Chronic kidney disease (CKD) is a true inflammatory condition and it is associated with multiple cardiovascular (CV) risk factors. In fact, patients with CKD are at significantly higher risk of suffering a CV event than individuals in the general population with normal kidney function. The main causes of CV complication in these patients are left ventricular hypertrophy and coronary arterial disease.
Clinical evidence has shown that visceral adipose tissue (VAT) is an important CV risk marker. For example, there seems to be a connection between VAT and CV disease in diseases which are as common as metabolic syndrome, diabetes and arterial hypertension. Recognition that adipocytes are a type of cell with complex functioning and endocrine, paracrine and autocrine capacity has aroused interest in researching them in disciplines such as molecular biology, endocrinology, nephrology, cardiology and immunology.
This makes it a fertile ground for scientific debate, given theirbroad heterogeneity in terms of location, functions, proteomics and metabolomics. In fact, these characteristics are of particular importance in VAT, where changes in function and volume are associated with greater cardiometabolic risk.
Epicardial adipose tissue
Anatomy and function: Different regions of extra-abdominal adipose tissue have been studied in recent years. Thus epicardial adipose tissue (EAT) has been said to be a specific risk marker in coronary disease.9,10 More specifically, EAT represents the fat that is confined within the pericardial sac and located on the surface of the heart, covering the epicardial portion of the coronary arteries.
It varies in volume within a range from 68 cm3 to 124 cm3, representing approximately from 15% to 20% of total cardiac volume and covering approximately 80% of the cardiac surface. In physiological terms it has mechanical, biochemical and heat-regulating functions.12 Nevertheless, under pathological conditions EAT affects the heart and coronary arteries locally by means of paracrine and vasocrine activity, with the secretion of proinflammatory cytokines.
The EAT may be detected by means of different imaging techniques. Ultrasound scan was one of the first techniques used for this purpose, and it is both economical and rapid to use. Nevertheless, magnetic resonance imaging and computed axial tomography (CAT) are able to give a better and more suitable visualisation and measurement of the tissue, due to their high spatial resolution.
Other cardiac fat deposits
EAT must not be confused with another type of localised cardiac fat deposit: pericardial adipose tissue (PAT) which, unlike EAT, is located outside the visceral pericardium over the external surface of the parietal pericardium.20 Both tissues have different origins: EAT originates in the splacno pleural layer of the mesoderm, as does VAT, while PAT originates in the primitive thoracic mesenchyme; this is why local circulation too differs in both tissues;
Thus epicardial fat is irrigated by the coronary arteries (sharing the same microcirculation as the myocardium), while pericardial fat is irrigated by the pericardiophrenic branches of the internal mammary artery.12 Due to this close relationship between EAT, the myocardium and the coronary arteries, the volume and function of EAT has been linked to the genesis and progression of coronary atherosclerosis.
Epicardial adipose tissue and metabolism
Current evidence indicates that it is possible that adipose tissue next to coronary vessel walls permits the diffusion or transport through the vasa vasorum of proinflammatory cytokines or adipocytokines produced by the adipocytes, such as tumour necrosis factor alpha, interleukin 6 (IL-6), leptin, resistin and visfatin, among others.As a whole these elements cause local endothelial dysfunction, with an increase in the lipotoxicity-mediated expression of adhesion and oxidative stress molecules towards the endoplasmatic reticule via overload of free fatty acids in the surrounding tissues, where hypertrigliceridemia and insulin resistance associated with obesity and metabolic syndrome degrade the conditions of this microenvironment.
Finally, this process favours the binding and increased dwell time in the subendothelium of low-density lipoproteins and other proatherogenic ApoB lipoproteins, such as intermediate density lipoprotein and (a) lipoprotein. The oxidative and non-oxidative modifications of these proteins make the subendothelium a niche for immunocompetent cells such as macrophages, T cells, monocytes and modified smooth muscle cells. When these cells interact within this medium they give rise to the functional and morphological alterations that typify the atherosclerotic plaque.
The possibility that EAT may activate myocardiocyte pathways that alter its proteomic pattern and in turn its endocrine secretor capacity is far more interesting. The discovery of natriuretic peptides therefore altered the view of the heart as a simple mechanical pump, showing it to be an organ that is able to modify its performance by interacting with the rest of the organism by producing these hormonal messengers.
Epicardial adipose tissue and chronic kidney disease
Although the literature which evaluates EAT in CKD is always developing, some studies have detected a connection between EAT and the presence of CAC in small groups of patients with kidney involvement. One of the first studies was undertaken in 80 patients with CKD under dialysis and 27 controls. They were tested to detect atherosclerosisinflammation-malnutrition syndrome (AIM) by measuring serum levels of albumin and reactive C protein, while CAT and EAT were quantified by CAT.
EAT was significantly associated with the components of AIM syndrome, and there was a proportional relationship between the increase in the volume of EAT and the presence of CAC. Kerr et al. studied 94 patients with grade CKD who were not in dialysis, reporting a lineal correlation with increased EAT and CAC and including other cytokines, such as IL-6 and fibroblastic growth factor 23, among others.
Another study in a cohort of 411 patients with grade CKD in dialysis who were being evaluated for kidney transplant found that EAT is a risk factor for alterations in myocardial perfusion, as is the presence of CAC. EAT was found to be independently associated with CAC when predicting myocardial perfusion defects. Karatas et al. recently proved that the thickness of the EAT measured by echocardiograph is significantly greater in patients undergoing haemodialysis in comparison with those in pre-dialysis stages or healthy subjects.
Obesity, nutrition and the kidneys
Nutritional alterations are often found in patients with kidney disease. The impact of kidney disease on body composition is in itself a morbimortality factor in this population. The most outstanding factors which lead to morbimortality include the presence of diabetes, hypertension, dyslipidemia, chronic inflammatory states, a lack of protein and calories in the diet, immune dysfunction, the depletion of lean mass, micronutrient deficiency and a negative nitrogen balance, among others.
Although obesity is known to be a CV risk factor and obese patients are at higher risk of suffering CKD and even progressing more swiftly to advanced CKD once they are under dialysis, paradoxically survival is longer the higher their BMI (inverse epidemiology). Although this phenomenon is contrary to what is observed in the general population, it has been observed in some risk groups (the elderly and patients with congestive heart failure).
Possible explanations for these findings include protein-calorie deficiency, a reduction in nutritional reserves, metabolic acidosis and inflammation.48 More specifically, this paradox observed in patients with CKD is associated with PEW (protein-energy wasting) and inflammation.49 Thus patients who have a lower BMI or bodyweight may have a higher degree of PEW, and this would be the cause of increased morbimortality. On the contrary, overweight patients would have less deficiency in their ingestion of protein or energy and lower probability of developing PEW.
Author: Luis D’Marcoa, Marie Cortez, María Salazar, Marcos Lima-Martínez, Valmore Bermúde