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Item Acute Kidney Injury Associated With Urinary Stone Disease in Children and Young Adults Presenting to a Pediatric Emergency Department(Frontiers Media, 2020-11-30) Farris, Nicholas; Raina, Rupesh; Tibrewal, Abhishek; Brown, Miraides; Colvis, Maria; Schwaderer, Andrew; Kusumi, Kirsten; Pediatrics, School of MedicineBackground: Acute kidney injury (AKI) due to urinary stone disease (USD) is rare in adults; AKI rates in children with USD may be higher, and emerging data links stones to chronic kidney disease (CKD) development in adults. Methods: This study is a retrospective analysis of USD patients at a single pediatric hospital system's emergency department (ED). Patients were initially identified by USD ICD codes; USD was then confirmed by imaging or physician documentation; patients had to have baseline creatinine (Cr) and Cr in the ED for comparison to be included. AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO), Acute Kidney Injury Network (AKIN), and Pediatric Risk, Injury, Failure, Loss, End Stage (pRIFLE). Results: Of the 589 total visits, 264/589 (45%) had data to evaluate for AKI, 23% were AKI(+) and 77% were AKI(-). pRIFLE was most common (82%) and 18% were only positive by AKIN/KDIGO. AKI(+) were more likely to be younger (16.7 vs. 17.4 years, p = 0.046) and more likely to present with vomiting {odds ratio [OR] [95% confidence interval (CI)]: 2.4 [1.4-4.3], p = 0.002}; also, the proportion of AKI(+) was significantly higher in <18 vs. ≥18 years [26.9 vs. 15.5%, p = 0.032, OR (95% CI): 2.0 (1.1-3.9)]. Urinary tract infection (UTI) and obstruction rates were similar between groups. AKI(+) patients had a significant OR <1 suggesting less risk of receiving non-steroidal anti-inflammatory drugs (NSAIDs); however, 51% of them did receive NSAIDs during their ED encounter. AKI(+) patients were more likely to require admission to the hospital (53 vs. 32%, p = 0.001). Conclusion: We have demonstrated a novel association between USD-induced renal colic and AKI in a group of young adults and children. AKI(+) patients were younger and were more likely to present with vomiting. AKI(+) patients did not have higher rates of obstruction or UTI, and 51% of AKI(+) received NSAIDs.Item Comparison of cost-effectiveness and postoperative outcomes following integration of a stiff shaft glidewire into percutaneous nephrolithotripsy(Sage, 2021-08-22) Valadon, Crystal; Abedali, Zain A.; Nottingham, Charles U.; Large, Tim; Krambeck, Amy E.; Urology, School of MedicineAims: To analyze the cost effectiveness of integrating a stiff shaft glidewire (SSGW) in percutaneous nephrolithotripsy (PCNL) relative to standard technique (ST). This is prudent because healthcare providers are experiencing increased pressure to improve procedure-related cost containment. Methods: ST for PCNL at our institution involves a hydrophilic glidewire during initial percutaneous access and then two new stiff shaft wires. The SSGW is a hydrophilic wire used for initial access and the remainder of the procedure. We collected operating room (OR) costs for all primary, unilateral PCNL cases over a 5-month period during which ST for PCNL was used at a single institution with a single surgeon and compared with a 6-month period during which a SSGW was used. Mean costs for each period were then compared along with stone-free rates and complications. Results: We included 17 total cases in the ST group and 22 in the SSGW group. The average operating room supply cost for the ST group was $1937.32 and $1559.39 in the SSGW group. The net difference of $377.93 represents a nearly 20% decrease in cost. This difference was statistically significant (p = 0.031). There was no difference in postoperative stone-free rates (82.4% versus 86.4%, p = 1.0, respectively) or complications (23.5% versus 13.6%, p = 0.677, respectively) between ST and SSGW groups. Conclusion: Transitioning to a SSGW has reduced OR supply cost by reducing the number of supplies required. The change in wire did not affect stone-free rates or complications.Item Comparison of Risk Factors for Pediatric Kidney Stone Formation: The Effects of Sex(Frontiers, 2019-02-12) Schwaderer, Andrew L.; Raina, Rupesh; Khare, Anshika; Safadi, Fayez; Moe, Sharon M.; Kusumi, Kirsten; Pediatrics, School of MedicineBackground: Urinary stones are affecting more children, and pediatric stone formers have unique pathophysiology compared to adults. While adult stone formers are most frequently male, children have an age dependent sex prevalence. Under 10 years, a majority of stone formers are boys; adolescent stone formers are mostly female. Previous adult studies have shown that stone composition is influenced by the sex and age of the stone former. Thus, we hypothesize that female and male stone forming children will also have sex and age specific stone phenotypes. Methods: Retrospective chart review of a large pediatric center's stone forming children 6/1/2009 to 6/1/2016. Patients