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Review

Food to Prevent Vascular Calcification in Chronic Kidney Disease

by
Diana Moldovan
1,2,*,
Crina Rusu
1,2,
Alina Potra
1,2,
Dacian Tirinescu
1,2,
Maria Ticala
1,2 and
Ina Kacso
1,2
1
Department of Nephrology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 400347 Cluj-Napoca, Romania
2
Nephrology Clinic, Emergency County Hospital Cluj-Napoca, 400347 Cluj-Napoca, Romania
*
Author to whom correspondence should be addressed.
Nutrients 2024, 16(5), 617; https://doi.org/10.3390/nu16050617
Submission received: 30 January 2024 / Revised: 14 February 2024 / Accepted: 16 February 2024 / Published: 23 February 2024
(This article belongs to the Special Issue Effect of Lifestyle and Dietary Interventions for People with Chronic Kidney Disease)
Browse Figure
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Abstract

:
Vascular calcification (VC) is a consequence of chronic kidney disease (CKD) which is of paramount importance regarding the survival of CKD patients. VC is far from being controlled with actual medication; as a result, in recent years, diet modulation has become more compelling. The concept of medical nutritional therapy points out the idea that food may prevent or treat diseases. The aim of this review was to evaluate the influence of food habits and nutritional intervention in the occurrence and progression of VC in CKD. Evidence reports the harmfulness of ultra-processed food, food additives, and animal-based proteins due to the increased intake of high absorbable phosphorus, the scarcity of fibers, and the increased production of uremic toxins. Available data are more supportive of a plant-dominant diet, especially for the impact on gut microbiota composition, which varies significantly depending on VC presence. Magnesium has been shown to prevent VC but only in experimental and small clinical studies. Vitamin K has drawn considerable attention due to its activation of VC inhibitors. There are positive studies; unfortunately, recent trials failed to prove its efficacy in preventing VC. Future research is needed and should aim to transform food into a medical intervention to eliminate VC danger in CKD.

1. Introduction

Chronic kidney disease (CKD) is an emerging public health priority associated with high mortality rates and demanding complex management, including lifestyle changes, medications, and, sometimes, renal replacement therapy. Due to its very high prevalence in over 10% of the general population, CKD has a heavy social and financial burdens [1]. Above all other effects, CKD produces a significant negative impact on patients’ lives, leading to complications that affect their quality and becoming life-threatening over time. One of the most important, yet unsolved, complications is chronic kidney disease—mineral and bone disorder (CKD-MBD) [2,3,4]. As CKD progresses, cardiovascular and osteo-articular complications occur and may have different impacts on patients’ quality of life. CKD-MBD leads to a multitude of symptoms, including decreased function and social roles, depression, and a shorter life span [4,5]. Vascular calcification (VC) is the main abnormality from the complex CKD-MBD in terms of associated cardiovascular morbidity and mortality [2,3,6]. The goals of management in different stages of CKD are to slow the progression of kidney disease, to postpone the need for replacement therapy, and to control complications, such as hyperkalemia, metabolic acidosis, inflammation, protein malnutrition, anemia, high blood pressure, and mineral and bone disorders, which are particularly important for chronic management [1].
Food and drug intake may sometimes have a poisonous effect on the kidneys; therefore, a large number of patients with kidney failure have reached a point of no return due to their everyday life choices. Lifestyle impacts epigenetics, body composition, and function, so people will eventually develop CKD if their habits are harmful. In the most prominent diseases of this century, including diabetes mellitus, hypertension, cardiovascular diseases, and cancer, studies have been carried out and have proven that different environmental factors contribute to each of these diseases’ pathogeny [7,8]. Type 2 diabetes mellitus is associated with a diet that is rich in sweets, soft drinks, snacks, nuggets, and other ultra-processed foods [7]; hypertension has a strong connection with salt intake [9]; and cardiovascular diseases have strong connections with fatty foods. And, as is well known, the above-mentioned illnesses are the main causes of CKD. The ageing process itself is associated with common “burden of lifestyle” diseases, which include CKD. Interestingly, aging and CKD share important features; CKD is a condition which leads to an increased biological age [10], and CKD-MBD raises its invalidity rate and death toll [11]. We live in times of increasing awareness of the potential of meals to damage health. Consequently, a useful idea that has captured public attention is that food may become a tool to prevent or treat diseases and might be considered as medicine. This idea was conceptualized as medical nutritional therapy [12] or food as medicine [13,14]. When properly used, food may heal and may slow down and alleviate disease. Besides all of these well-known factors, different dietary patterns may be important influencers for chronic diseases, including CKD and its main chronic complication, CKD-MBD. Energy and action define everyone’s way of living; therefore, smart choices must be made regarding food as energy supply based on valid scientific data. There is hope that lifestyle changes will slow or stop CKD-MBD features and prevent or even lead to regression in VC [15,16,17]. Clear knowledge about what to eat, how much to eat, and in what combination is necessary for patients with CKD-MBD [15]. Medical nutrition therapy (MNT) is an evidence-based process aiming to treat or manage a disease through nutrition. Its components are comprehensive and include the evaluation of nutritional status, intervention in diets, and nutrition therapies [12].
In this study, we aim to provide a comprehensive review of the effects of diet on VC as a part of the CKD-MBD spectrum that is known to be associated with severe clinical outcomes in patients with CKD. We will present the current state of this research field by reviewing the key publications from recent years, and we will highlight controversial and diverging hypotheses regarding this approach.

2. Vascular Calcification in CKD

CKD is characterized by features of accelerated ageing, such as increased levels of cellular senescence, and epigenetic modifications, such as telomere attrition, arterial calcification, osteoporosis, sarcopenia, frailty, and depression [11]. According to the KDIGO guidelines, the term “chronic kidney disease—mineral and bone disorder (CKD–MBD)” is a clinical syndrome which comprises mineral, bone, and calcific cardiovascular abnormalities in CKD. It includes modifications of calcium, phosphorus, parathyroid hormone (PTH), vitamin D, bone metabolism, and vascular or other soft-tissue calcification [2,3]. CKD-MBD is a consequence of CKD that has led to extended research and the development of a wide variety of treatments; despite specialists’ implications, it continues to produce a multitude of symptoms and deleterious effects for the people who have it, including the following:
  • Vascular calcification (VC) is a phenomenon involving the deposition of calcium and phosphorus within the layers of the arteries. Medial calcification, which presents as rail-train deposits along the vasculature, is particularly prevalent in patients suffering from CKD, but it is associated with aging and diabetes mellitus, too. It mainly affects the aorta and peripheral arteries. The deposition of mineral content within the media is preceded by phenotypic changes in vascular smooth muscle cells (VSMCs) and leads to arterial stiffness, significantly contributing to heart failure and increased cardiovascular morbidity. The accumulation of uremic toxins, the imbalance of calcium and phosphate, and a lack of calcification inhibitors have been implicated in the pathogenesis of calcification.
  • Intimal calcification displays a patchy distribution pattern and preferentially affects the coronary and carotid arteries. It is part of the atherosclerosis process. In patients with dyslipidemia and hypertension and smokers, atherosclerotic plaques occur as a consequence of inflammation and endothelial damage. It is common to find both types of calcifications in CKD patients. Accumulation of mineral content in atherosclerotic plaques may increase the risk of ischemic events such as stroke, ischemic coronary syndromes, or ischemic arteriopathy of the lower limbs [18,19].
  • Other ectopic extraskeletal calcifications may occur. Valvular calcification is highly prevalent in CKD patients, contributing to chronic heart failure; calcifications in the joints can cause pain and functional impotence, and calcifications in the subcutaneous tissue can lead to resistant pruritus.

3. Food for CKD Patients

According to Global Burden of Disease Study, dietary risk factors are major contributors to millions of deaths, leading to higher mortality rates than well-known risk factors such as smoking [20]. Lifestyle interventions, such as healthy nutritional habits, proved to be effective in reducing cardiovascular risk factors in the general population [21]. High intake of sodium and sugar and a low intake of whole grains, vegetables, and fruits can cause type 2 diabetes mellitus, hypertension, cardiovascular disease, cancer, and CKD [22]. A study conducted in the Netherlands on over 78,000 people with a follow-up of 3.6 years revealed new evidence that ultra-processed food consumption leads to kidney function decline [23]. An observational study from Brazil demonstrated that elderly patients on hemodialysis (HD) have a worse dietary quality and higher consumption of ultra-processed food than elderly without CKD [24]. Some diets, as the DASH (Dietary Approaches to Stop Hypertension) diet and Mediterranean diet, provided important evidence regarding efficacy in promoting health [25]; these diets especially involve the reduction in salt, fat, and processed food intake. Tyson et al. demonstrated in CKD patients that the reduced-sodium DASH diet is efficient in reducing blood pressure [26].
CKD people are constantly exposed to conditions that alter epigenetic regulation such as toxins and shifts in dietary patterns. CKD-MBD leads to changes in DNA or histones, which are heritable from one cell to its descendants [27]. Neytchev et al. compared dialysis patients with transplant patients and controls and demonstrated that the uremic milieu drives genome-wide methylation changes that are partially reversed with kidney failure replacement therapy [28]. Studies have shown that different life variables, including food choices, may lead to epigenomic reprogramming [27,29]. Recent research of these nutritional interventions in CKD patients with VC gives rise to the hope of finding solutions.

