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Endoscopic and biopsy findings have identified two distinct phenotypes among individuals with calcium oxalate (CaOx) kidney stones. The first type has normal renal papillae but shows interstitial mineral deposition, known as Randall's plaque. The other phenotype presents with collecting duct plugging and a higher incidence of loss of papilla tissue mass. With Randall's plaque, renal papilla injury involves the loss of small patches of calcified tissue (Randall's plaque detaching with the stone), which likely results in damage to only a few nephrons. In contrast, collecting duct mineral plugs are very large, causing obstruction to tubular flow. Since each terminal collecting duct drains thousands of nephrons, ductal plugs could lead to the degeneration of many nephrons and a significant loss of renal glomeruli. New visualization techniques for immune cells in papillary biopsies have revealed that the Randall's plaque phenotype is marked by the accumulation of macrophages around the plaque regions. In contrast, preliminary data on the plugging phenotype shows collecting duct damage with mineral plugs and increased T-lymphocytes throughout the papilla. These regions also show tubulitis, i.e., T-cell infiltration into nearby collecting duct epithelium. This suggests that while some CaOx stone formers may have some papillary inflammation but with minimal damage to nephrons, others suffer from obstruction to flow for many nephrons that may also include destructive inflammation in the renal tissue. We propose that CaOx stone formers with the plugging phenotype will have a higher long-term risk for loss of renal function., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Uromodulin is a protein made only by the kidney and released in urine, circulating in polymerizing and nonpolymerizing forms. This protein's multiple functions include inhibition of stone formation in the urine. The physiological determinants of uromodulin production are incompletely understood., Methods: We investigated changes in uromodulin levels and key factors governing its production and release in urine and serum. We performed an experiment to determine whether water loading, a common intervention to prevent stone formation, will alter the rate of uromodulin production. During a 2-day period, 17 stone forming participants and 14 control participants were subjected to water loading (day 1) and normal fluid intake (day 2). Uromodulin levels were measured on timed hourly collections in urine and plasma during the period of the study., Results: Water loading increased urinary uromodulin secretion (33±4 versus 10±4 μ g/min at baseline, P < 0.0001) in stone formers and control participants. Despite high urine volumes, most participants maintained relatively stable urinary uromodulin concentrations. Native Western blots for polymerizing and nonpolymerizing uromodulin suggest that polymerizing uromodulin was the predominant form at higher urinary flow volumes. Urine flow rates and sodium excretion were significant correlates of urinary uromodulin production. Water loading did not affect serum uromodulin levels, which were also not associated with urinary uromodulin., Conclusions: Water loading increases the secretion of polymerizing urinary uromodulin. This increased secretion reduces the variability of urinary uromodulin concentrations despite high urine volumes. Serum uromodulin levels were not affected by this treatment., (Copyright © 2023 by the American Society of Nephrology.)

Kidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The benefits of removing small (≤6 mm), asymptomatic kidney stones endoscopically is unknown. Current guidelines leave such decisions to the urologist and the patient. A prospective study involving older, nonendoscopic technology and some retrospective studies favor observation. However, published data indicate that about half of small renal stones left in place at the time that larger stones were removed caused other symptomatic events within 5 years after surgery., Methods: We conducted a multicenter, randomized, controlled trial in which, during the endoscopic removal of ureteral or contralateral kidney stones, remaining small, asymptomatic stones were removed in 38 patients (treatment group) and were not removed in 35 patients (control group). The primary outcome was relapse as measured by future emergency department visits, surgeries, or growth of secondary stones., Results: After a mean follow-up of 4.2 years, the treatment group had a longer time to relapse than the control group (P<0.001 by log-rank test). The restricted mean (±SE) time to relapse was 75% longer in the treatment group than in the control group (1631.6±72.8 days vs. 934.2±121.8 days). The risk of relapse was 82% lower in the treatment group than the control group (hazard ratio, 0.18; 95% confidence interval, 0.07 to 0.44), with 16% of patients in the treatment group having a relapse as compared with 63% of those in the control group. Treatment added a median of 25.6 minutes (interquartile range, 18.5 to 35.2) to the surgery time. Five patients in the treatment group and four in the control group had emergency department visits within 2 weeks after surgery. Eight patients in the treatment group and 10 in the control group reported passing kidney stones., Conclusions: The removal of small, asymptomatic kidney stones during surgery to remove ureteral or contralateral kidney stones resulted in a lower incidence of relapse than nonremoval and in a similar number of emergency department visits related to the surgery. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Veterans Affairs Puget Sound Health Care System; ClinicalTrials.gov number, NCT02210650.)., (Copyright © 2022 Massachusetts Medical Society.)

Calcium oxalate (CaOx) stones can grow attached to the renal papillary calcification known as Randall's plaque. Although stone growth on Randall's plaque is a common phenomenon, this mechanism of stone formation is still poorly understood. The objective of this study was to investigate the microenvironment of mature Randall's plaque, explore its molecular composition and differentiate plaque from CaOx overgrowth using multimodal imaging on demineralized stone sections. Fluorescence imaging showed consistent differences in autofluorescence patterns between Randall's plaque and calcium oxalate overgrowth regions. Second harmonic generation imaging established the presence of collagen only in regions of decalcified Randall's plaque but not in regions of CaOx overgrowth matrix. Surprisingly, in these stone sections we observed cell nuclei with preserved morphology within regions of mature Randall's plaque. These conserved cells had variable expression of vimentin and CD45. The presence of nuclei in mature plaque indicates that mineralization is not necessarily associated with cell death. The markers identified suggest that some of the entrapped cells may be undergoing dedifferentiation or could emanate from a mesenchymal or immune origin. We propose that entrapped cells may play an important role in the growth and maintenance of Randall's plaque. Further characterization of these cells and thorough analyses of the mineralized stone forming renal papilla will be fundamental in understanding the pathogenesis of Randall's plaque and CaOx stone formation., (© 2021 American Association for Anatomy.)

Introduction and Objective: In clinical trial NCT03873259, a 2.6-mm lower pole stone was treated transcutaneously and ex vivo with 390-kHz burst wave lithotripsy (BWL) for 40 minutes and failed to break. The stone was subsequently fragmented with 650-kHz BWL after a 4-minute exposure. This study investigated how to fragment small stones and why varying the BWL frequency may more effectively fragment stones to dust. Methods: A linear elastic theoretical model was used to calculate the stress created inside stones from shock wave lithotripsy (SWL) and different BWL frequencies mimicking the stone's size, shape, lamellar structure, and composition. To test model predictions about the impact of BWL frequency, matched pairs of stones (1-5 mm) were treated at (1) 390 kHz, (2) 830 kHz, and (3) 390 kHz followed by 830 kHz. The mass of fragments >1 and 2 mm was measured over 10 minutes of exposure. Results: The linear elastic model predicts that the maximum principal stress inside a stone increases to more than 5.5 times the pressure applied by the ultrasound wave as frequency is increased, regardless of the composition tested. The threshold frequency for stress amplification is proportionate to the wave speed divided by the stone diameter. Thus, smaller stones may be likely to fragment at a higher frequency, but not at a lower frequency below a limit. Unlike with SWL, this amplification in BWL occurs consistently with spherical and irregularly shaped stones. In water tank experiments, stones smaller than the threshold size broke fastest at high frequency ( p  = 0.0003), whereas larger stones broke equally well to submillimeter dust at high, low, or mixed frequencies. Conclusions: For small stones and fragments, increasing frequency of BWL may produce amplified stress in the stone causing the stone to break. Using the strategies outlined here, stones of all sizes may be turned to dust efficiently with BWL.

