Kidney Stone Disease (KSD) affects more than 10% of the global population and has a high likelihood of recurrence. Its prevalence has risen significantly in recent decades, posing a substantial economic burden. Moreover, KSD is linked to several comorbidities, amplifying its impact on general health and well-being. Environmental factors play a critical role in KSD development, acting upon an underlying genetic substratum. These genetic factors affect the regulation of stone-forming elements and natural inhibitors of crystallization within the kidney. Understanding the interplay between genetic and environmental factors is essential for improving KSD management. Tailored dietary interventions and targeted therapies can address individual risk profiles, reducing the burden of this complex disease. We believe that the common form of KSD, which is the one observed in the general population, is indeed a heterogeneous condition characterized by significant variability in the influence of environmental and genetic factors among patients, as well as distinct biological pathways involved in lithogenesis for each individual. The aim of this review is to describe the relevant biology of nephrolithiasis, leveraging 'experiments of nature,' specifically the known genetic associations of KSD and the resulting biological and physiological derangements. We hypothesize that the carriers, molecular pathways, and physiological processes identified in this manner play a major role in the biology of lithogenesis, not only in rare genetic nephrolithiasis but also in 'common' KSD.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2025 May 15 [Epub ahead of print]
Andrea Spasiano, Emmanuel Letavernier, Pietro Manuel Ferraro, Robert J Unwin, Giovanni Gambaro
Division of Nephrology, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata, Verona, Italy., Sorbonne Université, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1155, Paris, and Service d'Explorations Fonctionnelles et Multidisciplinaire (EFM), Tenon Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France., AstraZeneca Biopharmaceuticals R&D, Early Cardiovascular, Renal and Metabolism (CVRM), Cambridge, UK and Gothenburg, Sweden.