4. Phosphorus, Vitamin D, and Calcium and Vascular Calcification in CKD

In patients with CKD, mineral disorders are associated with hyperparathyroidism, renal osteodystrophy, arterial calcification, and cardiovascular mortality [30,31]. CKD-MBD is marked by high serum phosphate levels, low serum active vitamin D, and low serum calcium levels.
Increased phosphate levels lead to VC and high cardiovascular death. In their experimental study, Turner et al. discovered that the arteries acutely deposit large amounts of amorphous phosphate to control the elevation in the bloodstream, thereby altering the systemic disposition of phosphate; therefore, they identified the arteries as a participatory mineral homeostatic organ [32]. Nephrologists encounter serious difficulties in controlling phosphate levels, and phosphate impacts the CKD-MBD patients’ prognosis, even when receiving specific medication. Yet, the benefits of phosphate-lowering medication on VC, arterial stiffness, and clinical outcomes in predialysis CKD stages remain uncertain [33,34]. Nevertheless, there is evidence in favor of phosphate lowering; a recent Japanese study has proven that consistently strict phosphate control may slow the progression of coronary and valvular calcifications in incident patients undergoing HD (Table 1) [35].
In PROGREDIR study on non-dialysis CKD patients, Machado et al. demonstrated that an increased intake of phosphorus- and calcium-rich food is associated with coronary artery calcification (Table 1) [36].
Sources of phosphorus include meats, fish, poultry, dairy products, nuts, beans, and food additives. Animal foods and inorganic phosphorus from food additives and preservatives have higher phosphorus absorption than plant foods; the industrial use of phosphate in additives used for ultra-processed food is strongly linked to cardiorenal disease risk [59,60]. An increasing number of specialists recommend a more plant-based diet to control phosphate. Phosphate bioavailability is lower with a vegetarian diet compared to a diet based on animal protein or processed foods and beverages. Many foods that have traditionally been labeled high in phosphate (such as beans and nuts) may actually be acceptable because phosphate from these sources is only partially and slowly absorbed. The plant-derived phosphate found in unprocessed foods is in the form of phosphorus phytate, and the human intestine does not secrete phytase, the enzyme required for absorption [60,61]. In addition, such a diet, rich in legumes, nuts, and whole grains, may also result in higher fiber intake while offering wider food choices and preventing constipation with better digestive phosphorus elimination [62,63]. These data highlight the importance of phosphate bioavailability in different foods in CKD patients as a mediator of cardiovascular risk.
In cases of severe and progressive secondary hyperparathyroidism, the 2017 KDIGO guidelines recommend the use of calcitriol and vitamin D analogs [3]. We have to be aware of the potential double-edged sword effect of vitamin D, since both deficiency and excess may be related to VC. While deficiency produces hyperparathyroidism and VC, treatment with calcitriol and vitamin D analogs, even if reducing the PTH level, can lead to the development of VC by increasing the intestinal absorption of calcium and phosphate [64]. The intake of food rich in vitamin D, such as ergocalciferol and cholecalciferol, can decrease the required dose of active vitamin D, thus mitigating the VC risk associated with the latter. Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) are recognized as fat-soluble prohormones, having different sources. Part of vitamin D as a nutrient is synthesized by the body through the action of sunlight, and some foods are fortified with the vitamin. Yet, there are foods naturally rich in vitamin D, including salmon, herring, mackerel, sardines, mushrooms, cashews, and hazelnuts [22,65]. Well controlled studies are needed to determine whether nutritional vitamin D slows the rate of progression of VC.

5. Magnesium and Vascular Calcification in CKD

The capacity of magnesium to inhibit calcium phosphate crystallization has been well documented in the context of VC. Magnesium effectively suppresses phosphate-induced calcification of VSMCs, as proved in different experiments [66]. Magnesium is known to suppress the maturation of calciprotein particles, which may play a pivotal role in the pathogenesis of VC. A high-magnesium diet prevented aortic calcification in animal models of CKD, such as Klotho knockout mice [37] (Table 1).
Patients with diabetes and CKD on HD showed reduced carotid intima–media thickness after magnesium supplementation, emphasizing a preventive role against VC [38]. Sakaguchi conducted a randomized trial comparing magnesium oxide and oral carbon adsorbent in predialysis CKD patients with coronary artery calcifications. The study proved the efficacy of magnesium to prevent coronary artery calcification progression [39] (Table 1).
A systematic review analyzed prospective clinical trials testing interventions to attenuate VC in people with CKD. It concluded that, in general, data are insufficient or conflicting, yet magnesium appears to be one of the few promising therapies [67].
The more recent Magical-CKD trial failed to demonstrate an improvement of coronary artery calcification progression after magnesium supplementation [40] (Table 1). Nevertheless, magnesium is one of the few nutritional elements with supportive data in terms of VC protection. Hypomagnesemia is not rare in patients with CKD, and several causes can be identified; the dietary restriction of potassium limits the intake of magnesium, and diuretics are known to enhance its urinary excretion. Almonds, peanuts, cashew, and spinach are foods rich in magnesium; these can be a good source especially in patients with low serum magnesium levels.
Zinc is considered an essential nutrient, having numerous benefits for health. A recent study demonstrated associations of low blood zinc levels with coronary artery calcification and future cardiovascular events in CKD patients. Good sources of zinc include seafood, meat, nuts, whole grains, and dairy products, which are recommended to avoid a zinc deficit [41].

6. Vitamin K and Vascular Calcification in CKD

There is a close relationship between vitamin K and biomineralization. Vitamin K enables normal calcification processes in bones and soft tissues. This role is associated with vitamin-K-dependent proteins, including osteocalcin, matrix γ-carboxyglutamic acid (Gla) protein, and growth arrest specific 6 (Gas6). Matrix Gla protein, a vitamin K-dependent protein produced by VSMCs, is a powerful inhibitor of VC in culture cells with medial and intimal calcification. In view of the key role played by vitamin K, it is not surprising that patients with vitamin K deficiency and those who are using long-term anticoagulant therapy with vitamin K antagonists are prone to develop VC. There are two types of vitamin K. Vitamin K1 (phylloquinone) is found primarily in foods, especially plant-based oils, green vegetables (e.g., broccoli, spinach, and cabbage), and cow’s milk. The forms of vitamin K2 (menaquinones) are produced by bacteria, being found in meat, dairy products, and fermented foods, and are also synthesized in the intestine by colonic bacteria [68] (Figure 1).
McCabe et al. studied rats with adenine-induced chronic renal failure and showed that administration of a high dose of vitamin K protected against the development of warfarin-induced calcification [42] (Table 1).
In a study on HD patients, the levels of matrix Gla proteins displayed a significant increase in patients receiving vitamin K2 compared with vitamin K1 and placebo groups [43].
A study on HD patients from China demonstrated that the VC scores decreased as an effect of a vitamin-K-enriched dialysate [44].
Recently, a few randomized controlled trials were designed to test the anticalcification properties of vitamin K. Trevasc-HDK failed to prove that vitamin K2 can reduce progression of coronary artery calcification in HD patients [45]. The conclusion of RenaKvit, a double-blind, randomized, placebo-controlled trial, was that vitamin K supplementation does not modify the progression of arterial calcification in dialysis [46]. Similar results were reported by the iPACK-HD trial; there was improvement in vitamin K levels but no significant modification of VC progression [47] (Table 1).
In conclusion, vitamin K had no consistent benefit in VC reduction in CKD patients. Vitamin K1 showed better efficacy in correcting vitamin K status, and it had very positive results in experimental studies as a protector against VC. Further clinical studies are needed to shed light on the effect of vitamin K supplementation on arterial health, mostly because there is hope from experimental studies.
Regarding the effects of other vitamins, vitamin E has proven anti-atherogenic and antioxidant attributes, which have been correlated with improved cardiovascular outcomes. Wheat germ oil, sunflower seeds, and avocado have an increased content of vitamin E [69]. A recent study on non-dialysis CKD patients suggested that a higher intake of vitamin B5 (pantothenic acid) may have a small protective effect on coronary calcification [36].

7. Lipids and Vascular Calcification in CKD

Dyslipidemia plays a pivotal role in arterial intima calcification. Among the risk factors for atherosclerosis, cholesterol and lipid deposition are strongly associated with plaque formation and calcification. Clinical trials involving HMG-CoA reductase inhibitors showed good efficacy in reducing lipid levels and cardiovascular risk yet could not consistently demonstrate attenuation of VC [67]. KDOQI guidelines for nutrition in CKD highlight the importance of food choices and suggest that prescribing a Mediterranean diet may improve lipid profiles in adults with CKD 1–5 not on dialysis, having dyslipidemia or not. Prescribing increased fruit, legume, and vegetable intake may decrease body weight and blood pressure in CKD 1–4 patients [70].
Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid and docosahexaenoic acid, are part of a class of lipids with various biological functions. They reduce inflammation and atherogenesis, and, as a result, they can decrease the cardiovascular mortality [71]. Omega-3 PUFAs are used as medication for hypertriglyceridemia in patients with CKD. They are also a component of food, being present in fish oil; in a variety of microorganisms, including bacteria and marine microalgae; and in plant sources, such as flaxseeds, chia, and walnuts [72] (Figure 1). When it comes to mortality and cardiovascular disease, the current KDOQI guidelines in nutrition do not routinely recommend PUFA supplementation, even if it is acknowledged that lipid profile will be improved [70]. Several studies have investigated PUFAs’ effects in CKD; PUFAs increase the membrane potential and ATP levels in mitochondria with a protective effect on the kidneys and arteries. A recent study demonstrated that maslinic acid can reduce renal interstitial fibrosis and can prevent CKD progression and complications [73]. Interestingly, randomized controlled trials comparing the effect of omega-3 PUFA supplementation with placebo have shown significant relief of uremic pruritus, which is associated with CKD-MBD [74].
Experimental studies documented a preventive role of omega-3 fatty acids in pathological calcification, leading to decreased warfarin-induced medial arterial calcification in a rat model [48] (Table 1). It has been reported that patients with CKD have low serum expression of Klotho, which has been proved to be an arterial calcification inhibitor [75]. Nakamura et al. has shown that eicosapentaenoic acid can limit arterial calcification in Klotho mutant mice [49] (Table 1). A recent large study demonstrated an association of higher plasma levels of omega-3 PUFAs with an increased arterial elasticity [76].
Monounsaturated fatty acids are known to have deleterious effects on health (Figure 1). As opposed to PUFAs’ protective attributes, Son et al. demonstrated that the erythrocyte membrane content of monounsaturated fatty acids is significantly higher in HD patients with arterial medial calcification of the feet than in the patients without calcifications [50].
The ketogenic diet, which consists of a limited intake of carbohydrates and a liberal intake of fats, has recently attracted considerable interest. It is proven as an efficient intervention in controlling type 2 diabetes mellitus [77] and in slowing renal cyst growth [78]; therefore, patients with diabetic kidney disease and autosomal-dominant polycystic kidney disease may derive benefits from this diet, including a delay in progression and, eventually, in the complications rate [79]. It may cause a rise in cholesterol levels, so, when adopted, it should be accompanied by close monitoring and treatment for dyslipidemia [77]. Dietary modulation can increase and maintain circulating ketone bodies, especially β-hydroxybutyrate (β-HB), which is one of the most abundant ketone bodies in human circulation [80]. A very important finding was reported by Lan et al.; the ketone body β-hydroxybutyrate (BHB) produced in the ketogenic diet has been demonstrated to suppress VC in CKD through downregulation of HDAC9 [51] (Table 1).
Intermittent fasting, as a model of caloric restriction, has broad-spectrum benefits for many health conditions, such as atherosclerosis, cardiovascular disease, and obesity, as preclinical studies and clinical trials have shown [81]; as far as the impact on VC, it remains a topic for future studies.

