stone burden. MATERIALS AND METHODS:From November 2015 through August 2016, new patients prospectively enrolled into the Registry for Stones of the Kidney and Ureter (ReSKU) were included if they had computed tomography images available and an accompanying official radiologic report at the time of their urologist provider visit. Stone number and aggregate stone size were compared between the urologic interpretation and the corresponding radiologic reports. RESULTS:Of 219 patients who met the inclusion criteria, concordance between urologic and radiologic assessment of aggregate stone size was higher for single stone sizing (63%) compared with multiple stones (32%). Statistical significance was found in comparing the mean difference in aggregate stone size for single and multiple stones (P

PurposeCareful decontamination and sterilization of reusable flexible ureteroscopes used in ureterorenoscopy cases prevent the spread of infectious pathogens to patients and technicians. However, inefficient reprocessing and unavailability of ureteroscopes sent out for repair can contribute to expensive operating room (OR) delays. Time-driven activity-based costing (TDABC) was applied to describe the time and costs involved in reprocessing.Materials and methodsDirect observation and timing were performed for all steps in reprocessing of reusable flexible ureteroscopes following operative procedures. Estimated times needed for each step by which damaged ureteroscopes identified during reprocessing are sent for repair were characterized through interviews with purchasing analyst staff. Process maps were created for reprocessing and repair detailing individual step times and their variances. Cost data for labor and disposables used were applied to calculate per minute and average step costs.ResultsTen ureteroscopes were followed through reprocessing. Process mapping for ureteroscope reprocessing averaged 229.0 ± 74.4 minutes, whereas sending a ureteroscope for repair required an estimated 143 minutes per repair. Most steps demonstrated low variance between timed observations. Ureteroscope drying was the longest and highest variance step at 126.5 ± 55.7 minutes and was highly dependent on manual air flushing through the ureteroscope working channel and ureteroscope positioning in the drying cabinet. Total costs for reprocessing totaled $96.13 per episode, including the cost of labor and disposable items.ConclusionsUtilizing TDABC delineates the full spectrum of costs associated with ureteroscope reprocessing and identifies areas for process improvement to drive value-based care. At our institution, ureteroscope drying was one clearly identified target area. Implementing training in ureteroscope drying technique could save up to 2 hours per reprocessing event, potentially preventing expensive OR delays.

IntroductionEndoscopic tools have provided versatile examination and treatment for kidney stone procedures. Despite endourologists researching urinary stone disease using endoscopes to collect tissue, this tissue collection method is limited. Endoscopically removed tissues are small in size, restricting the types of genome-based examination possible. We investigated a new method of renal papilla biopsy and RNA extraction to establish a genomic research methodology for kidney stone disease.Patients and methodsWe conducted a prospective multi-institutional study and collected renal papilla specimens from consecutive percutaneous nephrolithotomy and ureteroscopy (URS) cases performed for removal of upper urinary tract stones. Renal papilla tissue was extracted using ureteroscopic biopsy forceps after stone removal. RNA was extracted using two different extraction kits, and their quantity and quality were examined. Additionally, the impact of biopsy on surgical complications was compared between cases performed with and without biopsy by matched case-control analysis adjusted for age, gender, body mass index, bilaterality, and stone burden.ResultsA total of 90 biopsies from 49 patients were performed, and the median duration between specimen collection and RNA extraction was 61 days. Both univariate and multivariate analyses showed BIGopsy® forceps usage significantly increased the total yield (p = 0.004) and quality (p = 0.001 for A260/280, p = 0.004 for A260/A230) of extracted RNA. Extraction using the RNeasy Micro Kit® also improved A260/A230, whereas reduced RNA integrity number of extracted RNA by univariate and multivariate analyses (p = 0.002 and p

Calcium-based renal calculi demonstrated significant heterogeneity in the structure, density, mineral composition, and material hardness not elucidated by routine clinical testing. Mineral density distributions within calcium oxalate stones revealed differential areas of low (590±80 mg/cc), medium (840±140 mg/cc), and high (1100±200 mg/cc) densities. Apatite stones also contained regions of low (700±200 mg/cc), medium (1100±200 mg/cc), and high (1400±140 mg/cc) densities within layers extending from single or multiple nucleation sites. Despite having lower average mineral density, calcium oxalate (CaOx) stones demonstrated higher material hardness compared to apatite stones, suggesting other chemical components might be involved in determining stone hardness properties. Carbon concentrated sites were identified between morphologic layers in CaOx stones and in stratified layers of apatite stones. Elemental analyses revealed numerous additional trace elements in both stone types. Despite the widespread assumption that stone mineral density is an indicator of susceptibility to lithotripsy, calcium stone mineral density estimates do not directly correlate with actual ex vivo stone hardness. Underlying stone heterogeneity in both structure and mineral density could explain why historical approaches have failed in accurately predicting response of stones to lithotripsy.

ObjectiveLithoVue™ is a novel, single-use, digital flexible ureteroscope that was released to the US market in January 2016. There are scant data regarding its performance in humans. Procedural outcomes comparing LithoVue with reusable ureteroscopes are presented in patients undergoing ureteroscopy for upper urinary tract pathology.Patients and methodsClinical outcomes between two groups of patients undergoing flexible ureteroscopy for upper urinary tract pathology were analyzed. The first group underwent surgery utilizing LithoVue, and the second group used reusable fiber-optic flexible ureteroscopes. Differences in procedural outcomes, operative times, and time spent in hospital were analyzed using two-tailed t-tests and chi-squared and Fisher's exact tests.ResultsOne hundred fifteen cases utilizing LithoVue and 65 cases utilizing reusable ureteroscopes were included in this study. Demographics, surgical indications, stone size, location, total stone burden, composition, procedural outcomes, and complications were comparable between groups. For all cases, LithoVue procedures lasted 54.1 ± 25.7 minutes compared with 64.5 ± 37.0 minutes for reusable scope procedures (p

Limited information exists on the anatomically-specific early stage events leading to clinically detectable mineral aggregates in the renal papilla. In this study, quantitative multiscale correlative maps of structural, elemental and biochemical properties of whole medullo-papillary complexes from human kidneys were developed. Correlative maps of properties specific to the uriniferous and vascular tubules using high-resolution X-ray computed tomography, scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy, and immunolocalization of noncollagenous proteins (NCPs) along with their association with anatomy specific biominerals were obtained. Results illustrated that intratubular spherical aggregates primarily form at the proximal regions distant from the papillary tip while interstitial spherical and fibrillar aggregates are distally located near the papillary tip. Biominerals at the papillary tip were closely localized with 10 to 50 μm diameter vasa recta immunolocalized for CD31 inside the medullo-papillary complex. Abundant NCPs known to regulate bone mineralization were localized within nanoparticles, forming early pathologic mineralized regions of the complex. Based on the physical association between vascular and urothelial tubules, results from light and electron microscopy techniques suggested that these NCPs could be delivered from vasculature to prompt calcification of the interstitial regions or they might be synthesized from local vascular smooth muscle cells after transdifferentiation into osteoblast-like phenotypes. In addition, results provided insights into the plausible temporal events that link the anatomically specific intratubular mineral aggregates with the interstitial biomineralization processes within the functional unit of the kidney.