Natural variation of magnesium stable isotopes in human kidney stones

Kidney stones, as typical biominerals produced within the human body, pose a significant threat to human health, affecting over 12% of the global population. However, the exact mechanisms underlying their formation are not fully understood. Recent metal isotopic analysis provides a new way to study the roles of metal cations in biological processes within organisms. Here, we report the Mg isotope ratios of human kidney stones for the first time. The total range of measured values for δ26Mg in kidney stones is 1.05‰, from -1.12‰ to -0.07‰. Our data exhibit a significant 24Mg enrichment compared with the values calculated from density functional theory. We suggest that the Mg-isotopic fractionations in vivo are linked to active Mg transport mediated by proteins during intestinal absorption and preferential renal reabsorption of ionized Mg2+ via tight junctional proteins. Our results indicate that the inhibitory effect of Mg on kidney stones is related to the kink-blocking mechanism, and the incorporation of hydrated Mg lessens the extent of inhibition and the magnitude of isotope discrimination. We show that metal isotopes provide new insights into the underlying biological processes and human health.