8. Uremic Toxins, Microbiota, Fibers, and Vascular Calcification in CKD

Accumulation of various uremic toxins, including inorganic phosphate (Pi), interleukins (IL-1β, IL-6), tumor necrosis factor alpha (TNFα), and indoxyl-sulfate, have been linked to VC. Pi induces the upregulation of several osteoblast-like transition molecules like BMP2 (bone morphogenetic protein 2), RUNX2 (Runt-related transcription factor 2), and osteopontin that initiate the pro-calcifying trans-differentiation of VSMCs. Indoxyl-sulfate stimulates transforming growth factor beta (TGFβ) expression and medial layer hyperplasia. Uremic toxins act on endothelial cells to induce vasoconstriction, upregulation of extracellular matrix degradation molecules such as matrix metalloproteinases 2 and 9, and oxidative stress. Calcium and Pi deposition in the form of hydroxyapatite crystals induces medial VC [82].
The load of uremic toxins can be reduced through dialysis, yet their production is influenced by dietary habits, mostly important in pre-dialysis stages. Some foods are sources for protein-bound uremic toxins (e.g., indoxyl sulphate). These are by-products of aromatic amino acids (phenylalanine, tryptophan, and tyrosine) from protein disintegration by gut microbiota [83]. Colonic bacteria transform tryptophan to indol, which, through oxidation and sulfation in the liver, will lead to indoxyl sulphate formation. Rodrigues et al. have similarly explained the pathophysiology of the interplay between gut microbiota, bone health, and VC in CKD [84]. Interesting results come from studies investigating the influence of different dietary habits on the uremic gut microbiota. Merino-Ribas et al. found differences in the type of microbiota of CKD on peritoneal dialysis with or without VC, namely Coprobacter, Coprococcus 3, Lactobacillus, and the Eubacterium eligens group in the gut and Cutibacterium, Pajaroellobacter, Devosia, Hyphomicrobium, and Pelomonas in the blood. These results may indicate a link between microbiota and VC in CKD patients on peritoneal dialysis [52] (Table 1). Such results from similar studies led to the hypothesis that inflammation and gut dysbiosis are important drivers of CKD–MBD [85]. An association between dietary inflammatory index and cardiovascular disease and mortality was recently proven [86]. A study identified an association of the proatherogenic metabolite trimethylamine N-oxide (TMAO), which increases due to gut dysbiosis, with cardiovascular outcomes in HD patients [87].
Lactobacillus rhamnosus GG is a probiotic with great promise in bone formation, but an experimental study recently proved an association with worsening of VC in CKD [53] (Table 1).
Fiber intake is an important health promoter in the general population. In their recent study, conducted on over 3800 Korean patients with CKD, Kwon et al. reported an inverse association between dietary fiber intake and all-cause mortality at 10 years in CKD patients [88]. Higher fiber intake was associated with less inflammation, less myocardial hypertrophy, and lower risk of cardiovascular events in dialysis patients [89]. Fibers are needed for the effective absorption of nutrients. Fibers demonstrated salutary benefits, including improved glycemic and lipid control, blood pressure, gastrointestinal motility, and gut microbiota composition [90]. In a study published on HD patients, increased dietary fiber intake led to the reduction in indoxyl sulphate levels by 29% [91].
Adequate consumption of phytate (containing myo-inositol hexaphosphate) can prevent abdominal aortic calcification in patients with CKD [54]. The phytate comes from whole-grain cereals, bran, and lentils. Nuts are also a good source of antioxidants and dietary fiber (Figure 1). The Calipso trial demonstrated the effect of myo-inositol hexaphosphate in slowing progression of cardiovascular calcification in patients on HD [55] as additional evidence for the usefulness of this component of fibers (Table 1).
Finding the balance in gut microbiota and regulating microbiota-derived metabolites by dietary intervention and probiotics are new targets for the improvement of the gut–kidney–arteries axis, which indicates innovative interventions of VC in CKD [16,92].

9. Protein Intake and Vascular Calcification in CKD

The foundation of nutrition intervention in CKD was laid for decades on a low-protein diet to slow progression and on restriction of plant foods, such as vegetables and fruits, to prevent hyperkalemia. Lately, this paradigm has changed, and the plant-dominant low-protein (PLADO) diets seem to have become a better choice for patients with CKD [21]. In a sub-analysis of the NHANES III study on 14,000 participants patients with a glomerular filtration rate < 60 mL/min, a diet with a higher proportion of protein from plant sources was associated with lower mortality, probably due to lower production of uremic toxins and lower serum phosphorus levels [30]. The vegetarian diet or a reduced intake of red meat has been associated with a reduction in the generation of uremic toxins [93,94,95,96]. Such a diet is based on fruits, vegetables, seeds, nuts, tea, cocoa, and whole-grain cereals [97]. Among plant-based foods, Brazil nuts seem to have important benefits in CKD, even in end-stage kidney disease patients, due to their contents of proteins, selenium, omega-3 fatty acids, and fibers [98,99] (Figure 1).
The DIET-HD study demonstrated for a large number on HD patients that the highest intake of fruit and vegetables had the lowest risk for all-cause and cardiovascular mortality [100,101]. On the contrary, the CRIC study did not find a significant association between higher diet scores and reduced risk for atherosclerosis or mortality [102] (Figure 1).
As for the risk of hyperkalemia, CKD patients have been advised for a long time to reduce their intake of fruits, vegetables, and nuts. Nevertheless, we must be aware that meat and ultra-processed food have a high content in potassium, with a high absorption rate [103,104,105,106,107,108,109].
Nuts have high content of phosphorus, which is one of the traditional nutrients restricted in advanced CKD to avoid hyperphosphatemia [108], but the latest studies demonstrated that non-animal protein does not lead to hyperphosphatemia, as previously believed [105,109].
To identify dietary components associated with abdominal aorta calcification, data from NHANES were employed in a cross-sectional study. Low contents of proteins, fiber and vitamin A, and high contents of lipids and caffeine exhibited an association with abdominal aorta calcification. High adherence to the plant-based pattern was associated with a lower risk of VC, as a new and valuable result in favor of PLADO [56].

10. Bioactive and Senolytic Food and Vascular Calcification in CKD

Bioactive and senolytic food has antioxidant and anti-inflammatory effects. Resveratrol, quercetin, curcumin, anthocyanins, and cruciferous and cocoa powder are part of this category [110] (Table 1). Anthocyanins, present in purple fruits and vegetables, exert their beneficial effects through improvements in oxidative stress, inflammation, gut microbiota, and modulation of neuropeptides. Their health benefits in humans include protection of the cardiovascular system and kidneys, among others [111].
Resveratrol, a dietary polyphenol compound, has anti-inflammatory and antioxidative properties [112]. Recently, studies also showed that resveratrol is a scavenger for many free radicals and ameliorates VC in CKD [57].
Cocoa contains fatty acids and polyphenolic bioactives, with proanthocyanidins being the most abundant and methylxanthine alkaloids. Dark chocolate led to a reduction in TNFα and no change in potassium and phosphorus plasma levels. These are the results of a clinical trial of 2 months on HD patients [113] (Table 1).
Blueberry, cranberry, raspberry, and strawberry are modulators of the gut microbiota and a target for treatment of gut dysbiosis in CKD [114] (Figure 1).
Dietary senolytics, such as quercetin (found in apples), fisetin (in strawberries), and organosulphur compounds and flavonoids (aged garlic) may be alternative approaches to reduce cardiovascular risk in CKD [13,115]. Quercetin exerted a protective effect on VC in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress [58] (Table 1).
Iron supplementation is highly recommended to improve cardiovascular function in CKD, but it remains controversial when it comes to VC. Recent studies demonstrated that iron targets some pathways of VC dependent on phosphorus-induced osteoblastic transformation of VSMCs to calciproteins, apoptosis, and inflammation, since it is effective both in prevention and when calcification is already established [116].
Selenium works as an antioxidant in the body by preventing vascular cell damage. In a recent study, a higher dietary selenium intake was negatively associated with severe abdominal aorta calcification incidence in CKD patients [117]. The selenium content of foods can vary considerably depending on the geographic area; nuts, oats, seeds, mushrooms, beans, and eggs can be good sources.
As for all the benefits discovered in the mentioned studies, the concept of food as medicine for protecting the kidneys and heart and avoiding VC in CKD patients seems to have moved closer to reality [118].

