Obesity, Metabolic Syndrome, Diabetes and Kidney Stones: Strengthening Links Over Time?

Long considered separate entities, obesity/type 2 diabetes/metabolic syndrome and kidney stone disease are now recognized as interconnected conditions, both from an epidemiological and pathophysiological perspective. Although the pathophysiological mechanisms between visceral obesity, metabolic syndrome and type 2 diabetes are well established, the link with an increased propensity to develop kidney stones may appear less clear at first glance. Over the past decade, data from retrospective analyses and prospective cohort studies have clarified the nature and the magnitude of this relationship. The common threads linking these pathophysiological entities, apparently distinct at first sight, are insulin resistance and systemic low-grade inflammation, which should be considered as the unifying pathological roots. Within the kidney, higher urinary levels of oxalate, calcium and uric acid, combined with a fall in urine pH, increase supersaturation of lithogenic salts. If unopposed, this physicochemical imbalance drives crystal nucleation, growth and aggregation, leading to precipitation of insoluble salts and, ultimately, to stone formation. This narrative review presents epidemiological and pathophysiological evidence that helps understand the extent to which seemingly unrelated conditions are, in fact, part of a broader metabolic disorder, the cardiovascular-kidney-metabolic syndrome, in which kidney stone disease can likely be integrated because common pathophysiological features are shared. The question then arises as to whether weight loss and modern treatments for type 2 diabetes, in particular glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors, influence the lithogenic risk.