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Review
. 2024 May 14;12(5):1085.
doi: 10.3390/biomedicines12051085.

Innovative Treatments to Counteract Endothelial Dysfunction in Chronic Kidney Disease Patients

Giulia Marrone  1 , Kevin Cornali  1 , Manuela Di Lauro  1 , Maria Josè Ceravolo  2 , Luca Di Marco  1 , Simone Manca di Villahermosa  1   2 , Anna Paola Mitterhofer  1   2 , Annalisa Noce  1   2
Affiliations
Review

Innovative Treatments to Counteract Endothelial Dysfunction in Chronic Kidney Disease Patients

Giulia Marrone et al. Biomedicines. .

Abstract

In chronic kidney disease (CKD) patients, several risk factors contribute to the development of endothelial dysfunction (ED), which can be described as an alteration in the cell structure or in the function of the endothelium. Among the well-known CKD-related risk factors capable of altering the production of endothelium-derived relaxing factors, we include asymmetric dimethylarginine increase, reduced dimethylarginine dimethylamine hydrolase enzyme activity, low-grade chronic systemic inflammation, hyperhomocysteinemia, oxidative stress, insulin resistance, alteration of calcium phosphorus metabolism, and early aging. In this review, we also examined the most important techniques useful for studying ED in humans, which are divided into indirect and direct methods. The direct study of coronary endothelial function is considered the gold standard technique to evaluate if ED is present. In addition to the discussion of the main pharmacological treatments useful to counteract ED in CKD patients (namely sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonist), we elucidate innovative non-pharmacological treatments that are successful in accompanying the pharmacological ones. Among them, the most important are the consumption of extra virgin olive oil with high intake of minor polar compounds, adherence to a plant-dominant, low-protein diet (LPD), an adaptive physical activity program and, finally, ketoanalogue administration in combination with the LPD or the very low-protein diet.

Keywords: bioactive natural compounds; chronic kidney disease; endothelial dysfunction; endothelium; inflammation; innovative treatments; insulin resistance; ketoanalogues; nitric oxide; oxidative stress.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Factors involved in ED genesis in CKD. Abbreviations: ADMA, asymmetric dimethylarginine; CKD, chronic kidney disease; COX, cicloxigenase; DDAH, dimethylarginine imethylaminohydrolase; ED, endothelial dysfunction; eNOS, endotelial nitric oxide synthase; ET-1, endothelin-1; FGF23, fibroblast growth factor 23; hs-CRP, high-sensitivity C-reactive protein; ICAM, intercellular adhesion molecule; IL, inteleukin; LDL, low-density lipoprotein; MAPK, mitogen-activated protein kinase; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; NO, nitric oxide; PI3K, phosphoinositide 3-kinases; TNF, tumor necrosis factor; VCAM, vascular cell adhesion molecule; VSMC, vascular smooth muscle cells; ↑ increase; ↓ decrease.
Figure 2
Figure 2
Methods for diagnosing endothelial dysfunction. Studying endothelial function is based on two main methods: indirect and direct. The first one consists of measuring the concentration of peripheral circulating biomarkers. The second method is based on endothelium-dependent vasomotor tests in order to assess coronary circulation and/or peripheral circulation. Abbreviations: ADMA, asymmetric dimethylarginine; FMD, flow-mediated dilatation; ICAM-1, intracellular adhesion molecule-1; miR-126, microRNA-126; PECAM-1, platelet endothelial cell adhesion molecule-1; QCA, quantitative coronary angiography; VCAM-1, vascular cellular adhesion molecule-1.
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