The Mutual Contribution of 3-NT, IL-18, Albumin, and Phosphate Foreshadows Death of Hemodialyzed Patients in a 2-Year Follow-Up

Abstract

Patients with chronic kidney disease (CKD), especially those who are hemodialyzed (HD), are at significantly high risk of contracting cardiovascular disease and having increased mortality. This study aimed to find potential death predictors, the measurement of which may reflect increased mortality in HD patients, and then combine the most promising ones in frames of a simple death risk assessment model. For this purpose, HD patients (n=71) with acute myocardial infarction in the last year (HD group) and healthy people (control group) as a comparative group (n=32) were included in the study. Various laboratory determinations and non-invasive cardiovascular tests were performed. Next, patients were followed for two years, and data on cardiovascular (CV) deaths were collected. On this basis, two HD groups were formed: patients who survived (HD-A, n=51) and patients who died (HD-D, n=20). To model HD mortality, 21 out of 90 potential variables collected or calculated from the raw data were selected. The best explanatory power (95.5%) was reached by a general linear model with four variables: interleukin 18, 3-nitrotyrosine, albumin, and phosphate. The interplay between immuno-inflammatory processes, nitrosative and oxidative stress, malnutrition, and calcium-phosphate disorders has been indicated to be essential in predicting CV-related mortality in studied HD patients. ClinicalTrials.gov Identifier: NCT05214872.

Chronic Kidney Disease as a Cardiovascular Disorder—Tonometry Data Analyses

“…These factors can be classified as (a) traditional, such as (1) advanced age, (2) diabetes mellitus, (3) hypertension, (4) dyslipidemia, and (b) non-traditional (CKD-specific), including (1) oxidative stress, (2) chronic inflammation, (3) immune deficiency, (4) anemia (reduction of erythrocytes lifespan, erythropoietin deficiency, and iron disturbances [3,4]), ( 5) proteinuria, (6) volume overload, (7) neuro-hormonal activation, increased sympathetic tone, (8) the impact of dialysis itself, ( 9) malnutrition (10) upregulation of the renin-angiotensin-aldosterone system, (11) increased salt sensitivity, and (12) calcium-phosphate balance disorders. As bone mineral metabolism worsens as CKD progresses, the associated hyperphosphatemia, secondary hyperparathyroidism, and inhibition of vitamin D synthesis lead to vascular calcification, causing hardening of the arteries [1,2,5,6]. All of these factors contribute to the structural changes in the heart and blood vessels with remodeling and stiffening of the arteries and the left ventricle.…”

Pathomechanisms of Disturbances Underlying Chronic Disorders

“…Nowadays, new treatment options for CKD, which is treated not only as a kidney disease but also as a chronic cardiovascular disorder [18], are being actively pursued. It is known that CKD is a complex multifactorial disease.…”