No description available.

4 pp. / Calcium is an essential mineral found in great abundance in the body. Ninety-nine percent of all the calcium in the body is found in the bones and teeth. The remaining one percent is in the blood. Calcium plays important roles in nerve conduction, muscle contraction, and blood clotting. If calcium levels in the blood drop below normal, calcium will be taken from bone and put into the blood in order to maintain blood calcium levels. Therefore, it is important to consume enough calcium to maintain adequate blood and bone calcium levels. Revised 2017, Revised 2011, Original 2004

INTRODUCTION: The incidence of pediatric nephrolithiasis (kidney stones) has been increasing over the past several years. While environmental factors, such as poor fluid intake, high-salt diet, and obesity, can play a role, underlying metabolic factors account for at least one-third of cases of nephrolithiasis. Nephrolithiasis and related disorders, such as nephrocalcinosis and hypercalciuria, can lead to long-term kidney problems, including renal scarring, acute and chronic kidney disease, decreased renal function, or end-stage renal disease. The best treatment is prevention and is best guided by knowing the underlying cause. The majority of kidney stones are primarily comprised of calcium, and abnormal calcium metabolism and regulation can lead to nephrolithiasis, nephrocalcinosis, and hypercalciuria. Vitamin D is an important factor in calcium regulation in the body. The physiologically active form of vitamin D is 1α,25-dihydroxyvitamin D (1,25(OH)2D), which increases serum calcium by stimulating intestinal absorption of calcium, increasing renal calcium reabsorption, and mobilizing calcium from bone. Excess 1,25(OH)2D has been shown to be associated with hyperabsorption of calcium in the intestine, nephrolithiasis, hypercalcemia, and hypercalciuria. Production of 1,25(OH)2D requires hydroxylation of 25-hydroxyvitamin D by the kidney enzyme 1α-hydroxylase, which is regulated in turn by serum calcium, parathyroid hormone (PTH), and by 1,25(OH)2D itself. Tight control of 1,25(OH)2D levels is maintained in part by the breakdown of 1,25(OH)2D by the enzyme 24-hydroxylase, which is encoded by the gene CYP24A1. In the past few years, CYP24A1 mutations leading to decreased activity of 24-hydroxylase have been implicated in some cases of idiopathic infantile hypercalcemia as well as nephrolithiasis, nephrocalcinosis, and hypercalciuria. The prevalence of 24-hydroxylase deficiency is not known, and the spectrum of its clinical manifestations is not yet fully understood. Our study aims to describe the clinical characteristics of patients with laboratory findings suggestive of 24-hydroxylase deficiency, specifically high-normal or elevated serum 1,25(OH)2D. We aimed to determine the prevalence of elevated 1,25(OH)2D among pediatric patients with nephrolithiasis, and to compare clinical outcomes and biochemical findings in patients with normal versus elevated 1,25(OH)2D. PATIENTS AND METHODS: This study was a retrospective chart review. To determine the prevalence of high-normal (56-75 pg/mL) and high (>75 pg/mL) serum 1,25(OH)2D, we reviewed electronic medical records of patients seen in the Boston Children's Hospital Stone Clinic. We identified 346 patients who were evaluated for nephrolithiasis, were under 18 years of age at the time of presentation, and had at least one measurement of 1,25(OH)2D. Patients were classified based on their highest measured level of 1,25(OH)2D. To determine the clinical characteristics of patients with elevated 1,25(OH)2D, we reviewed clinical records and laboratory data of patients at Boston Children's Hospital with a diagnosis of nephrolithiasis, nephrocalcinosis, or hypercalciuria. We identified 83 patients who met our inclusion criteria: age of onset <18 years, at least one measurement of 1,25(OH)2D, and a pre-treatment urine solute analysis. Data collected included demographic information, diagnoses, family history of kidney disease, treatments, laboratory data, and urine solute analyses. We compared findings in patients with normal 1,25(OH)2D (≤55 pg/mL) versus elevated 1,25(OH)2D (>55 pg/mL). RESULTS: Of 346 children with nephrolithiasis in whom 1,25(OH)2D was measured, 100 (28.9%) had high 1,25(OH)2D, and an additional 120 (34.7%) had high-normal 1,25(OH)2D. To determine the clinical characteristics of elevated 1,25(OH)2D, we analyzed the data of 40 patients with normal 1,25(OH)2D and 43 patients with elevated 1,25(OH)2D who had a history of nephrolithiasis, nephrocalcinosis, or hypercalciuria. Seventy-five children had nephrolithiasis, and 25/37 (67.6%) of children with elevated 1,25(OH)2D had a recurrence of nephrolithiasis, compared to only 9/38 (23.7%) of children with normal 1,25(OH)2D (p < .001). Urine calcium/creatinine ratio did not differ between the two groups. However, linear regression analysis showed an association between 1,25(OH)2D levels and urine calcium/creatinine ratio. Important secondary findings included a younger age of onset, higher serum 25-hydroxyvitamin D, and lower parathyroid hormone levels in patients with elevated 1,25(OH)2D. CONCLUSIONS: Important clinical findings of this study were the increased rate of recurrence and the younger age of onset in patients with elevated 1,25(OH)2D. While we recognize that mutations in CYP24A1 do not account for the majority of cases of elevated 1,25(OH)2D, we do advocate for special consideration for these patients. In the absence of a commercially-available assay for 24-hydroxylase activity, children with nephrolithiasis, nephrocalcinosis, or hypercalciuria and elevated 1,25(OH)2D should be closely monitored for recurrence or worsening of symptoms. Furthermore, we advise caution in the use of vitamin D repletion in at-risk patients.