Objective: The aim of this study is to evaluate if the use of a smart water bottle improves urine volume in stone forming patients., Methods: Adults with nephrolithiasis and low urine volume (<1.5 L) documented on a 24-hour urinalysis (24 hr U) were randomized to receive either standard dietary recommendations to increase fluid intake (DR arm), or DR and a smart water bottle (HidrateSpark®; Hydrate Inc., Minneapolis, MN) that recorded fluid intake, synced to the user's smartphone, and provided reminders to drink (SB arm). Participants completed baseline surveys assessing barriers to hydration. They then repeated a 24 hr U and survey at 6 and 12 weeks, respectively., Results: Eighty-five subjects (44 DR, 41 SB) were enrolled. The main baseline factor limiting fluid intake was not remembering to drink (60%). Follow-up 24 hr Us were available for 51 patients. The mean increase in volume was greater in the SB arm (1.37 L, 95% confidence interval -0.51 to 3.25) than the DR arm (0.79 L, 95% confidence interval -1.15 to 2.73) (P = .04). A smaller percentage of subjects in the SB arm reported not remembering to drink as the main factor limiting fluid intake in the follow-up questionnaire compared to baseline (45.4% vs. 68.4%, P < .05). This was not true for the DR arm (40.0% vs. 51.2%, P = .13)., Conclusions: Difficulty remembering to drink is a barrier to achieving sufficient fluid intake in stone formers. The use of a smart bottle was associated with greater increases in 24 hr U volumes and less difficulty remembering to drink., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We report stone comminution in the first 19 human subjects by burst wave lithotripsy (BWL), which is the transcutaneous application of focused, cyclic ultrasound pulses., Materials and Methods: This was a prospective multi-institutional feasibility study recruiting subjects undergoing clinical ureteroscopy (URS) for at least 1 stone ≤12 mm as measured on computerized tomography. During the planned URS, either before or after ureteroscope insertion, BWL was administered with a handheld transducer, and any stone fragmentation and tissue injury were observed. Up to 3 stones per subject were targeted, each for a maximum of 10 minutes. The primary effectiveness outcome was the volume percent comminution of the stone into fragments ≤2 mm. The primary safety outcome was the independent, blinded visual scoring of tissue injury from the URS video., Results: Overall, median stone comminution was 90% (IQR 20, 100) of stone volume with 21 of 23 (91%) stones fragmented. Complete fragmentation (all fragments ≤2 mm) within 10 minutes of BWL occurred in 9 of 23 stones (39%). Of the 6 least comminuted stones, likely causative factors for decreased effectiveness included stones that were larger than the BWL beamwidth, smaller than the BWL wavelength or the introduction of air bubbles from the ureteroscope. Mild reddening of the papilla and hematuria emanating from the papilla were observed ureteroscopically., Conclusions: The first study of BWL in human subjects resulted in a median of 90% comminution of the total stone volume into fragments ≤2 mm within 10 minutes of BWL exposure with only mild tissue injury.

Introduction: About 1 in 11 Americans will experience a kidney stone, but underlying causes remain obscure. The objective of the present study was to separate idiopathic calcium oxalate stone formers by whether or not they showed positive evidence of forming a stone on Randall's plaque (RP). Materials and Methods: In patients undergoing either percutaneous or ureteroscopic procedures for kidney stone removal, all stone material was extracted and analyzed using micro-CT imaging to identify those attached to RP. Twenty-four-hour urine samples were collected weeks after the stone removal procedure and patients were off of medications that would affect urine composition. The endoscopic video was analyzed for papillary pathology (RP, pitting, plugging, dilated ducts, and loss of papillary shape) by an observer blinded to the data on stone type. The percent papillary area occupied by RP and ductal plugging was quantified using image analysis software. Results: Patients having even one stone on RP ( N  = 36) did not differ from non-RP patients ( N  = 37) in age, sex, BMI, or other clinical characteristics. Compared with the non-RP group, RP stone formers had more numerous, but smaller, stones, more abundant papillary RP formation, and fewer ductal plugs, both by quantitative measurement of surface area (on average, three times more plaque area, but only 41% as much plug area as in non-RP patients) and by semiquantitative visual grading. Serum and blood values did not differ between RP and non-RP stone formers by any measure. Conclusions: Growth of many small stones on plaque seems the pathogenetic scheme for the RP stone-forming phenotype, whereas the non-RP phenotype stone pathogenesis pathway is less obvious. Higher papillary plugging in non-RP patients suggests that plugs play a role in stone formation and that these patients have a greater degree of papillary damage. Underlying mechanisms that create these distinctive phenotypes are presently unknown.

Jackstone 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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Pretreating the kidney with 100 low-energy shock waves (SWs) with a time pause before delivering a clinical dose of SWs (Dornier HM-3, 2000 SWs, 24 kV, and 120 SWs/min) has been shown to significantly reduce the size of the hemorrhagic lesion produced in that treated kidney, compared to a protocol without pretreatment. It has been assumed that a similar reduction in injury will occur with lithotripters other than the HM-3, but experiments to confirm this assumption are lacking. In this study, we sought to verify that the lesion protection phenomenon also occurs in a lithotripter using an electromagnetic shock source and dry-head coupling. Materials and Methods: Eleven female pigs were placed in a Dornier Compact S lithotripter where the left kidney of each animal was targeted for lithotripsy treatment. Some kidneys received 2500 SWs at power level (PL) = 5 (120 SWs/min) while some kidneys were pretreated with 100 SWs at PL = 1, with a 3-minute time pause, followed immediately by 2500 SWs at PL = 5 (120 SWs/min). Lesion size analysis was performed to assess the volume of hemorrhagic tissue injury created by each treatment regimen (% functional renal volume). Results: Lesion size fell by 85% ( p  = 0.01) in the 100 SW pretreatment group compared to the injury produced by a regimen without pretreatment. Conclusions: The results suggest that the treatment pause protection phenomenon occurs with a Dornier Compact S, a machine distinctly different from the Dornier HM-3. This result also suggests that this phenomenon may be observed generally in SW lithotripters.

Kidney stones frequently develop as an overgrowth on Randall's plaque (RP) which is formed in the papillary interstitium. The organic composition of RP is distinct from stone matrix in that RP contains fibrillar collagen; RP in tissue has also been shown to have two proteins that are also found in stones, but otherwise the molecular constituents of RP are unstudied. We hypothesized that RP contains unique organic molecules that can be differentiated from the stone overgrowth by fluorescence. To test this, we used micro-CT-guided polishing to expose the interior of kidney stones for multimodal imaging with multiphoton, confocal and infrared microscopy. We detected a blue autofluorescence signature unique to RP, the specificity of which was also confirmed in papillary tissue from patients with stone disease. High-resolution mineral mapping of the stone also showed a transition from the apatite within RP to the calcium oxalate in the overgrowth, demonstrating the molecular and spatial transition from the tissue to the urine. This work provides a systematic and practical approach to uncover specific fluorescence signatures which correlate with mineral type, verifies previous observations regarding mineral overgrowth onto RP and identifies a novel autofluorescence signature of RP demonstrating RP's unique molecular composition.

