Multitargeted interventions to reduce dialysis-induced systemic stress

Hemodialysis (HD) is a life-sustaining therapy as well as an intermittent and repetitive stress condition for the patient. In ridding the blood of unwanted substances and excess fluid from the blood, the extracorporeal procedure simultaneously induces persistent physiological changes that adversely affect several organs. Dialysis patients experience this systemic stress condition usually thrice weekly and sometimes more frequently depending on the treatment schedule. Dialysis-induced systemic stress results from multifactorial components that include treatment schedule (i.e. modality, treatment time), hemodynamic management (i.e. ultrafiltration, weight loss), intensity of solute fluxes, osmotic and electrolytic shifts and interaction of blood with components of the extracorporeal circuit. Intradialytic morbidity (i.e. hypovolemia, intradialytic hypotension, hypoxia) is the clinical expression of this systemic stress that may act as a disease modifier, resulting in multiorgan injury and long-term morbidity. Thus, while lifesaving, HD exposes the patient to several systemic stressors, both hemodynamic and non-hemodynamic in origin. In addition, a combination of cardiocirculatory stress, greatly conditioned by the switch from hypervolemia to hypovolemia, hypoxemia and electrolyte changes may create pro-arrhythmogenic conditions. Moreover, contact of blood with components of the extracorporeal circuit directly activate circulating cells (i.e. macrophages-monocytes or platelets) and protein systems (i.e. coagulation, complement, contact phase kallikrein-kinin system), leading to induction of pro-inflammatory cytokines and resulting in chronic low-grade inflammation, further contributing to poor outcomes. The multifactorial, repetitive HD-induced stress that globally reduces tissue perfusion and oxygenation could have deleterious long-term consequences on the functionality of vital organs such as heart, brain, liver and kidney. In this article, we summarize the multisystemic pathophysiological consequences of the main circulatory stress factors. Strategies to mitigate their effects to provide more cardioprotective and personalized dialytic therapies are proposed to reduce the systemic burden of HD.