11. Conclusions

The search for eternal youth, as an emblem for health, is as old as mankind. But in the case of the patients with CKD and VC, it is more of a struggle for life, a fight against many deadly factors, because VC is strongly associated with cardiovascular mortality. Most of the efforts are made to fix problems with a focus on the other end of the spectrum of CKD, and yet medication failed to show consistent efficacy in preventing VC.
Food is essential for life; thus, prevention of VC in CKD through nutrition seems to be the logical approach. High phosphorus absorption, high production of uremic toxins, and gut dysbiosis are consequences of the increased intake of animal-based proteins, processed food, salt, and sugar. Available research links all of the above with the presence of VC. A diet involving vitamin K, magnesium, plant-based diets, fibers, omega 3 fatty acids, or bioactive food appears to be the most promising in protecting against VC. These results are based on experimental and relatively small clinical studies but still are not negligible. Even though clinical trials on magnesium and vitamin K were not able to prove the efficacy of the nutritional interventions in CKD patients with VC, the effects exist, and more research needs to be conducted. Finding the best variants of meals may lead to reduced VC incidence and progression and may allow eating to be transformed into a scientific act and medical intervention with effective outcomes. Food is supplied for life, and data are available to be discovered on the best nutrient choices to disrupt the vicious cycle of the gut–kidney–arteries axis and prevent cardiovascular calcification in the CKD population.

Author Contributions

Conceptualization, D.M. and I.K.; gathering research literature, D.M., C.R. and I.K.; writing—original draft preparation, D.M.; writing—review and editing, A.P., D.T. and M.T; visualization, D.M., A.P., D.T. and M.T.; supervision, D.M. and I.K. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

