Cardiovascular disease is the most common cause of death in patients with end-stage renal disease (ESRD). The initiation of dialysis for treatment of ESRD exacerbates chronic electrolyte and ...hemodynamic perturbations. Rapid large shifts in effective intravascular volume and electrolyte concentrations ultimately lead to subendocardial ischemia, increased left ventricular wall mass, and diastolic dysfunction, and can precipitate serious arrhythmias through a complex pathophysiological process. These factors, unique to advanced kidney disease and its treatment, increase the overall incidence of acute coronary syndrome and sudden cardiac death. To date, risk prediction models largely fail to incorporate the observed cardiovascular mortality in the CKD population; however, multimodality imaging may provide an additional prognostication and risk stratification. This comprehensive review discusses the cardiovascular risks associated with hemodialysis, and explores the pathophysiology and the novel utilization of multimodality imaging in CKD to promote a personalized approach for these patients with implications for future research.
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Apolipoprotein B100 (apoB) is a large (520-kDa) complex secretory protein; its secretion is regulated posttranscriptionally
by several degradation pathways. The best described of these degradative ...processes is co-translational ubiquitinylation
and proteasomal degradation of nascent apoB, involving the 70- and 90-kDa heat shock proteins and the multiple components
of the proteasomal pathway. Ubiquitinylation involves several proteins, including ligases called E3s, that coordinate the
covalent binding of ubiquitin to target proteins. The recent discovery that tumor autocrine motility factor receptor, also
known as gp78, is an endoplasmic reticulum (ER)-associated E3, raised the possibility that this E3 might be involved in
the ER-associated degradation of nascent apoB. In a series of experiments in HepG2 cells, we demonstrated that overexpression
of gp78 was sufficient for increased ubiquitinylation and proteasomal degradation of apoB, with reduced secretion of apoB-lipoproteins.
This action of gp78 was specific: overexpression of the protein did not affect secretion of either albumin or apolipoprotein
AI. Furthermore, overexpression of a cytosolic E3, Itch, had no effect on apoB secretion. Finally, using an in vitro translation system, we demonstrated that gp78 led to increased ubiquitinylation and proteasomal degradation of apoB48.
Together, these results indicate that an ER-associated protein, gp78, is a bona fide E3 ligase in the apoB ER-associated degradation pathway.
Third-spacing of fluid is a common complication in hospitalized patients with decompensated cirrhosis. In addition to ascites, patients with advanced cirrhosis may develop significant peripheral ...edema, which may limit mobility and exacerbate debility and muscle wasting. Concomitant kidney failure and cardiac dysfunction may lead to worsening hypervolemia, which may ultimately result in pulmonary edema and respiratory compromise. Diuretic use in such patients may be limited by kidney dysfunction and electrolyte abnormalities, including hyponatremia and hypokalemia. A slow, continuous form of ultrafiltration known as aquapheresis is a method of extracorporeal fluid removal whereby a pump generates a transmembrane pressure that forces an isotonic ultrafiltrate across a semipermeable membrane. This leads to removal of an ultrafiltrate that is isotonic to blood without the need for dialysate or replacement fluid as is necessary in other forms of continuous kidney replacement therapy. This technique has been utilized in other conditions including acute decompensated heart failure, with trials showing mixed, but generally favorable results. Herein, we present a series of our own experience using aquapheresis among patients with cirrhosis, review the literature regarding its use in other hypervolemic states, and discuss how we may apply lessons learned from use of aquapheresis in heart failure to patients with end-stage liver disease.
Cardiovascular disease is the most common cause of death in patients with end-stage renal disease (ESRD). The initiation of dialysis for treatment of ESRD exacerbates chronic electrolyte and ...hemodynamic perturbations. Rapid large shifts in effective intravascular volume and electrolyte concentrations ultimately lead to subendocardial ischemia, increased left ventricular wall mass, and diastolic dysfunction, and can precipitate serious arrhythmias through a complex pathophysiological process. These factors, unique to advanced kidney disease and its treatment, increase the overall incidence of acute coronary syndrome and sudden cardiac death. To date, risk prediction models largely fail to incorporate the observed cardiovascular mortality in the CKD population; however, multimodality imaging may provide an additional prognostication and risk stratification. This comprehensive review discusses the cardiovascular risks associated with hemodialysis, and explores the pathophysiology and the novel utilization of multimodality imaging in CKD to promote a personalized approach for these patients with implications for future research.
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