The Influence of Salt Loading on Glomerular Filtration Rate and Blood Pressure Variability in Healthy Young Adults

Abstract

Purpose High dietary sodium (Na+) is associated with glomerular hyperfiltration in patients with hypertension. Glomerular hyperfiltration is predictive of future cardiovascular and kidney disease. High dietary Na+ is also associated with greater blood pressure variability (BPV), which is predictive of target organ damage. However, it is unclear if short-term Na+ loading influences glomerular filtration rate (GFR) and BPV in healthy young adults. Therefore, we tested the hypothesis that short-term high Na+ intake would induce glomerular hyperfiltration (GFR > 135 ml/min) and increase BPV in healthy young adults. Methods Twenty participants (12M/8F; age: 24±4 years; BMI: 23.1±0.6 kg/m2; BP: 112 ±10/64±9 mmHg; mean ± SD) participated in a double-blind, placebo-controlled, randomized, crossover study. For 10-days, we asked participants to consume a 2,300 mg/day Na+ diet and supplement with salt (3,900 mg/day of Na+) or placebo (dextrose) capsules. The conditions were separated by ≥ two weeks and we tested female participants during the placebo phase of oral contraception. Participants collected their urine for the final 24 hours of each supplementation period to assess Na+ excretion to verify diet adherence. We measured serum creatinine (Jaffe reaction) to assess estimated GFR via the CKD-EPI equation (along with sex, age and race), and serum/urine creatinine to measure creatinine clearance. We measured brachial (oscillometric) and beat-to-beat BP (photoplethysmography). We used the average real variability index and standard deviation (SD) to assess beat-to-beat systolic, diastolic and mean BPV. Our statistical analyses included paired t-tests, Wilcoxon, and Chi-squared tests. Results Compared to placebo, Na+ supplementation increased urinary Na+ excretion (placebo: 139.9±68.4 vs. Na+: 282±69.8 mmol/24 hours, p<0.001) without differences in mean arterial BP (placebo: 77±7 vs. Na+: 77±6 mmHg, p=0.64). Estimated GFR was not different between conditions (p=0.27). However, compared to placebo, creatinine clearance increased with Na+ supplementation when unadjusted (placebo: 111±33 vs. Na+: 145±24 ml/min, p<0.001) and adjusted (placebo: 106±31 vs. Na+: 137±24 ml/min/1.73m2, p<0.001) for body surface area. There was a trend for an increased prevalence of glomerular hyperfiltration in the Na+ condition compared to placebo when evaluating unadjusted (placebo: 6/20 [30%] vs. Na+: 12/20 [60%], p =0.057) but not adjusted creatinine clearance. There were no differences in measures of BPV except SD of systolic BP (placebo: 5.6±2.2 vs. Na+: 6.5±2.0 mmHg, p=0.035) was modestly increased with Na+ supplementation. Conclusion Our preliminary data suggests that compared to CKD-EPI, creatinine clearance is a more sensitive measure for detecting glomerular hyperfiltration with salt loading in healthy young adults. Moreover, salt loading doesn't increase BPV.