Sodium Intake and Blood Pressure in Patients with Chronic Kidney Disease: A Salty Relationship

Individuals with chronic kidney disease (CKD) generally have higher blood pressure (BP) levels than people with normal kidney function. These individuals are particularly sensitive to high salt intake, which may potentially have a greater impact on BP in patients with CKD than in those without CKD. This observation may be explained since by the reduction in the ability to excrete the salt load in the urine observed in patients with impaired kidney function. Salt reduction interventions offer the potential to lower BP in a simple, inexpensive, effective fashion, while also improving cardiovascular disease (CVD) and CKD progression risk. In this review article, we summarize the current knowledge related to the association between sodium consumption, BP, and the risk of CVD and CKD, and provide recommendations of how to achieve a reduction in sodium intake.

Sodium is an essential nutrient for the maintenance of plasma volume and plasma osmolality, and participates in several metabolic pathways essential to maintain life [1]. However, when consumed in excess, high sodium intake is an important risk factor for hypertension and is also associated with an increased risk of cardiovascular and kidney diseases [2, 3].

A systematic analysis of recently published, population-based studies from 90 countries concluded that in 2010, one third of the world’s adults had hypertension and that in one decade, the age-standardized prevalence of hypertension decreased by 2.6% in high-income countries, but increased by 7.7% in low and middle-income countries [4]. In fact, one of the important factors related to hypertension is high sodium consumption. The Global Burden of Diseases Nutrition and Chronic Diseases Expert Group concluded by means of a modeling study that 10% or 1.65 million deaths from cardiovascular causes that occurred in 2010 were attributed to sodium consumption above 2.0 g/day [5]. In fact, hypertension is known as the leading preventable risk factor for premature death and disability worldwide [6].

Therefore, based on solid scientific evidence, dietary guidelines recommend that sodium intake does not exceed 2–2.4 g/day [1, 7]. However, the current intake is far higher in most populations around the world. Also, regarding 2010, the estimated mean sodium intake worldwide was 3.95 g/day and in 51 countries (44.8% of the total adult population), it was over twice the recommended quantity [8].

CVD is the leading cause of mortality in CKD population, with an increased risk of 5–10 times to die due to CVD than to progress to advanced stages of CKD. Several factors contribute to the development of CVD in this population, mostly related to previous comorbidities such as hypertension and diabetes mellitus. However, other risk factors are peculiar to CKD, namely, anemia, bone mineral disorders and (particularly relevant to this review) the inability to excrete the amount of sodium needed and consequent fluid overload [9]. Indeed, dietary sodium intake has been associated with numerous modifiable risk factors for CVD in CKD patients, including increased BP, volume overload, left ventricular hypertrophy, inflammation and endothelial damage [10-12]. Furthermore, markers of kidney damage, such as proteinuria, are also associated with high sodium intake [13, 14], and are the key risk factors for subsequent all-cause and cardiovascular mortality [15, 16]. The main mechanisms involving sodium, BP, heart and kidney are presented in Figure 1.

Salt sensitivity, which is in part genetically determined, is one of the main determinants of BP response. Older age, obesity, diabetes mellitus, and particularly, renal malfunction can also modify the salt sensitivity process. A positive salt balance raises osmotic pressure, increases water intake and, as a consequence, rapidly causes hypervolemia [12, 17]. Along the time, the increase in peripheral vascular resistance through the process of auto-regulation becomes the dominant determinant of BP [12]. Non-osmotic storage of salt has also been well documented and seems to interfere in the increased risk of cardiovascular and renal disease in the population [12, 18, 19]. CKD patients have a reduced ability to excrete high sodium intake, which interferes in the sodium balance increasing the susceptibility to the adverse effects of dietary sodium in their organism, some already described above (Fig. 1) [19, 20].

The effect of high dietary sodium intake in promoting fibrosis and other lesions is not restricted to the kidney, but it is also observed in the cardiovascular system [21]. The effects of angiotensin II and aldosterone are known to be amplified by a high salt intake. However, other mechanisms involved in the direct and BP-independent effects of high salt intake have been identified, such as increased transforming growth factor expression in kidney and aortic endothelial cells, impacting the cardiovascular and renal structure and function [22, 23].

Recently, measurements of atrial natriuretic peptide and brain natriuretic peptide have documented how frequently hypervolemia is present even in patients with advanced CKD patients who achieved dry weight. Controlling hypervolemia could achieve normotensive BP levels, without BP medications and also the regression of left ventricular hypertrophy is possible, thereby associating reduction in salt intake and control of hypervolemia in all stages of CKD [24, 25].

Considering the cardiovascular effects of sodium, it has been amply documented that not only ventricular hypertrophy [26] but also characteristics of the vasculature such as pulse pressure and vascular stiffness, as a consequence of some mechanisms already described here, are influenced by salt intake independent of BP or amplifying the response to high BP [27]. Elevated BP, fluid overload and the development of kidney disease also as a consequence of increased sodium balance will add even more damage to the heart in the long way increasing the mortality risk in CKD patients.

Among CKD patients, the prevalence of hypertension is up to 92% [28-30] and inadequate sodium intake findings are not different from general population data. It has been demonstrated that 60–90% of these population consume sodium in excess [31-34], although literature had shown that efforts to reduce dietary sodium are particularly effective in reducing BP in this population (discussed further). This occurs because people with CKD are considered to represent a salt-sensitive population due to the inability to excrete a sodium load and diminished sodium-buffering capacity [25].

