IU Indianapolis ScholarWorks :: Browsing by Subject "Nephrolithiasis"

Browsing by Subject "Nephrolithiasis"

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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 Medicine
PURPOSE: 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.
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 Medicine
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.
Comparison of cost-effectiveness and postoperative outcomes following integration of a stiff shaft glidewire into percutaneous nephrolithotripsy
(Sage, 2021-08-22) Valadon, Crystal; Abedali, Zain A.; Nottingham, Charles U.; Large, Tim; Krambeck, Amy E.; Urology, School of Medicine
Aims: To analyze the cost effectiveness of integrating a stiff shaft glidewire (SSGW) in percutaneous nephrolithotripsy (PCNL) relative to standard technique (ST). This is prudent because healthcare providers are experiencing increased pressure to improve procedure-related cost containment. Methods: ST for PCNL at our institution involves a hydrophilic glidewire during initial percutaneous access and then two new stiff shaft wires. The SSGW is a hydrophilic wire used for initial access and the remainder of the procedure. We collected operating room (OR) costs for all primary, unilateral PCNL cases over a 5-month period during which ST for PCNL was used at a single institution with a single surgeon and compared with a 6-month period during which a SSGW was used. Mean costs for each period were then compared along with stone-free rates and complications. Results: We included 17 total cases in the ST group and 22 in the SSGW group. The average operating room supply cost for the ST group was $1937.32 and $1559.39 in the SSGW group. The net difference of $377.93 represents a nearly 20% decrease in cost. This difference was statistically significant (p = 0.031). There was no difference in postoperative stone-free rates (82.4% versus 86.4%, p = 1.0, respectively) or complications (23.5% versus 13.6%, p = 0.677, respectively) between ST and SSGW groups. Conclusion: Transitioning to a SSGW has reduced OR supply cost by reducing the number of supplies required. The change in wire did not affect stone-free rates or complications.
Demineralization and sectioning of human kidney stones: A molecular investigation revealing the spatial heterogeneity of the stone matrix
(Wiley, 2021-01) Canela, Victor Hugo; Bledsoe, Sharon B.; Lingeman, James E.; Gerber, Glenn; Worcester, Elaine M.; El-Achkar, Tarek M.; Williams, James C., Jr.; Anatomy and Cell Biology, School of Medicine
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.
First-in-human clinical trial of ultrasonic propulsion of kidney stones
(First in Human Clinical Trial of Ultrasonic Propulsion of Kidney Stones, 2016-04) Harper, Jonathan D.; Cunitz, Bryan W.; Dunmire, Barbrina; Lee, Franklin C.; Sorensen, Mathew D.; Hsi, Ryan S.; Thiel, Jeff; Wessells, Hunter; Lingeman, James E.; Bailey, Michael R.; Urology, School of Medicine
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.
Human jackstone arms show a protein-rich, X-ray lucent core, suggesting that proteins drive their rapid and linear growth
(Springer, 2022) Canela, Victor Hugo; Dzien, Cornelius; Bledsoe, Sharon B.; Borofsky, Michael S.; Boris, Ronald S.; Lingeman, James E.; El-Achkar, Tarek M.; Williams, James C., Jr.; Anatomy, Cell Biology and Physiology, School of Medicine
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.
In Vivo Entombment of Bacteria and Fungi during Calcium Oxalate, Brushite, and Struvite Urolithiasis
(Wolters Kluwer, 2020-12-23) Saw, Jessica J.; Sivaguru, Mayandi; Wilson, Elena M.; Dong, Yiran; Sanford, Robert A.; Fields, Chris J.; Cregger, Melissa A.; Merkel, Annette C.; Bruce, William J.; Weber, Joseph R.; Lieske, John C.; Krambeck, Amy E.; Rivera, Marcelino E.; Large, Timothy; Lange, Dirk; Bhattacharjee, Ananda S.; Romero, Michael F.; Chia, Nicholas; Fouke, Bruce W.; Urology, School of Medicine
Background: Human kidney stones form via repeated events of mineral precipitation, partial dissolution, and reprecipitation, which are directly analogous to similar processes in other natural and manmade environments, where resident microbiomes strongly influence biomineralization. High-resolution microscopy and high-fidelity metagenomic (microscopy-to-omics) analyses, applicable to all forms of biomineralization, have been applied to assemble definitive evidence of in vivo microbiome entombment during urolithiasis. Methods: Stone fragments were collected from a randomly chosen cohort of 20 patients using standard percutaneous nephrolithotomy (PCNL). Fourier transform infrared (FTIR) spectroscopy indicated that 18 of these patients were calcium oxalate (CaOx) stone formers, whereas one patient formed each formed brushite and struvite stones. This apportionment is consistent with global stone mineralogy distributions. Stone fragments from seven of these 20 patients (five CaOx, one brushite, and one struvite) were thin sectioned and analyzed using brightfield (BF), polarization (POL), confocal, super-resolution autofluorescence (SRAF), and Raman techniques. DNA from remaining fragments, grouped according to each of the 20 patients, were analyzed with amplicon sequencing of 16S rRNA gene sequences (V1-V3, V3-V5) and internal transcribed spacer (ITS1, ITS2) regions. Results: Bulk-entombed DNA was sequenced from stone fragments in 11 of the 18 patients who formed CaOx stones, and the patients who formed brushite and struvite stones. These analyses confirmed the presence of an entombed low-diversity community of bacteria and fungi, including Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, and Aspergillus niger. Bacterial cells approximately 1 μm in diameter were also optically observed to be entombed and well preserved in amorphous hydroxyapatite spherules and fans of needle-like crystals of brushite and struvite. Conclusions: These results indicate a microbiome is entombed during in vivo CaOx stone formation. Similar processes are implied for brushite and struvite stones. This evidence lays the groundwork for future in vitro and in vivo experimentation to determine how the microbiome may actively and/or passively influence kidney stone biomineralization.
