Several major diseases, such as cancer and cardiovascular abnormalities, may be linked to pathological deposition of minerals or organic compounds in various tissues. Thus, the detection of such minerals or compounds and understanding the physicochemical processes associated with their formation are essential. As underlined by Schmidt et al., in Europe and the U.S., breast cancer will occur in 1 in 10 women. If clustered calcifications are one of the mammographic signs of early breast cancer, their chemical nature must be determined. More precisely, calcium phosphates (CaPs) are frequently associated with malignancy, but calcium oxalates are present in benign lesions. From a medical viewpoint, pathological calcifications refer to at least three very different families of biominerals: concretions, metastatic calcifications and dystrophic calcifications. Concretions are found in hollow organs or ducts of the body. For example, kidney stones are solid concretions of dissolved minerals in urine found in the kidney. In contrast, metastatic and dystrophic calcifications, which can be considered ectopic calcifications, are defined as unexpected biomineralization occurring in soft tissues. In the absence of a systemic mineral imbalance, dystrophic calcification is often associated with tissue alteration or necrosis. In contrast, metastatic calcifications resulting from mineral imbalance are more systemic and affect various tissues (e.g., vessels, lungs, kidneys). A fourth family can be considered physiological calcification (bone), which becomes pathological with diseases such as arthrosis or osteoporosis.

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Characterization and Some Physicochemical Aspects of Pathological Microcalcifications

Kidney stone disease is a polygenic and multifactorial disorder with a worldwide distribution, and its incidence and prevalence are increasing. Although significant progress has been made in recent years towards identifying the specific factors that contribute to the formation of kidney stone, many questions on the pathogenesis of kidney stones remain partially or completely unanswered. However, none of the proposed mechanisms specifically consider the role(s) of the trace elements and, consequently, the contribution of trace constituents to the pathogenesis of kidney stones remains unclear and under debate. The findings of some studies seem to support a role for some major and trace elements in the initiation of stone crystallization, including as a nucleus or nidus for the formation of the stone or simply as a contaminant of the stone structure. Thus, the analysis of kidney stones is an important component of investigations on nephrolithiasis in order to understand the role of trace constituents in the formation of kidney stones and to formulate future strategies for the treatment and prevention of stone formation and its recurrence. The aim of this review is to compare and evaluate the methods/procedures commonly used in the analysis of urinary calculi. We also highlight the role of major and trace elements in the pathogenesis of kidney stones.

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Kidney stone analysis techniques and the role of major and trace elements on their pathogenesis: a review

Kidney stones were analyzed using laser-induced breakdown spectroscopy (LIBS), utilizing a high resolution multi-channel charge-coupled device (CCD) spectrometer and a nanosecond-pulse Nd : YAG laser. The kidney stones were also characterized using X-ray diffraction (XRD) and X-ray fluorescence (XRF) techniques for comparative analysis. It was found that the ratio of hydrogen (H) to carbon (C) was an important indicator of organic compounds such as uric acid. Advantages of LIBS, especially with regards to amount of sample required and sample preparation as well as the ability to carry out elemental analysis and classification of kidney stones simultaneously, over other analytical techniques such as XRD and XRF are discussed. The common minor elements detected in the kidney stones include P, S, Si, Ti, and Zn. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) of broadband LIBS spectra were employed for classifying different types of kidney stones. The results are beneficial in understanding kidney stone formation processes, which can lead to preventive therapeutic strategies and treatment methods for urological patients.

Analysis and Classification of Heterogeneous Kidney Stones Using Laser-Induced Breakdown Spectroscopy (LIBS)

Urolithiasis affects around 10% of the US population with an increasing rate of prevalence, recurrence and penetrance The causes for the formation of most urinary calculi remain poorly understood, but obtaining the chemical composition of these stones might help identify key aspects of this process and new targets for treatment The majority of urinary stones are composed of calcium that is complexed in a crystalline matrix with organic and inorganic components Surprisingly, mitigation of urolithiasis risk by altering calcium homeostasis has not been very effective Thus, studies to identify other therapeutic stone-specific targets, using proteomics, metabolomics and microscopy techniques, have been conducted, revealing a high level of complexity The data suggest that numerous metals other than calcium and many nonmetals are present within calculi at measurable levels and several have distinct distribution patterns Manipulation of the levels of some of these elemental components of calcium-based stones has resulted in clinically beneficial changes in stone chemistry and rate of stone formation The elementome--the full spectrum of elemental content--of calcium-based urinary calculi is emerging as a new concept in stone research that continues to provide important insights for improved understanding and prevention of urinary stone disease

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The elementome of calcium-based urinary stones and its role in urolithiasis.

The process of crystallization in the urinary tract occurs when the equilibrium between promoting and inhibiting factors is broken. Many theories have been published to explain the mechanism of urinary stones formation; however, none of these theories has paid attention to trace elements. Their role in lithogenesis is still unclear and under debate. The findings of some studies may support the thesis that some major and trace elements may take part in the initiation of stone crystallization for instance as a nucleus or nidus for the formation of the stone, or simply contaminate the stone structure. This review presents a comprehensive account of the basic principles of the basic data and the role of major and trace elements in lithogenesis.

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Major and trace elements in lithogenesis.

Many theories have been put forward to explain the mechanism of stone formation and growth. The aim of this study was to investigate the urinary, serum and stone levels of zinc, iron, magnesium, and copper in patients with calcium oxalate stones and to investigate urinary and serum element levels in healthy controls and to find a possible connection between the elements and calcium oxalate stone formation. A total of 104 patients with calcium oxalate stones ranging in age from 3 to 79 years (mean 44.0 ± 18.1) and 77 healthy controls ranging in age from 18 to 77 (mean 44.2 ± 17.9) were included in this study. The mean urinary iron and copper levels in stone patients were significantly higher than healthy controls (P = 0.000). The mean urinary zinc and magnesium levels in healthy controls were significantly higher than stone patients (P = 0.000). There was no significant difference in the serum levels of magnesium and copper in stone patients and healthy controls. Serum zinc and iron level were significantly high in healthy controls as compared to stone patients. Each stone had all 4 elements. Zn and Mg have inhibitory effect on calcium oxalate stone formation. Fe and Cu could be promotor of the calcium oxalate stone formation.

Hatice Gül

Papers

Serum, urinary and stone zinc, iron, magnesium and copper levels in idiopathic calcium oxalate stone patients