Endothelial function, arterial stiffness and Framingham risk score in chronic kidney disease: A prospective observational cohort study

Abstract

The aim of this study was to assess the role of endothelial function measured by the reactive hyperemia index (RHI), arterial stiffness measured by the augmentation index (AIx), and Framingham's cardiovascular disease (CVD) risk score (FRS) in kidney function decline in patients with chronic kidney disease (CKD). The RHI and AIx@75 (adjusted for 75 heart beats per minute), both derived from peripheral arterial tonometry (EndoPAT), were measured in 428 CKD patients aged 18 years old and older during hospitalization. We evaluated kidney function and its decline (incident ≥40% decline in estimated glomerular filtration rate [eGFR] or initiation of renal replacement therapy) associated with the RHI, AIx@75, and FRS during follow-up for a median of 36 months. The mean age of the participants was 56 years old, and 63.8% were men. In Spearman correlation analysis, the FRS, AIx@75, and RHI levels inversely correlated with eGFR. Over a median follow-up of 36 months, 122 participants experienced kidney function decline. In multivariate Cox analysis, only the FRS remained independently associated with the progression of kidney function (HR, 1.37; 95% CI, 1.14 to 1.64; P = 0.001). Multivariable-adjusted spline regression models showed a positive linear relationship between the FRS and the risk of kidney function decline (P-overall = 0.001, P-nonlinear = 0.701). However, adding the FRS to a model containing kidney function markers did not improve risk prediction for kidney outcome (category-free net reclassification improvement index [cf-NRI] = 0.179, P = 0.084; integrated discrimination improvement [IDI] = 0.017, P = 0.128). Additionally, the increased risk of the outcome associated with an elevated FRS was particularly evident among CKD patients with eGFR ≥60 ml/min/1.73 m² (eGFR ≥ 60 ml/min/1.73 m² vs.< 60 ml/min/1.73 m², P for interaction = 0.022). Participants with higher FRS levels were at increased risk of kidney function decline, emphasizing the important role of traditional CVD risk factors in the progression of CKD.

Keywords: Endothelial function; Framingham risk score; arterial stiffness.