Update on Hemodialysis-Induced Multiorgan Ischemia: Brains and Beyond

Abstract

Hemodialysis is a life-saving treatment for patients with kidney failure. However, patients requiring hemodialysis have a 10-20 times higher risk of cardiovascular morbidity and mortality than that of the general population. Patients encounter complications such as episodic intradialytic hypotension, abnormal perfusion to critical organs (heart, brain, liver, and kidney), and damage to vulnerable vascular beds. Recurrent conventional hemodialysis exposes patients to multiple episodes of circulatory stress, exacerbating and being aggravated by microvascular endothelial dysfunction. This promulgates progressive injury that leads to irreversible multiorgan injury and the well-documented higher incidence of cardiovascular disease and premature death. This review aims to examine the underlying pathophysiology of hemodialysis-related vascular injury and consider a range of therapeutic approaches to improving outcomes set within this evolved rubric.‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬.

Trial registration: ClinicalTrials.gov NCT05965934 NCT04603014 NCT04877041.

Figure 1

Schematic summarizing the organ systems that are vulnerable to hemodialysis-induced reductions in perfusion and the interconnected nature of these insults. Hemodialysis induces myocardial ischemia; this reduces ejection (1 and 2), potentiating the ischemic challenge to all the other vascular beds. Injury to the kidney reduces residual kidney function and, therefore, increases the ultrafiltration requirement (3), aggravating circulatory stress. Ischemic challenge to the gut (4) and liver (5) increases the exposure to uremic toxins (worsening uremic symptoms) and in particular endotoxin (6), with the result of worsening autoregulation, potentiating hypotension, promoting systemic inflammation (7), and in particular contributing to white matter injury in the brain (8).

Figure 2

Representative arterial spin labeling magnetic resonance images demonstrating severe reduction of brain blood flow induced by 3 hours of conventional hemodialysis. Images on the left are pre-hemodialysis, and images on right of the pane are obtained during hemodialysis after 3 hours of treatment. CBF, cerebral blood flow.

Figure 3

A representative magnetic resonance image demonstrating areas of change emerging within the brain of a patient receiving a hemodialysis in a single treatment session. Regions where fractional anisotropy (blue), axial (yellow), radial (red), and mean (green) diffusivity increased significantly (P < 0.05) at peak stress during hemodialysis. This is indicative of new cytotoxic and some secondary vasoactive edema.