The Influence of Salt Loading on the Kidney Injury Biomarker Neutrophil Gelatinase‐Associated Lipocalin in Healthy Young Adults

Abstract

PurposeThe kidneys play a critical role in blood pressure (BP) regulation. In hypertensive patients and in rodent models, long‐term high dietary sodium (Na+) causes a reduction in kidney function (reduced glomerular filtration rate; GFR). Rodent studies demonstrate that high dietary Na+ increases levels of novel kidney injury biomarkers, independent of changes in BP and GFR. However, it is unclear if short‐term high Na+ increases kidney injury biomarkers in healthy humans. Therefore, we tested the hypothesis that short‐term high Na+ intake increases urinary excretion of the novel kidney injury marker Neutrophil Gelatinase‐Associated Lipocalin (NGAL) in healthy, young adults.MethodsTwenty participants (12 M/8 F; 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, participants were asked 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 at least two weeks and female participants were tested during the placebo phase of their oral contraceptive cycle. Participants collected their urine for the final 24 hours of each supplementation period to assess urine flow rate, and Na+ excretion to verify diet adherence. Brachial BP was measured after at least five minutes of rest. We measured urine and serum creatinine (kinetic modification via the Jaffe reaction) to estimate GFR via creatinine clearance. We used enzyme‐linked immunosorbent assays (Toronto Bioscience) to measure urinary NGAL. Statistical analysis included paired t‐tests and Wilcoxon matched‐pairs signed rank tests.ResultsCompared to placebo, Na+ supplementation increased urinary Na+ excretion (139.9±68.4 vs. 282.5±69.8 mmol/24 hours, p<0.01) but there was no difference in mean arterial BP (77±7 vs. 77±6 mmHg, p=0.64). Serum creatinine concentrations (0.78±0.12 vs. 0.77±0.09 mg/dL, p=0.55) were not different between conditions. However, compared to placebo, Na+ supplementation increased creatinine clearance (110.5±32.9 vs. 145.0±24.9 mL/min, p<0.01) and increased urinary NGAL excretion indexed to urine flow rate (16.9±21.9 vs. 28.4±36.1 ng/min, p=0.02).DiscussionOur preliminary data suggests that salt loading does not alter serum creatinine concentration but increases creatinine clearance and urinary excretion of the kidney injury marker NGAL in healthy young adults.Support or Funding InformationFundingSupported by NIH grants R01HL128388 and K01HL147998, and ACSM Foundation Doctoral Student Research Grant 17‐00521