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

Abstract

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.

Figure 1

Elemental content of calcium-based urinary stones. The mean values of the elemental content of human urinary calculi reported in 15 studies summarized in Table 1 are represented in rank order of the overall median values. Only values for calcium-based stones were analysed, apart from the data reported by Abdel-Gawad et al. in which 78% were calcium-based stones.

Figure 2

Relationships between the elemental content in calcium-based urinary stones and normal urine. The reported elemental content of human urinary calculi was plotted against the clinical reference ranges of these elements in normal human urine. The reference range values are listed as a | daily amounts or b | concentrations, depending on how these values are usually reported. The bars in the X-axis dimension reflect standard deviations around the mean. The bars in the Y-axis dimension reflect upper and lower range limits around the median.