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      Dietary Salt Restriction in Chronic Kidney Disease: A Meta-Analysis of Randomized Clinical Trials

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          Abstract

          Background. A clear evidence on the benefits of reducing salt in people with chronic kidney disease (CKD) is still lacking. Salt restriction in CKD may allow better control of blood pressure (BP) as shown in a previous systematic review while the effect on proteinuria reduction remains poorly investigated. Methods. We performed a meta-analysis of randomized controlled trials (RCTs) evaluating the effects of low versus high salt intake in adult patients with non-dialysis CKD on change in BP, proteinuria and albuminuria. Results. Eleven RCTs were selected and included information about 738 CKD patients (Stage 1–4); urinary sodium excretion was 104 mEq/day (95%CI, 76–131) and 179 mEq/day (95%CI, 165–193) in low- and high-sodium intake subgroups, respectively, with a mean difference of −80 mEq/day (95%CI from −107 to −53; p <0.001). Overall, mean differences in clinic and ambulatory systolic BP were −4.9 mmHg (95%CI from −6.8 to −3.1, p <0.001) and −5.9 mmHg (95%CI from −9.5 to −2.3, p <0.001), respectively, while clinic and ambulatory diastolic BP were −2.3 mmHg (95%CI from −3.5 to −1.2, p <0.001) and −3.0 mmHg (95%CI from −4.3 to −1.7; p <0.001), respectively. Mean differences in proteinuria and albuminuria were −0.39 g/day (95%CI from −0.55 to −0.22, p <0.001) and −0.05 g/day (95%CI from −0.09 to −0.01, p = 0.013). Conclusion. Moderate salt restriction significantly reduces BP and proteinuria/albuminuria in patients with CKD (Stage 1–4).

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          Most cited references36

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          Assessing the influence of a single study in the meta-analysis estimate

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            Effects of Intensive BP Control in CKD

            The appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of <120 mm Hg (intensive group; n =1330) or <140 mm Hg (standard group; n =1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). Treatment effects did not differ between participants with and without CKD ( P values for interactions ≥0.30). The prespecified main kidney outcome, defined as the composite of ≥50% decrease in eGFR from baseline or ESRD, occurred in 15 intensive group and 16 standard group participants (HR, 0.90; 95% CI, 0.44 to 1.83). After the initial 6 months, the intensive group had a slightly higher rate of change in eGFR (−0.47 versus −0.32 ml/min per 1.73 m 2 per year; P <0.03). The overall rate of serious adverse events did not differ between treatment groups, although some specific adverse events occurred more often in the intensive group. Thus, among patients with CKD and hypertension without diabetes, targeting an SBP<120 mm Hg compared with <140 mm Hg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome.
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              Plasma sodium stiffens vascular endothelium and reduces nitric oxide release.

              Dietary salt plays a major role in the regulation of blood pressure, and the mineralocorticoid hormone aldosterone controls salt homeostasis and extracellular volume. Recent observations suggest that a small increase in plasma sodium concentration may contribute to the pressor response of dietary salt. Because endothelial cells are (i) sensitive to aldosterone, (ii) in physical contact with plasma sodium, and (iii) crucial regulators of vascular tone, we tested whether acute changes in plasma sodium concentration, within the physiological range, can alter the physical properties of endothelial cells. The tip of an atomic force microscope was used as a nanosensor to measure stiffness of living endothelial cells incubated for 3 days in a culture medium containing aldosterone at a physiological concentration (0.45 nM). Endothelial cell stiffness was unaffected by acute changes in sodium concentration <135 mM but rose steeply between 135 and 145 mM. The increase in stiffness occurred within minutes. Lack of aldosterone in the culture medium or treatment with the epithelial sodium channel inhibitor amiloride prevented this response. Nitric oxide formation was found down-regulated in cells cultured in aldosterone-containing high sodium medium. The results suggest that changes in plasma sodium concentration per se may affect endothelial function and thus control vascular tone.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                06 June 2018
                June 2018
                : 10
                : 6
                : 732
                Affiliations
                [1 ]Division of Nephrology, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; carlo.garofalo@ 123456hotmail.it (C.G.); dott.silvioborrelli@ 123456gmail.com (S.B.); michiprov@ 123456hotmail.it (M.P.); toni-ds@ 123456live.it (T.D.S.); carlovita90@ 123456gmail.com (C.V.); roberto.minutolo@ 123456unicampania.it (R.M.); luca.denicola@ 123456unicampania.it (L.D.N.)
                [2 ]Medical Statistics Unit, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; paolo.chiodini@ 123456unicampania.it
                Author notes
                [* ]Correspondence: giuseppe.conte@ 123456unicampania.it ; Tel.: +39-081-2549409
                Author information
                https://orcid.org/0000-0003-0139-2264
                Article
                nutrients-10-00732
                10.3390/nu10060732
                6024651
                29882800
                71263f23-da45-469a-af31-559d463746b3
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 May 2018
                : 04 June 2018
                Categories
                Review

                Nutrition & Dietetics
                dietary salt restriction,blood pressure,proteinuria,chronic kidney disease

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