Data are contained within the article.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Kalantar-Zadeh, K.; Jafar, T.H.; Nitsch, D.; Neuen, B.L.; Perkovic, V. Chronic kidney disease. Lancet 2021, 398, 786–802. [Google Scholar] [CrossRef] [PubMed]
  2. Eckardt, K.-U.; Kasiske, B.L. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int. 2009, 76, S1–S130. [Google Scholar] [CrossRef] [PubMed]
  3. Kidney Disease: Improving Global Outcomes (KDIGO). CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int. 2017, 7, 1–59. [Google Scholar] [CrossRef] [PubMed]
  4. Cannata-Andía, J.B.; Martín-Carro, B.; Martín-Vírgala, J.; Rodríguez-Carrio, J.; Bande-Fernández, J.J.; Alonso-Montes, C.; Carrillo-López, N. Chronic kidney disease—Mineral and bone disorders: Pathogenesis and management. Calcif. Tissue Int. 2021, 108, 410–422. [Google Scholar] [CrossRef] [PubMed]
  5. Bikbov, B.; Purcell, C.A.; Levey, A.S.; Smith, M.; Abdoli, A.; Abebe, M.; Owolabi, M.O. Global, regional, and national burden of chronic kidney disease, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet 2020, 395, 709–733. [Google Scholar] [CrossRef] [PubMed]
  6. Moldovan, D.; Rusu, C.; Potra, A.; Bondor, C.; Ticala, M.; Tirinescu, D.; Coman, A.; Orasan, O.; Moldovan, I.; Orasan, R.; et al. Arterial calcifications and osteoprotegerin in chronic hemodialysis patients: Impact on 6-year survival. Int. Urol. Nephrol. 2022, 54, 1135–1143. [Google Scholar] [CrossRef] [PubMed]
  7. Srour, B.; Fezeu, L.K.; Kesse-Guyot, E.; Allès, B.; Debras, C.; Druesne-Pecollo, N.; Chazelas, E.; Deschasaux, M.; Hercberg, S.; Galan, P.; et al. Ultraprocessed food consumption and risk of type 2 diabetes among participants of the NutriNet-Santé prospective cohort. JAMA Intern. Med. 2019, 180, 283–291. [Google Scholar] [CrossRef] [PubMed]
  8. Liu, X.; Wu, S.; Song, Q.; Wang, X. Reversion from pre–diabetes mellitus to normoglycemia and risk of cardiovascular disease and all-cause mortality in a chinese population: A prospective cohort study. J. Am. Heart Assoc. 2021, 10, e019045. [Google Scholar] [CrossRef]
  9. Kawarazaki, W.; Fujita, T. Kidney and epigenetic mechanisms of salt-sensitive hypertension. Nat. Rev. Nephrol. 2021, 17, 350–363. [Google Scholar] [CrossRef]
  10. Wen, L.; Yang, H.L.; Lin, L.; Ma, L.; Fu, P. The Emerging role of epigenetic methylation in kidney disease. Curr. Med. Chem. 2022, 29, 3732–3747. [Google Scholar] [CrossRef]
  11. Chou, Y.H.; Chen, Y.M. Aging and renal disease: Old questions for new challenges. Aging Dis. 2021, 12, 515–528. [Google Scholar] [CrossRef]
  12. Kalantar-Zadeh, K.; Mattix-Kramer, H.J.; Moore, L.W. Culinary medicine as a core component of the medical nutrition therapy for kidney health and disease. J. Ren. Nutr. 2021, 31, 1–4. [Google Scholar] [CrossRef]
  13. Mafra, D.; Borges, N.A.; Lindholm, B.; Shiels, P.G.; Evenepoel, P.; Stenvinkel, P. Food as medicine: Targeting the uraemic phenotype in chronic kidney disease. Nat. Rev. Nephrol. 2021, 17, 153–171. [Google Scholar] [CrossRef]
  14. Alvarenga, L.; Reis, D.C.; Kemp, J.A.; Teixeira, K.T.R.; Fouque, D.; Mafra, D. Using the concept of food as medicine to mitigate inflammation in patients undergoing peritoneal dialysis. In Therapeutic Apheresis and Dialysis; Wiley: Hoboken, NJ, USA, 2024. [Google Scholar] [CrossRef]
  15. Hu, E.A.; Steffen, L.M.; Grams, M.E.; Crews, D.C.; Coresh, J.; Appel, L.J.; Rebholz, C.M. Dietary patterns and risk of incident chronic kidney disease: The atherosclerosis risk in communities study. Am. J. Clin. Nutr. 2019, 110, 713–721. [Google Scholar] [CrossRef] [PubMed]
  16. Yin, L.; Li, X.; Ghosh, S.; Xie, C.; Chen, J.; Huang, H. Role of gut microbiota-derived metabolites on vascular calcification in CKD. J. Cell. Mol. Med. 2021, 25, 1332–1341. [Google Scholar] [CrossRef] [PubMed]
  17. Cretoiu, D.; Ionescu, R.F.; Enache, R.M.; Cretoiu, S.M.; Voinea, S.C. Gut microbiome, functional food, atherosclerosis, and vascular calcifications—Is there a missing link? Microorganisms 2021, 9, 1913. [Google Scholar] [CrossRef] [PubMed]
  18. Ebert, T.; Neytchev, O.; Witasp, A.; Kublickiene, K.; Stenvinkel, P.; Shiels, P.G. Inflammation and oxidative stress in chronic kidney disease and dialysis patients. Antioxid. Redox Signal. 2021, 35, 1426–1448. [Google Scholar] [CrossRef]
  19. Hutcheson, J.D. Cardiovascular calcification heterogeneity in chronic kidney disease. Circ. Res. 2023, 132, 993–1012. [Google Scholar] [CrossRef] [PubMed]
  20. Fraser, S.D.S.; Roderick, P.J. Kidney disease in the Global Burden of Disease Study 2017. Nat. Rev. Nephrol. 2019, 15, 193–194. [Google Scholar] [CrossRef] [PubMed]
  21. Chen, Y.; Wu, J.; Yu, D.; Liu, M. Plant or animal-based or PLADO diets: Which should chronic kidney disease patients choose? J. Ren. Nutr. 2023, 33, 228–235. [Google Scholar] [CrossRef]
  22. Afshin, A.; Sur, P.J.; Fay, K.A.; Cornaby, L.; Ferrara, G.; Salama, J.S.; Murray, C.J. Health effects of dietary risks in 195 countries, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet 2019, 393, 1958–1972. [Google Scholar] [CrossRef] [PubMed]
  23. Cai, Q.; Duan, M.J.; Dekker, L.H.; Carrero, J.J.; Avesani, C.M.; Bakker, S.J.L.; de Borst, M.H.; Navis, G.J. Ultraprocessed food consumption and kidney function decline in a population-based cohort in the Netherlands. Am. J. Clin. Nutr. 2022, 116, 263–273. [Google Scholar] [CrossRef] [PubMed]
  24. Martins, A.M.; Moreira, A.S.B.; Canella, D.S.; Rodrigues, J.; Santin, F.; Wanderley, B.; Lourenço, R.A.; Avesani, C.M. Elderly patients on hemodialysis have worse dietary quality and higher consumption of ultraprocessed food than elderly without chronic kidney disease. Nutrition 2017, 41, 73–79. [Google Scholar] [CrossRef] [PubMed]
  25. Appel, L.J.; Moore, T.J.; Obarzanek, E.; Vollmer, W.M.; Svetkey, L.P.; Sacks, F.M.; Bray, G.A.; Vogt, T.M.; Cutler, J.A.; Windhauser, M.M.; et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N. Engl. J. Med. 1997, 336, 1117–1124. [Google Scholar] [CrossRef] [PubMed]
  26. Tyson, C.C.; Lin, P.-H.; Corsino, L.; Batch, B.C.; Allen, J.; Sapp, S.; Barnhart, H.; Nwankwo, C.; Burroughs, J.; Svetkey, L.P. Short-term effects of the DASH diet in adults with moderate chronic kidney disease: A pilot feeding study. Clin. Kidney J. 2016, 9, 592–598. [Google Scholar] [CrossRef] [PubMed]
  27. Vineis, P.; Chatziioannou, A.; Cunliffe, V.T.; Flanagan, J.M.; Hanson, M.; Kyrtopoulos, S.; Kirsch-Volders, M. Epigenetic memory in response to environmental stressors. FASEB J. 2017, 31, 2241. [Google Scholar] [CrossRef]
  28. Neytchev, O.; Witasp, A.; Nordfors, L.; Qureshi, A.R.T.; Wennberg, L.; Erlandsson, H.; Stenvinkel, P. FC 123 Renal transplantation mitigates increased biological (epigenetic) age in chronic kidney disease. Nephrol. Dial. Transplant. 2021, 36 (Suppl. S1), gfab147-002. [Google Scholar] [CrossRef]
  29. Witasp, A.; Luttropp, K.; Qureshi, A.R.; Barany, P.; Heimbürger, O.; Wennberg, L.; Ekström, T.J.; Shiels, P.G.; Stenvinkel, P.; Nordfors, L. Longitudinal genome-wide DNA methylation changes in response to kidney failure replacement therapy. Sci. Rep. 2022, 12, 470. [Google Scholar] [CrossRef]
  30. Chang, A.R.; Lazo, M.; Appel, L.J.; Gutierrez, O.M.; Grams, M.E. High dietary phosphorus intake is associated with all-cause mortality: Results from NHANES III. Am. J. Clin. Nutr. 2014, 99, 320–327. [Google Scholar] [CrossRef] [PubMed]
  31. Moldovan, D.; Rusu, C.; Potra, A.; Moldovan, I.; Patiu, I.M.; Gherman-Caprioara, M.; Kacso, I.M. Osteoprotegerin and uremic osteoporosis in chronic hemodialysis patients. Int. Urol. Nephrol. 2017, 49, 895–901. [Google Scholar] [CrossRef] [PubMed]
  32. Turner, M.E.; Rowsell, T.S.; Lansing, A.P.; Jeronimo, P.S.; Lee, L.H.; Svajger, B.A.; Adams, M.A. Vascular calcification maladaptively participates in acute phosphate homeostasis. Cardiovasc. Res. 2023, 119, 1077–1091. [Google Scholar] [CrossRef] [PubMed]
  33. Lioufas, N.M.; Pascoe, E.M.; Hawley, C.M.; Elder, G.J.; Badve, S.V.; Block, G.A.; Johnson, D.W.; Toussaint, N.D. Systematic review and meta-analyses of the effects of phosphate-lowering agents in nondialysis CKD. J. Am. Soc. Nephrol. 2022, 33, 59–76. [Google Scholar] [CrossRef] [PubMed]
  34. Toussaint, N.D.; Pedagogos, E.; Lioufas, N.M.; Elder, G.J.; Pascoe, E.M.; Badve, S.V.; IMPROVE-CKD Trial Investigators. A randomized trial on the effect of phosphate reduction on vascular end points in CKD (IMPROVE-CKD). J. Am. Soc. Nephrol. 2020, 31, 2653–2666. [Google Scholar] [CrossRef] [PubMed]
  35. Shimizu, M.; Fujii, H.; Kono, K.; Goto, S.; Watanabe, K.; Sakamoto, K.; Nishi, S. Clinical implication of consistently strict phosphate control for coronary and valvular calcification in incident patients undergoing hemodialysis. J. Atheroscler. Thromb. 2023, 30, 64159. [Google Scholar] [CrossRef]
  36. Machado, A.D.; Gómez, L.M.; Marchioni, D.M.L.; Dos Anjos, F.S.N.; Molina, M.D.C.B.; Lotufo, P.A.; Benseñor, I.J.M.; Titan, S.M.O. Association between dietary intake and coronary artery calcification in non-dialysis chronic kidney disease: The PROGREDIR Study. Nutrients 2018, 10, 372. [Google Scholar] [CrossRef]