were identified by ICD 9 codes: N20, N20.1, and N20.9. Charts were reviewed for radiographic evidence of stones or documented visualized stone passage. Results: One hundred and thirty six subjects: 54 males and 82 females. Females were older, median age 14 years [interquartile range (IQR): 11, 15] vs. males' median age 12 years (IQR: 11, 14) (p < 0.01). Females had lower height z-scores, median 0.2 (IQR: -0.8, 0.8) vs. males' median 0.8 (IQR: -0.2, 1.8) (p < 0.01). Presenting symptoms were similar except flank pain affecting 39% of females vs. 22% of males (p = 0.04). Leukocyte esterase was positive in more females than males (33 vs. 4%) (p < 0.001). Males had a higher BUN/Cr ratio, mean ± standard deviation of 19.8 ± 6.3 vs. 16.6 ± 6.5 in females (p = 0.01). Glomerular hyperfiltration was present in 9% of patients while 35% of patients had estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m2. Treatment strategies and clinical course were similar except females were told to increase dietary citrate more frequently than males (21 vs. 4%) (p < 0.01). Conclusion: We have provided a novel analysis and demonstrated that low height z-score and pyuria are more common in female stone formers. We have also shown that 9% of pediatric stone formers have labs consistent with hyperfiltration. Whether high protein intake and/or chronic dehydration are associated with hyperfiltration and long-term renal function in children with kidney stones will be an area for future research.Item Effect of age, BMI, and gender on urinary risk factors in pediatric idiopathic stone formers(Elsevier, 2021) Fang, Andrew M.; Gibson, Elena; Oster, Robert A.; Dangle, Pankaj P.; Urology, School of MedicineIntroduction: The incidence of pediatric urolithiasis has been increasing over the years; however, the etiology of this increase is not well understood. Age, body mass index, and gender have been examined as possible risk factors for stone disease, but with inconsistent and variable associations. Objective: We aim to investigate the urine chemistry factors, as assessed by 24-h urinary parameters, in pediatric stone formers at a large volume tertiary referral center in the highest areas in the United States, the Southeast, based on age, body mass index, and gender. Study design: We retrospectively reviewed all pediatric stone formers who completed a 24-h study between 2005 and 2016. Patients were stratified by age (3-10 versus 11-18 years of age), overweight status (above versus below the 85th percentile for body mass index), and gender (male versus female) (Summary Figure). Statistical analysis included analysis of variance and logistic regression. Results: 243 patients were included in our analysis. Patients in the first decade of life were found to have greater numbers of urinary risk factors than those in the second decade. Non-overweight patients were more likely to have hyperoxaluria and hyperuricosuria, while overweight patients were more likely to have hypocitraturia. Female patients were more likely to have higher hyperoxaluria, while male patients were more likely to have hypercalciuria. Discussion: In contrast to prior publications, obesity is not linked to increased risk of urolithiasis with non-overweight individuals having a greater number of risk factors than the overweight cohort. Despite stone disease being more prevalent in adolescents, the greatest number of risk factors were present in the first decade of life. Lastly, female children had more urinary risk factors than males. Further understanding of the underlying causes of stone disease in various pediatric populations is warranted. Conclusion: While more urinary risk factors were identified in younger, non-overweight, and female patients, there remains no consensus on the urinary risk factors for pediatric urolithiasis. Further study is needed to elucidate the risk factors and pathophysiology of pediatric stone disease.Item First In-Human Burst Wave Lithotripsy for Kidney Stone Comminution: Initial Two Case Studies(Mary Ann Liebert, Inc., 2021) Harper, Jonathan D.; Metzler, Ian; Hall, Michael Kennedy; Chen, Tony T.; Maxwell, Adam D.; Cunitz, Bryan W.; Dunmire, Barbrina; Thiel, Jeff; Williams, James C., Jr.; Bailey, Michael R.; Sorensen, Mathew D.; Anatomy, Cell Biology and Physiology, School of MedicinePurpose: To test the effectiveness (Participant A) and tolerability (Participant B) of urinary stone comminution in the first-in-human trial of a new technology, burst-wave lithotripsy (BWL). Materials and Methods: An investigational BWL and ultrasonic propulsion system was used to target a 7-mm kidney stone in the operating room before ureteroscopy (Participant A). The same system was used to target a 7.5 mm ureterovesical junction stone in clinic without anesthesia (Participant B). Results: For Participant A, a ureteroscope inserted after 9 minutes of BWL observed fragmentation of the stone to <2 mm fragments. Participant B tolerated the procedure without pain from BWL, required no