SODIUM-MEDIATED BLOOD PRESSURE RISE IN CHRONIC KIDNEY DISEASE IS ASSOCIATED WITH REDUCED CYCLIC GUANOSINE MONOPHOSPHATE AVAILABILITY

Objective: Chronic kidney disease (CKD) is characterized by endothelial dysfunction, partly caused by the reduced bioavailability of NO. Endothelial dysfunction may lead to impaired vasodilation, thus contributing to hypertension in CKD. Excessive sodium intake can influence oxidative stress, potentially disrupting endothelial function and vascular tone. However, underlying mechanisms of the sodium-induced blood pressure (BP) and vascular responses in CKD are unknown. This randomized crossover study aimed to identify the factors in the responses in the context of excessive sodium. Design and method: CKD patients (KDIGO stage G2-3A, proteinuria >0.5 g/d) and healthy controls (HC) followed a 7-day low-sodium control diet (<50mmol/d) and high-sodium diet (>200mmol/d) in random order. After each diet, hemodynamic profiles were assessed using 24-h blood pressure measurements and systemic vascular resistance (SVR) calculations. Biomarker analysis was performed, measuring plasma cyclic guanosine monophosphate (cGMP), renin, aldosterone, and endothelin-1 (ET-1); and urinary cGMP, 3-nitrotyrosine (3-NT), thrombospondine-1 (THBS1), and ET-1 corrected for creatinine excretion. Results: We included 16 CKD patients (mean age, 46 yrs; median proteinuria 0.8 g/d; mean eGFR 56 ml/min/1.73m2 and 16 HC (41 yrs). Dietary salt intervention was comparable in both CKD and HC. After HSD, mean (SD) systolic BP increased in CKD by 7.2 (7.6; p<0.01) as compared to 3.1 (6.0; p=0.10) mmHg in HC, respectively. SVR change in CKD was 125 (263) and significant different compared to -109 (358) dyn∗sec∗cm-5 in HC (p=0.04). After HSD, a significant increase of 3-NT in both CKD and HC (170%; p<0.01 and 141%; p<0.05, respectively) was seen. Plasma cGMP decreased with 18.8% in CKD (p<0.05), but did not significantly change in HC. Renin and aldosterone levels decreased significantly in both groups, but no differences in THBS1 and ET-1 levels were observed. Conclusions: The sodium-mediated BP response in CKD was associated with a distinct change in SVR compared to HC. HSD reduced cGMP, a downstream mediator of NO, in CKD but not in HC. These findings suggest that the reduced ability to modulate vascular tone in response to excessive sodium, leading to high BP in CKD, is attributable to endothelial dysfunction.