The molecular mechanisms by which kidney stones grow are largely unknown. Organic molecules from the urine combine with mineral crystals to form stones, but analysis of the stone matrix has revealed over a thousand different proteins, with no clues as to which are important for stone growth. Molecules that are present in every layer of a stone would be candidates for having an essential function, and thus the analysis of the stone matrix at a microscopic level is necessary. For this purpose, kidney stones were demineralized, sectioned, stained, and imaged by microscopy, using micro CT for precise orientation. Histological staining demonstrated heterogeneity in the density of adjacent layers within stones. Additional results also showed brilliant and unique autofluorescence patterns in decalcified nephroliths, indicating heterogeneous organic composition in adjacent layers. Regions of calcium oxalate (CaOx) stones were dissected using laser microdissection (LMD) for protein analysis. LMD of broad regions of demineralized CaOx stone sections yielded the same proteins as those found in different specimens of pulverized CaOx stones. These innovative methodologies will allow spatial mapping of protein composition within the heterogeneous stone matrix. Proteins that consistently coincide spatially with mineral deposition would be candidates for molecules essential for stone growth. This kind of analysis will be required to assess which of the thousand proteins in the stone matrix may be fundamental for stone growth., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objective: To compare perioperative outcomes between lower, mid, and upper pole access locations for patients undergoing single-access, unilateral percutaneous nephrolithotomy (PCNL)., Methods: We queried our institutional PCNL database to include patients who had unilateral, single access procedures. We excluded patients who had a contralateral procedure during the same admission or multiaccess procedures. Patients were grouped by the site of PCNL access (lower, mid, or upper pole). Among groups, we compared postoperative day 1 (POD1) stone-free rates as measured by abdominal CT scan or plain-film X-ray and consequent need for a secondary procedure. We further compared postoperative complication rates., Results: We included 767 patients for analysis, with the majority of access locations being in the lower pole (80.2%). Patients across groups had similar age, body mass index, and stone laterality. Patients with horseshoe kidneys more commonly had mid or upper pole access compared to lower pole. The percentage of patients with no residual stone fragments seen on POD 1 imaging was similar for lower, mid, and upper pole groups (57.7% vs 65.0% vs 61.6%, respectively; P = .526). Additionally, we observed no difference in the percentage of patients requiring a secondary procedure among the above groups (33.5% vs 22.5% vs 31.3%, respectively; P = .337). Patients experienced no difference in complications among groups., Conclusion: When performing unilateral PCNL using a single site of access, we observed no difference in stone-free rates or complications between lower, mid, and upper pole locations. Appropriate selection of access location in PCNL should be individualized to patient factors and surgeon experience., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the clinical significance of discordant stone analyses in patients undergoing bilateral ureteroscopy., Materials and Methods: A retrospective chart review was performed for all patients undergoing stone extraction with bilateral ureteroscopy at our institution in an aim to identify patients who had bilateral stone analysis and 24-h urine chemistry data available. Stones were then classified based upon the dominant present (> 50%). Twenty-four hour urinalysis results were reviewed and statistical analysis performed comparing discordant and concordant patient populations, assessing significant differences that would potentially influence clinical management., Results: We identified 79 patients (158 renal units) who had bilateral stones removed at the time of ureteroscopy. The majority of stones were classified as calcium oxalate (CaOx) (60.1%) followed by calcium phosphate (CaP) (27.8%), brushite (5.1%), uric acid (UA) (4.4%), and cystine (2.5%). Discrepancies in stone classifications were present 24% of the time. Evaluation of 24-h urinalysis results demonstrated that patients with CaOx:CaP stone discordance compared to CaOx:CaOx concordant stone formers were more likely to have an elevated pH (p = 0.02) and lower uric acid supersaturation (p = 0.01)., Conclusions: Discrepancies in stone mineral content are common in patients with bilateral stone disease. A single stone analysis from one side in the setting of bilateral stone disease is insufficient for management of patients with bilateral renal stones, and may lead to mismanagement when this misrepresented information is utilized in addition to 24-h urinalysis results. At least one stone analysis should be performed from both sides during a bilateral stone extraction procedure.

Objectives: To describe the papillary pathology found in uric acid (UA) stone formers, and to investigate the mineral form of tissue deposits. Materials and Methods: We studied eight UA stone formers treated with percutaneous nephrolithotomy. Papillae were imaged intraoperatively using digital endoscopy, and cortical and papillary biopsies were taken. Biopsies were analyzed by light microscopy, micro-CT, and microinfrared spectroscopy. Results: As expected, urine pH was generally low. UA supersaturation exceeded one in all but one case, compatible with the stone material. By intraoperative imaging, the renal papillae displayed a heterogeneous mixture of plaque and plugging, ranging from normal to severe. All patients had mineral in ducts of Bellini and inner medullary collecting ducts, mainly apatite with lesser amounts of urate and/or calcium oxalate in some specimens. Papillary and cortical interstitial tissue injury was modest despite the tubule plugging. No instance was found of a stone growing attached to either plaque or plugs. Conclusions: UA stone formers resemble those with ileostomy in having rather low urine pH while forming tubule plugs that contain crystals that can only form at pH values above those of their bulk urine. This discrepancy between tissue mineral deposits and stone type suggests that local tubular pH exceeds that of the bulk urine, perhaps because of localized tubule injury. The manner in which UA stones form and the discordance between tubule crystals and stone type remain open research questions.

Introduction: There is evidence that patients with a history of ileostomies, who produce acidic urine and form uric acid or calcium oxalate stones, may plug some collecting ducts with calcium phosphate (CaP) and urate crystals. This is a paradoxical finding as such minerals should not form at an acid pH. One possible explanation is the presence of acidification defects due to focal damage to inner medullary collecting duct and Bellini duct (BD) cells. We sought to further investigate this hypothesis through direct measurement of ductal pH in dilated BDs in patients with ileostomies undergoing percutaneous nephrolithotomy (PCNL) for stone removal. Methods: After obtaining institutional review board approval, we used a fiber-optic pH microsensor with a 140-μm-diameter tip to measure intraluminal pH from the bladder, saline irrigant, and dilated BDs of patients undergoing PCNL. Results: Measurements were taken from three patients meeting inclusion criteria. Measured pH of bladder urine ranged from 4.97 to 5.58 and pH of saline irrigant used during surgery ranged from 5.17 to 5.75. BD measurements were achieved in 11 different BDs. Mean intraductal BD pH was more than 1 unit higher than bulk urine (6.43 ± 0.22 vs 5.31 ± 0.22, p  < 0.01). Conclusions: This is the first evidence for focal acidification defects within injured/dilated BDs of human kidneys producing highly acidic bulk phase urine. These results may help explain the paradoxical finding of CaP and urate plugs in dilated ducts of patients with stone-forming diseases characterized by highly acidic urine.

Objective: To evaluate feasibility of percutaneous nephrolithotomy (PCNL) for complex nephrolithiasis in patients 80 years of age and older compared to younger individuals., Methods: From an institutional IRB-approved database, 1,647 patients were identified who underwent PCNL from 1999 to 2019. Patients were stratified by age: group 1 (20-59), group 2 (60-79), and group 3 (>80). Statistics were performed using chi-square and ANOVA to compare outcomes., Results: Of the 1,647 patients, median age was 46, 66, and 83, respectively (P <0.0001). Three patients within group 3 were 90 or older. Females made up 54%, 46%, 56% of patients (P = 0.02). Average stone size with SD was 2.6 ± 2.2, 2.5 ± 2.3, 2.2± 1.9 cm for each group (P = 0.06). Mean preoperative hemoglobin (Hgb) was significantly lower in the 80+ group (13.8, 13.4, 13.1 g/dL, P <.0001). Change in Hgb was not significantly different. There were more Clavien II-IV complications (10.4, 14.4, 28.8%; P = 0.02) and transfusions (2.3, 4.7, 10.2%; P <0.001) in the elderly. The most common complications in the 80+ group were bleeding related (10.1%). No difference in readmission rates or ICU admissions was noted., Conclusion: PCNL is feasible in the extremely elderly; however with a higher rate of complications and longer hospitalizations. No long-term sequelae or deaths in the 80 and older cohort were seen. This study allows us to appropriately counsel older patients on a realistic postoperative course and supports use of PCNL as the best means of long-term survival., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Renal papillary pits are commonly encountered during ureteroscopy. The mechanism by which such pits arise is unclear. One hypothesis is that pits represent sites where stones overgrowing Randall's plaque (RP) were dislodged. We sought to examine this theory by using digital ureteroscopy and stone μCT., Materials and Methods: Patients undergoing endoscopic stone removal had procedures recorded and stones analyzed by using μCT. Stones with evidence of Randall's plaque anchors (RPAs) were identified in a blinded fashion. Surgical videos were reviewed independently by two urologists., Results: Twenty-eight patients had μCT-confirmed stones with RPA. Among them, 93% were recurrent stone formers and 75% had had prior stone procedures. Metabolic abnormalities were present in 87%, with 79% classified as idiopathic calcium oxalate stone formers. A mean of 7.6 stones with RPA were identified per procedure. In each case, papillary pits were visualized before any stone manipulation and in several cases the active dislodgement of an attached stone led to immediate identification of an underlying pit. Such stones routinely demonstrated an RPA on μCT. The average depth of RPA was 302 ± 172 μm, consistent with the corresponding shallow pits visualized on the papillary surface., Conclusions: Stones overgrowing RP are capable of pulling away a piece of papilla when dislodged, resulting in a visible papillary pit. This process manifests as an RPA on the undersurface of the stone and a papillary pit on the corresponding area of attachment. Identification of pits may help identify patients who form stones primarily by the RP mechanism.