anesthesia, and passed the stone on day 15. Conclusions: The first-in-human tests of BWL pulses were successful in that a renal stone was comminuted in <10 minutes, and BWL was also tolerated by an awake subject for a distal ureteral stone.Item First Series Using Ultrasonic Propulsion and Burst Wave Lithotripsy to Treat Ureteral Stones(American Urological Association Education and Research, Inc., 2022) Hall, M. Kennedy; Thiel, Jeff; Dunmire, Barbrina; Samson, Patrick C.; Kessler, Ross; Sunaryo, Peter; Sweet, Robert M.; Metzler, Ian S.; Chang, Helena C.; Gunn, Martin; Dighe, Manjiri; Anderson, Layla; Popchoi, Christina; Managuli, Ravi; Cunitz, Bryan W.; Burke, Barbara H.; Ding, Lisa; Gutierrez, Brianna; Liu, Ziyue; Sorensen, Mathew D.; Wessells, Hunter; Bailey, Michael R.; Harper, Jonathan D.; Biostatistics and Health Data Science, School of MedicinePurpose: Our goal was to test transcutaneous focused ultrasound in the form of ultrasonic propulsion and burst wave lithotripsy to reposition ureteral stones and facilitate passage in awake subjects. Materials and methods: Adult subjects with a diagnosed proximal or distal ureteral stone were prospectively recruited. Ultrasonic propulsion alone or with burst wave lithotripsy was administered by a handheld transducer to awake, unanesthetized subjects. Efficacy outcomes included stone motion, stone passage, and pain relief. Safety outcome was the reporting of associated anticipated or adverse events. Results: Twenty-nine subjects received either ultrasonic propulsion alone (n = 16) or with burst wave lithotripsy bursts (n = 13), and stone motion was observed in 19 (66%). The stone passed in 18 (86%) of the 21 distal ureteral stone cases with at least 2 weeks follow-up in an average of 3.9±4.9 days post-procedure. Fragmentation was observed in 7 of the burst wave lithotripsy cases. All subjects tolerated the procedure with average pain scores (0-10) dropping from 2.1±2.3 to 1.6±2.0 (P = .03). Anticipated events were limited to hematuria on initial urination post-procedure and mild pain. In total, 7 subjects had associated discomfort with only 2.2% (18 of 820) propulsion bursts. Conclusions: This study supports the efficacy and safety of using ultrasonic propulsion and burst wave lithotripsy in awake subjects to reposition and break ureteral stones to relieve pain and facilitate passage.Item Human jackstone arms show a protein-rich, X-ray lucent core, suggesting that proteins drive their rapid and linear growth(Springer, 2022) Canela, Victor Hugo; Dzien, Cornelius; Bledsoe, Sharon B.; Borofsky, Michael S.; Boris, Ronald S.; Lingeman, James E.; El-Achkar, Tarek M.; Williams, James C., Jr.; Anatomy, Cell Biology and Physiology, School of MedicineJackstone calculi, having arms that extend out from the body of the stone, were first described over a century ago, but this morphology of stones has been little studied. We examined 98 jackstones from 50 different patient specimens using micro-computed tomography (micro CT) and infrared (IR) spectroscopy. Micro CT showed that jackstone arms consisted of an X-ray lucent core within each arm. This X-ray lucent core frequently showed sporadic, thin layers of apatite arranged transversely to the axis of the arm. The shells of the jackstones were always composed of calcium oxalate (CaOx), and with the monohydrate form the majority or sole mineral. Study of layering in the shell regions by micro CT showed that growth lines extended from the body of the stone out onto jack arms and that the thickness of the shell covering of jack arms often thinned with distance from the stone body, suggesting that the arms grew at a faster radial rate than did the stone body. Histological cross-sections of decalcified jackstone arms showed the core to be more highly autofluorescent than was the CaOx shell, and immunohistochemistry showed the core to be enriched in Tamm-Horsfall protein. We hypothesize that the protein-rich core of a jack arm might preferentially bind more protein from the urine and resist deposition of CaOx, such that the arm grows in a linear manner and at a faster rate than the bulk of the stone. This hypothesis thus predicts an enrichment of certain urine proteins in the core of the jack arm, a theory that is testable by appropriate analysis.Item In Vivo Entombment of Bacteria and Fungi during Calcium Oxalate, Brushite, and Struvite Urolithiasis(Wolters Kluwer, 2020-12-23) Saw, Jessica J.; Sivaguru, Mayandi; Wilson, Elena M.; Dong, Yiran; Sanford, Robert A.; Fields, Chris J.; Cregger, Melissa A.; Merkel, Annette C.; Bruce, William J.; Weber, Joseph R.; Lieske, John C.; Krambeck, Amy E.; Rivera, Marcelino E.; Large, Timothy; Lange, Dirk; Bhattacharjee, Ananda S.; Romero, Michael F.; Chia, Nicholas; Fouke, Bruce W.; Urology, School of MedicineBackground: Human kidney stones form via repeated events of mineral precipitation, partial dissolution, and reprecipitation, which are directly analogous to similar processes in other natural and manmade environments, where