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Item Clinical and Metabolic Correlates of Pure Stone Subtypes(Liebert, 2021) Brinkman, John E.; Large, Tim; Nottingham, Charles U.; Stoughton, Christa; Krambeck, Amy E.; Urology, School of MedicineBackground: There are multiple stone types, each forming under different urinary conditions. We compared clinical and metabolic findings in pure stone formers to understand if there are consistent factors that differentiate these groups in terms of underlying etiology and potential for empiric treatment. Materials and Methods: Pure SFs based on infrared spectroscopic analysis of stones obtained at our institution between 01/2002 and 07/2018 with a corresponding 24-hour urinalysis were retrospectively evaluated. Results: 121 apatite, 54 brushite, 50 calcium oxalate dihydrate, 104 calcium oxalate monohydrate, and 82 uric acid patients were analyzed. Apatite, brushite, and calcium oxalate dihydrate patients were younger than calcium oxalate monohydrate and uric acid patients. Uric acid patients had the highest male predominance (76.8%), while apatite patients were predominantly female (80.2%). Uric acid was most associated with diabetes mellitus (45.3%), and calcium oxalate monohydrate with cardiovascular disease (27.2%) and malabsorptive gastrointestinal conditions (19.2%). Brushite patients had the highest prevalence of primary hyperparathyroidism (17%). Apatite, brushite, and calcium oxalate dihydrate patients demonstrated high rates of hypercalciuria (66.1%, 79.6%, 82%). Apatite and brushite patients had the highest urinary pH. Apatite patients exhibited the highest rate of hypocitraturia while calcium oxalate dihydrate patients exhibited the lowest (55.4%, 30%). Calcium oxalate monohydrate patients had the highest rate of hyperoxaluria (51.9%). Uric acid patients had the lowest urinary pH. There were no observable differences in the rates of hyperuricosuria or hypernatriuria. Conclusions: These results demonstrate that pure stone composition correlates with certain urinary and clinical characteristics. This data can help guide empiric clinical decision-making.Item Discrepancy Between Stone and Tissue Mineral Type in Patients with Idiopathic Uric Acid Stones(Liebert, 2020-03) Evan, Andrew P.; Coe, Fredric L.; Worcester, Elaine M.; Williams, James C., Jr.; Heiman, Joshua; Bledsoe, Sharon; Philips, Carrie L.; Lingeman, James E.; Anatomy and Cell Biology, School of MedicineObjectives: 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.Item Idiopathic hypercalciuria and formation of calcium renal stones(Nature Publishing group, 2016-09) Coe, Fredric L.; Worcester, Elaine M.; Evan, Andrew P.; Anatomy and Cell Biology, School of MedicineThe most common presentation of nephrolithiasis is idiopathic calcium stones in patients without systemic disease. Most stones are primarily composed of calcium oxalate and form on a base of interstitial apatite deposits, known as Randall’s plaque. By contrast some stones are composed largely of calcium phosphate, as either hydroxyapatite or brushite (calcium monohydrogen phosphate), and are usually accompanied by deposits of calcium phosphate in the Bellini ducts. These deposits result in local tissue damage and might serve as a site of mineral overgrowth. Stone formation is driven by supersaturation of urine with calcium oxalate and brushite. The level of supersaturation is related to fluid intake as well as to the levels of urinary citrate and calcium. Risk of stone formation is increased when urine citrate excretion is <400 mg per day, and treatment with potassium citrate has been used to prevent stones. Urine calcium levels >200 mg per day also increase stone risk and often result in negative calcium balance. Reduced renal calcium reabsorption has a role in idiopathic hypercalciuria. Low sodium diets and thiazide-type diuretics lower urine calcium levels and potentially reduce the risk of stone recurrence and bone diseasItem Initial Clinical Experience with Swiss LithoClast Trilogy During Percutaneous Nephrolithotomy(Liebert, 2019) Nottingham, Charles U.; Large, Tim; Cobb, Kaitlan; Sur, Roger L.; Canvasser, Noah; Stoughton, Christa L.; Krambeck, Amy E.; Urology, School of MedicineIntroduction and Objective: Current available lithotrites have clinical stone clearance rates averaging 24 to 32 mm2/minute. The objective of this study was to critically evaluate the initial experience with the Swiss LithoClast® Trilogy lithotrite during percutaneous nephrolithotomy (PCNL). Methods: We prospectively enrolled patients with a minimum of 15 mm of stone in axial diameter at three locations (Indiana University, University of California Davis, and University of California San Diego) scheduled to undergo PCNL for nephrolithiasis over a 60-day trial period. We assessed objective measures of stone clearance time, stone clearance rate, device malfunction, stone-free rate, and complications. Each surgeon also evaluated subjective parameters from each case related to the use of Trilogy on a 1 to 10 scale (10 = extremely effective), and compared it with their usual lithotrite on a 1 to 5 scale (5 = much better). Results: We included 43 patients and had 7 bilateral (16.3%) cases, for a total of 50 renal units. One case was a mini-PCNL. Two cases experienced device malfunctions requiring troubleshooting but no transition to another lithotrite. The mean stone clearance rate was 68.9 mm2/minute. The stone-free rate on postoperative imaging was 67.6% (25 of 37 patients with available imaging). The lowest subjective rating was the ergonomic score of 6.7, and the highest subjective rating was the ease of managing settings score of 9.2. The surgeon impressions of ultrasound (7.3), ballistics (8.1), combination of ultrasound and ballistics (8.7), and suction (8.4) were high. One patient experienced an intraoperative renal pelvis perforation, one patient required a blood transfusion, one patient had a pneumothorax requiring chest tube placement, and one patient had a renal artery pseudoaneurysm requiring endovascular embolization. Conclusions: This multi-institutional study evaluated a new and efficient combination lithotrite that was perceived by surgeons to be highly satisfactory, with an excellent safety and durability profile.Item Initial Experience with Novel Single-Use Disposable Ureteroscopy: A Prospective, Single Arm 90-Day Trial of the Axis Ureteroscope(AUA, 2021) Large, Tim; Rivera, Marcelino; Nottingham, Charles; Agarwal, Deepak; Mellon, Matthew; Krambeck, Amy; Urology, School of MedicineIntroduction: Novel digital disposable ureteroscopes are becoming more commonplace in endourological practices. We trialed the Axis™ single-use ureteroscope, which is distributed within the United States by Dornier MedTech. Our goal was to demonstrate clinical equivalence to our reusable platform and to evaluate the cost-effectiveness of a single-use digital ureteroscope. Methods: We conducted a prospective 90-day trial where all flexible ureteroscopic procedures were completed using the single-use ureteroscope. The cases were monitored for scope failure, scope deficiencies and surgeon satisfaction scores via an immediate postoperative REDCap® survey. We also performed a cost analysis between reusable scopes and the single-use ureteroscope. The cost of the reusable platform included the amortized initial purchase, maintenance and clean processing. Results: Over a 90-day period, we performed 93 flexible ureteroscopy procedures with a single-use ureteroscope, of which 74 were completed using Axis. After controlling for operating room time and disposable items used, the utilization of Axis was associated with an average reduction of $140.31 per case. Extrapolating the per-case savings over an annual case volume, we estimate a total savings of $56,127.15. There were no disposable scope malfunctions. There were 4 (4.3%) cases converted to reusable scopes due to image quality (1), inadequate secondary deflection (2) and a tight ureter (1). Mean±SD score for image quality, mobility and ergonomics was 9.1±1.1, 8.9±1.1, 9.3±1.1, respectively. The 90-day complication rates were equal to our controls. Conclusions: We demonstrated that the Axis single-use digital ureteroscope is equivalent in function to our digital reusable scope and reduced the cost of flexible ureteroscopy.Item Intronic deletions in the SLC34A3 gene: A cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria(Elsevier B.V., 2014-02) Ichikawa, Shoji; Tuchman, Shamir; Padgett, Leah R.; Gray, Amie K.; Baluarte, H. Jorge; Econs, Michael J.; Department of Medicine, IU School of MedicineHereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6 ½-year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24- hour urine calcium excretion with high serum calcium, low intact parathyroid hormone (PTH) levels, and elevated 1,25(OH)2D level. In addition, the patient had low to low-normal serum phosphorus with high urine phosphorus. The patient had normal stature; without rachitic or boney deformities or a history of fractures. Genetic analysis of SLC34A3 revealed the patient to be a compound heterozygote for a novel single base pair deletion in exon 12 (c.1304delG) and 30-base pair deletion in intron 6 (g.1440–1469del). The single-base pair mutation causes a frameshift, which results in premature stop codon. The intronic deletion is likely caused by misalignment of the 4-basepair homologous repeats and results in the truncation of an already small intron to 63 bp, which would impair proper RNA splicing of the intron. This is the fourth unique intronic deletion identified in patients with HHRH, suggesting the frequent occurrence of sequence misalignments in SLC34A3 and the importance of screening introns in patients with HHRH.Item Preoperative Bladder Urine Culture as a Predictor of Intraoperative Stone Culture Results: Clinical Implications and Relationship to Stone Composition(Elsevier, 2016-09) Paonessa, Jessica E.; Gnessin, Ehud; Bhojani, Bhojani; Williams, James C.; Lingeman, James E.; Anatomy and Cell Biology, School of MedicinePurpose 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.Item Preoperative Bladder Urine Culture as a Predictor of Intraoperative Stone Culture Results: Clinical Implications and Relationship to Stone Composition(Elsevier, 2016-09) Paonessa, Jessica E.; Gnessin, Ehud; Bhojani, Naeem; Williams, James C.; Lingeman, James E.; Anatomy and Cell Biology, School of MedicinePurpose 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.Item Salvage Percutaneous Nephrolithotomy: Analysis of Outcomes Following Initial Treatment Failure(Elsevier, 2016-04) Borofsky, Michael S.; Wollin, Daniel A.; Reddy, Thanmaya; Shah, Ojas; Assimos, Dean G.; Lingeman, James E.; Department of Urology, IU School of MedicinePurpose 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.Item Stone free outcomes of flexible ureteroscopy for renal calculi utilizing CT imaging(Elsevier, 2018) York, Nadya E.; Zheng, Mengmeng; Elmansy, Hazem M.; Rivera, Marcelino E.; Krambeck, Amy E.; Lingeman, James E.; Urology, School of MedicineObjectives To assess stone free rates following URS for renal calculi at our institution using low dose renal only CT (LDCT). 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 SFR 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 pre-operative stone size was 6.2mm 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: 1mm in 2% (7/288), 2-4 mm in 16% (46/288), and >4 mm in 9% of kidneys (26/288). Conclusions 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.