Objective: To assess stone-free rates following ureteroscopy (URS) for renal calculi at our institution using low-dose renal only computed tomography (CT)., Methods: A retrospective review of patients undergoing flexible URS for renal stones only with subsequent CT scan within 3 months. Meticulous basketing of all stone fragments was performed whenever possible. A "true" zero-fragment stone-free rate was determined by reviewing the CT scan and radiologist's report. Patients with nephrocalcinosis (as determined by visual inspection of papilla at the time of URS) were assigned the "stone-free" category., Results: Flexible URS was performed in 288 renal units of 214 patients with renal calculi from 2013 to 2016. Median preoperative stone size was 6.2 mm with the average kidney containing 6.4 stones. An access sheath was used in 92% of cases. A total of 73% (209/288) renal units were completely stone free by CT assessment. Patients with residual fragments were as follows: 1 mm in 2% (7/288), 2-4 mm in 16% (46/288), and >4 mm in 9% of kidneys (26/288)., Conclusion: The true stone-free rate in patients undergoing flexible URS for renal calculi utilizing active basketing of fragments as determined by strict CT assessment was 73%. In patients with residual fragments, the majority are 2-4 mm in size making URS a treatment option for renal calculi with excellent stone-free results., (Copyright © 2018. Published by Elsevier Inc.)

Randall's plaque, an attachment site over which calcium oxalate stones form, begins in the basement membranes of thin limbs of the loop of Henle. The mechanism of its formation is unknown. Possibly, enhanced delivery of calcium out of the proximal tubule, found in many stone formers, increases reabsorption of calcium from the thick ascending limb into the interstitium around descending vasa recta, which convey that calcium into the deep medulla, and raises supersaturations near thin limbs ("vas washdown"). According to this hypothesis, plaque should form preferentially on ascending thin limbs, which do not reabsorb water. We stained serial sections of papillary biopsies from stone-forming patients for aquaporin 1 (which is found in the descending thin limb) and the kidney-specific chloride channel ClC-Ka (which is found in the ascending thin limb). Plaque (which is detected using Yasue stain) colocalized with ClC-Ka, but not with aquaporin 1 (χ 2  = 464, P < 0.001). We conclude that plaque forms preferentially in the basement membranes of ascending thin limbs, fulfilling a critical prediction of the vas washdown theory of plaque pathogenesis. The clinical implication is that treatments such as a low-sodium diet or thiazide diuretics that raise proximal tubule calcium reabsorption may reduce formation of plaque as well as calcium kidney stones.

High fluid intake is an effective preventative strategy against recurrent kidney stones but is known to be challenging to achieve. Recently, a smart water bottle (Hidrate Spark™, Minneapolis, MN) was developed as a non-invasive fluid intake monitoring system. This device could help patients who form stones from low urine volume achieve sustainable improvements in hydration, but has yet to be validated in a clinical setting. Hidrate Spark™ uses capacitive touch sensing via an internal sensor. It calculates volume measurements by detecting changes in water level and sends data wirelessly to users' smartphones through an application. A pilot study was conducted to assess accuracy of measured fluid intake over 24 h periods when used in a real life setting. Subjects were provided smart bottles and given short tutorials on their use. Accuracy was determined by comparing 24-h fluid intake measurements calculated through the smart bottle via sensor to standard volume measurements calculated by the patient from hand over the same 24 h period. Eight subjects performed sixty-two 24-h measurements (range 4-14). Mean hand measurement was 57.2 oz/1692 mL (21-96 oz/621-2839 mL). Corresponding mean smart bottle measurement underestimated true fluid intake by 0.5 ozs. (95% CI -1.9, 0.9). Percent difference between hand and smart bottle measurements was 0.0% (95% CI - 3%, 3%). Intraclass correlation coefficient (ICC), calculated to assess consistency between hand measures and bottle measures, was 0.97 (0.95, 0.98) indicating an extremely high consistency between measures. 24-h fluid intake measurements from a novel fluid monitoring system (Hidrate Spark™) are accurate to within 3%. Such technology may be useful as a behavioral aide and/or research tool particularly among recurrent stone formers with low urinary volume.

Objective: To compare the sensitivity of noncontrast computed tomography (CT) with endoscopy for detection of renal calculi. Imaging modalities for detection of nephrolithiasis have centered on abdominal x-ray, ultrasound, and noncontrast CT. Sensitivities of 58%-62% (abdominal x-ray), 45% (ultrasound), and 95%-100% (CT) have been previously reported. However, these results have never been correlated with endoscopic findings., Methods: Idiopathic calcium oxalate stone formers with symptomatic calculi requiring ureteroscopy were studied. At the time of surgery, the number and the location of all calculi within the kidney were recorded followed by basket retrieval. Each calculus was measured and sent for micro-CT and infrared spectrophotometry. All CT scans were reviewed by the same genitourinary radiologist who was blinded to the endoscopic findings. The radiologist reported on the number, location, and size of each calculus., Results: Eighteen renal units were studied in 11 patients. Average time from CT scan to ureteroscopy was 28.6 days. The mean number of calculi identified per kidney was 9.2 ± 6.1 for endoscopy and 5.9 ± 4.1 for CT (P <.004). The mean size of total renal calculi (sum of the longest stone diameters) per kidney was 22.4 ± 17.1 mm and 18.2 ± 13.2 mm for endoscopy and CT, respectively (P = .06)., Conclusion: CT scan underreports the number of renal calculi, probably missing some small stones and being unable to distinguish those lying in close proximity to one another. However, the total stone burden seen by CT is, on average, accurate when compared with that found on endoscopic examination., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: We hypothesized that adding sodium bicarbonate (bicarb) to normal saline (NS) irrigation during ureteroscopy in patients with uric acid (UA) nephrolithiasis may assist in dissolving small stone fragments produced during laser lithotripsy. In vitro testing was performed to determine whether dissolution of UA fragments could be accomplished within 1 hour., Materials and Methods: In total 100% UA renal calculi were fragmented, filtered, and separated by size. Fragment sizes were <0.5 mm and 0.5 to 1 mm. Similar amounts of stone material were agitated in solution at room temperature. Four solutions were tested (NS, NS +1 ampule bicarb/L, NS +2, NS +3). Both groups were filtered to remove solutions after fixed periods. Filtered specimens were dried and weighed. Fragment dissolution rates were calculated as percent removed per hour. Additional testing was performed to determine whether increasing the temperature of solution affected dissolution rates., Results: For fragments <0.5 mm, adding 2 or 3 bicarb ampules/L NS produced a dissolution rate averaging 91% ± 29% per hour. This rate averaged 226% faster than NS alone. With fragments 0.5 to 1 mm, addition of 2 or 3 bicarb ampules/L NS yielded a dissolution rate averaging 22% ± 7% per hour, which was nearly five times higher than NS alone. There was a trend for an increase in mean dissolution rate with higher temperature but this increase was not significant (p = 0.30)., Conclusions: The addition of bicarbonate to NS more than doubles the dissolution rate of UA stone fragments and fragments less than 0.5 mm can be completely dissolved within 1 hour. Addition of bicarb to NS irrigation is a simple and inexpensive approach that may assist in the dissolution of UA fragments produced during ureteroscopic laser lithotripsy. Further studies are needed to determine whether a clinical benefit exists.