Although highly recommended, it is difficult to decrease and maintain adequate sodium intake due to many reasons. First, it seems that current health care does not provide patients with the necessary support to incorporate the sodium treatment guidelines into their daily life [35]. Second, even when support is available, sodium intake is often not evaluated in people with CKD in clinical practice due to the lack of a simple method [36]. The considered gold standard method by the World Health Organization – repeated 24-h urine collection – is subject to limitations such as high participant burden, the high cost of analysis, susceptibility to under- or over-collection of urine [37]. On the other hand, dietary assessment methods are considered easy to perform but are susceptible to errors related to memory lapses, reporting bias and interviewer skills [38, 39]. The use of spot urine collection to estimate 24-h sodium intake is simpler and has been explored recently, but up to now, no single formula has performed adequately when tested in different CKD populations [33, 40, 41].

Third, there are several additional barriers that make it difficult for a patient’s engagement to a low-sodium diet daily. Among Bangladeshis living in England, De Brito-Ashurst et al. [42] found that barriers to sodium restriction were deeply rooted dietary beliefs, attitudes and a culturally established taste for salt. Patients’ lack of practical knowledge and intrinsic motivation, the maladaptive illness perceptions and refusal skills, the lack of social support and feedback regarding disease progression and sodium intake, and the availability of low-sodium foods were barriers to Dutch patients as revealed by an investigation with focus groups [43].

Recently, Meuleman et al. [35] studied 156 patients with CKD and identified that although they believed that limiting dietary sodium is beneficial, they still experience multiple difficulties. The domains classified as very important barriers were high sodium content in products, lack of sodium feedback, lack of goal setting and discussing strategies for sodium reduction, and not experiencing CKD-related symptoms. Furthermore, sodium reduction barrier domains were associated with age, level of education, number of comorbidities, perceived autonomy support, depressive symptoms and self-efficacy.

These studies identified the following as a facilitator that helped one to adhere to a low-sodium diet: developing acceptable strategies for cooking with less salt without affecting palatability [42] (particularly important in countries where cooking salt is the main sodium source in habitual diet). Moreover, support strategies that target various sodium reduction barriers and strengthen beliefs regarding self-efficacy and autonomy support are extremely important [35]. Additionally, interventions to reduce sodium levels in processed foods, improve sodium-related product labels and increase consumer awareness are essential mainly in places where these products are the main source of sodium intake [35, 43].

Few studies analyzed the effects of salt restriction in CKD. In 2015, McMahon et al. [44] performed a systematic review including the results of 8 randomized controlled trials, with a total of 258 patients included, the average study duration being 6 weeks (summarized in Table 1). Five were performed in CKD patients with heterogeneous intervention methods, and most mostly including patients in early stages of CKD. Interestingly, reducing sodium intake was consistently associated with a decrease in BP by 8/3 mm Hg mirrored by a drop in proteinuria ranging from 20 to 50% [44].

Two randomized controlled trials were published after the mentioned meta-analysis. In the cross-over study of Saran et al. [45], in which 58 patients were advised to reduce sodium intake for 4 weeks; a decrease of 1.3 g sodium resulted in a decrease of 10.8 mm Hg in systolic BP, without impacting albuminuria. Meuleman et al. [46] compared patients in regular follow-up for over 6 months with those who received additional intervention with a focus on education, motivational interview, coaching and self-monitoring of BP and sodium consumption. They found modest improvement in outcomes after the first 3 months (sodium excretion, BP, and proteinuria), which decreased the follow-up time [46]. Thus, although effective in improving the control of risk factors for renal and cardiovascular outcomes in short periods, the clinical practice also shows that the adherence to a low-sodium diet for longer periods is a huge challenge for medical staff and patients.

Regarding the effect of lowering sodium intake in renal and cardiovascular outcomes, no clinical trial was performed. Available data on this relationship are from post-hoc analysis and observational studies. The avoidance of high sodium intake increased the effect of renin-angiotensin-aldosterone system blockade in 2 post hoc analyses of clinical trials in these outcomes [47, 48]. The analysis of a large cohort of people with established CKD demonstrated the prospective association of high urinary sodium excretion with adverse outcomes, such as CVD incidence [49], CKD progression and all-cause mortality [50].

The KDIGO 2012 Clinical Practice Guideline for the Management of BP in Chronic Kidney Disease recommends lowering salt intake to <90 mmol (<2 g) per day of sodium (corresponding to 5 g of sodium chloride), unless contraindicated (level of evidence: 1C) [51]. Specific strategies are important in the implementation of these recommendations. Sodium intake and dietary patterns vary enormously worldwide, and therefore, the strategies need to be based on the local reality. Some practical strategies developed in Brazil, South Africa, Japan and Italy are published; they can serve as examples of implementation at the local level taking into account local patterns and peculiarities [52-55].

There is good evidence supporting the positive effects in decreasing sodium intake on surrogate markers of cardiovascular events (BP) and progression of kidney disease (albuminuria) in CKD patients. Moreover, most of the trials available in the area have a relatively shorter follow-up, and the long-term sustainability of a low-sodium diet is a major challenge, since it involves not only patient’s self-motivation but also tailored multidisciplinary approach, family involvement and government actions. Larger studies with longer follow-up periods looking at hard endpoints will be important to drive future recommendations related to sodium intake, and particularly efficient strategies for implementation of this low-cost measure with potential impact in kidney and cardiovascular disease are to be developed.

F.B.N. and V.C.-S. have no disclosure. R.P.-F. receives Speake fees and research honoraria from Janssen, AstraZeneca, Novartis, Akebia, Baxter, and Fresenius Medical Care.