Oxidative Stress and Endothelial Dysfunction in Patients with Hypertensive Nephropathy: Role of the Mediterranean...

Essential hypertension is a leading cause of chronic kidney disease (CKD) and is frequently complicated by hypertensive nephropathy, characterized by nephroangiosclerosis and increased intrarenal vascular resistance, assessable by renal resistive index (RRI). Oxidative stress and endothelial dysfunction contribute to CKD progression, and the Mediterranean diet (MD) has been associated with a more favorable oxidative and endothelial profile, although data linking diet to renal microcirculation in hypertensive nephropathy remain limited. The aim of this study is to evaluate the relationship between RRI, oxidative stress, endothelial function, and adherence to the Mediterranean diet in patients with essential hypertension and hypertensive nephropathy. We performed a cross-sectional single-center study and we enrolled 99 patients with essential hypertension, hypertensive nephropathy, and CKD stages G1-G4 (KDIGO). All patients underwent laboratory testing, measurement of oxidative stress markers (sNOX2-dp, H₂O₂) and endothelial function (NO), renal ultrasound with interlobar RRI assessment, and PREDIMED questionnaire for MD adherence. A significant direct correlation was observed between RRI and oxidative stress markers (sNOX2-dp and H₂O₂) (p = 0.002, r = 0.302; p = 0.002, r = 0.322), while a significant inverse correlation was found between RRI and the endothelial function marker (NO) (p = 0.013, r = -0.302). The correlation between RRI and PREDIMED questionnaire scores did not reach statistical significance, but there was a trend toward an inverse association (p = 0.06, r = -0.18). In addition, a significant inverse correlation was observed between RRI and eGFR (p = 0.005, r = -0.27), consistent with published data. We also found a significant inverse correlation between sNOX2-dp and PREDIMED scores (p = 0.034, r = -0.21); no statistically significant correlations with H₂O₂ and NO were observed in this analysis. Higher intrarenal vascular resistance is associated with heightened oxidative stress, impaired endothelial function, and lower eGFR. Adherence to the Mediterranean diet is linked to lower NOX2-mediated oxidative stress, supporting a potential association between higher MD adherence and lower NOX2-related oxidative stress. These findings are hypothesis-generating and require confirmation in adequately powered longitudinal and interventional studies before any clinical inference on CKD progression can be made.