Objective: To discuss complications of simultaneous bilateral percutaneous nephrolithotomy (SB-PCNL) when compared with unilateral percutaneous nephrolithotomy and survey surgeon preference in bilateral stone disease management., Patients and Methods: A database of all participating percutaneous nephrolithotomy (PCNL) patients who underwent treatment at Indiana University Health Methodist Hospital within a 10-year period from 2006 to 2015 by a single surgeon (JL) was utilized. Perioperative data, as well as complications, defined according to the Clavien grading system, were recorded. A survey of members of the Endourological Society was performed regarding surgical management in the setting of bilateral stone disease., Results: A total of 563 patients were identified over the study period with 129 undergoing SB-PCNL. Overall, SB-PCNL patients had a longer procedure (176.9 vs 115.6 minutes, P <.0001), were more likely to undergo a secondary procedure (73% vs 44, P <.001), and had a longer hospital stay (3.2 vs 2.3 days, P <.001). Notably, there were no differences in the number or the severity of complications between the 2 groups. A total of 153 endourologists completed the survey. Of these endourologists, 58 (38%) performed bilateral PCNL under anesthesia. The top reasons for electing not to perform bilateral PCNLs included the duration of bilateral procedures (53%), bilateral renal injury (48%), and rare performance of bilateral surgery (35%)., Conclusion: Although the procedure length was longer in the SB-PCNL group, there were similar rates of complications and severity between unilateral PCNL and SB-PCNL. A majority of endourologists surveyed do not perform bilateral PCNL but would perform bilateral ureteroscopy with the duration of the procedure and concern for bilateral renal injury representing the most common reasons., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Mechanisms of early stone retention in the kidney are under studied and poorly understood. To date attachment via Randall's plaque is the only widely accepted theory in this regard, which is best described in idiopathic calcium oxalate stone formers. Brushite stone formers are known to have distinct papillary morphology relative to calcium oxalate stone formers. As such we sought to determine whether stone attachment mechanisms in such patients may be similarly unique., Materials and Methods: Patients undergoing percutaneous and or ureteroscopic procedures for stone removal consented to endoscopic renal papillary examination and individual stone collection. Each removed stone was processed using micro computerized tomography to assess the 3-dimensional microstructure and the minerals contained, and search for common structural features indicative of novel mechanisms of early growth and attachment to renal tissue., Results: A total of 25 intact brushite stones were removed from 8 patients and analyzed. Video confirmed attachment of 13 of the 25 stones with the remainder believed to have been accidently dislodged during the procedure. Microscopic examination by light and computerized tomography failed to show evidence of Randall's plaque associated with any stone containing brushite. Conversely each brushite stone demonstrated microstructural evidence of having grown attached to a ductal plug formed of apatite., Conclusions: Three-dimensional analysis of small brushite stones suggests overgrowth on ductal apatite plugs as a mechanism of early stone growth and retention. Such findings represent what is to our knowledge the initial supporting evidence for a novel mechanism of stone formation which has previously been hypothesized but never verified., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the efficiency (stone fragmentation and removal time) and complications of three models of intracorporeal lithotripters in percutaneous nephrolithotomy (PCNL)., Materials and Methods: Prospective, randomized controlled trial at nine centers in North America from 2009 to 2016. Patients were randomized to one of three lithotripter devices: the Cyberwand, a dual-probe ultrasonic device; the Swiss Lithoclast Select, a combination pneumatic and ultrasonic device; and the StoneBreaker, a portable pneumatic device powered by CO 2 cartridges. Since the StoneBreaker lacks an ultrasonic component, it was used with the LUS-II ultrasonic lithotripter to allow fair comparison with combination devices., Results: Two hundred seventy patients were enrolled, 69 were excluded after randomization. Two hundred one patients completed the study: 71 in the Cyberwand group, 66 in the Lithoclast Select group, and 64 in the StoneBreaker group. The baseline patient characteristics of the three groups were similar. Mean stone surface area was smaller in the StoneBreaker group at 407.8 mm 2 vs 577.5 mm 2 (Lithoclast Select) and 627.9 mm 2 (Cyberwand). The stone clearance rate was slowest in the StoneBreaker group at 24.0 mm 2 /min vs 28.9 mm 2 /min and 32.3 mm 2 /min in the Lithoclast Select and Cyberwand groups, respectively. After statistically adjusting for the smaller mean stone in the StoneBreaker group, there was no difference in the stone clearance rate among the three groups (p = 0.249). Secondary outcomes, including complications and stone-free rates, were similar between the groups., Conclusions: The Cyberwand, Lithoclast Select, and the StoneBreaker lithotripters have similar adjusted stone clearance rates in PCNL for stones >2 cm. The safety and efficacy of these devices are comparable.

Objective: To describe our experience with the circle nephrostomy tube (NT) (Cook Medical), a drainage system uniquely designed for use after multiple-access percutaneous nephrolithotomy (PNL)., Methods: A retrospective review of 1317 consecutive patients undergoing 1599 PNLs at IU Health Methodist Hospital was performed. All multiple access cases utilizing circle NTs were reviewed and analyzed. The method of insertion of circle NT was demonstrated., Results: A total of 1843 accesses were obtained in 1599 renal units (RUs): 380 upper pole, 129 interpolar, and 1334 lower pole. Multiple accesses in this series were required in 282 RUs (17.6%). Following multiple-access PNL, circle NTs, Cope loop, and reentry Malecot NTs were inserted in 91 RUs (32.3%), 208 RUs (73.8%), and 31 RUs (11%), respectively. None of the patients who had circle NT experienced clogging, dislodgement, or obstruction of the tube. The cost of circle, Cope loop, and Malecot NTs are 121.73 USD, 95.20 USD, and 81 USD, respectively., Conclusion: Circle NTs are easy to insert, secure, cost-effective compared with inserting two NTs. Circle NTs provide excellent drainage and facilitate secondary procedures., (Copyright © 2017 Elsevier Inc. All rights reserved.)

How stones are retained within the kidney while small in size is still not fully understood. In this paper, we show two examples of how stones are retained during early growth: one is growth on Randall's (interstitial) plaque, and the other is growth on mineral that has formed as a luminal plug in a terminal collecting duct. These two mechanisms of stone retention during early growth have distinctive morphologic features that can be seen by methods that show the microscopic structure of the stones. Stones growing on Randall's plaque display an apatite region that is typically not large in size (<0.5 mm across) but which usually shows luminal spaces, which are signs of its origin in the connective tissue of the papilla. Stones growing on ductal plugs also show attachment to a piece of apatite, but the apatite regions are typically larger (often >1 mm long and >0.5 mm wide), and they are solid, without spaces running through them. We propose that knowing the mechanisms of stone retention during early stone formation could allow for better treatment of stone diseases., Competing Interests: none

Objective: This study was conducted to assess the reliability and precision of an endoscopic grading scale to identify renal papillary abnormalities across a spectrum of equipment, locations, graders, and patients., Materials and Methods: Intra- and interobserver reliability of the papillary grading system was assessed using weighted kappa scoring among 4 graders reviewing a single renal papilla from 50 separate patients on 2 occasions. Grading was then applied to a cohort of patients undergoing endoscopic stone removal procedures at two centers. Patient factors were compared with papillary scores on the level of the papilla, kidney, and patient., Results: Graders achieved substantial (kappa >0.6) intra- and inter-rater reliability in scored domains of ductal plugging, surface pitting, and loss of contour. Agreement for Randall's Plaque (RP) was moderate. Papillary scoring was then performed for 76 patients (89 kidneys, 533 papillae). A significant association was discovered between pitting and RP that held both within and across institutions. A general linear model was then created to further assess this association and it was found that RP score was a highly significant independent correlate of pitting score (F = 7.1; p < 0.001). Mean pitting scores increased smoothly and progressively with increasing RP scores. Sums of the scored domains were then calculated as a reflection of gross papillary abnormality. When analyzed in this way, a history of stone recurrence and shockwave lithotripsy were strongly predictive of higher sums., Conclusions: Renal papillary pathology can be reliably assessed between different providers using a newly described endoscopic grading scale. Application of this scale to stone-forming patients suggests that the degree of RP appreciated in the papilla is strongly associated with the presence of pitting. It also suggests that patients with a history of recurrent stones and lithotripsy have greater burdens of gross papillary disease., Competing Interests: Author Disclosure Statement Dr. Lingeman is a consultant/advisor, investor, meeting participant/lecturer, and scientific study trial participant for Boston Scientific Corp., and owner, medical director, for Beck Analytical; Dr. Coe is a consultant for Labcorp; and for the remaining authors, no competing financial interests exist.

