Recent developments in the study of cellular inflammation in the papillae of stone formers.

Kidney stone disease has long been thought to involve tissue inflammation, but direct evidence linking inflammation as a causative factor in human stone formation remains limited. This review focuses on studies in human stone formers, highlighting variation in stone former phenotypes. Histological and molecular studies of kidney tissues reveal increased immune cell density and gene expression changes in stone formers, with notable differences between calcium oxalate and brushite stone pathologies. Phenotyping stone formers by tissue mineralization patterns-such as Randall's plaque or ductal plugging-shows significant heterogeneity in tissue damage, and thus presumably also inflammation. Systemic markers, such as elevated serum C-reactive protein, suggest a link between active stone disease and inflammation, although relationships vary with age, gender, and comorbidities. Such systemic markers have not been studied well in stone formers separated by phenotype. These insights underline the importance of stratifying patients by stone type and tissue pathology to identify inflammation pathways specific to each phenotype. Such an approach may pave the way for targeted anti-inflammatory therapies to reduce recurrence in this heterogeneous disease.