Two-Step Clinical Pathways to Cardiovascular Mortality in Chronic Kidney Disease and Dialysis -- A Narrative Review

Patients with chronic kidney disease (CKD) face a markedly elevated risk of death from cardiovascular disease (CVD); in particular, those requiring hemodialysis have a 10- to 30-fold higher risk than the general population. This extremely increased risk of CVD death reflects the coexistence of multiple traditional and nontraditional risk factors. The present narrative review considers two distinct steps: first, the occurrence of a CVD event, and second, death resulting from an inability to recover from the CVD event. Patients undergoing hemodialysis are at an increased risk for both of these steps, accounting for the dramatically higher risk of CVD death in this population. High risk for the second step-death following a CVD event-may be driven by conditions called decreased physical resilience and increased frailty. Studies of patients on hemodialysis show that predictors for death at this stage include key components of malnutrition-inflammation-atherosclerosis syndrome-also called the malnutrition-inflammation-complex-syndrome or protein-energy wasting-such as lower body mass index, lower serum albumin, and higher C-reactive protein. Other important contributors include higher age, longer dialysis duration, diabetic kidney disease, phosphate, calcium, serum calcification propensity (T50), and insulin-like growth factor 1 levels. Notably, some of these factors also predict death following infection, suggesting that the risk predictors for the second step are shared between CVD and infection. Recognizing these steps may facilitate prevention and greater preparedness for CVD, infection, and other stressful events among patients with CKD.