Browsing by Author "Lingeman, James E."
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Item A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease(Nature, 2023-07-19) Canela, Victor Hugo; Bowen, William S.; Ferreira, Ricardo Melo; Syed, Farooq; Lingeman, James E.; Sabo, Angela R.; Barwinska, Daria; Winfree, Seth; Lake, Blue B.; Cheng, Ying-Hua; Gaut, Joseph P.; Ferkowicz, Michael; LaFavers, Kaice A.; Zhang, Kun; Coe, Fredric L.; Worcester, Elaine; Jain, Sanjay; Eadon, Michael T.; Williams, James C., Jr.; El-Achkar, Tarek M.; Urology, School of MedicineKidney 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.Item Accuracy of Daily Fluid Intake Measurements Using a "Smart" Water Bottle(Springer, 2017) Borofsky, Michael S.; Dauw, Casey A.; York, Nadya; Terry, Colin; Lingeman, James E.; Urology, School of MedicineHigh 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.Item Addition of Sodium Bicarbonate to Irrigation Solution May Assist in Dissolution of Uric Acid Fragments During Ureteroscopy(Liebert, 2018) Paonessa, Jessica E.; Williams, James C., Jr.; Lingeman, James E.; Urology, School of MedicineIntroduction: 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.Item ALLN-177, oral enzyme therapy for hyperoxaluria(Springer Nature, 2019-04) Lingeman, James E.; Pareek, Gyan; Easter, Linda; Pease, Rita; Grujic, Danica; Brettman, Lee; Langman, Craig B.; Urology, School of MedicinePURPOSE: To evaluate the potential of ALLN-177, an orally administered, oxalate-specific enzyme therapy to reduce urine oxalate (UOx) excretion in patients with secondary hyperoxaluria. METHODS: Sixteen male and female subjects with both hyperoxaluria and a kidney stone history were enrolled in an open-label study. Subjects continued their usual diets and therapies. During a 3-day baseline period, two 24-h (24-h) urines were collected, followed by a 4-day treatment period with ALLN-177 (7,500 units/meal, 3 × day) when three 24-h urines were collected. The primary endpoint was the change in mean 24-h UOx from baseline. Safety assessments and 24-h dietary recalls were performed throughout. RESULTS: The study enrolled 5 subjects with enteric hyperoxaluria and 11 with idiopathic hyperoxaluria. ALLN-177 was well tolerated. Overall mean (SD) UOx decreased from 77.7 (55.9) at baseline to 63.7 (40.1) mg/24 h while on ALLN-177 therapy, with the mean reduction of 14 mg/24 h, (95% CI - 23.71, - 4.13). The calcium oxalate-relative urinary supersaturation ratio in the overall population decreased from a mean of 11.3 (5.7) to 8.8 (3.8) (- 2.8; 95% CI - 4.9, - 0.79). This difference was driven by oxalate reduction alone, but not any other urinary parameters. Mean daily dietary oxalate, calcium, and fluid intake recorded by frequent diet recall did not differ by study periods. CONCLUSION: ALLN-177 reduced 24-h UOx excretion, and was well tolerated. The results of this pilot study provided justification for further investigation of ALLN-177 in patients with secondary hyperoxaluria.Item Association Between Randall's Plaque Stone Anchors and Renal Papillary Pits(Mary Ann Liebert, 2019-04-01) Borofsky, Michael S.; Williams, James C., Jr.; Dauw, Casey A.; Cohen, Andrew; Evan, Andrew C.; Coe, Fredric L.; Worcester, Elaine; Lingeman, James E.; Anatomy and Cell Biology, School of MedicineIntroduction: 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.Item Biopsy proven medullary sponge kidney: clinical findings, histopathology, and role of osteogenesis in stone and plaque formation(John Wiley & Sons, Inc., 2015-05) Evan, Andrew P.; Worcester, Elaine M.; Williams, James C., Jr.; Sommer, Andre J.; Lingeman, James E.; Phillips, Carrie L.; Coe, Fredric L.; Department of Anatomy & Cell Biology, IU School of MedicineMedullary 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.Item The Circle Nephrostomy Tube: An Attractive Nephrostomy Drainage System Following Complex Percutaneous Nephrolithotomy(Elsevier, 2017-05) El Tayeb, Marawan M.; Borofsky, Michael S.; Lingeman, James E.; Urology, School of MedicineObjective 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.Item