Role of CT attenuation values in kidney stones: a combination of clinical investigations and molecular mechanism elucidation

Abstract

Abstract Randall's plaque theory suggests a systemic process that affects the kidneys, and unenhanced computed tomography (uCT) scans can identify changes in tissue density during stone formation. We carried out a retrospective cohort study comprising 163 kidney stone formers (KSFs) and 168 healthy control participants. The CT attenuation values of renal papillae in KSFs are significantly higher than those in controls. Multivariable regression demonstrated that kidney stone formation was associated with age, CT attenuation values, serum calcium, eGFR, hematuria and urinary leukocyte. KSFs with abdominal aortic calcification had significantly higher aortic calcification index (ACI) than the controls, and there was a significant interaction between ACI and CT attenuation values. The gene expression profiles of aortic calcification and nephrolithiasis were subjected to bioinformatics analysis. Twenty-five common differentially expressed genes (cDEGs) were identified, and the IL-17 signaling pathway was found to be predominantly enriched among the upregulated cDEGs according to KEGG analysis. The expression of MMP1, CCL7, HSP 90α/β, NF-κb p65, and p-NF-κb p65 was elevated in cell or animal models and clinical samples. Triptolide treatment inhibited stone formation and preserved kidney function by blocking IL-17 signaling transduction in the nephrolithiasis rats model.