High sodium intake, glomerular hyperfiltration and protein catabolism in patients with essential hypertension

Rossitto, G. et al. (2021) High sodium intake, glomerular hyperfiltration and protein catabolism in patients with essential hypertension. Cardiovascular Research, 117(5), pp. 1372-1381. (doi: 10.1093/cvr/cvaa205) (PMID:33053160) (PMCID:PMC8064429)

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Aims: A blood pressure-independent metabolic shift toward a catabolic state upon high sodium (Na+) diet, ultimately favouring body fluid preservation, has recently been described in pre-clinical controlled settings. We sought to investigate the real-life impact of high Na+ intake on measures of renal Na+/water handling and metabolic signatures, as surrogates for cardiovascular risk, in hypertensive patients. Methods and results: We analysed clinical and biochemical data from 766 consecutive patients with essential hypertension, collected at the time of screening for secondary causes. The systematic screening protocol included 24h urine collection on usual diet and avoidance of renin-angiotensin-aldosterone system-confounding medications. Urinary 24h-Na+ excretion, used to define classes of Na+ intake (Low ≤2.3g/d; Medium 2.3-5g/d; High >5g/d), was an independent predictor of glomerular filtration rate after correction for age, sex, blood pressure, BMI, aldosterone and potassium excretion (p = 0.001; Low: 94.1 [69.9-118.8] vs High: 127.5 [108.3-147.8] ml/min/1.73m2). Renal Na+ and water handling diverged, with higher fractional excretion of Na+ and lower fractional excretion of water in those with evidence of High Na+ intake (FENa: Low 0.39% [0.30-0.47] vs. High 0.81% [0.73-0.98], p < 0.001; FEwater: Low 1.13% [0.73-1.72] vs. High 0.89% [0.69-1.12], p = 0.015). Despite higher FENa, these patients showed higher absolute 24h Na+ reabsorption and higher associated tubular energy expenditure, estimated by tubular Na+/ATP stoichiometry, accordingly (ΔHigh-Low = 18 [12-24] kcal/d, p < 0.001). At non-targeted LC/MS plasma metabolomics in an unselected subcohort (n = 67), metabolites which were more abundant in High vs. Low Na+ intake (p < 0.05) mostly entailed intermediates or end products of protein catabolism/urea cycle. Conclusions: When exposed to high Na+ intake, kidneys dissociate Na+ and water handling. In hypertensive patients, this comes at the cost of higher glomerular filtration rate, increased tubular energy expenditure and protein catabolism from endogenous (muscle) or excess exogenous (dietary) sources. Glomerular hyperfiltration and the metabolic shift may have broad implications on global cardiovascular risk independent of blood pressure.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Montezano, Dr Augusto and Rossitto, Dr Giacomo and Samji, Dr Sheon and Blackburn, Dr Gavin and Welsh, Dr Paul and Petrie, Professor Mark and Touyz, Professor Rhian and Delles, Professor Christian and Daly, Dr Ronan
Authors: Rossitto, G., Maiolino, G., Lerco, S., Ceolotto, G., Blackburn, G., Mary, S., Antonelli, G., Berton, C., Bisogni, V., Cesari, M., Seccia, T. M., Lenzini, L., Pinato, A., Montezano, A., Touyz, R. M., Petrie, M. C., Daly, R., Welsh, P., Plebani, M., Rossi, G. P., and Delles, C.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Cardiovascular Research
Publisher:Oxford University Press
ISSN (Online):1755-3245
Published Online:16 July 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Cardiovascular Research 117(5): 1372-1381
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190814BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177Institute of Cardiovascular & Medical Sciences
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science
173707Institutional Strategic Support Fund (2016)Anna DominiczakWellcome Trust (WELLCOTR)204820/Z/16/ZInstitute of Cardiovascular & Medical Sciences