Browsing by Subject "Randall’s plaque"

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    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 Medicine
    Objectives: 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.
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    Endoscopic observations as a tool to define underlying pathology in kidney stone formers
    (Springer, 2019-10) Pless, Maria Sloth; Williams, James Caldwell, Jr.; Andreassen, Kim Hovgaard; Jung, Helene Ulrich; Osther, Susanne Sloth; Christensen, Dorte Ravnsmed; Osther, Palle Jörn Sloth; Anatomy and Cell Biology, School of Medicine
    PURPOSE: Advancements in endoscopy offer the possibility of inspection of intrarenal anatomy and pathology. The aim of the study was to evaluate renal papillary appearance in kidney stone formers and to correlate papillary findings with stone type and patient metabolic data. MATERIALS AND METHODS: A consecutive cohort of 46 kidney stone formers undergoing retrograde intrarenal surgery was enrolled. During surgery, renal papillae were characterized in the domains of ductal Plugging (DP), surface Pitting, Loss of papillary contour, and Amount of Randall's plaque (RP, PPLA scoring). Stone material was analyzed using micro-CT and infrared spectroscopy, and blood and urine were collected for metabolic evaluation. RESULTS: In all patients, renal papillae had changes in at least one of the domains of the PPLA score. Examining the total population, it was evident that patients with predominantly plugging (DP > 0) all had very low RP scores. There were no significant trends between mean PPLA scores and urinary analytes for the total group. CONCLUSION: Efforts to prevent renal stone formation have so far been insufficient in majority of patients. Digital endoscopy reveals that kidney stone formers have different and distinct papillary morphologies that seem to be linked to specific stone-forming pathways. Since renal papillary abnormalities may be easily identified during endoscopy, this may in the future prove to be an important method for tailoring prevention strategies in kidney stone patients.
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    Randall's plaque in stone formers originates in ascending thin limbs
    (American Physiological Society, 2018-11) Evan, Andrew P.; Coe, Fredric L.; Lingeman, James; Bledsoe, Sharon; Worcester, Elaine M.; Anatomy and Cell Biology, School of Medicine
    Randall's plaque, an attachment site over which calcium oxalate stones form, begins in the basement membranes of thin limbs of the loop of Henle. The mechanism of its formation is unknown. Possibly, enhanced delivery of calcium out of the proximal tubule, found in many stone formers, increases reabsorption of calcium from the thick ascending limb into the interstitium around descending vasa recta, which convey that calcium into the deep medulla, and raises supersaturations near thin limbs ("vas washdown"). According to this hypothesis, plaque should form preferentially on ascending thin limbs, which do not reabsorb water. We stained serial sections of papillary biopsies from stone-forming patients for aquaporin 1 (which is found in the descending thin limb) and the kidney-specific chloride channel ClC-Ka (which is found in the ascending thin limb). Plaque (which is detected using Yasue stain) colocalized with ClC-Ka, but not with aquaporin 1 (χ2 = 464, P < 0.001). We conclude that plaque forms preferentially in the basement membranes of ascending thin limbs, fulfilling a critical prediction of the vas washdown theory of plaque pathogenesis. The clinical implication is that treatments such as a low-sodium diet or thiazide diuretics that raise proximal tubule calcium reabsorption may reduce formation of plaque as well as calcium kidney stones.
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    Using mid infrared to perform investigations beyond the diffraction limits of microcristalline pathologies: advantages and limitation of Optical PhotoThermal IR spectroscopy
    (Academie des Sciences, 2022) Bazin, Dominique; Bouderlique, Elise; Tang, Ellie; Daudon, Michel; Haymann, Jean-Philippe; Frochot, Vincent; Letavernier, Emmanuel; Van de Perre, Els; Williams, James C.; Lingeman, James E.; Borondics, Ferenc; Urology, School of Medicine
    Understanding the physico-chemistry related to cristalline pathologies constitutes a challenge in several medical specialities such as nephrology, dermatology or oncology. Regarding nephrology, the chemical diversity of concretions such as kidney stones calls for characterization techniques to determine the chemical composition of concretions. The starting point of this contribution is given by Fourier Transform InfraRed (FTIR) spectroscopy which is routinely used at the hospital to determine the chemical composition of kidney stones as well as ectopic calcifications present in kidney biopsy. For kidney stones, the quantity of sample is sufficient to perform a significant analysis through classical FTIR. For ectopic calcifications, FTIR can be inefficient in the case of calcification in the tissue when their size is less than 10 m. For such samples, Optical PhotoThermal IR (OPT-IR) spectroscopy may constitute a way to overcome this experimental difficulty through the acquisition of IR spectrum with a spatial resolution close to 500 nm. To illustrate such opportunity, we first compare the IR spectrum acquired with a classical experimental set-up related to classical IR spectroscopy to IR spectrum collected with a OPT-IR one for different compounds namely calcium oxalate monohydrate, calcium oxalate dehydrate, calcium phosphate apatite and magnesium ammonium phosphate hexahydrate. Such comparison helps us to assess specificity of OPT-IR. Then, we consider several pathological calcifications associated to hyperoxaluria, adenine phosphoribosyltransferase (APRT) deficiency or the presence of Randall’s plaque. We will see that the nanometer spatial resolution constitutes a major advantage versus a micrometre one. Also, in the case of Randall’s plaque, we show that OPT-IR can determine the chemical composition of microscopic concretion without any kind of preparation. Such experimental fact is clearly a major advantage. Finally, we also extended this first investigation in nephrology by considering breast calcifications. In that case, if the number of chemical phases is quite low compared to the number of chemical phases identified in ectopic calcifications present in kidney (four instead of 24), the challenge is related to the possibility to distinguish between the different calcium phosphate namely amorphous carbonated calcium phosphate, CA and whitlockite. The complete set of data indicates the limitations and the advantages of OPT-IR spectroscopy.