  37. Ter Braake, A.D.; Smit, A.E.; Bos, C.; van Herwaarden, A.E.; Alkema, W.; van Essen, H.W.; Bravenboer, N.; Vervloet, M.G.; Hoenderop, J.G.J.; de Baaij, J.H.F. Magnesium prevents vascular calcification in Klotho deficiency. Kidney Int. 2020, 97, 487–501. [Google Scholar] [CrossRef]
  38. Talari, H.R.; Zakizade, M.; Soleimani, A.; Bahmani, F.; Ghaderi, A.; Mirhosseini, N.; Eslahi, M.; Babadi, M.; Mansournia, M.A.; Asemi, Z. Effects of magnesium supplementation on carotid intima-media thickness and metabolic profiles in diabetic haemodialysis patients: A randomised, double-blind, placebo-controlled trial. Br. J. Nutr. 2019, 121, 809–817. [Google Scholar] [CrossRef]
  39. Sakaguchi, Y.; Hamano, T.; Obi, Y.; Monden, C.; Oka, T.; Yamaguchi, S.; Matsui, I.; Hashimoto, N.; Matsumoto, A.; Shimada, K.; et al. A randomized trial of magnesium oxide and oral carbon adsorbent for coronary artery calcification in predialysis CKD. J. Am. Soc. Nephrol. 2019, 30, 1073–1085. [Google Scholar] [CrossRef]
  40. Bressendorff, I.; Hansen, D.; Schou, M.; Kragelund, C.; Svensson, M.; Hashemi, B.; Brandi, L. The effect of magnesium supplementation on vascular calcification in CKD: A randomized clinical trial (MAGiCAL-CKD). J. Am. Soc. Nephrol. 2023, 34, 886–894. [Google Scholar] [CrossRef]
  41. Zhang, D.; Zhu, Y.; Li, H.; Wang, Y.; Niu, Z.; Zhou, W.; Wang, D. Associations of whole blood zinc levels with coronary artery calcification and future cardiovascular events in CKD patients. Biol. Trace Elem. Res. 2024, 202, 46–55. [Google Scholar] [CrossRef] [PubMed]
  42. McCabe, K.M.; Booth, S.L.; Fu, X.; Shobeiri, N.; Pang, J.J.; Adams, M.A.; Holden, R.M. Dietary vitamin K and therapeutic warfarin alter the susceptibility to vascular calcification in experimental chronic kidney disease. Kidney Int. 2013, 83, 835–844. [Google Scholar] [CrossRef] [PubMed]
  43. El Shinnawy, H.; Elsaid, T.; Farid, S.; Shamseldin, A.; Ibrahim, S.; Elsharabasy, R. The effect of oral vitamin K2 versus K1 on vascular calcification in hemodialysis patients: A randomized controlled trial. Nephrol. Dial. Transplant. 2022, 37 (Suppl. S3), gfac080.026. [Google Scholar] [CrossRef]
  44. Li, Y.; Xie, Z.; Xu, D. Inhibition of maintenance hemodialysis related vascular calcification by vitamin K in chronic kidney disease. Int. J. Clin. Exp. Med. 2017, 10, 15309–15315. [Google Scholar]
  45. Haroon, S.; Davenport, A.; Ling, L.H.; Tai, B.C.; Schurgers, L.; Chen, Z.; Wong, W.K. Randomized controlled clinical trial of the effect of treatment with vitamin K2 on vascular calcification in hemodialysis patients (Trevasc-HDK). Kidney Int. Rep. 2023, 8, 1741–1751. [Google Scholar] [CrossRef] [PubMed]
  46. Levy-Schousboe, K.; Frimodt-Møller, M.; Hansen, D.; Peters, C.D.; Kjærgaard, K.D.; Jensen, J.D.; Strandhave, C.; Elming, H.; Larsen, C.T.; Sandstrøm, H.; et al. Vitamin K supplementation and arterial calcification in dialysis: Results of the double-blind, randomized, placebo-controlled RenaKvit trial. Clin. Kidney J. 2021, 14, 2114–2123. [Google Scholar] [CrossRef] [PubMed]
  47. Holden, R.M.; Booth, S.L.; Zimmerman, D.; Moist, L.; Norman, P.; Day, A.G.; Heyland, D.K. Inhibit progression of coronary artery calcification with vitamin k in hemodialysis patients (the iPACK-HD study): A randomized, placebo-controlled multi-centre, pilot trial. Nephrol. Dial. Transplant. 2022, 38, 746–756. [Google Scholar] [CrossRef] [PubMed]
  48. Kanai, S.; Uto, K.; Honda, K.; Hagiwara, N.; Oda, H. Eicosapentaenoic acid reduces warfarin-induced arterial calcification in rats. Atherosclerosis 2011, 215, 43–51. [Google Scholar] [CrossRef]
  49. Nakamura, K.; Miura, D.; Saito, Y.; Yunoki, K.; Koyama, Y.; Satoh, M.; Ito, H. Eicosapentaenoic acid prevents arterial calcification in klotho mutant mice. PLoS ONE 2017, 12, e0181009. [Google Scholar] [CrossRef]
  50. Son, Y.K.; Lee, S.M.; Kim, S.E.; Kim, K.H.; Lee, S.Y.; Bae, H.R.; Han, J.Y.; Park, Y.; An, W.S. Association between vascular calcification scores on plain radiographs and fatty acid contents of erythrocyte membrane in hemodialysis patients. J. Ren. Nutr. 2012, 22, 58–66. [Google Scholar] [CrossRef]
  51. Lan, Z.; Chen, A.; Li, L.; Ye, Y.; Liang, Q.; Dong, Q.; Yan, J. Downregulation of HDAC9 by the ketone metabolite β-hydroxybutyrate suppresses vascular calcification. J. Pathol. 2022, 258, 213–226. [Google Scholar] [CrossRef]
  52. Merino-Ribas, A.; Araujo, R.; Pereira, L.; Campos, J.; Barreiros, L.; Segundo, M.A.; Silva, N.; Costa, C.F.F.A.; Quelhas-Santos, J.; Trindade, F.; et al. Vascular calcification and the gut and blood microbiome in chronic kidney disease patients on peritoneal dialysis: A pilot study. Biomolecules 2022, 12, 867. [Google Scholar] [CrossRef] [PubMed]
  53. Wei, J.; Li, Z.; Fan, Y.; Feng, L.; Zhong, X.; Li, W.; Guo, T.; Ning, X.; Li, Z.; Ou, C. Lactobacillus rhamnosus GG aggravates vascular calcification in chronic kidney disease: A potential role for extracellular vesicles. Life Sci. 2023, 331, 122001. [Google Scholar] [CrossRef] [PubMed]
  54. Sanchis, P.; Buades, J.M.; Berga, F.; Gelabert, M.M.; Molina, M.; Íñigo, M.V.; Grases, F. Protective effect of myo-inositol hexaphosphate (phytate) on abdominal aortic calcification in patients with chronic kidney disease. J. Ren. Nutr. 2016, 26, 226–236. [Google Scholar] [CrossRef] [PubMed]
  55. Raggi, P.; Bellasi, A.; Bushinsky, D.; Bover, J.; Rodriguez, M.; Ketteler, M.; Chertow, G.M. Slowing progression of cardiovascular calcification with SNF472 in patients on hemodialysis: Results of a randomized phase 2b study. Circulation 2020, 141, 728–739. [Google Scholar] [CrossRef] [PubMed]
  56. Li, W.; Huang, G.; Tang, N.; Lu, P.; Jiang, L.; Lv, J.; Lei, D. Identification of dietary components in association with abdominal aortic calcification. Food Funct. 2023, 14, 8383–8395. [Google Scholar] [CrossRef]
  57. Zhang, P.; Li, Y.; Du, Y.; Li, G.; Wang, L.; Zhou, F. Resveratrol ameliorated vascular calcification by regulating Sirt-1 and Nrf2. Transplant. Proc. 2016, 48, 3378–3386. [Google Scholar] [CrossRef]
  58. Chang, X.Y.; Cui, L.; Wang, X.Z.; Zhang, L.; Zhu, D.; Zhou, X.R.; Hao, L.R. Quercetin attenuates vascular calcification through suppressed oxidative stress in adenine-induced chronic renal failure rats. BioMed Res. Int. 2017, 2017, 5716204. [Google Scholar] [CrossRef]
  59. Calvo, M.S.; Dunford, E.K.; Uribarri, J. Industrial use of phosphate food additives: A mechanism linking ultra-processed food intake to cardiorenal disease risk? Nutrients 2023, 15, 3510. [Google Scholar] [CrossRef]
  60. Su, G.; Saglimbene, V.; Wong, G.; Bernier-Jean, A.; Carrero, J.J.; Natale, P.; Strippoli, G.F. Dietary phosphorus, its sources, and mortality in adults on haemodialysis: The DIET-HD Study. Nutrients 2022, 14, 4064. [Google Scholar] [CrossRef] [PubMed]
  61. Miyamoto, K.I.; Oh, J.; Razzaque, M.S. Common Dietary Sources of Natural and Artificial Phosphate in Food. In Phosphate Metabolism; Springer: Cham, Switzerland, 2022; pp. 99–105. [Google Scholar]
  62. Byrne, F.N.; Gillman, B.A.; Kiely, M.; Palmer, B.; Shiely, F.; Kearney, P.M.; Earlie, J.; Bowles, M.B.; Keohane, F.M.; Connolly, P.P.; et al. Pilot randomized controlled trial of a standard versus a modified low-phosphorus diet in hemodialysis patients. Kidney Int. Rep. 2020, 5, 1945–1955. [Google Scholar] [CrossRef] [PubMed]
  63. Moorthi, R.N.; Armstrong, C.L.; Janda, K.; Ponsler-Sipes, K.; Asplin, J.R.; Moe, S.M. The effect of a diet containing 70% protein from plants on mineral metabolism and musculoskeletal health in chronic kidney disease. Am. J. Nephrol. 2014, 40, 582. [Google Scholar] [CrossRef]
  64. Henley, C.; Colloton, M.; Cattley, R.C.; Shatzen, E.; Towler, D.A.; Lacey, D.; Martin, D. 1,25-Dihydroxyvitamin D3 but not cinacalcet HCl (Sensipar/Mimpara) treatment mediates aortic calcification in a rat model of secondary hyperparathyroidism. Nephrol. Dial. Transplant. 2005, 20, 1370–1377. [Google Scholar] [CrossRef]
  65. Lee, S.M.; An, W.S. Supplementary nutrients for prevention of vascular calcification in patients with chronic kidney disease. Korean J. Intern. Med. 2019, 34, 459–469. [Google Scholar] [CrossRef]
  66. Ter Braake, A.D.; Shanahan, C.M.; de Baaij, J.H.F. Magnesium counteracts vascular calcification: Passive interference or active modulation? Arterioscler. Thromb. Vasc. Biol. 2017, 37, 1431–1445. [Google Scholar] [CrossRef] [PubMed]
  67. Xu, C.; Smith, E.R.; Tiong, M.K.; Ruderman, I.; Toussaint, N.D. Interventions to attenuate vascular calcification progression in chronic kidney disease: A systematic review of clinical trials. J. Am. Soc. Nephrol. 2022, 33, 1011–1032. [Google Scholar] [CrossRef] [PubMed]
  68. Cozzolino, M.; Fusaro, M.; Ciceri, P.; Gasperoni, L.; Cianciolo, G. The role of vitamin K in vascular calcification. Adv. Chronic Kidney Dis. 2019, 26, 437–444. [Google Scholar] [CrossRef] [PubMed]
  69. Kumar, M.; Deshmukh, P.; Bhatt, A.; Sinha, A.H.; Chawla, P. Vitamin E Supplementation and Cardiovascular Health: A Comprehensive Review. Cureus 2023, 15, e48142. [Google Scholar] [CrossRef]
