Exeter Fellow Co-Authors Landmark Study on Genetic Risk Factors for Kidney Stones 

Exeter College Supernumerary Fellow, Associate Professor Sarah Howles, has co-authored a significant study published in the Journal of Clinical Investigation on 15 May 2025. The research identifies genetic variants that increase the risk of kidney stone disease (KSD), offering new avenues for personalised treatment strategies. 

The study, conducted by an international team of researchers, uncovered 79 genetic signals across 71 loci associated with KSD. Notably, variants near the genes DGKD, SLC34A1, and CYP24A1 were found to disrupt calcium and phosphate balance in the body, contributing to stone formation. Laboratory experiments demonstrated that these genetic alterations impair calcium-sensing receptor (CaSR) signalling, a key pathway in mineral metabolism. 

Importantly, the research suggests that pharmacological modulation of these pathways could significantly reduce the risk of kidney stones. For instance, the drug cinacalcet, which enhances CaSR signalling, was shown to mitigate the effects of certain DGKD variants in vitro. These findings pave the way for targeted therapies aimed at individuals with specific genetic predispositions to KSD. 

Associate Professor Howles, who leads the Oxford Stone Group at the Nuffield Department of Surgical Sciences, focuses her research on understanding the pathophysiology of kidney stone disease and developing precision medicine approaches for its prevention. Her work integrates genomic data with clinical insights to identify novel therapeutic targets. 

For more information on Associate Professor Howles’s work, visit the Oxford Stone webpage.