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.
Removal of small, asymptomatic kidney stones during surgery to remove ureteral or contralateral stones resulted in less relapse than nonremoval and in similar numbers of subsequent emergency ...department visits.
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 preoperative stone cultures in almost a quarter of cases. There has been a notable shift toward gram-positive organisms in this cohort of patients.
Shock wave lithotripsy (SWL) is the only noninvasive method for stone removal. Once considered as a primary option for the treatment of virtually all stones, SWL is now recognized to have important ...limitations that restrict its use. In particular, the effectiveness of SWL is severely limited by stone burden, and treatment with shock waves carries the risk of acute injury with the potential for long-term adverse effects. Research aiming to characterize the renal response to shock waves and to determine the mechanisms of shock wave action in stone breakage and renal injury has begun to suggest new treatment strategies to improve success rates and safety. Urologists can achieve better outcomes by treating at slower shock wave rate using a step-wise protocol. The aim is to achieve stone comminution using as few shock waves and at as low a power level as possible. Important challenges remain, including the need to improve acoustic coupling, enhance stone targeting, better determine when stone breakage is complete, and minimize the occurrence of residual stone fragments. New technologies have begun to address many of these issues, and hold considerable promise for the future.
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.
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.
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.
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.
Stone analysis is a critical part of the clinical characterization of urolithiasis. This article reviews the strengths and limitations of micro CT in the analysis of stones. Using micro CT alone in a ...series of 757 stone specimens, micro CT identified the 458 majority calcium oxalate specimens with a sensitivity of 99.6% and specificity of 95.3%. Micro CT alone was also successful in identifying majority apatite, brushite, uric acid, and struvite stones. For some minor minerals-such as apatite in calcium oxalate or calcium salts in uric acid stones-micro CT enables the detection of minute quantities well below 1%. The addition of a standard for calibrating X-ray attenuation values improves the ability of micro CT to identify common stone minerals. The three-dimensional nature of micro CT also allows for the visualization of surface features in stones, which is valuable for the study of stone formation.
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.
Mechanisms of human kidney stone formation Evan, Andrew P.; Worcester, Elaine M.; Coe, Fredric L. ...
Urolithiasis,
01/2015, Letnik:
43, Številka:
Suppl 1
Journal Article
Recenzirano
Odprti dostop
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.
Abstract Context The introduction of new lithotripters has increased problems associated with shock wave application. Recent studies concerning mechanisms of stone disintegration, shock wave ...focusing, coupling, and application have appeared that may address some of these problems. Objective To present a consensus with respect to the physics and techniques used by urologists, physicists, and representatives of European lithotripter companies. Evidence acquisition We reviewed recent literature (PubMed, Embase, Medline) that focused on the physics of shock waves, theories of stone disintegration, and studies on optimising shock wave application. In addition, we used relevant information from a consensus meeting of the German Society of Shock Wave Lithotripsy. Evidence synthesis Besides established mechanisms describing initial fragmentation (tear and shear forces, spallation, cavitation, quasi-static squeezing), the model of dynamic squeezing offers new insight in stone comminution. Manufacturers have modified sources to either enlarge the focal zone or offer different focal sizes. The efficacy of extracorporeal shock wave lithotripsy (ESWL) can be increased by lowering the pulse rate to 60–80 shock waves/min and by ramping the shock wave energy. With the water cushion, the quality of coupling has become a critical factor that depends on the amount, viscosity, and temperature of the gel. Fluoroscopy time can be reduced by automated localisation or the use of optical and acoustic tracking systems. There is a trend towards larger focal zones and lower shock wave pressures. Conclusions New theories for stone disintegration favour the use of shock wave sources with larger focal zones. Use of slower pulse rates, ramping strategies, and adequate coupling of the shock wave head can significantly increase the efficacy and safety of ESWL.
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.
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.
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.
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.
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