COEXISTING PROSTATE CANCER FOUND AT THE TIME OF HOLMIUM LASER ENUCLEATION OF THE PROSTATE FOR BENIGN PROSTATIC HYPERPLASIA: PREDICTING ITS PRESENCE AND GRADE IN ANALYZED TISSUE(Liebert, 2015-01) Bhojani, Naeem; Boris, Ronald S.; Monn, M. Francesca; Mandeville, Jessica A.; Lingeman, James E.; Department of Urology, IU School of MedicineObjective: To determine the incidence of prostate cancer identified on holmium laser enucleation of the prostate (HoLEP) specimens and evaluate variables associated with prostate cancer identification. Patients and Methods: All patients undergoing HoLEP between 1998 and 2013 were identified. Patients with a known history of prostate cancer were excluded. Multivariable logistic regression assessed variables associated with identification of prostate cancer on HoLEP specimens and Gleason 7 or higher prostate cancer among the malignant cases. The Gleason grade was used as a proxy for disease severity. Each of the models was adjusted for age, preoperative prostate-specific antigen (PSA), and HoLEP specimen weight. Results: The cohort comprised 1272 patients, of whom 103 (8.1%) had prostate cancer identified. Prostate cancer cases had higher pre-HoLEP PSA (p=0.06) but lower HoLEP specimen weight (p=0.01). On multivariate logistic regression, age and preoperative PSA were associated with increased odds of prostate cancer being present (p<0.01 each), while increasing HoLEP specimen weight was associated with decreased odds of prostate cancer (p<0.001). Men older than 80 had 20% predicted probability of being diagnosed with prostate cancer. Seventy-eight percent of prostate cancer cases were Gleason 6 or less. The pre-HoLEP PSA was associated with increased adjusted odds of intermediate- or high-grade prostate cancer. Conclusion: Prostate cancer identified by HoLEP is not uncommon, but is generally a low-risk disease. Older patients with smaller prostate glands have the highest odds of prostate cancer identification.Item Collagen fibrils and cell nuclei are entrapped within Randall's plaques but not in CaOx matrix overgrowth: A microscopic inquiry into Randall's plaque stone pathogenesis(Wiley, 2022) Canela, Victor Hugo; Bledsoe, Sharon B.; Worcester, Elaine M.; Lingeman, James E.; El-Achkar, Tarek M.; Williams, James C., Jr.; Anatomy, Cell Biology and Physiology, School of MedicineCalcium 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.Item Comparison of Perioperative Outcomes Between Holmium Laser Enucleation of the Prostate and Robot-Assisted Simple Prostatectomy(Liebert, 2017-09) Zhang, Mimi W.; El Tayeb, Marawan M.; Borofsky, Michael S.; Dauw, Casey A.; Wagner, Kristofer R.; Lowry, Patrick S.; Bird, Erin T.; Hudson, Tillman C.; Lingeman, James E.; Urology, School of MedicineObjectives: To compare perioperative outcomes for patients undergoing holmium laser enucleation of the prostate (HoLEP) and robotic-assisted simple prostatectomy (RSP) for benign prostatic hypertrophy (BPH).Methods: Patient demographics and perioperative outcomes were compared between 600 patients undergoing HoLEP and 32 patients undergoing RSP at two separate academic institutions between 2008 and 2015.Results: Patients undergoing HoLEP and RSP had comparable ages (71 vs 71, p = 0.96) and baseline American Urological Association Symptom Scores (20 vs 24, p = 0.21). There was no difference in mean specimen weight (96 g vs 110 g, p = 0.15). Mean operative time was reduced in the HoLEP cohort (103 minutes vs 274 minutes, p < 0.001). Patients undergoing HoLEP had lesser decreases in hemoglobin, decreased transfusions rates, shorter hospital stays, and decreased mean duration of catheterization. There was no difference in the rate of complications Clavien grade 3 or greater (p = 0.33).Conclusions: HoLEP and RSP are both efficacious treatments for large gland BPH. In expert hands, HoLEP appears to have a favorable perioperative profile. Further studies are necessary to compare long-term efficacy, cost, and learning curve influences, especially as minimally invasive approaches become more widespread.