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      Morphological characteristics and microstructure of kidney stones using synchrotron radiation μCT reveal the mechanism of crystal growth and aggregation in mixed stones

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          Abstract

          Understanding the mechanisms of kidney stone formation, development patterns and associated pathological features are gaining importance due to an increase in the prevalence of the disease and diversity in the presentation of the stone composition. Based on the microstructural characteristics of kidney stones, it may be possible to explain the differences in the pathogenesis of pure and mixed types of stones. In this study, the microstructure and distribution of mineral components of kidney stones of different mineralogy (pure and mixed types) were analyzed. The intact stones removed from patients were investigated using synchrotron radiation X-ray computed microtomography (SR-μCT) and the tomography slice images were reconstructed representing the density and structure distribution at various elevation planes. Infrared (IR) spectroscopes, X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to confirm the bulk mineral composition in the thin section stones. Observations revealed differences in the micro-morphology of the kidney stones with similar composition in the internal 3-D structure. Calcium oxalate monohydrate stones showed well-organised layering patterns, while uric acid stones showed lower absorption signals with homogenous inner structure. Distinct mineral phases in the mixed types were identified based on the differential absorption rates. The 3-D quantitative analysis of internal porosity and spatial variation between nine different types of stones were compared. The diversity among the microstructure of similar and different types of stones shows that the stone formation is complex and may be governed by both physiological and micro-environmental factors. These factors may predispose a few towards crystal aggregation and stone growth, while, in others the crystals may not establish stable attachment and/or growth.

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          Most cited references 35

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          Kidney Stone Disease: An Update on Current Concepts

          Kidney stone disease is a crystal concretion formed usually within the kidneys. It is an increasing urological disorder of human health, affecting about 12% of the world population. It has been associated with an increased risk of end-stage renal failure. The etiology of kidney stone is multifactorial. The most common type of kidney stone is calcium oxalate formed at Randall's plaque on the renal papillary surfaces. The mechanism of stone formation is a complex process which results from several physicochemical events including supersaturation, nucleation, growth, aggregation, and retention of urinary stone constituents within tubular cells. These steps are modulated by an imbalance between factors that promote or inhibit urinary crystallization. It is also noted that cellular injury promotes retention of particles on renal papillary surfaces. The exposure of renal epithelial cells to oxalate causes a signaling cascade which leads to apoptosis by p38 mitogen-activated protein kinase pathways. Currently, there is no satisfactory drug to cure and/or prevent kidney stone recurrences. Thus, further understanding of the pathophysiology of kidney stone formation is a research area to manage urolithiasis using new drugs. Therefore, this review has intended to provide a compiled up-to-date information on kidney stone etiology, pathogenesis, and prevention approaches.
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            The Role of Urinary Kidney Stone Inhibitors and Promoters in the Pathogenesis of Calcium Containing Renal Stones

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              Molecular modulation of calcium oxalate crystallization by osteopontin and citrate.

              Calcium oxalate monohydrate (COM), which plays a functional role in plant physiology, is a source of chronic human disease, forming the major inorganic component of kidney stones. Understanding molecular mechanisms of biological control over COM crystallization is central to development of effective stone disease therapies and can help define general strategies for synthesizing biologically inspired materials. To date, research on COM modification by proteins and small molecules has not resolved the molecular-scale control mechanisms. Moreover, because proteins directing COM inhibition have been identified and sequenced, they provide a basis for general physiochemical investigations of biomineralization. Here, we report molecular-scale views of COM modulation by two urinary constituents, the protein osteopontin and citrate, a common therapeutic agent. Combining force microscopy with molecular modeling, we show that each controls growth habit and kinetics by pinning step motion on different faces through specific interactions in which both size and structure determine the effectiveness. Moreover, the results suggest potential for additive effects of simultaneous action by both modifiers to inhibit the overall growth of the crystal and demonstrate the utility of combining molecular imaging and modeling tools for understanding events underlying aberrant crystallization in disease.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: ResourcesRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 March 2019
                2019
                : 14
                : 3
                Affiliations
                [1 ] Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
                [2 ] Department of Urology, Yenepoya Medical College, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
                [3 ] Technical Physics Division, Bhabha Atomic Research Centre, Indore-Mumbai, India
                Institute of Materials Science, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                [¤]

                Current address: ICAR–Indian Institute of Spices Research, Kozhikode, Kerala, India

                Article
                PONE-D-18-32718
                10.1371/journal.pone.0214003
                6430423
                30901364
                © 2019 Manzoor et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 5, Tables: 1, Pages: 14
                Product
                Funding
                The authors acknowledge the Yenepoya University for the seed grant for carrying out this study. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Nephrology
                Kidney Stones
                Medicine and Health Sciences
                Urology
                Kidney Stones
                Physical Sciences
                Chemistry
                Chemical Compounds
                Oxalates
                Physical Sciences
                Chemistry
                Chemical Compounds
                Acids
                Uric Acid
                Physical Sciences
                Materials Science
                Material Properties
                Porosity
                Physical Sciences
                Materials Science
                Materials
                Crystals
                Physical Sciences
                Physics
                Condensed Matter Physics
                Solid State Physics
                Crystallography
                Crystal Growth
                Medicine and Health Sciences
                Nephrology
                Mineral Metabolism and the Kidney
                Physical Sciences
                Physics
                Condensed Matter Physics
                Solid State Physics
                Crystallography
                Crystal Structure
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized

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