resident microbiomes strongly influence biomineralization. High-resolution microscopy and high-fidelity metagenomic (microscopy-to-omics) analyses, applicable to all forms of biomineralization, have been applied to assemble definitive evidence of in vivo microbiome entombment during urolithiasis. Methods: Stone fragments were collected from a randomly chosen cohort of 20 patients using standard percutaneous nephrolithotomy (PCNL). Fourier transform infrared (FTIR) spectroscopy indicated that 18 of these patients were calcium oxalate (CaOx) stone formers, whereas one patient formed each formed brushite and struvite stones. This apportionment is consistent with global stone mineralogy distributions. Stone fragments from seven of these 20 patients (five CaOx, one brushite, and one struvite) were thin sectioned and analyzed using brightfield (BF), polarization (POL), confocal, super-resolution autofluorescence (SRAF), and Raman techniques. DNA from remaining fragments, grouped according to each of the 20 patients, were analyzed with amplicon sequencing of 16S rRNA gene sequences (V1-V3, V3-V5) and internal transcribed spacer (ITS1, ITS2) regions. Results: Bulk-entombed DNA was sequenced from stone fragments in 11 of the 18 patients who formed CaOx stones, and the patients who formed brushite and struvite stones. These analyses confirmed the presence of an entombed low-diversity community of bacteria and fungi, including Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, and Aspergillus niger. Bacterial cells approximately 1 μm in diameter were also optically observed to be entombed and well preserved in amorphous hydroxyapatite spherules and fans of needle-like crystals of brushite and struvite. Conclusions: These results indicate a microbiome is entombed during in vivo CaOx stone formation. Similar processes are implied for brushite and struvite stones. This evidence lays the groundwork for future in vitro and in vivo experimentation to determine how the microbiome may actively and/or passively influence kidney stone biomineralization.Item Recent advances in lithotripsy technology and treatment strategies: A systematic review update(Elsevier, 2016-12) Elmansy, H.E.; Lingeman, J.E.; Urology, School of MedicineINTRODUCTION: Shock wave lithotripsy (SWL) is a well - established treatment option for urolithiasis. The technology of SWL has undergone significant changes in an attempt to better optimize the results while reducing failure rates. There are some important limitations that restrict the use of SWL. In this review, we aim to place these advantages and limitations in perspective, assess the current role of SWL, and discuss recent advances in lithotripsy technology and treatment strategies. METHODS: A comprehensive review was conducted to identify studies reporting outcomes on ESWL. We searched for literature (PubMed, Embase, Medline) that focused on the physics of shock waves, theories of stone disintegration, and studies on optimising shock wave application. Relevant articles in English published since 1980 were selected for inclusion. RESULTS: Efficacy has been shown to vary between lithotripters. To maximize stone fragmentation and reduce failure rates, many factors can be optimized. Factors to consider in proper patient selection include skin - to - stone distance and stone size. Careful attention to the rate of shock wave administration, proper coupling of the treatment head to the patient have important influences on the success of lithotripsy. CONCLUSION: Proper selection of patients who are expected to respond well to SWL, as well as attention to the technical aspects of the procedure are the keys to SWL success. Studies aiming to determine the mechanisms of shock wave action in stone breakage have begun to suggest new treatment strategies to improve success rates and safety.Item Retention and growth of urinary stones: insights from imaging(Springer, 2013-01) Williams, James C., Jr.; McAteer, James A.; Medicine, School of MedicineRecent work in nephrolithiasis has benefited from 2 special kinds of imaging: endoscopic study of patient kidneys with high-quality instruments, and examination of stones with microscopic computed tomography (micro CT). The combination of these has provided new evidence that there is more than 1 mechanism by which stones are retained in the kidney until they achieve sizes to be clinically relevant. This review describes what is known about the formation of stones on Randall's plaque, the formation of stones on ductal plugs and the ways in which stones may grow in free solution within the calyceal or pelvic spaces. Studies of urolithiasis need to recognize that any group of "stone formers" likely includes patients who differ fundamentally regarding which mechanism of stone formation is the primary route for their stones. Separation of patients on the basis of which mechanism (or combination of mechanisms) underlies their disease will be important for advancing research in the area of urolithiasis.