Abstract Body: Background: Chronic kidney disease (CKD) and diabetic kidney disease (DKD) patients are advised to limit salt intake, because of its detrimental effects on blood pressure (BP) and albuminuria. The salt-sensitive BP response in these patients may be attributed to impaired renal ability to excrete sodium (Na+) resulting in fluid overload and/or vasodysfunction. To define which factor relates to BP sensitivity in both CKD and DKD, we studied the Na+-mediated BP response in these patients as compared to healthy volunteers (HV).

Methods: In this randomized crossover study, CKD patients (KDIGO stage G2/3A, proteinuria >0.5 g/d), Type 2 DKD patients (KDIGO stage G2/3A, proteinuria 0.2 - 0.5 g/d) and HV followed a 7-day low sodium diet (LSD, <50mmol/d) and high sodium diet (HSD, >200mmol/d), respectively. After each diet, assessment of the hemodynamic profile included daytime BP (Mobil-O-Graph) and cardiac output (CO) measurements (using NexfinTM), by which SVR was calculated accordingly. Extracellular fluid volume (ECV) change was assessed with multi-frequency body impedance spectroscopy (Fresenius).

Results: We included 20 CKD (mean age 48 yrs, median (IQR) proteinuria 0.7 (0.6-1.6) g/d, mean (SD) eGFR 60.7 (16.3) ml/min/1.73m2) and 8 DKD patients (age 68 yrs, proteinuria 0.3 (0.2-0.4) g/d, eGFR 59.0 (15.9) ml/min/1.73m2), and 16 HV (age 41 yrs). Dietary salt intervention was successful with mean difference in urine Na+ excretion of 185, 168, and 209 mmol/day in CKD, DKD and HV respectively. After HSD, mean (SD) systolic BP change was 9.3 mmHg (8.9; p<0.001) in CKD and 13.8 mmHg (10.4; p<0.01) in DKD, while systolic BP change (3.1 mmHg (6)) in HV was not significant. After HSD, we observed significant ECV expansion in all groups without differences between groups (CKD 1.6 L, DKD 1.6 L, HV 1.4 L, p=0.27), while no effects on CO were observed. After HSD, the mean (SD) SVR in CKD increased with 125.7 dyn*sec*cm-5 (247.9, p=0.04) and in DKD with 125.5 dyn*sec*cm-5 (142.6, p=0.04), while in HC a non-significant decline of -109.2 dyn*sec*cm-5 was observed (358.2, p=0.24).

Conclusion: The Na+-mediated BP rise in both CKD and DKD coincides with an increase in SVR. The absence of differences in ECV and CO between the three groups indicates that salt sensitivity in both CKD and DKD is not completely based on fluid overload but might be due to an inability to induce vasodilation.