Nephrolithiasis can be a painful problem due to presence of kidney stones. Kidney stone is among the common painful disorders of the urinary system. Various imaging modalities are used to diagnose patients with symptoms of renal or urinary tract disease such as plain kidney, ureter, bladder x-ray (KUB), intravenous pyelography (IVP), and computed tomography (CT). As a traditional three-dimensional (3D) nephrolithiasis and kidney stones detection technique, computed tomography (CT) provides detailed cross-sectional images as well as 3D structure of kidney from moving the x-ray beam in a circle around the body. However, the risk of CT scans of the kidney is relatively higher exposure to radiation which is more than regular x-rays. C-arm technique is a new x-ray imaging modality that uses 2D array detector and cone shaped x-ray beam to create 3D information about the scanned object. Both x-ray source and 2D array detector cells mounted on C-shaped wheeled structure (C-arm). A series of projection images are acquired by rotating the C-arm around the patient in along circular path with a single rotation. The characteristic structure of C-arm allows to provide wide variety of movements around the patient that helps to remain the patient stationary during scanning time. In this work, we investigated a C-arm technique to generate a series of tomographic images for nephrolithiasis and detection of kidney stones. C-arm tomographic technique (C-arm tomosynthesis) as a new three dimensional (3D) kidney imaging method that provides a series of two dimensional (2D) images along partial circular orbit over limited view angle. Our experiments were done with kidney phantom which formed from a pig kidney with two embedded kidney stones inside it and low radiation dosage. Radiation dose and scanning time needed for kidney imaging are all dramatically reduced due to the cone beam geometry and also to limitation of angular rotation. To demonstrate the capability of our C-arm tomosynthesis to generate 3D kidney information for kidney stone detection, two groups of tomographic image reconstruction algorithms were developed for C-arm tomosynthesis: direct algorithms such as filtered back projection (FBP) and iterative algorithms such as simultaneous algebraic reconstruction technique (SART), maximum likelihood expectation maximization (MLEM), ordered- subset maximum likelihood expectation maximization (OS-MLEM) and Pre-computed penalized likelihood reconstruction (PPL). Three reconstruction methods were investigated including: pixel-driven method (PDM), ray-driven method (RDM) and distance driven method (DDM). Each method differs in their efficiency of calculation accuracy per computing time. Preliminary results demonstrated the capability of proposed technique to generate volumetric data about the kidney for nephrolithiasis and kidney stone detection by using all investigated reconstruction algorithms. In spite of each algorithms differs in their strategies, embedded kidney stone can be clearly visualized in all reconstruction results. Computer simulation studies were also done on simulated phantom to evaluate the results for each reconstruction algorithm. To mimic kidney phantom, simulated phantom was simulated with two different size kidney stones. Dataset of projection images was collated by using a virtual C-arm tomosynthesis with geometric configuration similar to real technique. All investigated algorithms were used to reconstruct 3D information. Different of image quality functions were applied to evaluate the imaging system and the reconstruction algorithms. The results show the capability of C-arm tomosynthesis to generate 3D information of kidney structures and to identify the size and location of kidney stones with limited amount of radiation dose.