Introduction: The holmium laser has revolutionized the practice of minimally invasive endoscopy for kidney stones. Recently, a novel, rigid handpiece for use in percutaneous nephrolithotomy (PCNL) that couples the holmium laser with suction has been developed. To date, limited data exist regarding the usability and ergonomics of such treatment systems. We thus sought to compare surgeon-rated usability with three different suction laser handpieces in a porcine model., Materials and Methods: We performed bilateral reverse PCNL on four female domestic farm pigs. After induction of general anesthesia, percutaneous access was obtained into each kidney by using biplanar fluoroscopy and 8 mm stones (plaster of Paris) were inserted into the calix or renal pelvis for treatment. Four surgeons tested the LASER Suction Tube (Karl Storz ® , Germany), LithAssist™ (Cook ® Medical), and Suction Handpiece (HP) (Lumenis ® , Israel) by using a combination of fragmentation (5 Joules/20 Hertz) and dusting (0.8 Joules/80 Hertz) settings on the Lumenis pulse 120 H laser. The primary outcome assessed was the ease of use of the three devices as measured by a surgeon questionnaire., Results: A total of 15 stones were treated in 8 renal units. The mean time required for stone fragmentation was 8 min. The mean handling and suction efficiency scores were similar between devices. The Suction HP offered the best laser fiber visibility during lithotripsy., Conclusion: Suction laser handpieces offer an option to treat renal stones via PCNL, with limited differences noted in most surgeon ratings between devices.

Introduction: Percutaneous nephrolithotomy (PCNL) is considered the gold standard for treatment of large renal calculi. Although several investigators have examined the feasibility and outcomes associated with PCNL in obese patients, these studies have been limited by small sample size, lack of a comparator group, or few patients at body mass index (BMI) extremes. We thus compared outcomes of superobese (BMI >50) patients undergoing PCNL vs both an "overweight" and "ideal" cohort., Methods: We used a prospectively maintained database to identify ideal (BMI 18.5-25), overweight (BMI 25.1-49.9), and superobese (BMI ≥50) patients who underwent PCNL. Our primary objective was to compare surgical outcomes between groups measured by the percent of patients who required secondary PCNL. We then compared complication rates, need for transfusion, and length of stay (LOS) using chi-square testing and ANOVA where appropriate., Results: A total of 1152 patients were identified of which 254 were classified as ideal, 840 as overweight, and 58 as superobese. The overweight cohort had a higher mean age and greater proportion of males, whereas staghorn stones were more common in the superobese group. Comorbid conditions were more commonly observed in the superobese cohort. Otherwise, the groups were similar. Surgical outcomes were comparable with 47.2%, 42.0%, and 38.0% of ideal, overweight, and superobese patients requiring secondary PCNL (p = 0.25) with no difference in complication rates, need for transfusion, or LOS., Conclusion: PCNL can be effectively and safely performed in superobese patients with no difference in surgical outcomes or complications when compared to ideal or overweight patient cohorts.

Purpose: Pretreating a pig kidney with 500 low-energy shock waves (SWs) before delivering a clinical dose of SWs (2000 SWs, 24 kV, 120 SWs/min) has been shown to significantly reduce the size of the hemorrhagic lesion produced in that treated kidney, compared with a protocol without pretreatment. However, since the time available for patient care is limited, we wanted to determine if fewer pretreatment SWs could be used in this protocol. As such, we tested if pretreating with 300 SWs can initiate the same reduction in renal lesion size as has been observed with 500 SWs., Materials and Methods: Fifteen female farm pigs were placed in an unmodified Dornier HM-3 lithotripter, where the left kidney of each animal was targeted for lithotripsy treatment. The kidneys received 300 SWs at 12 kV (120 SWs/min) followed immediately by 2000 SWs at 24 kV (120 SWs/min) focused on the lower pole. These kidneys were compared with kidneys given a clinical dose of SWs with 500 SW pretreatment, and without pretreatment. Renal function was measured both before and after SW exposure, and lesion size analysis was performed to assess the volume of hemorrhagic tissue injury (% functional renal volume, FRV) created by the 300 SW pretreatment regimen., Results: Glomerular filtration rate fell significantly in the 300 SW pretreatment group by 1 hour after lithotripsy treatment. For most animals, low-energy pretreatment with 300 SWs significantly reduced the size of the hemorrhagic injury (to 0.8% ± 0.4%FRV) compared with the injury produced by a typical clinical dose of SWs., Conclusions: The results suggest that 300 pretreatment SWs in a voltage ramping treatment regimen can initiate a protective response in the majority of treated kidneys and significantly reduce tissue injury in our model of lithotripsy injury., Competing Interests: Author Disclosure Statement No competing financial interests exist.

Purpose: We examine the relationship between urine and stone cultures in a large cohort of patients undergoing percutaneous stone removal and compare the findings in infectious vs metabolic calculi., Materials and Methods: A total of 776 patients treated with percutaneous nephrolithotomy who had preoperative urine cultures and intraoperative stone cultures were included in the study. Statistical analysis used chi-square or logistic fit analysis as appropriate., Results: Preoperative urine culture was positive in 352 patients (45.4%) and stone cultures were positive in 300 patients (38.7%). There were 75 patients (9.7%) with negative preoperative cultures who had positive stone cultures, and in patients with both cultures positive the organisms differed in 103 (13.3%). Gram-positive organisms predominated in preoperative urine and stone cultures., Conclusions: Preoperative urine cultures in patients undergoing percutaneous nephrolithotomy are unreliable as there is a discordance with intraoperative stone cultures in almost a quarter of cases. There has been a notable shift toward gram-positive organisms in this cohort of patients., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Ultrasonic propulsion is a new technology using focused ultrasound energy applied transcutaneously to reposition kidney stones. We report what are to our knowledge the findings from the first human investigational trial of ultrasonic propulsion toward the applications of expelling small stones and dislodging large obstructing stones., Materials and Methods: Subjects underwent ultrasonic propulsion while awake without sedation in clinic, or during ureteroscopy while anesthetized. Ultrasound and a pain questionnaire were completed before, during and after propulsion. The primary outcome was to reposition stones in the collecting system. Secondary outcomes included safety, controllable movement of stones and movement of stones less than 5 mm and 5 mm or greater. Adverse events were assessed weekly for 3 weeks., Results: Kidney stones were repositioned in 14 of 15 subjects. Of the 43 targets 28 (65%) showed some level of movement while 13 (30%) were displaced greater than 3 mm to a new location. Discomfort during the procedure was rare, mild, brief and self-limited. Stones were moved in a controlled direction with more than 30 fragments passed by 4 of the 6 subjects who had previously undergone a lithotripsy procedure. The largest stone moved was 10 mm. One patient experienced pain relief during treatment of a large stone at the ureteropelvic junction. In 4 subjects a seemingly large stone was determined to be a cluster of small passable stones after they were moved., Conclusions: Ultrasonic propulsion was able to successfully reposition stones and facilitate the passage of fragments in humans. No adverse events were associated with the investigational procedure., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Percutaneous nephrolithotomy has high potential for morbidity or failure. There are limited data regarding risk factors for failure and to our knowledge no published reports of surgical outcomes in patients with prior failed attempts at percutaneous stone removal., Materials and Methods: We identified patients referred to 3 medical centers after prior failed attempts at percutaneous nephrolithotomy. A retrospective chart review was performed to analyze reasons for initial failure and outcomes of salvage percutaneous nephrolithotomy. Outcomes were compared to those in a prospectively maintained database of more than 1,200 patients treated with a primary procedure., Results: Salvage percutaneous nephrolithotomy was performed in 31 patients. Unsuitable access to the stone was the reason for failure in 80% of cases. Other reasons included infection, bleeding and inadequate instrument availability in 6.5% of cases each. Compared to patients who underwent primary percutaneous nephrolithotomy those treated with salvage were more likely to have staghorn calculi (61.3% vs 31.4%, p <0.01) and a larger maximum stone diameter (3.7 vs 2.5 cm, p <0.01), and require a secondary procedure (65.5% vs 42.1%, p <0.01). There was no significant difference between the cohorts in the remaining demographics or perioperative outcomes. All patients were deemed completely stone free except one who elected observation for a 3 mm nonobstructing fragment., Conclusions: Despite the more challenging nature and prior unsuccessful attempts at treatment, the outcomes of salvage percutaneous nephrolithotomy were no different from those of primary percutaneous nephrolithotomy when performed by experienced surgeons., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The appearance of the renal papillae in patients with nephrolithiasis can be quite variable and can range from entirely healthy to markedly diseased. The implications of such findings remain unknown. One potential reason is the lack of a standardized system to describe such features. We propose a novel grading scale to describe papillary appearance at the time of renal endoscopy., Methods: Comprehensive endoscopic renal assessment and mapping were performed on more than 300 patients with nephrolithiasis. Recurring abnormal papillary characteristics were identified and quantified based on degree of severity., Results: Four unique papillary features were chosen for inclusion in the PPLA scoring system- ductal Plugging, Pitting, Loss of contour, and Amount of Randall's plaque. Unique scores are calculated for individual papillae based on reference examples., Conclusions: The description and study of renal papillary appearance in stone formers have considerable potential as both a clinical and research tool; however, a standardized grading system is necessary before using it for these purposes.

