A myriad of determinants modify the BRS in ESRD patients, such as the renin-angiotensin-aldosterone system, vascular resistance, uremic toxins, anemia, sodium and water retention, mineral metabolism, and endocrinological disruption; the combination of these factors causes cardiac damage, which eventually leads to heart failure, ischemic heart disease, and sudden death [32]. The gene discussed is REN; the disease is anemia (phenotype).