Background: Kidney stones are a common, painful disorder that can affect as many as one of 11 people in the United States (Goldfarb & Arowojolu, 2013). The gold standard for diagnosing kidney stones is currently computed tomography (CT). However, because CT scans emit radiation during the exam, they could be causing more harm than good. According to recent research, ultrasound may be used to diagnose kidney stones with close to similar accuracy and reliability. Ultrasounds are also safer and more cost effective for patients and the healthcare system. Purpose: The purpose of this project is to describe nurse practitioners (NPs) use of ultrasound to diagnose kidney stones in the emergency department (ED). The information from this project was compared with the recent literature and used to develop an evidence-based practice recommendation for diagnosing suspected kidney stones in the ED. Methods: A 15-item survey was mailed to emergency department NPs across the United States. Descriptive statistics were used to analyze the quantitative results. One open-ended question was also posed, and findings were grouped by commonalities of clinical experiences. Results: Analysis of survey responses indicates that all of the respondents use CT scan to diagnose kidney stones. However, the majority of the respondents also feel that ultrasound could be used in the ED to diagnose kidney stones. The results also demonstrate that even though there is no nationally or internationally accepted standardized guideline for diagnosing kidney stones in the ED, many EDs across the country are instituting their own protocols.

Indiana University-Purdue University Indianapolis (IUPUI) / Nephrolithiasis will affect one-in-eleven people, and more than half of those individuals will have stone recurrence within a decade of their first episode. Despite decades of biomedical research on nephrolithiasis and extraordinary advances in molecular and cell biology, the precise mechanisms of kidney stone formation are not fully understood. Currently, there are limited treatments or preventative measures for nephrolithiasis. Therefore, it is crucial to scrutinize kidney stones from a molecular and cell biology perspective to better understand its pathogenesis and pathophysiology; and to, hereafter, contribute to effective therapeutic targets and preventative strategies. Kidney stones are composed of an admixture of crystal aggregated material and an organic matrix. 80% of all kidney stones are composed of calcium oxalate (CaOx) and half of all CaOx patients grow their stones on to Randall’s plaques (RP). RP are interstitial calcium phosphate mineral deposits in the renal papilla. Thus, we developed and optimized methodologies to directly interrogate CaOx stones. CaOx stones were demineralized, sectioned, and imaged by microscopy, utilizing micro CT for precise orientation. Laser microdissection (LMD) of specific regions of stone matrix analyzed by proteomics revealed various proteins involved in inflammation and the immune response. Analyses on jackstone calculi, having arm protrusions that extend out from the body of the stone, revealed that they are a rare subtype of CaOx stone formation. Micro CT analyses on 98 jackstones showed a radiolucent, organic-rich core in the arm protrusions. Fluorescence imaging on RP stones showed consistent differences in autofluorescence patterns between RP and CaOx overgrowth regions. Moreover, cell nuclei were discovered with preserved morphology in RP regions, along with variable expressions of vimentin and CD45. In comparing spatial transcriptomic expression of reference and CaOx kidney papillae, CaOx patients differentially expressed genes associated with pathways of immune cell activation, reactive oxygen damage and injury, extracellular remodeling, and ossification. Our findings provide novel methodologies to better understand the role of molecules and cells in CaOx stone matrix. Several of the proteins and cells identified in these studies may serve as potential biomarkers, and future therapeutic targets in preventing kidney stone disease.

No description available.

A population based cross-sectional time series analysis was conducted using three Ontario administrative databases, to assess trends over time in the surgical management of kidney stone disease. All kidney stone treatments performed with extracorporeal shockwave lithotripsy (SWL), ureteroscopy (URS) and percutaneous nephrolithotomy between July 1, 1991 and December 31, 2010, were included. Time series modeling with exponential smoothing and autoregressive integrated moving average models demonstrated a significant increase in the utilization of URS over time (23.69% to 59.98%, p<0.0001), with a reciprocal significant decrease in the utilization of SWL (68.77% to 33.36%, p<0.0001). As a result of this shift in treatment paradigm, time series modeling also demonstrated an associated significant decrease in the need for ancillary treatment over time (22.12% to 16.01%, p<0.0001) and a significant increase in the need for hospital readmission (8.01% to 10.85%, p<0.0001) or emergency room visit (7.58% to 9.95%, p=0.0024) within 7 days following treatment.

A population based cross-sectional time series analysis was conducted using three Ontario administrative databases, to assess trends over time in the surgical management of kidney stone disease. All kidney stone treatments performed with extracorporeal shockwave lithotripsy (SWL), ureteroscopy (URS) and percutaneous nephrolithotomy between July 1, 1991 and December 31, 2010, were included. Time series modeling with exponential smoothing and autoregressive integrated moving average models demonstrated a significant increase in the utilization of URS over time (23.69% to 59.98%, p<0.0001), with a reciprocal significant decrease in the utilization of SWL (68.77% to 33.36%, p<0.0001). As a result of this shift in treatment paradigm, time series modeling also demonstrated an associated significant decrease in the need for ancillary treatment over time (22.12% to 16.01%, p<0.0001) and a significant increase in the need for hospital readmission (8.01% to 10.85%, p<0.0001) or emergency room visit (7.58% to 9.95%, p=0.0024) within 7 days following treatment.

