1. IntroductionPatients with end stage kidney disease (ESKD) on hemodialysis (HD) have an increased risk of premature mortality that is approximately ten times higher than in the general population [1], and a 40% increased risk of death is from cardiovascular disease [2]. There is limited evidence on whether any preventive or treatment strategies significantly reduce the risk of mortality in this high-risk vulnerable population. Lifestyle and dietary changes are potentially modifiable factors that have been shown to have significant public health benefits in the general population. Studies have also shown that a plant-based diet is associated with lower risk of cardiovascular morbidity and mortality in the general population [3,4,5]. The Dietary Approach to Stop Hypertension diet (DASH) and the Mediterranean diet emphasize increased fruits, vegetables, and fish intake, and recommend reducing fat, saturated fat, refined sugars and meat. Studies have shown that these diets are associated with a 10–30% reduction in cardiovascular event mortality in the general population [6,7,8]. This effect is thought to be achieved by the reduction of insulin resistance, oxidative stress, and inflammation, and improved serum lipids, blood pressure (BP), endothelial function, and arterial compliance [7,9,10].Mediterranean diet adherence is shown to be associated with reduced mortality among patients with chronic kidney disease (CKD) [11] and evidence also suggests that it may prevent or decrease progression of CKD [12]. A recent systematic review also showed that each one-point-higher adherence to the Mediterranean diet was associated with a 10% reduction of progression of CKD [13]. However, the effects of the DASH diet on clinical outcomes among ESKD patients are inconsistent, and it remains unclear if it has any beneficial effect in this population [14,15,16,17,18,19,20]. Current dietary guidelines for ESKD patients usually recommend the restriction of specific nutrients (sodium, potassium, phosphorus, etc.) and recommend high protein and calorie intake [21,22,23]. However, there is limited evidence showing the clinical benefits of restricted nutrients in ESKD patients. The literature has been inconsistent regarding the benefits of a DASH diet in the chronic kidney disease population, and only a small number of studies are available in ESKD patients [14,15,16,17,18,19,20]. In this systematic review, we evaluated the impact of a DASH, Mediterranean, or plant-based diet on clinical outcomes, including all-cause and cardiovascular mortality, left ventricular hypertrophy (LVH), and hyperkalemia in ESKD patients. 4. DiscussionThis systematic review provides new insight into the effect of dietary patterns on clinical outcomes in ESKD patients. Current dietary recommendations mainly focus on the role of individual nutrients rather than whole dietary patterns. These current recommendations include a diet low in sodium, potassium, and phosphorus, and high in energy and proteins [23]. In contrast, the Mediterranean, DASH, and plant-based diets, which have been shown to improve all-cause and cardiovascular mortality in the general population [3,4,5,6,7,8], are rich in potassium and phosphorus while low in animal proteins. There is limited evidence regarding the impact of these dietary patterns on ESKD patients. In this systematic review involving 9400 patients with ESKD on dialysis (both HD and PD), we demonstrated that there was no significant impact of dietary pattern (Mediterranean, DASH, or plant-based) on overall incidence of all-cause or cardiovascular mortality in ESKD patients. However, we also showed that despite the lack of benefits on mortality outcomes, these dietary patterns did not contribute to harm in ESKD patients with respect to hyperkalemia, mortality, or adverse cardiovascular outcomes.The lack of benefit between these dietary patterns and mortality can have several explanations. The magnitude of ESKD’s deleterious effect on health in a unique population with multiple comorbidities compared to the general population may be so significant that it can override any discernible beneficial impact of these dietary patterns [31,32,33,34,35]. The higher frailty and lower socioeconomic status in the ESKD population compared to the general population could also have biased the results [36,37,38,39]. Finally, the follow-up duration for these included studies was relatively short, so it may have reduced the detection of any significant association.The absence of a cardiovascular benefit from a Mediterranean, DASH, or plant-based diet can be hypothesized that in the general population, the cardioprotective mechanisms of these diets are largely driven by improved lipid, glycemic, and blood pressure control [3,4,5,40,41]. In HD patients, it has been shown that there are multiple nontraditional factors that can be associated with increased cardiovascular events and mortality, including increased oxidative stress, inflammation, uremic effects, altered calcium-phosphate regulation, and endothelial dysfunction [22,42]. That could explain why any beneficial physiological changes caused by a Mediterranean, DASH, or plant-based diet may not be sufficient to improve cardiovascular outcomes.Higher adherence to a Mediterranean diet was associated with decreased adverse cardiovascular outcome markers as measured by LVH in ESKD patients [16]. Becharaki et al. [16] also showed that a higher Mediterranean diet score was associated with a lower prevalence of crescentic and eccentric cardiac geometry. A prior meta-analysis that evaluated secondary cardiovascular outcomes for a Mediterranean diet in the general population did not show a significant association [43], however, they did not evaluate the geometry of the heart. There is limited literature regarding the dietary effect on cardiac geometry in CKD patients, but it has been shown that CKD was associated with significant changes in left ventricular geometry [44,45]. Previous studies have demonstrated that diets rich in phosphorus and sodium are associated with increased cardiac hypertrophy in ESKD patients [46,47]. A Mediterranean diet with lower salt and phosphorus compared to the Western diet could explain the reduced prevalence of LVH in ESKD patients. However, there might be some unattributed dietary component in the Mediterranean diet translating to improved cardiovascular outcomes [15].

Our systematic review interestingly showed that despite being on a Mediterranean, DASH, or plant-based diet that is rich in potassium, ESKD patients did not develop hyperkalemia compared to controls. Notably, while our study did not show significant the benefit of a Mediterranean, DASH, or plant-based diet on ESKD patients for the respective outcomes noted above, it also, conversely, did not show harm with these dietary patterns. This review may provide evidence against the commonly accepted blanket practice of dietary modifications in ESKD patients that includes the avoidance of many plant-based diets due to the concern of hyperkalemia.

Efforts to mitigate the significant morbidity and mortality in ESKD patients have been largely frustratingly inadequate. Future studies are needed that evaluate the efficacy of a multitarget approach that encompasses a simultaneous treatment strategy that revisits prior treatment efforts such as dietary therapy, statin, blood pressure control, fluid management, CKD-MBD, and other interventions. As ESKD is a solitary organ system failure that results in systemic and widespread multiorgan deleterious effects, a preventative and therapeutic approach may require a similar comprehensive treatment strategy in this high-risk population.

This study has several limitations. First, there was low level but statistically significant heterogeneity between studies in this meta-analysis. The possible source of this heterogeneity includes the difference in assessment of the dietary patterns and comparator groups utilized among the included studies. However, this heterogeneity was relatively insignificant in the analyses assessing the incidence of all-cause mortality, cardiovascular mortality, and rate of hyperkalemia. Second, this is a meta-analysis of observational studies. Thus, it can only at best identify associations between dietary patterns and adverse outcomes in ESKD, but not a causal relationship. Another limitation is that this meta-analysis did not investigate other cardiovascular outcomes of interest (such as LVEF, diastolic dysfunction, NYHA class, history of PCI or CABG) or other adverse effects (nutritional status such as low BMI, exercise tolerance, and serum albumin). In addition, while this current study is the first systematic review and meta-analysis that summarizes all available data on Mediterranean, DASH, or plant-based diets in ESKD patients, the number of relevant studies existing and included in the meta-analysis are limited, and thus future studies with long-term follow-up are required.