Purpose: Nephrocalcinosis is commonly present in primary hyperparathyroidism, distal renal tubular acidosis and medullary sponge kidney disease. To our knowledge it has not been studied in patients with calcium phosphate stones who do not have systemic disease., Materials and Methods: We studied patients undergoing percutaneous nephrolithotomy who had calcium phosphate or calcium oxalate stones and did not have hyperparathyroidism, distal renal tubular acidosis or medullary sponge kidney disease. On postoperative day 1 all patients underwent noncontrast computerized tomography. If there were no residual calcifications, the patient was categorized as not having nephrocalcinosis. If there were residual calcifications, the patient underwent secondary percutaneous nephrolithotomy. If the calcifications were found to be stones, the patient was categorized as not having nephrocalcinosis. If the calcifications were not stones, the patient was categorized as having nephrocalcinosis. Patients were grouped based on the type of stones that formed, including hydroxyapatite, brushite and idiopathic calcium oxalate. The extent of nephrocalcinosis was quantified as 0--absent nephrocalcinosis to 3--extensive nephrocalcinosis. Patients with residual calcifications on postoperative day 1 noncontrast computerized tomography who did not undergo secondary percutaneous nephrolithotomy were excluded from analysis. The presence or absence of nephrocalcinosis was correlated with metabolic studies., Results: A total of 67 patients were studied, including 14 with hydroxyapatite, 19 with brushite and 34 with idiopathic calcium oxalate calculi. Nephrocalcinosis was present in 10 of 14 (71.4%), 11 of 19 (57.9%) and 6 of 34 patients (17.6%) in the hydroxyapatite, brushite and idiopathic calcium oxalate groups, respectively (chi-square p = 0.01). The mean extent of nephrocalcinosis per group was 1.98, 1.32 and 0.18 for hydroxyapatite, brushite and idiopathic calcium oxalate, respectively (p ≤0.001). The presence of nephrocalcinosis positively correlated with urine calcium excretion (mean ± SD 287.39 ± 112.49 vs 223.68 ± 100.67 mg per day, p = 0.03)., Conclusions: Patients without systemic disease who form hydroxyapatite and brushite stones commonly have coexistent nephrocalcinosis. Nephrocalcinosis can occur in calcium oxalate stone formers but the quantity and frequency of nephrocalcinosis in this group are dramatically less., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Treatment options for kidney stones and ureteral stones have evolved considerably over the past several decades, to the point where almost any stone can now be considered for treatment with a noninvasive or a minimally invasive approach including shock wave lithotripsy, ureteroscopy or percutaneous nephrolithotomy. The safety and morbidity associated with these techniques are favourable relative to traditional open surgical approaches to stone removal. However, they also require unique skillsets, access to instrumentation and relatively high maintenance costs, potentially limiting their use on a global scale. Coincident with the emergence of endourology have been considerable improvements in laparoscopic surgical techniques to the point that nearly any open surgery can be performed in a minimally invasive laparoscopic fashion. Such approaches, including those with robotic assistance, have potential application for the treatment of upper urinary tract stones, particularly in complex senarios as well as in areas where access to endourological instruments might be limited.

Objective: To describe the initial clinical experience with the UreTron (Med-Sonics, Erie, PA), a new ultrasonic lithotriptor. Historically, ultrasound-only intracorporeal lithotriptors have been considered the gold standard for stone removal during percutaneous nephrolithotomy. Recently, they have lost favor to newer dual and combination devices believed by many to be more efficient. The UreTron features patented technology to precisely control probe vibration and achieve more efficient output potentially improving efficiency of stone clearance. To date, the clinical efficacy of this new device has yet to be tested relative to alternative state-of-the-art lithotriptors., Methods: Thirty-one patients with renal stones >2 cm undergoing percutaneous nephrolithotomy were studied. All cases were performed by the same surgeon, and data were recorded prospectively using the same protocol established for a separate ongoing comparison study designed to assess performance of 3 separate state-of-the-art lithotriptors (CyberWand, StoneBreaker, and LithoClast Select). Bivariate analysis was performed between the UreTron cohort and the combined cohort of the alternative state-of-the-art lithotriptors (n = 51)., Results: The UreTron achieved the highest stone clearance rate (51.9 mm(2)/min) of any device. It also had little decrease in clearance efficiency when used on "hard" stones (48.5 mm(2)/min). The UreTron had a faster clearance rate than the alternative lithotriptor cohort (51.9 vs 36.0 mm(2)/min; P = .02) with no differences in stone-free rate, secondary procedures, clinical complications, or device malfunctions (P >.05)., Conclusion: The UreTron compares favorably with alternative state-of-the-art intracorporeal lithotriptors with faster stone clearance rates and equivalent clinical outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Medullary sponge kidney (MSK) is associated with recurrent stone formation, but the clinical phenotype is unclear because patients with other disorders may be incorrectly labeled MSK. We studied 12 patients with histologic findings pathognomonic of MSK. All patients had an endoscopically recognizable pattern of papillary malformation, which may be segmental or diffuse. Affected papillae are enlarged and billowy, due to markedly enlarged inner medullary collecting ducts (IMCD), which contain small, mobile ductal stones. Patients had frequent dilation of Bellini ducts, with occasional mineral plugs. Stones may form over white (Randall's) plaque, but most renal pelvic stones are not attached, and have a similar morphology as ductal stones, which are a mixture of calcium oxalate and apatite. Patients had no abnormalities of urinary acidification or acid excretion; the most frequent metabolic abnormality was idiopathic hypercalciuria. Although both Runx2 and Osterix are expressed in papillae of MSK patients, no mineral deposition was seen at the sites of gene expression, arguing against a role of these genes in this process. Similar studies in idiopathic calcium stone formers showed no expression of these genes at sites of Randall's plaque. The most likely mechanism for stone formation in MSK appears to be crystallization due to urinary stasis in dilated IMCD with subsequent passage of ductal stones into the renal pelvis where they may serve as nuclei for stone formation., (© 2015 Wiley Periodicals, Inc.)