In Vivo Renal Tubule pH in Stone-Forming Human Kidneys
(Mary Ann Liebert, Inc., 2020-02) Borofsky, Michael S.; Handa, Rajash K.; Evan, Andrew P.; Williams, James C., Jr.; Bledsoe, Sharon; Coe, Fredric L.; Worcester, Elaine M.; Lingeman, James E.; Urology, School of Medicine
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.
Incidence of Emergency Department Presentations of Symptomatic Stone Disease in Pediatric Patients: A Southeastern Study
(Springer Nature, 2022-11-01) Zhang, Shirley Y.; Collingwood, Joshua D.; Fujihashi, Ayaka; He, Kai; Oliver, Lauren A.; Dangle, Pankaj; Pediatrics, School of Medicine
Background: The incidence of nephrolithiasis during childhood has increased significantly over recent decades. Some studies indicate a rapid rise in adolescents, particularly in African American women. This study serves to identify trends in symptomatic pediatric nephrolithiasis presentations to the emergency department (ED) as a result of increasing incidence and to determine associations between demographic variables at our single-site tertiary pediatric hospital in the Southeast United States. Methods: After IRB approval, a review of the data provided by the Pediatric Health Information System, a pediatric database that includes clinical and resource utilization data for 51 of the largest children’s hospitals in the nation, yielded 644 pediatric occurrences of nephrolithiasis at single-site emergency departments from 2006 to 2020. The percent change and average percent change in three-year intervals were calculated to establish a trend over time. A chi-square test of independence was performed to assess associations between race, gender, and age groups. Results: A total of 780 stone occurrences and associated patient demographic data were reviewed for 644 children (364, 56.52% female) with median age of 183 ± 45.11 months (9-397 months). Of the 644 children, 79 (12.3%) were noted to have recurrent symptomatic nephrolithiasis, contributing to 136/780 stone events. There was a marked increase of 84.4% in confirmed pediatric nephrolithiasis occurrences over 15 years, with an average percent increase of 16.1% every three years. A Chi2 test of independence was performed between gender and age group (>/< 10yr), gender and race, and race and age group. No expected cell frequencies were less than five. There is no statistically significant relationship between gender and age group, χ2 (1, N=644) = 3.30, p=0.692. There is no significant association between race (Caucasian vs. non-Caucasian) and age group (>/< 10yr), χ2 (1, N=644) = 0.393, p=0.531. There is a statistically significant relationship between gender and race (Caucasian vs. non-Caucasian), χ2 (1, N=644) = 5.28, p=0.021. Caucasian females were more likely to present to our tertiary pediatric hospital’s emergency department with nephrolithiasis than Caucasian males or non-Caucasian males or females. Additionally, our data reflected a greater percentage of symptomatic nephrolithiasis presentations occurred in the second decade of life (85.4% vs 14.3%, 552 vs 92 stone events). Conclusion: Based on our data, there is a marked increase of 84.4% in pediatric nephrolithiasis occurrences from 2006 to 2020, with a mean increase of 16.1% every three years at our single-site tertiary referral pediatric hospital in the Southeast. Among demographic groups, white adolescent females have an increased risk of developing kidney stones.
Integration and utilization of modern technologies in nephrolithiasis research
(Nature Publishing Group, 2016-09) Borofsky, Michael S.; Dauw, Casey A.; Cohen, Andrew; Williams, James C., Jr.; Evan, Andrew P.; Lingeman, James E.; Urology, School of Medicine
Nephrolithiasis, or stones, is one of the oldest urological diseases, with descriptions and treatment strategies dating back to ancient times. Despite the enormous number of patients affected by stones, a surprising lack of conceptual understanding of many aspects of this disease still exists. This lack of understanding includes mechanisms of stone formation and retention, the clinical relevance of different stone compositions and that of formation patterns and associated pathological features to the overall course of the condition. Fortunately, a number of new tools are available to assist in answering such questions. New renal endoscopes enable kidney visualization in much higher definition than was previously possible, while micro-CT imaging is the optimal technique for assessment of stone microstructure and mineral composition in a nondestructive fashion. Together, these tools have the potential to provide novel insights into the aetiology of stone formation that might unlock new prevention and treatment strategies, and enable more effective management of patients with nephrolithiasis.

Browsing by Subject "Nephrolithiasis"

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