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High Sodium Intake, Glomerular Hyperfiltration and Protein Catabolism in Patients with Essential Hypertension.

Abstract：

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. TRANSLATIONAL PERSPECTIVE:We herein show that high Na intake can adversely impact not only blood pressure control, but also renal function and metabolic balance in hypertensive patients. At variance with experimental preclinical studies, the catabolism of proteins appears to include also exogenous sources. Interventional studies where caloric intake is controlled but not restricted may identify preferential metabolic handling in different subjects/populations and test the effect of specific dietary strategies. Similarly, the potential benefit of medications like sodium-glucose cotransporter (SGLT)-2 inhibitors, which are known to reduce both glomerular hyperfiltration and excess tubular Na+ reabsorption, in non-diabetic hypertensive patients deserves further investigation in relation to the described Na+-reno-metabolic mechanisms.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Rossitto G,Maiolino G,Lerco S,Ceolotto G,Blackburn G,Mary S,Antonelli G,Berton C,Bisogni V,Cesari M,Seccia TM,Lenzini L,Pinato A,Montezano A,Touyz RM,Petrie MC,Daly R,Welsh P,Plebani M,Rossi GP,Delles C

doi

10.1093/cvr/cvaa205

subject

Has Abstract

pub_date

2020-07-16 00:00:00

eissn

0008-6363

issn

1755-3245

pii

5872526

pub_type

杂志文章

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High Sodium Intake, Glomerular Hyperfiltration and Protein Catabolism in Patients with Essential Hypertension.