Abstract
Advanced glycation end product (AGE) clearance may cause renal tubular injuries, such as changes in sodium reabsorption. We hypothesize that AGEs interact with sodium metabolism to influence blood pressure (BP). The study participants were outpatients who were suspected of having hypertension but had not been treated with antihypertensive medication. Clinic and ambulatory blood pressures were measured at baseline (n = 989) and during follow-up (median, 4.4 years, n = 293). Plasma AGE concentrations were measured by enzyme-linked immunosorbent assay. Twenty-four-hour urine was collected for measurements of creatinine, sodium and lithium. In a cross-sectional analysis (n = 989), subjects in the top quintile versus quintiles 1–4 of plasma AGE concentration had significantly (P ≤ 0.004) lower fractional excretion of lithium (18.3% vs. 21.6%) and fractional distal reabsorption rate of sodium (95.0% vs. 95.8%) but similar BP (P ≥ 0.25). However, there was an interaction between plasma AGE concentration and urinary sodium excretion in relation to diastolic BP (P ≤ 0.058). Only in participants with low urinary sodium chloride excretion (≤6 grams/day, n = 189), clinic (84.3 vs. 80.2 mmHg), 24-h (83.9 vs. 80.4 mmHg), daytime (87.8 vs. 84.8 mmHg) and nighttime (75.1 vs. 72.1 mmHg) diastolic BP at baseline were higher (P ≤ 0.05) in the top quintile than in quintiles 1–4 of plasma AGE concentration. In the longitudinal study (n = 383), similar trends were observed, with significant (P ≤ 0.05) differences in the increment in daytime diastolic BP (6.8 vs. −1.7 mmHg) and incidence of ambulatory and treated hypertension (hazard ratio 3.73) during follow-up. In conclusion, AGEs were associated with high BP, probably via enhanced proximal sodium handling and on low dietary sodium intake.
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Acknowledgements
We gratefully acknowledge the voluntary participation of all patients and the expert technical support of the technical staff from The Shanghai Institute of Hypertension (Junwei Li, Beiwen Lv, Jiaye Qian, Yuzhong Shi, Qian Yu, Jie Zhou, Yi Zhou, Yini Zhou, and Jiajun Zong).
Funding
This study was financially supported by grants from the National Natural Science Foundation of China (grants 81970353, 82070432, 82070435, 81770455, 91639203, 81400312 and 81470533); the Ministry of Science and Technology (2016YFC0900902, 2016YFC1300100, and 2018YFC1704902), Beijing, China; the Shanghai Commissions of Science and Technology (grants 19ZR1443300, 19YF1441000, 15XD1503200 and 14ZR1436200); the Shanghai Municipal Health Commission (201940297, 20204Y0001, 2017BR025, 15GWZK0802 and a Grant for Leading Academics); and the Three-year Action Program of Shanghai Municipality for Strengthening the Construction of Public Health System (GWV-10.1-XK05) Big Data and Artificial Intelligence Application, Shanghai, China.
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Huang, QF., Cheng, YB., Guo, QH. et al. Clinic and ambulatory blood pressure in relation to the interaction between plasma advanced glycation end products and sodium dietary intake and renal handling. Hypertens Res 45, 665–674 (2022). https://doi.org/10.1038/s41440-021-00805-z
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DOI: https://doi.org/10.1038/s41440-021-00805-z
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