  70. Ikizler, T.A.; Burrowes, J.D.; Byham-Gray, L.D.; Campbell, K.L.; Carrero, J.-J.; Chan, W.; Fouque, D.; Friedman, A.N.; Ghaddar, S.; Goldstein-Fuchs, D.J.; et al. KDOQI Clinical Practice Guideline for Nutrition in CKD: 2020 Update. Am. J. Kidney Dis. 2020, 76, S1–S107. [Google Scholar] [CrossRef] [PubMed]
  71. Endo, J.; Arita, M. Cardioprotective mechanism of omega-3 polyunsaturated fatty acids. J. Cardiol. 2016, 67, 22–27. [Google Scholar] [CrossRef] [PubMed]
  72. Saini, R.K.; Prasad, P.; Sreedhar, R.V.; Akhilender Naidu, K.; Shang, X.; Keum, Y.-S. Omega−3 polyunsaturated fatty acids (PUFAs): Emerging plant and microbial sources, oxidative stability, bioavailability, and health benefits—A review. Antioxidants 2021, 10, 1627. [Google Scholar] [CrossRef]
  73. Sun, W.; Byon, C.H.; Kim, D.H.; Choi, H.I.; Park, J.S.; Joo, S.Y.; Kim, S.W. Renoprotective effects of maslinic acid on experimental renal fibrosis in unilateral ureteral obstruction model via targeting MyD88. Front. Pharmacol. 2021, 12, 708575. [Google Scholar] [CrossRef]
  74. Panahi, Y.; Dashti-Khavidaki, S.; Farnood, F.; Noshad, H.; Lotfi, M.; Gharekhani, A. Therapeutic effects of omega-3 fatty acids on chronic kidney disease-associated pruritus: A literature review. Adv. Pharm. Bull. 2016, 6, 509–514. [Google Scholar] [CrossRef]
  75. Kitagawa, M.; Sugiyama, H.; Morinaga, H.; Inoue, T.; Takiue, K.; Ogawa, A.; Makino, H. A decreased level of serum soluble Klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidney disease. PLoS ONE 2013, 8, e56695. [Google Scholar] [CrossRef]
  76. Garg, P.K.; Guan, W.; Nomura, S.; Weir, N.L.; Karger, A.B.; Duprez, D.; Tsai, M.Y. Associations of plasma omega-3 and omega-6 PUFA levels with arterial elasticity: The multi-ethnic study of atherosclerosis. Eur. J. Clin. Nutr. 2022, 76, 1770–1775. [Google Scholar] [CrossRef]
  77. O’Neill, B.; Raggi, P. The ketogenic diet pros and cons. Atherosclerosis 2019, 292, 119–126. [Google Scholar] [CrossRef]
  78. Carriazo, S.; Perez-Gomez, M.V.; Cordido, A.; García-González, M.A.; Sanz, A.B.; Ortiz, A.; Sanchez-Niño, M.D. Dietary care for ADPKD patients: Current status and future directions. Nutrients 2019, 11, 1576. [Google Scholar] [CrossRef] [PubMed]
  79. Torres, J.A.; Kruger, S.L.; Broderick, C.; Amarlkhagva, T.; Agrawal, S.; Dodam, J.R.; Mrug, M.; Lyons, L.A.; Weimbs, T. Ketosis ameliorates renal cyst growth in polycystic kidney disease. Cell Metab. 2019, 30, 1007–1023. [Google Scholar] [CrossRef] [PubMed]
  80. Han, Y.M.; Ramprasath, T.; Zou, M.H. β-hydroxybutyrate and its metabolic effects on age-associated pathology. Exp. Mol. Med. 2020, 52, 548–555. [Google Scholar] [CrossRef] [PubMed]
  81. De Cabo, R.; Matsson, M.P. Effects of intermittent fasting on health, aging and disease. N. Engl. J. Med. 2019, 381, 2541–2551. [Google Scholar] [CrossRef]
  82. Dube, P.; DeRiso, A.; Patel, M.; Battepati, D.; Khatib-Shahidi, B.; Sharma, H.; Gupta, R.; Malhotra, D.; Dworkin, L.; Haller, S.; et al. Vascular calcification in chronic kidney disease: Diversity in the vessel wall. Biomedicines 2021, 9, 404. [Google Scholar] [CrossRef] [PubMed]
  83. Ravid, J.D.; Kamel, M.H.; Chitalia, V.C. Uraemic solutes as therapeutic targets in CKD-associated cardiovascular disease. Nat. Rev. Nephrol. 2021, 17, 402–416. [Google Scholar] [CrossRef] [PubMed]
  84. Rodrigues, F.G.; Ormanji, M.S.; Heilberg, I.P.; Bakker, S.J.L.; de Borst, M.H. Interplay between gut microbiota, bone health and vascular calcification in chronic kidney disease. Eur. J. Clin. Investig. 2021, 51, e13588. [Google Scholar] [CrossRef] [PubMed]
  85. Evenepoel, P.; Stenvinkel, P.; Shanahan, C.; Pacifici, R. Inflammation and gut dysbiosis as drivers of CKD–MBD. Nat. Rev. Nephrol. 2023, 19, 646–657. [Google Scholar] [CrossRef] [PubMed]
  86. Sun, S.N.; Ni, S.H.; Li, Y.; Liu, X.; Deng, J.P.; Ouyang, X.L.; Kuang, X.Y. Association between dietary inflammatory index with all-cause and cardiovascular disease mortality among older US adults: A longitudinal cohort study among a nationally representative sample. Arch. Gerontol. Geriatr. 2024, 118, 105279. [Google Scholar] [CrossRef] [PubMed]
  87. Shafi, T.; Powe, N.R.; Meyer, T.W.; Hwang, S.; Hai, X.; Melamed, M.L.; Banerjee, T.; Coresh, J.; Hostetter, T.H. Trimethylamine N-oxide and cardiovascular events in hemodialysis patients. J. Am. Soc. Nephrol. 2017, 28, 321–331. [Google Scholar] [CrossRef]
  88. Kwon, Y.J.; Lee, H.S.; Park, G.E.; Lee, J.W. Association between dietary fiber intake and all-cause and cardiovascular mortality in middle aged and elderly adults with chronic kidney disease. Front. Nutr. 2022, 9, 863391. [Google Scholar] [CrossRef]
  89. Wang, A.Y.-M.; Sea, M.M.-M.; Ng, K.; Wang, M.; Chan, I.H.-S.; Lam, C.W.-K.; Sanderson, J.E.; Woo, J. Dietary fiber intake, myocardial injury, and major adverse cardiovascular events among end-stage kidney disease patients: A prospective cohort study. Kidney Int. Rep. 2019, 4, 814–823. [Google Scholar] [CrossRef]
  90. Wang, K.; Qian, D.; Hu, Y.; Cheng, Y.; Ge, S.; Yao, Y. Nut consumption and effects on chronic kidney disease and mortality in the United States. Am. J. Nephrol. 2022, 53, 503–512. [Google Scholar] [CrossRef]
  91. Sirich, T.L.; Plummer, N.S.; Gardner, C.D.; Hostetter, T.H.; Meyer, T.W. Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients. Clin. J. Am. Soc. Nephrol. 2014, 9, 1603–1610. [Google Scholar] [CrossRef]
  92. Filipska, I.; Winiarska, A.; Knysak, M.; Stompór, T. Contribution of gut microbiota-derived uremic toxins to the cardiovascular system mineralization. Toxins 2021, 13, 274. [Google Scholar] [CrossRef] [PubMed]
  93. Black, A.P.; Anjos, J.S.; Cardozo, L.; Carmo, F.L.; Dolenga, C.J.; Nakao, L.S.; de Carvalho Ferreira, D.; Rosado, A.; Eduardo, J.C.C.; Mafra, D.; et al. Does low-protein diet influence the uremic toxin serum levels from the gut microbiota in nondialysis chronic kidney disease patients? J. Ren. Nutr. 2018, 28, 208–214. [Google Scholar] [CrossRef] [PubMed]
  94. Kandouz, S.; Shendi, A.M.; Zheng, Y.; Sandeman, S.R.; Davenport, A. Reduced protein bound uraemic toxins in vegetarian kidney failure patients treated by haemodiafiltration. Hemodial. Int. 2016, 20, 610–617. [Google Scholar] [CrossRef] [PubMed]
  95. Gluba-Brzózka, A.; Franczyk, B.; Rysz, J. Vegetarian diet in chronic kidney disease—A friend or foe. Nutrients 2017, 9, 374. [Google Scholar] [CrossRef] [PubMed]
  96. Kalantar-Zadeh, K.; Joshi, S.; Schlueter, R.; Cooke, J.; Brown-Tortorici, A.; Donnelly, M.; Schulman, S.; Lau, W.-L.; Rhee, C.M.; Streja, E.; et al. Plant-dominant low-protein diet for conservative management of chronic kidney disease. Nutrients 2020, 12, 1931. [Google Scholar] [CrossRef] [PubMed]
  97. Carrero, J.J.; González-Ortiz, A.; Avesani, C.M.; Bakker, S.J.L.; Bellizzi, V.; Chauveau, P.; Clase, C.M.; Cupisti, A.; Espinosa-Cuevas, A.; Molina, P.; et al. Plant-based diets to manage the risks and complications of chronic kidney disease. Nat. Rev. Nephrol. 2020, 16, 525–542. [Google Scholar] [CrossRef]
  98. Stockler-Pinto, M.B.; Mafra, D.; Moraes, C.; Lobo, J.; Boaventura, G.T.; Farage, N.E.; Silva, W.S.; Cozzolino, S.F.; Malm, O. Brazil nut (Bertholletia excelsa, H.B.K.) improves oxidative stress and inflammation biomarkers in hemodialysis patients. Biol. Trace Elem. Res. 2014, 158, 105–112. [Google Scholar] [CrossRef]
  99. Narasaki, Y.; Rhee, C.M.; Kalantar-Zadeh, K. Going nuts to protect kidneys and to live longer with kidney disease. Am. J. Nephrol. 2022, 53, 423–426. [Google Scholar] [CrossRef]
  100. Saglimbene, V.M.; Wong, G.; Craig, J.C.; Ruospo, M.; Palmer, S.C.; Campbell, K.; Garcia-Larsen, V.; Natale, P.; Teixeira-Pinto, A.; Carrero, J.-J.; et al. The association of Mediterranean and DASH diets with mortality in adults on hemodialysis: The DIET-HD multinational cohort study. J. Am. Soc. Nephrol. 2018, 29, 1741–1751. [Google Scholar] [CrossRef]
  101. Su, G.; Saglimbene, V.; Wong, G.; Natale, P.; Ruospo, M.; Craig, J.C.; Strippoli, G.F. Healthy lifestyle and mortality among adults receiving hemodialysis: The DIET-HD study. Am. J. Kidney Dis. 2022, 79, 688–698. [Google Scholar] [CrossRef]
  102. Ricardo, A.C.; Anderson, C.A.; Yang, W.; Zhang, X.; Fischer, M.J.; Dember, L.M.; Fink, J.C.; Frydrych, A.; Jensvold, N.G.; Lustigova, E.; et al. Healthy lifestyle and risk of kidney disease progression, atherosclerotic events, and death in CKD: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study. Am. J. Kidney Dis. 2015, 65, 412–424. [Google Scholar] [CrossRef] [PubMed]
  103. Sherman, R.A.; Mehta, O. Phosphorus and potassium content of enhanced meat and poultry products: Implications for patients who receive dialysis. Clin. J. Am. Soc. Nephrol. 2009, 4, 1370–1373. [Google Scholar] [CrossRef] [PubMed]
  104. Clegg, D.J.; Headley, S.A.; Germain, M.J. Impact of dietary potassium restrictions in CKD on clinical outcomes: Benefits of a plant-based diet. Kidney Med. 2020, 2, 476–487. [Google Scholar] [CrossRef] [PubMed]
  105. Sakaguchi, Y.; Kaimori, J.Y.; Isaka, Y. Plant-dominant low protein diet: A potential alternative dietary practice for patients with chronic kidney disease. Nutrients 2023, 15, 1002. [Google Scholar] [CrossRef] [PubMed]