Objective: To provide a contemporary look at vascular complications after percutaneous nephrolithotomy (PNL) with access performed solely by a urologist using fluoroscopic guidance., Methods: A retrospective review of 2792 patients who had 3338 PNLs at Indiana University Health Methodist Hospital and Mayo Clinic Rochester was performed. Patients who experienced significant bleeding requiring diagnostic renal angiography and superselective embolization (SSE) were reviewed and compared with the overall database., Results: There were 15 patients (16 renal units) requiring renal angiography and SSE (0.48%). Mean time from PNL to bleeding was 7 days (range, 1-15 days) and to SSE was 9.6 days (range, 2-18 days). Mean drop in hemoglobin was 5.3 g/dL (range, 2-9 g/dL). Transfusion was needed in 9 patients (60%). There were no differences between the vascular complications group and the uneventful PNL group in mean age (55.06 vs 52.2 years; P = .519), UTI history (40% vs 38%; P = .92), mean operative time (125.8 vs 102.47 minutes; P = .192), the need for multiple access (18.75% vs 18%; P = .939), and access location. The vascular complications group had a lower stone burden than the uneventful PNL group (stones > 2 cm; 43.7% vs 74.03%; P = .014)., Conclusion: The incidence of vascular complications in this contemporary series is one of the lowest reported to date. At our centers, vascular bleeding complications appear to be a random and rare event after PNL as we were unable to identify any specific risk factors. Early SSE avoided the need for blood transfusion in many patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: We assessed patient outcomes using 2 widely different contemporary lithotripters., Materials and Methods: We performed a consecutive case series study of 355 patients in a large private practice group using a Modulith® SLX electromagnetic lithotripter in 200 patients and a LithoGold LG-380 electrohydraulic lithotripter (TRT, Woodstock, Georgia) in 155. Patients were followed at approximately 2 weeks. All preoperative and postoperative films were reviewed blindly by a dedicated genitourinary radiologist. The stone-free rate was defined as no residual fragments remaining after a single session of shock wave lithotripsy without an ancillary procedure., Results: Patients with multiple stones were excluded from analysis, leaving 76 and 142 treated with electrohydraulic and electromagnetic lithotripsy, respectively. The stone-free rate was similar for the electrohydraulic and electromagnetic lithotripters (29 of 76 patients or 38.2% and 69 of 142 or 48.6%, p = 0.15) with no difference in the stone-free outcome for renal stones (20 of 45 or 44.4% and 33 of 66 or 50%, p = 0.70) or ureteral stones (9 of 31 or 29% and 36 of 76 or 47.4%, respectively, p = 0.08). The percent of stones that did not break was similar for the electrohydraulic and electromagnetic devices (10 of 76 patients or 13.2% and 23 of 142 or 16.2%) and ureteroscopy was the most common ancillary procedure (18 of 22 or 81.8% and 30 of 40 or 75%, respectively). The overall mean number of procedures performed in patients in the 2 groups was similar (1.7 and 1.5, respectively)., Conclusions: We present lithotripsy outcomes in the setting of a suburban urology practice. Stone-free rates were modest using shock wave lithotripsy alone but access to ureteroscopy provided satisfactory outcomes overall. Although the acoustic characteristics of the electrohydraulic and electromagnetic lithotripters differ substantially, outcomes with these 2 machines were similar., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Micro-computed tomographic imaging (micro-CT) provides unprecedented information on stone structure and mineral composition. High-resolution micro-CT even allows visualization of the lumens of tubule and/or vessels within Randall's plaque, on stones or in papillary biopsies, thus giving a non-destructive way to study these sites of stone adhesion. This paper also shows an example of a stone growing on a different anchoring mechanism: a mineral plug within the lumen of a Bellini duct (BD plug). Micro-CT shows striking structural differences between stones that have grown on Randall's plaque and those that have grown on BD plugs. Thus, Randall's plaque can be distinguished by micro-CT, and this non-destructive method shows great promise in helping to elucidate the different mechanisms by which small stones are retained in the kidney during the development of nephrolithiasis.

Introduction: Renal stones are one of the most painful medical conditions patients experience. For many they are also a recurrent problem. Fortunately, there are a number of drug therapies available to treat symptoms as well as prevent future stone formation., Areas Covered: Herein, we review the most common drugs used in the treatment of renal stones, explaining the mechanism of action and potential side effects. Search of the Medline databases and relevant textbooks was conducted to obtain the relevant information. Further details were sourced from drug prescribing manuals. Recent studies of drug effectiveness are included as appropriate., Expert Opinion: Recent controversies include medical expulsive therapy trials and complex role of urinary citrate in stone disease. Future directions in research will involve new medical therapies for stone prevention, for example new drugs for hyperoxaluria.

The precise mechanisms of kidney stone formation and growth are not completely known, even though human stone disease appears to be one of the oldest diseases known to medicine. With the advent of the new digital endoscope and detailed renal physiological studies performed on well phenotyped stone formers, substantial advances have been made in our knowledge of the pathogenesis of the most common type of stone former, the idiopathic calcium oxalate stone former as well as nine other stone forming groups. The observations from our group on human stone formers and those of others on model systems have suggested four entirely different pathways for kidney stone formation. Calcium oxalate stone growth over sites of Randall's plaque appear to be the primary mode of stone formation for those patients with hypercalciuria. Overgrowths off the ends of Bellini duct plugs have been noted in most stone phenotypes, do they result in a clinical stone? Micro-lith formation does occur within the lumens of dilated inner medullary collecting ducts of cystinuric stone formers and appear to be confined to this space. Lastly, cystinuric stone formers also have numerous small, oval, smooth yellow appearing calyceal stones suggestive of formation in free solution. The scientific basis for each of these four modes of stone formation are reviewed and used to explore novel research opportunities.

Purpose: We determined whether shock wave lithotripsy of the kidney of pigs with metabolic syndrome would worsen glucose tolerance or increase the risk of diabetes mellitus., Materials and Methods: Nine-month-old female Ossabaw miniature pigs were fed a hypercaloric atherogenic diet to induce metabolic syndrome. At age 15 months the pigs were treated with 2,000 or 4,000 shock waves (24 kV at 120 shock waves per minute) using an unmodified HM3 lithotripter (Dornier MedTech, Kennesaw, Georgia). Shock waves were targeted to the left kidney upper pole calyx to model treatment that would also expose the pancreatic tail to shock waves. The intravenous glucose tolerance test was done in conscious fasting pigs before lithotripsy, and 1 and 2 months after lithotripsy with blood samples taken for glucose and insulin measurement., Results: Pigs fed the hypercaloric atherogenic diet were obese, dyslipidemic, insulin resistant and glucose intolerant, consistent with metabolic syndrome. Assessments of insulin resistance, glucose tolerance and pancreatic β cell function from fasting plasma glucose and insulin levels, and the glucose and insulin response profile to the intravenous glucose tolerance test were similar before and after lithotripsy., Conclusions: The metabolic syndrome status of pigs treated with shock wave lithotripsy was unchanged 2 months after kidney treatment with 2,000 high amplitude shock waves or overtreatment with 4,000 high amplitude shock waves. These findings do not support a single shock wave lithotripsy treatment of the kidney as a risk factor for the onset of diabetes mellitus., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Our previous work has shown that stone formers who form calcium phosphate (CaP) stones that contain any brushite (BRSF) have a distinctive renal histopathology and surgical anatomy when compared with idiopathic calcium oxalate stone formers (ICSF). Here we report on another group of idiopathic CaP stone formers, those forming stone containing primarily hydroxyapatite, in order to clarify in what ways their pathology differs from BRSF and ICSF. Eleven hydroxyapatite stone formers (HASF) (2 males, 9 females) were studied using intra-operative digital photography and biopsy of papillary and cortical regions to measure tissue changes associated with stone formation. Our main finding is that HASF and BRSF differ significantly from each other and that both differ greatly from ICSF. Both BRSF and ICSF patients have significant levels of Randall's plaque compared with HASF. Intra-tubular deposit number is greater in HASF than BRSF and nonexistent in ICSF while deposit size is smaller in HASF than BRSF. Cortical pathology is distinctly greater in BRSF than HASF. Four attached stones were observed in HASF, three in 25 BRSF and 5-10 per ICSF patient. HASF and BRSF differ clinically in that both have higher average urine pH, supersaturation of CaP, and calcium excretion than ICSF. Our work suggests that HASF and BRSF are two distinct and separate diseases and both differ greatly from ICSF., (Copyright © 2014 Wiley Periodicals, Inc.)