<p>The primary goal of this dissertation was to assess the feasibility of transforming an electromagnetic (EM) shock wave lithotripter with an acoustic lens as its focusing device from the original axisymmetric pressure distribution to a non-axisymmetric steerable acoustic field. This work was motivated by the desire to better match the distribution of effective acoustic pressure and pulse energy with the trajectory and anatomical features around renal and ureteral calculi during clinical shock wave lithotripsy (SWL). The acoustic field transformation was accomplished by the design of a fan-shaped acoustic barrier (mask) placed on top of the lithotripter acoustic lens to selectively reduce the source aperture along the direction of the barrier axis, therefore effectively broadening the beam width (<italic>BW</italic>) of the lithotripter field in this preferred direction. Moreover, the geometry of the original lens (L₁) was modified so that the acoustic focus of the new lens (L₂) at high output voltages (necessitated by the incorporation of the mask) is closely aligned with the lithotripter focus. The mask was further driven by a motor-controlled gear system to rotate around the lithotripter axis, generating a steerable and non-axisymmetric acoustic field. In this dissertation project, a linear acoustic model was first used for parametric studies to assess the effects of mask geometry (opening angle and thickness) on beam elongation and peak pressure reduction. Based on this analysis, two mask geometries (L₂+M₈₀₂₅ and L₂+M₉₀₃₀) were selected for modest and maximum beam elongation within the acceptable output range of the shock wave source. The acoustic and cavitation fields of the new lens with masks, as well as the corresponding field produced by the original lens, were characterized using fiber optical probe hydrophone measurements and stereoscopic high-speed imaging. Different output voltage settings were used for each lens configuration (i.e., 14 kV for L₁, 15.8 kV for L₂+M₈₀₂₅, and 17 kV L₂+M₉₀₃₀) to produce equivalent acoustic pulse energy of 45 mJ in all setups, measured in the lithotripter focal plane. Under this condition, L₂+M₈₀₂₅ and L₂+M₉₀₃₀ generate lower peak pressure (38.2 and 36.8 MPa) with a significantly broadened BW_y (11.4 and 14.3 mm) along the y-axis (head-to-toe direction of the patient), which is aligned with the mask axis, compared to the high peak pressure (44.1 MPa) and moderate <italic>BW</italic> (7.5 mm) of L₁. It is worth noting that L₂+M₈₀₂₅ and L₂+M₉₀₃₀ produce a <italic>BW</italic>_x (7.6 and 7.5 mm) in the orthogonal direction to the mask axis, which is also comparable to L₁. Similarly, the beam width of the cavitation field was broadened from 8.1 to 12.2 mm for L₂+M₈₀₂₅, and from 10.9 to 17.9 mm for L₂+M₉₀₃₀, compared to the range of 8.8 to 9.4 mm measured from L₁. In comparison, L₂+M₈₀₂₅ produces a denser and narrower bubble cloud along the y-axis than L₂+M₉₀₃₀. In vitro stone comminution (<italic>SC</italic>) tests in a tube holder (Diameter = 14 mm) have demonstrated that L₂+M₈₀₂₅ and L₂+M₉₀₃₀ are more effective at off-axis positions and during simulated respiratory motion along the elongated beam direction. The results of <italic>SC</italic> also confirmed the correlation between <italic>SC</italic> and the average peak pressure, p_+(avg), and effective acoustic pulse energy, E_eft, delivered to the stone, as shown in previous studies. Furthermore, a ureter model was developed and used to assess the performance of L₂+M₉₀₃₀, which has the maximally elongated <italic>BW</italic> under various static and simulated respiratory motion conditions. The results suggest that L₂+M₉₀₃₀ can produce significantly better <italic>SC</italic> than L₁ when the elongated beam is effectively aligned with the stone/fragments in the ureter or with their motion trajectory during the course of SWL treatment. Altogether, the results of this dissertation work have demonstrated <italic>in vitro</italic> that a non-axisymmetric and steerable acoustic field can significantly enhance stone comminution under clinically relevant SWL conditions. Future work is warranted to optimize the mask design and steering protocol to maximize the benefit of such an adaptable and versatile design to improve the performance and safety of clinical EM lithotripters.</p> / Dissertation