  106. Cases, A.; Cigarrán-Guldrís, S.; Mas, S.; Gonzalez-Parra, E. Vegetable-based diets for chronic kidney disease? It is time to reconsider. Nutrients 2019, 11, 1263. [Google Scholar] [CrossRef] [PubMed]
  107. Narasaki, Y.; Rhee, C.M. Dietary Therapy for Managing Hyperphosphatemia. Clin. J. Am. Soc. Nephrol. 2020, 16, 9–11. [Google Scholar] [CrossRef]
  108. Narasaki, Y.; Okuda, Y.; Kalantar, S.S.; You, A.S.; Novoa, A.; Nguyen, T.; Streja, E.; Nakata, T.; Colman, S.; Kalantar-Zadeh, K.; et al. Dietary potassium intake and mortality in a prospective hemodialysis cohort. J. Ren. Nutr. 2021, 31, 411–420. [Google Scholar] [CrossRef]
  109. Joshi, S.; McMacken, M.; Kalantar-Zadeh, K. Plant-based diets for kidney disease: A guide for clinicians. Am. J. Kidney Dis. 2021, 77, 287–296. [Google Scholar] [CrossRef]
  110. Tchkonia, T.; Kirkland, J.L. Aging, cell senescence, and chronic disease: Emerging therapeutic strategies. JAMA 2018, 320, 1319–1320. [Google Scholar] [CrossRef]
  111. Panchal, S.K.; John, O.D.; Mathai, M.L.; Brown, L. Anthocyanins in chronic diseases: The power of purple. Nutrients 2022, 14, 2161. [Google Scholar] [CrossRef]
  112. Marx, W.; Kelly, J.; Marshall, S.; Nakos, S.; Campbell, K.; Itsiopoulos, C. The effect of Polyphenol-rich interventions on cardiovascular risk factors in haemodialysis: A systematic review and meta-analysis. Nutrients 2017, 9, 1345. [Google Scholar] [CrossRef]
  113. Ribeiro, M.; Fanton, S.; Paiva, B.R.; Baptista, B.G.; Alvarenga, L.; Ribeiro-Alves, M.; Cardozo, L.F.; Mafra, D. Dark chocolate (70% cocoa) attenuates the inflammatory marker TNF-a in patients on hemodialysis. Clin. Nutr. ESPEN 2023, 53, 189–195. [Google Scholar] [CrossRef]
  114. Coutinho-Wolino, K.S.; Melo, M.F.; Mota, J.C.; Mafra, D.; Guimarães, J.T.; Stockler-Pinto, M.B. Blueberry, cranberry, raspberry, and strawberry as modulators of the gut microbiota: Target for treatment of gut dysbiosis in chronic kidney disease? From current evidence to future possibilities. Nutr. Rev. 2024, 82, 248–261. [Google Scholar] [CrossRef] [PubMed]
  115. Gurău, F.; Baldoni, S.; Prattichizzo, F.; Espinosa, E.; Amenta, F.; Procopio, A.D.; Albertini, M.C.; Bonafè, M.; Olivieri, F. Anti-senescence compounds: A potential nutraceutical approach to healthy aging. Ageing Res. Rev. 2018, 46, 14–31. [Google Scholar] [CrossRef] [PubMed]
  116. Ciceri, P.; Cozzolino, M. The emerging role of iron in heart failure and vascular calcification in CKD. Clin. Kidney J. 2021, 14, 739–745. [Google Scholar] [CrossRef] [PubMed]
  117. Dong, W.; Liu, X.; Ma, L.; Yang, Z.; Ma, C. Association between dietary selenium intake and severe abdominal aortic calcification in the United States: A cross-sectional study. Food Funct. 2024, 15, 1575–1582. [Google Scholar] [CrossRef]
  118. Cardozo, L.F.; Borges, N.A.; Ribeiro, M.; Wang, A.Y.M.; Mafra, D. Protect the kidneys and save the heart using the concept of food as medicine. J. Ren. Nutr. 2023, 33, S110–S117. [Google Scholar] [CrossRef]
Nutrients 16 00617 g001
Figure 1. Food and vascular calcification (VC) in chronic kidney disease (CKD). Green arrows refer to a protective effect of the nutritional components against VC and red arrows indicate favorable VC development.
Figure 1. Food and vascular calcification (VC) in chronic kidney disease (CKD). Green arrows refer to a protective effect of the nutritional components against VC and red arrows indicate favorable VC development.
Nutrients 16 00617 g001
Table 1. The effects of food on vascular calcification in patients with CKD.
Table 1. The effects of food on vascular calcification in patients with CKD.
ArticleDesign Results
Shimizu 2023 [35]Japanese study
64 incident HD patients
Phosphate levels
CAC by CT scans		Consistently strict phosphate control may slow the progression of coronary and valvular calcifications
Machado 2018 [36]PROGREDIR study
373 non-dialysis CKD patients
Food questionnaire
Coronary artery calcification (CAC) by CT scans 		Increased intake of food rich in phosphorus, calcium, and magnesium is associated with CAC
Ter Braake 2020 [37]Klotho-deficient mice
High dietary Mg 		Mg prevents VC in Klotho deficiency
Talari 2019 [38]RCT
54 HD patients with diabetes
Mg oxide or placebo		Decrease in intima–media thickness after Mg supplementation
Sakaguchi 2019 [39]RCT of 96 non-dialysis CKD patients
Mg oxide versus carbon adsorbent
CAC by CT scans
Follow-up 2 years 		CAC score was significantly smaller in the Mg oxide group
Bressendorf 2023 [40]Magical-CKD study
150 CKD patients
Supplementation with Mg for 12 months
CAC by CT scans		No effect on CAC
Zhang 2023 [41]170 CKD patients and 62 healthy controls
Blood zinc levels
CAC by CT scans 		Low zinc with moderate–severe CAC and CDV events
McCabe 2013 [42]Rats with adenine-induced chronic renal failure and warfarin-induced VCHigh dietary vitamin K1 increased vitamin K tissue concentrations and blunted the development of VC
El Shinnawy 2022 [43]RCT on 120 HD patients given supplements of vitamin K2, vitamin K1, and placebo
Matrix Gla protein levels		Matrix Gla protein levels showed a significant increase in the vitamin K2 group compared with vitamin K1 and placebo groups
Li 2017 [44]100 HD patients
Used vitamin-K-enriched dialysate		Decreased VC scores as the effect of vitamin K
Haroon 2023 [45]Trevasc-HDK
RCT on 138 HD patients; CAC scores
Vitamin K2 supplementation		No effect on VC
Levy-Schousboe 2021 [46]RenaKvit
RCT on 48 dialysis patients
Vitamin K or placebo for 2 years
Abdominal aortic calcification		No difference in VC
Holden 2022 [47]iPACK-HD
RCT on 86 HD patients
Vitamin K1 for 12 months
Coronary artery calcium score 		No difference in progression of coronary artery calcification
Kanai 2011 [48]Warfarin-induced medial arterial calcification in a rat modelDecreased medial arterial calcification after omega-3 fatty acid supplementation
Nakamura 2017 [49] Eicosapentaenoic acid in Klotho mutant miceEicosapentaenoic acid limit VC
Son 2012 [50]Cross-sectional study
31 HD patients
Erythrocyte membrane content of monounsaturated fatty acids
Plain radiographs for VC		Monounsaturated fatty acid erythrocyte content is significantly higher in HD patients with arterial medial calcification of the feet than in those without calcifications
Lan 2022 [51]Cell culture
Animal studies
Ketone body β-hydroxybutyrate and VC in CKD model		Ketogenic diet through β-hydroxybutyrate suppresses VC in CKD through downregulation of HDAC9
Merino-Ribas 2022 [52]Cross-sectional study
44 CKD patients on peritoneal dialysis (PD)
Gut and blood microbiomes
VC on plain radiographs		Differences in microbiota between PD patients with and without VC
Wei 2023 [53]CKD Rats with 1,25-dihydroxyvitamin D3 induced VC.
Lactobacillus rhamnosus		Lactobacillus rhamnosus GG supplements worsened the VC in CKD
Sanchis 2016 [54]69 non-dialysis CKD patients
Food questionnaire evaluated the phytate (Myo-inositol hexaphosphate) intake.
VC on plain radiographs		Increased phytate intake was associated with less abdominal aorta calcification
Raggi 2020 [55]RCT
274 HD patients
Myo-inositol hexaphosphate
Cardiovascular calcification on CT scan
52 weeks		Slowed progression of cardiovascular calcification with myo-inositol hexaphosphate
Li 2023 [56]Data from NHANES
1862 participants
Information on 35 dietary components
VC on plain radiographs		Low contents of proteins, fiber and vitamin A and high contents of lipids and caffeine were associated with abdominal aorta calcification.
High adherence to the plant-based pattern was associated with a lower risk of VC
Zhang 2016 [57]Resveratrol Resveratrol is a scavenger for many free radicals and ameliorates VC in CKD
Chang 2017 [58]Rats with adenin-induced chronic renal failure.
Quercetin 		Quercetin exerted a protective effect on VC
Abbreviations: CKD, chronic kidney disease; CAC, coronary artery calcification; HD, hemodialysis; Mg, magnesium; VC, vascular calcification; RCT, randomized control trial; HDAC9, histone deacetylase 9; NHANES, National Health and Nutrition Examination Survey.
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Moldovan, D.; Rusu, C.; Potra, A.; Tirinescu, D.; Ticala, M.; Kacso, I. Food to Prevent Vascular Calcification in Chronic Kidney Disease. Nutrients 2024, 16, 617. https://doi.org/10.3390/nu16050617

AMA Style

Moldovan D, Rusu C, Potra A, Tirinescu D, Ticala M, Kacso I. Food to Prevent Vascular Calcification in Chronic Kidney Disease. Nutrients. 2024; 16(5):617. https://doi.org/10.3390/nu16050617

Chicago/Turabian Style

Moldovan, Diana, Crina Rusu, Alina Potra, Dacian Tirinescu, Maria Ticala, and Ina Kacso. 2024. "Food to Prevent Vascular Calcification in Chronic Kidney Disease" Nutrients 16, no. 5: 617. https://doi.org/10.3390/nu16050617

APA Style

Moldovan, D., Rusu, C., Potra, A., Tirinescu, D., Ticala, M., & Kacso, I. (2024). Food to Prevent Vascular Calcification in Chronic Kidney Disease. Nutrients, 16(5), 617. https://doi.org/10.3390/nu16050617

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